StemCell Therapy

Tamara Watkins was in her late twenties when she started to get severe back pain and headaches.

The young mother-of-three went to her GP, who ordered an x-ray, but the image showed nothing unusual.

Unsure what was wrong, her GP referred her to an osteopath in the hope that regular massage sessions would help her get on top of the chronic pain.

But Watkins' symptoms just kept getting worse.

"I remember going to the osteo and being on her table and just vomiting uncontrollably," Watkins told 9news.com.au.

"I was getting extreme headaches and tingling down my arm and into my leg."

Just turning her neck could induce sudden feelings of nausea, Watkins said.

Concerned, Watkins' osteopath pushed her to get more tests done.

An MRI revealed the cause of her debilitating pain - a bone spur on her spine brought on by osteoarthritis.

"It looked like a bird's beak and it was growing into my spine," she said.

"If it hadn't been picked up it could have resulted in more permanent damage."

Watkins needed high-risk surgery to remove the spur and replace a crushed disc.

"It took three years to find a surgeon that would operate," she said.

Doctors also gave Watkins some confronting news.

"The saddest part was when the doctors advised me against having any more children because of my condition," she said.

Watkins said she was also shocked to be diagnosed with arthritis at the age of 28.

"I didn't actually think of it as arthritis, because when you think of arthritis you think of 80 year-old-men who are crippled with it.

"I didn't really put myself into that category."

Watkins, who is now 46, went on to have a successful surgery.

She also defied the odds by having another healthy child, who is now six years old.

While she still experiences some pain due to her osteoarthritis, Watkins said the symptoms had become manageable with the help of regular treatments with her osteopath.

Data from the 2021 Census shows that about 2.2 million Australians are now living with arthritis.

This makes arthritis the second-most common long-term health condition, after issues relating to mental health.

Almost one in five Aussies said their pain would have to be so bad that they were unable to move before seeking the help of a health professional.

Osteopathy Australia president Dr Michelle Funder said it was a misconception that having arthritis meant you had to suffer through severe pain.

"Although there is no cure for arthritis, osteopathy may help to reduce pain, ease swelling and improve mobility and range of joint movement," Funder said.

"Early diagnosis and improving a person's lifestyle are key to preventing further degeneration, and to help them perform daily activities more easily."

Contact reporter Emily McPherson at empcherson@nine.com.au.

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Tamara was just 28 when she was diagnosed with a condition affecting 2.2 million Australians - 9News

In a little-noticed study published earlier this year, scientists from Oregon Health & Science University reported the birth of three mouse pups that had been created with a never-before-used recipe for reproduction. Using a common cloning technique, researchers removed the genetic material from one females eggs and replaced them with nuclear DNA from the skin cells of another. Then with a novel chemical cocktail, they nudged the eggs to lose half their new sets of chromosomes and fertilized them with mouse sperm.

In a big step toward achieving in vitro gametogenesis one of reproductive medicines more ambitious moonshots the group led by pioneering fertility researcher Shoukrat Mitalipov now intends to use the same method to make artificial human embryos in a test tube.

If successful, the research holds enormous potential for treating infertility, preventing heritable diseases, and opening up the possibility for same-sex couples to have genetically related children.

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Its one of those high-risk, high reward type of projects, said Paula Amato, an OB-GYN and infertility specialist at OHSU who collects the human eggs used in Mitalipovs experiments. We have no idea yet if it will work, but age-related fertility decline remains an intractable problem in our field, so were eternally grateful to these private funders who are filling a real need here.

Mitalipov directs the Center for Embryonic Cell and Gene Therapy at OHSU. Established in 2013, the center focuses on combining assisted reproductive technologies with genetic correction techniques, with the goal of one day preventing inherited disease.

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The groups work on in vitro gametogenesis (IVG) in human cells is being made possible by an award from Open Philanthropy a grant-making organization primarily funded by Facebook co-founder Dustin Moskovitz and his wife Cari Tuna which will supply the researchers with $4 million over the next three years. The infusion of funds and the involvement of a scientist as storied as Mitalipov makes the ethical and legal questions surrounding mass egg and sperm production more urgent, experts told STAT.

In the U.S., there are no federal laws that prohibit this type of IVG work. However, Congress has barred any research that creates, destroys, or knowingly harms human embryos from receiving federal funding. At the state level, laws governing human embryo research vary widely with 11 states banning it entirely, five states expressly permitting it, and a lot of gray areas in between.

For IVG to move from the research lab to a fertility clinic would require permission from the Food and Drug Administration. Its still unclear if thats something the agency would be able to consider a spending bill rider currently prevents the FDA from receiving any requests to pursue clinical trials involving starting pregnancies with embryos that have been genetically manipulated. In 2019, Congress considered modifying the ban, following a push from scientists and advocates of mitochondrial replacement therapy, also known as three-person IVF, but ultimately renewed it. Mitochondrial replacement therapy is a procedure that combines genetic material from an egg and sperm with mitochondria from a female donor.

Somatic cell nuclear transfer for IVG could fall under the same provision, if the somatic DNA and the egg came from different people. But if they came from the same person, that might represent a loophole.

Some bioethicists worry that the easy availability of IVG could usher in a new era of eugenics, scenarios where prospective parents could create large numbers of embryos and use genetic tools to select the best one. IVG also raises the specter of nonconsensual parenthood something most state laws are currently ill-equipped to handle.

Should this become clinically available, there will be legitimate questions about whose cells can be used and under what conditions that will need regulatory answers, said Hank Greely, director of the Stanford Center for Law and Bioscience, whose book, The End of Sex, examines the future of in vitro gametogenesis. Will that happen? We dont know. But Mitalipov has certainly proven himself a bold and creative scientist, and from my perspective, having his group join the effort to help people who want to have genetic babies but cant is a good thing, provided they can do it safely and effectively.

Mitalipovs lab has long been an incubator for envelope-pushing science. In 2009, he and his colleagues figured out a way to swap out glitchy mitochondrial DNA for healthy versions in the egg cells of monkeys a groundbreaking advance that paved the way for mitochondrial replacement therapy in humans. In 2013, they created lines of embryonic stem cells from cloned human embryos for the first time. A few years later, they became the first team in the U.S. to attempt to correct a genetic mutation in viable human embryos using CRISPR.

But until recently, in vitro gametogenesis, or IVG, wasnt on his to-do list.

Gametes are the cells capable of giving rise to future generations: sperm and eggs. The idea behind IVG is to produce those kinds of cells in test tubes, rather than inside a developing animals body.

In recent years, scientists have made headlines producing artificial gametes from induced pluripotent stem cells. But Mitalipovs group plans to revive a much older technology, which saw some early success in IVG before being abandoned: somatic cell nuclear transfer.

Somatic cell nuclear transfer was pioneered by researchers at the Roslin Institute in Scotland. After they succeeded in using the technique to clone the first mammal a sheep named Dolly scientists realized it might be used to generate artificial gametes, if they could overcome a few additional hurdles.

In cloning, the emptied egg receives a full set of chromosomes from the somatic cell donor and is stimulated in the lab to make it start dividing. Any offspring that result will be genetically identical to that somatic cell.

The procedure for making an artificial oocyte is technically similar to cloning, but would generate unique individuals after fertilization with sperm. However, in order for any resulting embryos to have the right number of chromosomes, the donor DNA has to be cut in half, a process known as haploidization. Oocytes are equipped with the machinery to make that adjustment, if the somatic DNA is introduced at the right phase of their cell cycle.

In 2000, four years after Dolly was born, researchers in Spain generated the first human artificial oocytes using this method. They fertilized three of them, and froze the resulting embryos at the two-cell stage. The plan was to transfer the frozen embryos to the uterus of a woman who had been unable to conceive, and consented to having her somatic DNA slipped into donor eggs as a last-ditch attempt to have genetically related children with her husband.

But when the same protocol was tested in mice where its effects could be examined more closely the chromosomes didnt separate as intended. Shortly thereafter, somatic cell nuclear transfer for human reproduction was banned in many countries, including Spain.

The IVG field moved on, buoyed by the discovery a few years later of a method for taking any kind of cell and rewinding its developmental clock to a more primitive state. With the right chemical cues, a team of Japanese scientists nudged these pluripotent stem cells to produce functional gametes in mice; first sperm in 2011, then eggs, five years later. But they struggled to generate similar results in humans.

In 2018, the group succeeded for the first time in making immature human eggs from scratch. But the process wasnt very efficient and it involved incubating the human stem cells in mini-ovaries theyd created in the lab from mouse embryonic cells a resource-intensive process not exactly suited to mass manufacturing.

So when a post-doc at OHSU named Eunju Kang proposed revisiting the idea of somatic cell nuclear transfer for IVG, Mitalipov was initially skeptical. But data from her initial mouse experiments proved persuasive. Mitalipov threw his support behind the project, and teamed up with a group at Weill Cornell Medicine in New York, including reproductive endocrinologist Gianpiero Palermo, who had successfully generated artificial human oocytes using cloning technology back in 2002. They published the results of their mice experiments in Nature Communications Biology in January.

The OHSU team is now adapting those methods to see if they can generate artificial human eggs with properly separated chromosomes. If successful, they plan to then fertilize those eggs with sperm and grow the resulting embryos in the lab for five or six days to see if they develop normally.

They are betting that this method, while older, will prove better than the induced pluripotent stem cell technologies currently being advanced by artificial egg-making start-up outfits like Conception, Ivy Natal and Gameto.

That approach requires the cells to be cultured for months rather than days, which can lead to epigenetic programming errors and chromosomal instability. Mitalipov also believes that starting with natural eggs will make it easier to strip the donor DNA of its cellular memory and return it to the primitive state known as totipotency a critical step in enabling the embryo to eventually develop all the specialized tissues that make up a human body.

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Researchers revive abandoned technique in effort to make artificial human eggs in a test tube - STAT

SACRAMENTO, Calif. The steel-bar cells inside the courtrooms of Sacramento County Main Jails Patino Justice Center and Gordon Schaber Courthouse are some of the busiest spaces in a bustling Sacramento Superior Court. The cells are as much a part of the courtrooms as the judges bench or jurors box.

Eight courtrooms in all have cells within their courtrooms: Departments 4, 5, 8 and 9 on the second floor of the Schaber Courthouse at 720 9th St., and Departments 60 through 63 in the main jails Patino courts on I Street.

But as the framework of a towering new 17-story, 53-courtroom courthouse rises behind the jail courts near the citys Railyard district, lingering questions of the cells utility, and resultant issues of equity, fairness and attorney access have re-emerged.

The lock-and-key bays will soon give way to plexiglass docks at the new Sacramento County Courthouse, scheduled to be completed in November 2023, but concerns remain. Schematics of the new Sacramento courthouse provided to The Sacramento Bee by court officials give a preview of courtrooms and in-court confinement.

Six courtrooms will have arraignment docks within the courtroom. Each will be approximately 20 feet wide by 6 feet deep, the schematics show; Schabers and Patinos bars replaced with the new facilitys plexiglass.

Its incredibly prejudicial for people viewing it family, neighbors, victims, said Sacramento attorney and former federal public defender Mark Reichel. Hes in orange. Hes in a cage. Hes like some kind of monster.

Criminal defendants are granted the right under the Constitution to confront accusers and witnesses against them in criminal proceedings. The Judicial Council of Californias standards for the states trial court facilities lay out clear objectives for transporting and accommodating defendants held in custody while in the courthouse.

Provide a safe and secure environment for transporting and accommodating jail inmates while in the courthouse.

Maintain the safety and welfare of the judiciary, court staff and public in the courthouse.

Prevent contraband from coming into the building.

The Sheriffs Office manages all in-custody holding and sets protocols for how inmates are held.

Courthouses must be a safe harbor to which members of the public come to resolve disputes that often are volatile. Once courthouses themselves are perceived as dangerous, the integrity and efficacy of the entire judicial process are in jeopardy, Ronald M. George, former chief justice of California, once said.

But the arraignment cells, whether steel bars or a plexiglass box, also expose troubling equity concerns, striking an unfair balance between safety and defendants rights, defense attorneys and criminal justice advocates say.

Each day, a steady stream of orange-clad county inmates held on suspicion of minor offenses to more serious crimes stand, for lack of bail, inside the 7-by-3-foot cages of the existing Sacramento courts. They consult briefly through the bars with their attorneys, await a judges reading of the charges they face, the date of their next court appearance or, if they have entered a plea, the sentence they will receive.

A printed sign taped to the bars warns spectators: No communication of any kind with inmates. Its against the law.

In Sacramento Superior Court, poor or indigent in-custody defendants who cannot post bail make their initial court appearances behind the bars of an arraignment courtrooms cell. The equity issue that poses is one reason why advocates California Attorneys for Criminal Justice, a statewide association of criminal defense attorneys, has opposed cash bail.

There is an adverse effect because of the appearance of the defendant behind bars, said attorney Stephen Munkelt, executive director of California Attorneys for Criminal Justice. Munkelt said the cells also point to more systemic issues in criminal justice.

CACJ believes the right to liberty has been severely undervalued by the court in the last 40 years (beginning) with the War on Drugs, the decadeslong campaign to stem the illegal drug trade in the U.S., to deleterious effect on Black and brown communities from long prison sentences for non-violent drug offenders to mass incarceration.

Before that, judges understood the right to liberty. People were released pretrial, Munkelt said. Over time, he said, public and political attitudes and media coverage of crime and criminal justice have worked to influence the bench.

It is an ongoing and systemic issue, he said.

Sacramento courts leaders had long argued for a new, modern courthouse to replace the Schaber courthouse, a building for years seen as cramped, obsolete and unsafe. The downtown arraignment cells on Ninth Street and on I Street are among the relics that have long been part of the judicial routine in Sacramento Superior Court.

With new courthouses in Yolo, Placer, Sutter and San Joaquin counties opening in recent years, the arraignment cells inside Sacramentos courtrooms are among the last holdovers from an earlier era. But other local courts, for years, have had their own troubled history.

Yolo County jail inmates as late as 2015 were shepherded in chain gangs from a sheriffs holding facility and through the crowded corridors of the countys century-old courthouse on Court Street. The procession was both a security risk to the court-attending public and an injustice to the inmates facing criminal charges.

Its prejudicial to be chained up in those striped uniforms and led across the street. Its a perp walk, Woodland attorney Steven Sabbadini said in a 2014 interview, as construction was beginning on the new Yolo courthouse. When theyre walking through the halls, its not a good thing for them, for jurors, for witnesses and alleged victims or for family members.

But the cells are also likely a reflection of attitudes on courtroom security and in-courtroom confinement at the time construction of the Patino courtrooms was completed in 1989; and the influence more broadly of county sheriffs officials in the design of court facilities, Munkelt said.

Its a sign of political power and delegation of responsibilities to the sheriff and security staff, Munkelt said. When designers go to construction, the sheriff has basically designed them. The state of the art at the time (that Schaber was built) was to put (inmates) in a box. Im sure thats how it came about.

Sheriffs offices today continue to exert great influence on courthouse security.

Sacramento County sheriffs deputies, as well sheriffs offices as in nearly all of Californias 58 counties marshals in the case of two counties supply courthouses bailiffs and courtroom security, according to the Judicial Council of California, which oversees the states superior courts.

That is as far as the Sheriffs Offices responsibility goes, said Lt. Rodney Grassmann, a Sacramento County sheriffs spokesman. Legislation enacted 20 years ago, the Superior Court Law Enforcement Act of 2002, calls for the presiding judge of each court to contract with the countys sheriff or marshal for the necessary level of law enforcement services subject to the courts available funding.

The courthouse buildings, including the arraignment cells, are the responsibility of the Superior Court, Grassmann said.

But officials at the Judicial Council of California say sheriffs offices play a much greater role, working closely with the court, courthouse designers and the design teams security consultants, to define security operations, procedures, and staffing levels proposed for the new courthouse.

The superior court relies on the sheriff to provide bailiffs and courtroom security, so they have a large amount of influence on how the courts are run and that leads to ongoing problems that concern myself and other criminal defense lawyers, Munkelt said. He says the defense bar should also have some input into how courthouses are designed but says the ability to influence those construction details is extremely limited.

Today at Yolo Superior Courts new Main Street courthouse in Woodland, a basement holding facility holds as many as 140 inmates, with secure elevators to transport those in custody to hearings and trial.

The chain gangs parades through crowded hallways are over. New inmate docks enclosed in plexiglass are now standard equipment in the Woodland courthouses arraignment courts.

The old Yolo courthouse was just not big enough to accommodate a growing county, Yolo County District Attorney Jeff Reisig, said in 2015 upon the opening of the new five-story facility. Its not safe we had chain gangs going up and down the hallways, Reisig said. The new downtown courthouse, he said, was modern, consolidated, high-tech.

At Placer Superior Courts Santucci Justice Center in Roseville, its Department 20 inside the South Placer Adult Correctional Facility opened in 2018. It replaced the tiny, cramped and now-closed Department 13 shoehorned inside Placer County Jail in Auburn. Department 20 features the plexiglass-enclosed arraignment dock standard now in newly built courthouses.

Serious matters are heard in courtrooms. Whether you are here as someone who has been charged with a crime or as a victim or victims relative, legal proceedings need to be done in a dignified, safe and efficient manner, then-Placer Superior Court Presiding Judge Alan V. Pineschi said upon Department 20s debut. Our new Department 20 will provide for that.

Munkelt recalls the construction and opening of Department 20.

Department 20 was built with a large plexiglass box to seat inmates, Munkelt said. When they finished the courtroom and started using it, they said, Its all ready to go.

Only, Munkelt said, attorneys could not communicate through the glass with their clients.

We said, Thats illegal. If the attorney and defendant cant speak to each other.... he said. The defendant had to be out of the box, so we set up a method to speak to them.

Munkelt successfully argued the right of defendants to have face-to-face jail visits with their attorneys before the states Third District Court of Appeal, a decision that has since been used to argue to provide similar access in new California courtrooms.

The appeals court in its 2015 decision, County of Nevada v. Superior Court, ruled that Nevada County Sheriffs Department unconstitutionally barred attorneys and their clients from meeting in jail visiting rooms without glass partitions under the guise of safety and security concerns.

Several inmates wanted to restore the face-to-face contact visits in non-partitioned rooms as had been the practice for years at Nevada Countys Wayne Brown Correctional Facility.

The Nevada Sheriffs Office and other law enforcement organizations across California opposed it on various grounds but appeals judges ruled in favor of defense attorneys and their clients.

Any kind of barrier is a barrier to communication, Munkelt told The Bee. That decision was used in a number of new (courthouse) construction cases. That doesnt mean the problem is solved.

2022 The Sacramento Bee. Visit sacbee.com. Distributed by Tribune Content Agency, LLC.

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'Incredibly prejudicial': Why Sacramento courts have caged cells, and why that'll change - Walla Walla Union-Bulletin

ReportLinker

during the forecast period. Factors such asrising cases of neurological diseases and cancer, growing gene therapy product approvals, and increasing investment in gene therapy related research and development drive the market growth.

New York, Aug. 02, 2022 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Gene Therapy Market by Vectors, Indication, Delivery Method, Region - Global Forecast to 2027" - https://www.reportlinker.com/p05843076/?utm_source=GNW However,factors like high cost of gene therapy is restraining the growth of this market.

The cancer segment accounted for the highest growth ratein the gene therapy market, by indication, during the forecast periodIn 2021, cancer segment accounted for the highest growth rate. Growing disease burden of cancer across the globe coupled with rising demand for gene therapies to treat cancer will augment the segmental growth of cancer over the forecast period.

Asia Pacific: The fastest-growing region in the gene therapy marketThe Asia Pacific market is estimated to record the highest CAGR during the forecast period. The high growth rate of this market can be attributed to the improving healthcare expenditure in emerging economies, increasing product launches, and increasing incidence of cancer and neurological diseases.

The primary interviews conducted for this report can be categorized as follows: By Company Type: Tier 1- 32%, Tier 2- 44%, and Tier 3-24% By Designation: C-level (Managers) - 30%, D-level(CXOs, Directors)- 34%, and Others (Executives) - 36% By Region: North America -50%, Europe -32%, Asia-Pacific -10%, Rest of the World -8%

List of Companies Profiled in the Report: Biogen (US) Sarepta Therapeutics (US) Gilead Sciences, Inc. (US) Amgen, Inc. (US) Novartis AG (Switzerland) Orchard Therapeutics Plc (UK) Spark Therapeutics, Inc. (A Part Of ?F. Hoffmann-La Roche) (US) AGC Biologics (US) Anges, Inc. (Japan) Bluebird Bio, Inc. (US) Jazz Pharmaceuticals Plc (Ireland) Dynavax Technologies (US) Human Stem Cells Institute (Russia) SibionoGenetech Co., Ltd. (China) Shanghai Sunway Biotech Co., Ltd. (China) Uniqure N.V. (Netherland) Gensight Biologics S.A. (France) Celgene Corporation (A Bristol-Myers Squibb Company) (US) Cellectis (France) Sangamo Therapeutics (US) Mustang Bio (US) AGTC (Applied Genetic Technologies Corporation) (US) Poseida Therapeutics, Inc. (US)

Research Coverage:This report provides a detailed picture of the global gene therapy market.It aims at estimating the size and future growth potential of the market across different segments such as vectors, indication, delivery method, and region.

The report also includes an in-depth competitive analysis of the key market players along with their company profiles recent developments and key market strategies.

Key Benefits of Buying the Report:The report will help market leaders/new entrants by providing them with the closest approximations of the revenue numbers for the overall gene therapy market and its subsegments.It will also help stakeholders better understand the competitive landscape and gain more insights to better position their business and make suitable go-to-market strategies. This report will enable stakeholders to understand the markets pulse and provide them with information on the key market drivers, challenges,trends,and opportunities.Read the full report: https://www.reportlinker.com/p05843076/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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The global gene therapy market is valued at an estimated USD 7.3 billion in 2022 and is projected to reach USD 17.2 billion by 2027, at a CAGR of...

Dateline Moscow, Minks, Kyiv, and Aspen: Updates on the hybrid war.

Ukraine at D+148: Spycraft, traditional and cyber. (The CyberWire) Russia's offensives remain stalled, as MI6 and CIA think the Russian army has "run out of steam." Russian cyberespionage continues as traditional espionage runs up against apparently effective European counterespionage measures. And hackers spread disinformation over nine Ukrainian radio stations.

Russia-Ukraine war: List of key events, day 149 (Al Jazeera) As the Russia-Ukraine war enters its 149th day, we take a look at the main developments.

Ukraine latest: Russia 'destroys' four US-supplied Himars rocket systems (The Telegraph) Russia's defence ministry has claimed its forces have destroyed four US-supplied Himars rocket systems in July alone.

Russia Moves to Annex Occupied Ukrainian Land by September (Bloomberg) Kremlin prepares for referendums in areas seized by its troops. Officials say votes planned on merging with Russia by Sept. 15.

End the war to prevent nuclear abyss, warns Lukashenko (The Telegraph) The Belarus president and Putin ally insisted that Kyiv could end the war if it re-started talks with Moscow and accepted Russia's demands

How Putins Flawed Assumptions Doomed Russian Victory in Ukraine (Foreign Affairs) A Conversation With Lawrence Freedman

Greenpeace Says IAEA Downplayed Damage at Chernobyl by Russian Troops (Newsweek) The environmental organization conducted its own survey at Chernobyl after "very limited data" was provided by the International Atomic Energy Agency.

Russia-Ukraine war: UK vows to send thousands more weapons to Kyiv after Kremlin's threat of escalation (The Telegraph) Britain will send scores of artillery guns and more than 1,600 anti-tank weapons to Ukraine, in the latest supply of Western arms to the fury of the Kremlin.

UK Spy Chief Sees Russias Military Running Out of Steam Soon (Bloomberg) MI6 head Richard Moore sees no sign Putin is in poor health. Big advantage of US, UK over China is we have allies.

Exhausted Russian army gives Ukraine chance to strike back, says British spy chief (The Telegraph) Richard Moore, the head of MI6, says intelligence shows Vladimir Putins army is running out of steam

'Cut by half' Putin's masterplan backfires as 400 Russian spies thrown out of Europe (Express) RUSSIA has lost "half" of its ability to spy on European countries, the UK's foreign intelligence chief has said.

Half of Russian spies in Europe expelled since Ukraine invasion, says MI6 chief (the Guardian) Richard Moore says 400 intelligence officers operating under diplomatic cover have been expelled

MI6 chief: Russias spies not having a great war in Ukraine (The Record by Recorded Future) Hundreds of Russian spies have been expelled from Europe in recent months, dealing a major blow to Moscows intelligence efforts during its war with Ukraine, said the head of Britains Secret Intelligence Service, or MI6, on Thursday.

CIA chief says 15,000 Russians killed in war, dismisses Putin health rumors (Washington Post) Russias territorial gains in Ukraine have been minimal and have come at a very high cost, senior U.S. officials said Wednesday, illustrating the deadly grind of the conflict while dismissing concerns about President Vladimir Putins health.

CIA Chief Says Russias Iran Drone Deal Shows Military Weakness (Bloomberg) William Burns says the two countries dont trust each other. China is unsettled by Russias war performance, Burns says.

Putin thinks he'll break America's will in Ukraine, but he's wrong, says the CIA director (CNBC) Putins view of Americans is that we always suffer from attention deficit disorder, and well get distracted, said CIA Director William Burns at the Aspen Security Forum.

Ukraine can win (Atlantic Council) If the West takes active measures to ensure Ukraine can't defeat Putin's Russia, it won't. But if it commits to supplying the range of capabilities required for modern, high intensity warfare, Ukraine can win, and it will win.

Ukraine says air force needs western fighter jets, and the US is preparing to help (Defense News) Older U.S. systems are a possibility as Ukraine builds its future air force, U.S. Air Force Secretary Frank Kendall said.

Western fighter jets could be sent to Ukraine to boost forces under US plans (The Telegraph) Training Ukrainian pilots is also being discussed by military chiefs as part of a future support package

Inside the multinational logistics cell coordinating military aid for Ukraine (Defense News) Since early March, a cohort of U.S. servicemembers and a rotating crew of multinational partners have set up shop in U.S. European Command headquarters to ensure equipment gets from the donor nation to Ukraines doorstep.

Ukraines Wartime Politics Takes a New Turn (Wilson Center) Political processes change dramatically during a time of war. In the early stages of the war, the usual competition between the ruling group and the opposition is dampened, while society becomes more disciplined and united around the government. But the longer the war goes on, the more politics adapts: either it further organizes around the leader of the nation at war or the usual competition returns, but posing an unusual threat to national security.

Ukraine confronts Kremlin infiltration threat at unreformed state bodies (Atlantic Council) Last week's dismissal by President Zelenskyy of two key figures from Ukraine's state security and prosecution services has highlighted the threat posed by Kremlin agents infiltrating unreformed Ukrainian state bodies.

US seeking to understand Russias failure to project cyber power in Ukraine (Defense News) With regard to the Russian use of cyber and our takeaways, Anne Neuberger said, there are any number of theories for what we saw and what, frankly, we didnt see.

Battling Moscow's hackers prior to invasion gave Kyiv 'full dress rehearsal' for today's cyber warfare (CyberScoop) Years of cyberattacks have helped prepare Ukraine to fight back against Russia's arsenal of digital weapons.

Defence officials warn of possible risk of social engineering attacks through MS Teams (DELFI) Virtual communication software MS Teams can be exploited for social engineering attacks without necessary changes to its external access settings, Lithuania's Ministry of National Defense warned on Thursday, adding that this could pose risk to the security of organizations using the software.

Cyber criminals attack Ukrainian radio network, broadcast fake message about Zelensky's health (CyberScoop) The company that operates nine radio stations across Ukraine said the message did "not correspond to reality."

How Russia promoted the claim that Ukraine re-sold French howitzers for profit (Medium) Kremlin media amplified narrative until mainstream coverage on the risk of weapons smuggling allegedly gave it credence

Ukraine invites allies to check on their weapons donations (POLITICO) Ukraine has created a temporary special commission to monitor the flow of billions of dollars in Western weapons into the country.

Google to be banned in Ukraines occupied Donetsk and Luhansk regions (the Guardian) Leader of self-proclaimed Donetsk Peoples Republic accuses search engine of promoting terrorism and violence against all Russians

Deal for Ukraine grain exports due to be sealed in Istanbul (AP NEWS) Russia and Ukraine were expected to sign an agreement Friday that would allow Ukraine to resume grain shipments to world markets and Russia to export grain and fertilizers, ending a standoff that threatened world food security while the two countries are at war in Ukraine .

Russian gas attack: Europe must not give in to Putins energy blackmail (Atlantic Council) The CEO of Ukrainian energy giant Naftogaz has told European leaders to prepare for a complete Russian gas cut off and warned that any concessions to the Kremlin will only serve to encourage further energy blackmail.

Russia requests North Korean labourers be sent to Donbas in exchange for wheat and machinery (The Telegraph) Providing technology to Pyongyang would violate UN sanctions that Moscow has supported in the past

How Conti ransomware hacked and encrypted the Costa Rican government (BleepingComputer) Details have emerged on how the Conti ransomware gang breached the Costa Rican government, showing the attack's precision and the speed of moving from initial access to the final stage of encrypting devices.

Anatomy of Attack: Truth Behind the Costa Rica Government Ransomware 5-Day Intrusion (AdvIntel) This report data is derived from Andariels adversarial collections, which enable visibility into Cobalt Strike commands which bypass a known EDR solution in a play-by-play format. The ransomware and exfiltration operation took approximately five days from the initial access on April 11, 2022 primarily due to the massive data exfiltration prolonging the exploitation operation prior to the ransomware deployment. On May 8, 2022, the new preside

Conti Criminals Resurface as Splinter RaaS Groups (Security Boulevard) Contione of the most ruthless and successful Russian ransomware groupshas been quiet since the group publicly announced it would cease operations in the

LockBit 3.0 Update | Unpicking the Ransomware's Latest Anti-Analysis and Evasion Techniques (SentinelOne) The self-proclaimed 'oldest ransomware affiliate on the planet' has new tricks and new features and continues to beat enterprise defenses.

A Fake Google Search YouTube Ad Redirects to Scam Windows Defender Security Alert (iTech Post) An unsettlingly lifelike Google Search "malvertising" campaign was misusing Google ads. (Photo : ISSOUF SANOGO/AFP via Getty Images) Malwarebytes, a cybersecurity company, revealed on Thursday that it had found a "major" malvertising campaign that was misusing Google ads.

Understanding the Evolution of Cybercrime to Predict its Future (SecurityWeek) A study of the evolution of cybercrime suggests the threat will only get worse as financially motivated malware gangs become more and more professional.

Matanbuchus with Cobalt Strike: Not Your Favorite Combo (CircleID) For US$2,500, threat actors can employ Matanbuchus, a malware-as-a-service (MaaS) package found delivering Cobalt Strike beacons through phishing and spam messages. Cobalt Strike is a powerful security tool that threat actors are increasingly using as a reconnaissance and post-exploitation weapon.

The Evolution of Cybercrime: Why the Dark Web is Supercharging the Threat Landscape and How to Fight Back (HP Wolf Security) Dont let cyber threats get the best of you. Read our post, The Evolution of Cybercrime: Why the Dark Web is Supercharging the Threat Landscape and How to Fight Back, to learn more about cyber threats and cyber security.

Bitdefender identifies 192 active ransomware families worldwide (SecurityBrief New Zealand) Bitdefender says the most prevalent of the 192 active ransomware families was WannaCry, which accounted for 42% of detections.

Atlassian warns of several new critical vulnerabilities potentially being exploited in wild (The Record by Recorded Future) Atlassian is warning its customers and partners about three different critical vulnerabilities affecting Confluence Server, Confluence Data Center as well as several other products from Bamboo, BitBucket, Fisheye and Jira.

Atlassian Warns Confluence Users of Critical Hardcoded Credentials Bug (Decipher) After an external party publicly disclosed the hardcoded password on Twitter, Atlassian said the issue is likely to be exploited in the wild.

Exploitation of Recent Chrome Zero-Day Linked to Israeli Spyware Company (SecurityWeek) An actively exploited Chrome zero-day for which Google released a patch on July 4 has been linked to an Israeli spyware company and used in targeted attacks in the Middle East.

Spyware maker Candiru exploited Google Chrome zero-day to target journalists (Computing) The vulnerability has already been patched by Google

Candiru surveillance spyware DevilsTongue exploited Chrome Zero-Day to target journalists (Security Affairs) The spyware developed by Israeli surveillance firm Candiru exploited recently fixed CVE-2022-2294 Chrome zero-day in attacks on journalists. Researchers from the antivirus firm Avast reported that the DevilsTongue spyware, developed, by Israeli surveillance firm Candiru, was used in attacks against journalists in the Middle East and exploited recently fixed CVE-2022-2294 Chrome zero-day. The flaw, which []

Hackers for Hire: Adversaries Employ 'Cyber Mercenaries' (Threatpost) Also known as the Atlantis Cyber-Army, the emerging organization has an enigmatic leader and a core set of admins that offer a range of services, including exclusive data leaks, DDoS and RDP.

Hundreds of ICS Vulnerabilities Disclosed in First Half of 2022 (SecurityWeek) More than 600 vulnerabilities were disclosed in the first half of 2021 and more than 60% are critical or high severity.

Google blocks site of largest computing society for being harmful (BleepingComputer) Google Search and Drive are erroneously flagging links to Association for Computing Machinery (ACM) research papersand websites as malware. BleepingComputer has successfully reproducedthe issue, first reported by researcherMaximilian Golla.

IowaWorks.gov website restored after cyber attack that caused outage (WQAD) The state says no user data was compromised and the delivery of unemployment benefit payments was not impacted.

Ransomware Group Says It Has Breached Colorado Towns Network (GovTech) The town of Frederick, Colo., is currently investigating claims about a breach in their network. Officials are working with digital forensics experts to determine exactly if and how the community might be impacted.

Waterloo Regional District School Board says it was hit by cyberattack (Global News) In a letter issued to parents late Wednesday night, the Waterloo Regional District School Board says it recently discovered that it had been hacked.

Windows 11 is getting a new security setting to block ransomware attacks (ZDNet) Microsoft releases a new default policy to thwart credential attacks, which is also heading to Windows 10.

Microsoft resuming default block of Office VBA macros (The Record by Recorded Future) Microsoft confirmed that it is resuming the roll out of a popular change that blocked Visual Basic for Applications (VBA) macros by default in Office apps.

Google Chrome security update fixes 'high risk' flaws (ZDNet) Google releases 11 fixes for Chrome - and CISA says users should apply them.

Google Releases Security Updates for Chrome (CISA) Google has released Chrome version 103.0.5060.134 for Windows, Mac, and Linux. This version addresses vulnerabilities that an attacker could exploit to take control of an affected system. CISA encourages users and administrators to review the Chrome Release Noteand apply the necessary updates.

Central Florida construction firm: Ex-employee snatched personal records in data breach (Florida Politics) Williams Company has a portfolio of major projects at SeaWorld Orlando and Legoland Florida.

Drupal Releases Security Update (CISA) Drupal has released security updates to address vulnerabilities affecting Drupal 9.3 and 9.4. An attacker could exploit some of these vulnerabilities to take control of an affected system. CISA encourages users and administrators to review Drupal security advisory SA-CORE-2022-015and apply the necessary update.

Oracle Releases July 2022 Critical Patch Update (CISA) Oracle has released its Critical Patch Update for July 2022 to address 349 vulnerabilities across multiple products. A remote attacker could exploit some of these vulnerabilities to take control of an affected system. CISA encourages users and administrators to review the Oracle July 2022 Critical Patch Updateand apply the necessary updates.

ABB Drive Composer, Automation Builder, Mint Workbench (CISA) 1. EXECUTIVE SUMMARY CVSS v3 7.8 ATTENTION: Low attack complexity Vendor: ABB Equipment: Drive Composer, Automation Builder, Mint Workbench Vulnerability: Improper Privilege Management 2. RISK EVALUATION Successful exploitation of this vulnerability could allow remote code execution. 3. TECHNICAL DETAILS 3.1 AFFECTED PRODUCTS The following ABB products are affected:

Johnson Controls Metasys ADS, ADX, OAS (CISA) 1. EXECUTIVE SUMMARY CVSS v3 5.3 ATTENTION: Exploitable remotely/low attack complexity Vendor: Johnson Controls, Inc Equipment: Metasys ADS, ADX, OAS with MUI Vulnerability: Missing Authentication for Critical Function 2. RISK EVALUATION Successful exploitation of this vulnerability could allow an unauthenticated user to access Metasys web API and enumerate users.

Rockwell Automation ISaGRAF Workbench (CISA) 1. EXECUTIVE SUMMARY CVSS v3 8.6 ATTENTION: Low attack complexity Vendor: Rockwell Automation Equipment: ISaGRAF Workbench Vulnerabilities: Deserialization of Untrusted Data, Path Traversal 2. RISK EVALUATION Successful exploitation of these vulnerabilities could result in directory traversal, privilege escalation, and arbitrary code execution.

ICONICS Suite and Mitsubishi Electric MC Works64 Products (CISA) 1. EXECUTIVE SUMMARY CVSS v3 9.8 ATTENTION: Low attack complexity Vendors: ICONICS, Mitsubishi Electric Equipment: ICONICS Product Suite, MC Works64 Vulnerabilities: Path Traversal, Deserialization of Untrusted Data, Inclusion of Functionality from Untrusted Control Sphere, Out-of-Bounds Read 2.

AutomationDirect Stride Field I/O (CISA) 1. EXECUTIVE SUMMARY CVSS v3 9.6 ATTENTION: Exploitable remotely/low attack complexity Vendor: AutomationDirect Equipment: Stride Field I/O Vulnerability: Cleartext Transmission of Sensitive Information. 2. RISK EVALUATION Successful exploitation of this vulnerability could allow an attacker to obtain user credentials.

Intelligence Insights: July 2022 (Red Canary) Qbot returns with a vengeance, Emotet climbs the charts, and BumbleBee changes tactics.

Report: Financial Institutions Overly Complacent About Current Authentication Methods (PR Newswire) HYPR, The Passwordless Company and Vanson Bourne, today released a new report that reveals the financial sector is failing to combat the...

Halborn Raises $90M in Series AFunding (FinSMEs) Halborn, a Miami, FL-based cybersecurity firm serving both traditional finance and blockchain-based clients, raised $90M in Series A funding

VIPCs Virginia Venture Partners Investment in Fend Fosters Cybersecurity Solutions For Critical Infrastructure (EIN News) Specialty hardware focuses on developing innovative solutions that protect critical assets against cyberattacks

Microsoft closes unfilled job openings in cloud and security (Register) Despite growth and strong demand in these areas, Redmond keeps trimming investment

Devo Expands SciSec Team with Data Science Leaders to Accelerate Delivery of Autonomous SOC (Devo) Devo names data-science experts Kevin Zhou and Chaz Lever to leadership positions on its SciSec threat research team.

New infosec products of the week: July 22, 2022 (Help Net Security) The featured infosec products this week are from: Cato Networks, CoSoSys, Darktrace, EnGenius, Orca Security, Persona, and Resecurity.

Kovrr Launches Cyber-Sphere to Simplify Enterprise Cyber Risk Management Decisions (Business Wire) Kovrr, a leading provider of cyber risk quantification (CRQ) solutions for global enterprises and (re)insurers, announced today the launch of the Cybe

Axonius Adds Key Integrations with AWS (PR Newswire) Axonius, a cybersecurity asset management provider, today announced integrations with Amazon Macie, Amazon GuardDuty, and AWS SecurityHub while...

Proximus selects Zimperium mobile threat defence to protect subscribers against surging mobile attacks (VanillaPlus) Brussels, Belgium. 20July 2022 Zimperium, a global provider of mobile security, has struck a deal with Proximus starting from 1st July 2022, Belgiums

NIST Revises Cybersecurity Guidelines Specifically for HIPAA (Nextgov.com) NIST will accept comments on the updated draft publication regarding HIPAAs Security Rule until September 21.

Standing shoulder to shoulder - building a resilient healthcare ecosystem with Health-ISAC (Google Cloud Blog) Google Cloud has joined the Health Information Sharing and Analysis Center (Health-ISAC) as its first Ambassador Partner in the cloud.

Lack of staff and resources drives smaller teams to outsource security (Help Net Security) This Help Net Security video highlights how a lack of staff, skills, and resources drives smaller teams to outsource their security.

Education institutions hit hard by ransomware - study (SecurityBrief New Zealand) The findings reveal that education institutions are increasingly being hit with ransomware, with 60% suffering attacks in 2021 compared to 44% in 2020.

Do we need a cyber NATO to address the changing threat landscape? [Q&A] (BetaNews) The threat landscape facing enterprises is changing constantly. In recent months, major vulnerabilities like Log4j and malware-based threats have demonstrated the need for organizations to move quickly in order to defend themselves.

British recycle old arguments for borking encryption (Register) Levy and Robinson are at it again

China Has a Problem With Data Leaks. One Reason Is Its Surveillance State. (Wall Street Journal) Cybersecurity researchers say the Chinese governments mass collection of personal information aids in social control but undermines national security.

Why suspected Chinese spy gear remains in Americas telecom networks (POLITICO) In an already hectic year, Congress is now on the hook to find billions of dollars to help some 200 small U.S. telecom carriers finally rip out risky Chinese equipment.

Senators intro bill to foster federal move to quantum-resistant technology (The Record by Recorded Future) A bipartisan pair of senators on Thursday introduced legislation to motivate federal agencies to shift their information systems to quantum-resistant cryptography.

Congress Might Pass an Actually Good Privacy Bill (Wired) A bill with bipartisan support might finally give the US a strong federal data protection law.

FACT SHEET: National Cyber Workforce and Education Summit (The White House) On July 19, 2022, National Cyber Director Chris Inglis hosted the National Cyber Workforce and Education Summit at the White House. The event focused on

Biden Administration Looks to Jumpstart Cyber Training (Nextgov.com) At a White House event, the Labor and Commerce Departments announced a 120-day apprenticeship sprint to offer pathways into cybersecurity jobs.

USA's plan to build its cyber workforce, improve skills-based pathways to cyber jobs (Help Net Security) The USA is focused on building the cyber workforce, improving skills-based pathways to cyber jobs, and educating Americans.

Its not just the private sector agencies are competing with each other for cyber talent (Federal News Network) OPM wants to level the playing field for agencies trying to recruit and retain cybersecurity specialists.

Where 5 programs are investing to close cyber skills gap (Cybersecurity Dive) In line with a White House driven push to close the cyber skills gap, technology firms, nonprofits and other organizations have launched a range of programs to develop a new generation of workers.

Florida Follows North Carolina in Prohibiting State Agencies from Paying Ransoms (Bake Hostetler Data Counsel) We recently wrote about North Carolinas new law prohibiting state agencies including public schools and universities from paying a ransom or even

New York providing cybersecurity resources to local governments (NY1) The effort includes anti-ransomware attack tools.

The Unsolved Mystery Attack on Internet Cables in Paris (Wired) As new details about the scope of the sabotage emerge, the perpetratorsand the reason for their vandalismremain unknown.

Panama Papers whistleblower speaks out: Politicians must act now (the Guardian) In first public comments since 2016, leaker discusses their life in hiding and leaders failure to clamp down on tax havens

Former Coinbase Employee Charged in Alleged Insider-Trading Scheme (Wall Street Journal) The first-ever cryptocurrency insider-trading case could have broad ramifications for the industry.

Ex-Coinbase Manager Arrested in US Crypto Insider-Trading Case (Bloomberg) Criminal charges follow probe launched in April by SDNY. SEC also sues former employee and two others over conduct.

SEC lists nine crypto tokens as securities following Coinbase insider trading charges (The Block) The SEC has listed nine cryptocurrencies on Coinbase that it says are securities, providing more clarity on its views.

Jason Calacanis Rips Into Grifting VCs Flipping Crypto Tokens to Retail (Bloomberg) Watch out venture capital, the regulators are coming.

Secret Service watchdog knew in February that texts had been purged (Washington Post) A watchdog agency learned in February that the Secret Service had purged nearly all cellphone texts from around the time of the Jan. 6, 2021, attack on the Capitol, but chose not to alert Congress, according to three people briefed on the internal discussions.

SF police plan to monitor video ignites controversy (Axios) A proposal for cops to access privately owned video cams raises criticism from privacy advocates.

Read this article:
Conti's fate and effects. Ukrainian radio stations hacked. Espionage, counterespionage, and sabotage during the hybrid war. - The CyberWire

New Jersey, United States TheCell ExpansionMarket research guides new entrants to obtain precise market data and communicates with customers to know their requirements and preferences. It spots outright business opportunities and helps to bring new products into the market. It identifies opportunities in the marketplace. It aims at doing modifications in the business to make business procedures smooth and make business forward. It helps business players to make sound decision making. Cell Expansion market report helps to reduce business risks and provides ways to deal with upcoming challenges. Market information provided here helps new entrants to take informed decisions making. It emphasizes on major regions of the globe such as Europe, North America, Asia Pacific, Middle East, Africa, and Latin America along with their market size.

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Key Players Mentioned in the Cell Expansion Market Research Report:

Thermo Fisher Scientific, Inc., GE Healthcare (A Wholly Owned Subsidiary of General Electric Company), Lonza Group Ltd., Becton, Dickinson and Company, Corning, Inc., Merck KGAA, Beckman Coulter, Inc. (Subsidiary of Danaher Corporation), MiltenyiBiotec, Stemcell Technologies, Terumo BCT, Inc. (A Subsidiary of Terumo Corporation).

Cell ExpansionMarket report consists of important data about the entire market environment of products or services offered by different industry players. It enables industries to know the market scenario of a particular product or service including demand, supply, market structure, pricing structure, and trend analysis. It is of great assistance in the product market development. It further depicts essential data regarding customers, products, competition, and market growth factors. Cell Expansion market research benefits greatly to make the proper decision. Future trends are also revealed for particular products or services to help business players in making the right investment and launching products into the market.

Cell ExpansionMarket Segmentation:

Cell Expansion Market, By Product

Consumables Instruments Others

Cell Expansion Market, By Cell Type

Human Cells Animal Cells

Cell Expansion Market, By Application

Regenerative Medicine and Stem Cell Research Cancer and Cell-Based Research Others

Cell Expansion Market, By End-user

Research Institutes Biotechnology and Biopharmaceutical Companies Cell Banks Other End Users

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For Prepare TOC Our Analyst deep Researched the Following Things:

Report Overview:It includes major players of the Cell Expansion market covered in the research study, research scope, market segments by type, market segments by application, years considered for the research study, and objectives of the report.

Global Growth Trends:This section focuses on industry trends where market drivers and top market trends are shed light upon. It also provides growth rates of key producers operating in the Cell Expansion market. Furthermore, it offers production and capacity analysis where marketing pricing trends, capacity, production, and production value of the Cell Expansion market are discussed.

Market Share by Manufacturers:Here, the report provides details about revenue by manufacturers, production and capacity by manufacturers, price by manufacturers, expansion plans, mergers and acquisitions, and products, market entry dates, distribution, and market areas of key manufacturers.

Market Size by Type:This section concentrates on product type segments where production value market share, price, and production market share by product type are discussed.

Market Size by Application:Besides an overview of the Cell Expansion market by application, it gives a study on the consumption in the Cell Expansion market by application.

Production by Region:Here, the production value growth rate, production growth rate, import and export, and key players of each regional market are provided.

Consumption by Region:This section provides information on the consumption in each regional market studied in the report. The consumption is discussed on the basis of country, application, and product type.

Company Profiles:Almost all leading players of the Cell Expansion market are profiled in this section. The analysts have provided information about their recent developments in the Cell Expansion market, products, revenue, production, business, and company.

Market Forecast by Production:The production and production value forecasts included in this section are for the Cell Expansion market as well as for key regional markets.

Market Forecast by Consumption:The consumption and consumption value forecasts included in this section are for the Cell Expansion market as well as for key regional markets.

Value Chain and Sales Analysis:It deeply analyzes customers, distributors, sales channels, and value chain of the Cell Expansion market.

Key Findings:This section gives a quick look at the important findings of the research study.

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Cell Expansion Market Size, Scope, Growth Opportunities, Trends by Manufacturers And Forecast to 2029 This Is Ardee - This Is Ardee

Introduction

The skin is the largest organ in the body, accounting for 15% of the total body weight. It is the first line of defense against physical, chemical, and biological factors.1,2 In some cases, the anatomical structure and biological function of the skin are impaired due to internal (local blood obstruction, inflammation, or underlying diseases) or external factors (mechanical injury, chemical corrosion, electric injury, or thermal injury).1,3

After damage, skin can self-heal, and this process involves four phases: hemostasis, inflammation, proliferation, and remodeling (Figure 1).4,5 In the first few minutes after skin damage, the platelets accumulate around the wound and get activated, forming a scab to preventing bleeding.6 After 23 days, the inflammatory phase starts around the wound, and the immune cells remove the dead and devitalized tissues and prevent microbial infections.4 The proliferation phase occurs after the inflammation phase, and it is characterized by the activation of keratinocytes, fibroblasts, endothelial cells, and macrophages, which contribute to wound closure, matrix formation and angiogenesis.7 In the 12 or more months after the primary repair is completed, the regenerated skin tissue is remodeled. During this phase, the processes activated after injury slow down, and the healed wound reaches it maximum mechanical strength.4,5

Figure 1 Phases of wound healing, including the hemostasis, inflammatory, proliferation, and remodeling phase.

Notes: Reprinted from: Tavakoli S, Klar AS. Advanced Hydrogels as Wound Dressings. Biomolecules. 2020;10(8):1169. doi:10.3390/biom10081169.5 2020 by the authors. Licensee MDPI, Basel, Switzerland. Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).

However, in some cases, the skins self-healing property is inadequate, leading to the formation of chronic wounds. Chronic wounds are defined as wounds that remain unhealed even after 12 weeks.8 The main factors delaying wound repair include diabetes, infections, and long-term inflammation. Diabetic mellitus damages the microenvironment of skin tissue, which is involved in wound regeneration. It causes increases in reactive oxygen species (ROS) levels and poor collagen deposition.911 The hyperglycemia weakens the functions of fibroblasts, keratinocytes, endothelial cells, and stem cells or progenitor cells involved in wound healing.12 Microbial infections deplete the energy and cells required for tissue regeneration, and the bacteria can form biofilms that display antibiotic resistance, immune evasion, and wound adherence.13,14 In unhealed skin, excess inflammation also contributes to wound chronicity owing to its cytotoxic effects and the induced tissue damage, both of which delay wound healing.1517 Traditionally, the chronic wounds are treated with wound dressing made of gauze, skin grafting, or even flap transplantation. Moreover, targeted antibiotics are administered in case of infection. However, Surgery for chronic wounds can be challenging due to limited donor sites, donor damage, scar formation, and even severe functional and psycho-social disorders.1820 Moreover, antibiotic overuse can lead to drug resistance, creating new problems for infectious chronic wounds.21,22 Moreover, chronic wounds become refractory due to infections, diabetes, ischemia, over-degradation of collagen, and other factors, leading to the failure of traditional treatment methods. Thus, novel methods for treating chronic wounds need to be explored.

Skin wounds are the most common type of tissue injury, and they can be caused by trauma, surgery, burns, chronic diseases, or cancers.4,23 Under adverse conditions, wounds often turn chronic. The acceleration of wound repair and improvement of the healing process are the primary objectives of chronic wound treatment. Nanobiotechnology, which involves the use of nano-sized particles in biological systems, represents the convergence of several scientific fields, including chemistry, biology, physics, optics, mechanics, and nanoscale Science and technology. Nanobiotechnology can provide tools and technologies for examining and modulating biological systems.24,25 By applying nanotechnology in the field of bioMedicine, several novel biomaterials, biosensors, and bio-therapies have been designed and studied. It is believed that the combination of nanotechnology and biology can aid in wound management, monitoring, and repair.26,27 Initially, the application of nanobiotechnology in chronic wound treatment was focused on the provision of scaffolds for cell migration and the replacement of traditional gauze dressing.2830 However, with the development of nanotechnology and our understanding of wound healing mechanisms, various nanobiotechnology-based wound-treatments systems including drug and gene delivery platforms, antimicrobial systems, and cell-carrying systems have been developed and found to have prospective applications.3136 Nevertheless, despite these advances, wound dressings remain largely primitive and lack functions that allow wound monitoring and dynamic wound responses. Therefore, smart hydrogels or bandage systems developed using nano-sized biomaterials, which can respond to stimuli or monitor the status of chronic wounds, have been examined.37,38

This review article provides a summary of nanobiotechnology-based scaffold, delivery, antimicrobial, cell-carrying, collagen modulating, stimuli-responsive, and wound monitoring systems for chronic wound healing. Further, the prospects of nanobiotechnology to achieve better treatment outcomes for chronic wounds are discussed.

Physiologically, the wound healing process is affected by several factors, including gene expression; cell functions such as migration, proliferation, and differentiation; the skin microenvironment; infection; ischemiahypoxia; inflammation; and collagen formation and arrangement.1,3,17,3942 These factors are used as references for the design of nanobiotechnology systems that promote chronic wound repair (Figure 2) and need to be carefully considered before designing such systems.

Figure 2 Nanoplatform for chronic wound healing.

To repair tissue defects in the wound area, a platform for cell adhesion, migration, and proliferation ie, a scaffold for cells needs to be established. Such a scaffold can also serve as a platform for multi-functional modification. Given their good biocompatibility, angiogenic capacity, and biomimetic behavior to natural human skin, nano-scaffold systems are widely used in tissue engineering.4346

Tradition treatment methods for chronic wounds that show delayed Union involve local or systemic drug administration. However, the performance of these drugs is suboptimal owing to limitations such as low solubility and low bioactivity. Nanobiotechnology has thus been leveraged for the development of drug, gene, and exosome delivery systems that can help in overcoming these limitations.34,47,48

Infections, which impede tissue repair, should receive careful attention in chronic wound treatment. Silver nano-particles, a product of nanobiotechnology, have been used clinically in the treatment of microbial infection for decades. Moreover, several more recent studies have explored new nanoplatform-based anti-infection therapies, including potential anti-infection nanoparticles (NPs).4952

Cell therapy, especially stem cell therapy, is currently a focus in regenerative medicine and diabetic wound repair. In some basic medical and preclinical studies, chronic wound treatment with stem cells has shown excellent outcomes.5355 However, despite its great potential, the clinical translation of stem cell therapy for chronic wound healing is hindered by the lack of appropriate methods for cell encapsulation and transplantation. Thus, the development of nanobiotechnology-based cell-carrying systems can provide improved therapeutic effects.56,57

With the development of precision medicine, therapeutic systems that monitor wounds and respond to individual stimuli are expected to become popular. One such system is based on ferrihydrite NPs, which can respond to blue light and are effective for antimicrobial and wound healing treatments.58 More stimuli-responsive materials and monitoring systems for chronic wound healing can be generated through nanobiotechnology.

The term scaffold system generally refers to materials that can integrate with living tissues and cells and can be implanted into different tissues where they supplement natural tissue function based on specific conditions. In order to enable seed cells to proliferate and differentiate, a scaffold composed of biological materials that acts as an artificial extracellular matrix (ECM) is required. Scaffolds are critical for tissue engineering systems, including those for bone, cartilage, blood vessels, nerves, skin, and artificial organs (eg, liver, spleen, kidney, and bladder).

Nano-scaffold systems aimed at chronic wound healing need to possess certain important features.

1. Safety and good biocompatibility: Scaffolds should be safe. Furthermore, their chemical components and degradation products should cause minimal immune or inflammatory responses in the body during a predetermined period.59

2. Appropriate size, dimensions, and mechanical strength: The chemical features of the scaffold should provide suitable microenvironments and maintain the biological activity of loaded cells or tissues for a long time.

3. Appropriate pore size and distribution: Scaffolds should have a highly and well-connected porous structure with an ideal pore size to allow cells, drugs, and bioactive molecules to get evenly distributed throughout the scaffold.60

4. Excellent biological behaviors: Scaffolds and the substances present in the scaffold should promote the proliferation and migration of fibroblasts, keratinocytes, and endothelial cells, thus promoting wound healing.61,62

5. Appropriate wound healing environment: The scaffold system should be able to absorb the wound exudate and prevent wound dehydration, reducing surface necrosis on the wound.63,64

Scaffold systems can be classified as follows based on the source and function of the materials.

When designing scaffold systems for chronic wound, an appropriate matrix source needs to be selected. Table 1 lists a few sources of nanocomposites used in wound dressing. Natural nanomaterials and their derivates have good biocompatibility and can be degraded by enzymes or water. However, their characters and quality differ from batch to batch and cannot be standardized. In contrast, synthetic biomaterials, such as polyethylene glycol (PEG) nano-scaffolds, show more stable structural properties and can be chemically modified. However, the biosafety of synthetic materials needs to be strictly examined.

Table 1 Sources of Nanocomposites

According to their functions, tissue engineering materials can be used for bones, nerves, blood vessels, skin, and other tissues (eg, tendon, ligament, cornea, liver, and kidneys).

Tissue engineering scaffolds for the skin can be of several types. These include natural polymers (chitosan, hyaluronic acid, and collagen), nanocomposite scaffolds (eg, nanobioactive glass and metal NPs), and conducting polymers (eg, polyaniline, polypyrrole, and polythiophene).7375 Taghiabadi et al synthesized an intact amniotic membrane-based scaffold for cultivating adipose-derived stromal cells (ASCs). By ASCs on an acellular human amniotic membrane (HAM), they created a neoteric skin substitute.76 Zhang et al designed a conductive and antibacterial hydrogel based on polypyrrole and functionalized Znchitosan molecules for the management of infected chronic wounds. They demonstrated the promising potential of the hydrogel in promoting the healing of the infected chronic wound after electrical stimulation. Currently, other tissue engineering scaffolds such as calcium phosphates and composite materials (eg, hydroxyapatite, -tricalcium phosphate, and whitlockite) for bone tissue engineering and amniotic membranes for corneal tissue engineering are under research.69,77

Skin tissue engineering scaffolds can be categorized as porous, fibrous, microsphere, hydrogel, composite, and acellular materials.73 Typically, natural biomaterials and their derivatives are biodegradable, absorbable, and harmless to the body, but their strength and processing performance are poor and their degradation speed cannot be controlled. Hence, in order to improve the mechanical and biological properties of scaffolds (eg, adhesion, strength, processing performance, and degradation speed) and accelerate wound healing, composite scaffolds have been developed by combining the characteristics and advantages of different materials. Depending on their constituents, these composite scaffolds can achieve specific functions. Currently, most novel scaffolds being developed use composite materials to obtain multifunctional characteristics.

Delivery systems are used to deliver drugs, cells, genes, and other neoteric bioactive molecules to the body or target area via transplantation or injection.78 Traditionally, delivery systems are broadly divided into two categories, drug delivery and cell delivery. With continuous Innovation in scientific research, new approaches, including gene delivery and the delivery of bioactive molecules such as growth factors, proteins, and peptides, are being developed.

Recently, there has been a significant increase in new biotechnology-based treatments, among which cell and gene therapies are quite sophisticated. Exosomes have shown superior therapeutic potential against various conditions, and delivery methods are being devised to maximize their therapeutic effectiveness. Moreover, exosomes are also emerging as a delivery system for other substances (eg, small molecules and miRNAs).79 NPs are essential for the delivery of these refined substances. In addition to serving as delivery vehicles, NPs can also act as diagnostic and therapeutic agents for some diseases.80 Research on nanoparticle-based drug delivery has mainly been focused on targeted drug delivery, and especially tumor-targeted drug delivery.81

A drug delivery system serves as a vehicle for therapeutic molecules. It allows drug delivery in the body, improves drug efficacy, and allows safe and controlled drug release.

The conventional routes for drug delivery80 are gastrointestinal drug delivery (eg, oral and rectal), parenteral administration (eg, subcutaneous, intramuscular, and intravenous injection) and topical administration (eg, percutaneous injection and wound dressings). Novel drug delivery systems for wound healing can be classified into the following categories: NPs, microcarriers, and tissue-engineered scaffolds.82 Skin tissue engineering scaffolds have been introduced earlier in this review, and NPs and microcarriers will be introduced in detail here (Table 2).

Table 2 Drug Delivery Systems Developed Using Nanotechnology

Drug-loaded nano-scaffolds that promote wound healing after topical administration have been developed. However, due to their poor solubility, short half-life, and other drawbacks, some drugs do not accumulate at an optimal concentration at the wound site for a long duration.83 Nano-scaffolds with varying porous structures can be used to load drugs or bioactive molecules, and the porous structure can provide a breathable environment for the wound.84 NPs carrying poorly soluble drugs are widely used to prepare controlled drug delivery systems. Nano-scaffolds typically show slow degradation, allowing long-term drug release and thereby maintaining an ideal concentration of the drug in the plasma.85 Shamloo et al developed polyvinyl alcohol (PVA)/chitosan/gelatin hydrogels to overcome the short half-life of basic fibroblast growth factor (bFGF). The biocompatibility of the hydrogel supported the continuous delivery of bFGF and significantly accelerated wound healing.86

During the treatment of chronic wounds, the drug is usually applied directly on affected region. Nanotechnology-based drug delivery systems could enable controlled drug release. Meanwhile, the degradability and stability of the drug could also be modified using nanosystems. Hence, these drug delivery systems could improve treatment compliance among patients with chronic wounds by reducing the application frequency and the cost of treatment.

It is widely acknowledged that metal ion-based biomaterials exhibit promising antimicrobial activity when applied to wounds, making them very suitable for the management of diabetic wounds, which are prone to infection. Given their reducing properties, under oxidative stress, cuprous ions provide a promising therapeutic option for diabetic wounds. Copper ions have also been reported to promote angiogenesis.115117 Equipped with infrared absorption and efficient heat generation abilities, semiconductor cuprous sulfide (Cu2S) NPs are widely employed as photothermal agents. Wang et al utilized the photothermal effect of Cu2S and the angiogenic effect of Cu ions to prepare electrospun fibers containing Cu2S NPs, achieving a combination of advantages based on the components and successfully promoting diabetic wound healing. Moreover, their biomaterial could also effectively inhibit the growth of skin tumors both in vivo and in vitro.70 This system demonstrated the effectiveness of bifunctional tissue engineering biomaterials, providing a novel method for drug delivery for the treatment of biological conditions.

Classic gene therapy generally involves the expression of exogenous genes or the silencing of target genes via viral or non-viral delivery.118,119 In general, gene delivery via viral transfection may be carcinogenic.119 Most gene therapies for diabetic wounds are based on siRNAs. Gene therapy has become a promising strategy for the treatment of various diseases, and its effects are mediated via the regulation of RNA and protein expression.120 Many unmodified gene therapy agents, such as proteins, peptides, and nucleic acids, are rapidly degraded or eliminated from systemic circulation before they can accumulate at effective concentrations at the target site. Owing to poor pharmacokinetics, repeated administration is warranted. This, in addition to the narrow range of safe doses, often leads to adverse effects during treatment.121

Several studies on wound management and especially chronic diabetic wound management have focused on gene- or RNA-based (eg, mRNA, microRNA, circRNA, and lncRNA) therapies.122 Subcutaneous local injections can be used to directly deliver RNAs or proteins to the wound site.123 However, due to the short half-life of the therapeutic agent, repeated administration is required, often leading to pain and poor treatment compliance. Drug delivery systems not only solve these problems but also protect gene-related small molecules from degradation and eliminated from the body. The greatest challenge in gene therapy is ensuring the successful transduction or transfection of target genes into host cells by crossing extracellular and intracellular barriers. Therefore, the engineering of gene delivery vehicles is complex.118 Moreover, the materials used to encapsulate gene-related small molecules are required to have low toxicity and promote a high transfection efficiency.124 Currently, the NPs that deliver siRNAs to promote wound management are composed of lipids, polymers (eg, chitosan, PEG), hyperbranched cationic polysaccharides (HCP), and silicon.125130

Shaabani et al developed layer-by-layer self-assembled siRNA-loaded gold NPs with two different outer layers Chitosan ([emailprotected]) and Poly L-arginine ([emailprotected]).126 They compared the two types of NPs, which had a similar core structure. They found that the two polymers had different escape mechanisms: the buffering capacity of chitosan resulted in endosome disruption,131 while PLA bound to the endosome lipid bilayer and promoted escaped through pore formation. Their results indicated that an outer layer of PLA allows the endosomal escape of siRNA, thus improving transfection efficiency and delivering target molecules to promote diabetic wound healing. Given that naked siRNAs are easily eliminated from the body, Li et al and Lan et al designed four HCP derivative-based vehicles128,129 for the delivery of siRNA against MMP9. This treatment led to the knockdown of MMP9, which prevents the healing of diabetic wounds, and thus promoted diabetic wound healing. Currently, nanocomposite-based gene delivery applications are focused on siRNA. However, efforts to deliver other products such as miRNA, lncRNA, or even DNA will be required in the future.

Exosomes are endosome-derived vesicles (30 to 150 nm in size) secreted by a variety of cells, including adipose stem cells (ADSCs), bone marrow stem cells (BMSCs), and mesenchymal stem cells (MSCs).132,133 Different types of cells secrete exosomes with different specific markers, which account for their specific functions. Despite their different origins, exosomes have a similar appearance and size and often have a common composition. Once they are isolated from an extracellular medium or from biological fluids, the source of exosomes cannot be ascertained of.134 Exosomes can be employed as small molecules for wound treatment. The combination of exosomes with porous NPs can increase therapeutic effects while maintaining the advantages of a scaffold. Importantly, exosomes can also be used as nanocarriers for drug delivery and targeted therapy, and these are called engineered exosomes.133,135

Exosomes can effectively promote diabetic wound healing.136,137 Shiekh et al embedded ADSC-derived exosomes (ADSC-exo) into antioxidant polyurethane scaffolds to achieve sustained exosome release. Their nanosystem leveraged the advantages of the scaffold, including antioxidant and antibacterial effects, to accelerate diabetic wounds healing both in vivo and in vitro.71 To prolong the half-life and lower the clearance rate of exosomes, Lei et al designed an ultraviolet-shielding nano-dressing based on polysaccharides that allowed exosome delivery and had self-healing, anti-infection and thermo-sensitive properties.61 These findings indicate that exosomes can be stabilized and well-delivered to target cells by combining them with porous NPs or nanocarriers and can be applied for treating chronic wounds.

It is widely accepted that infection is an important factor to monitor during the wound healing process as it can lead to progression of the chronic wound or even sepsis.138140 Conventional prevention and treatment approaches for wound infection involve local or systemic antibiotic administration, which can lead to failed anti-infection treatment or even antibiotic resistance.141,142 Several nano-formulations that have antimicrobial ability have been developed and used in anti-infectious wound therapy, playing a critical role in infection management. Table 3 lists some antimicrobial nanobiotechnology-based systems used in wound healing.

Table 3 Nanomaterials Used in Anti-Microbial Wound Dressing

Metals have been used as inorganic antimicrobial agents for thousands of years and were even used as anti-infection agents in ancient Persia.162 Metal NPs, such as AgNPs, AuNPs, and CuNPs, have attracted great attention due to their anti-infection properties and low toxicity.163 Given that metal NPs do not cause antimicrobial resistance and release metal ions or produce ROS which can kill microorganisms they appear to be suitable alternatives to antibiotics as.164,165

AgNPs, which are the more well-known metal NPs, have been used widely in clinical practice and basic medical research. Wound treatment products containing AgNPs have been commercially available for decades.166 AgNPs can continuously generate Ag+, which reacts with proteins and nucleic acids, causing molecular defects and killing bacteria and viruses.167170 Several studies have shown that AgNPs have good potential as antiseptics. Luna-Hernndez et al found that a combination of functional chitosan and silver nanocomposites showed antibacterial effects against S. aureus and P. aeruginosa in burn wounds.152 Moreover, in mice treated with the composite dressing, silver accumulation was found to be far lower than that in mice treated with the clinically used AcasinTM nanosilver dressing. Zlatko et al demonstrated that the AgNPs hydrogel serves as a versatile platform, with features such as antibacterial efficacy, exudate absorbance, low cost, biocompatibility, hemocompatibility, and improved healing for chronic wounds.171 Huang et al constructed an organic framework-based microneedle patch containing AgNPs. The product showed transdermal delivery and could prevent S. aureus, E. coli, and P. aeruginosa infections in diabetic wounds.172 In addition, several commercialized products containing AgNPs have been developed for clinical treatment. These include Acticoat, Allevyn Ag, Aquacel Ag Surgical, Atrauman Ag, Biatain Silicone Ag, Flaminal, Mepilex Transfer Ag, SILVERCEL, and Urgo Clean Ag.

Nano-sized gold is also useful as an anti-infection agent. It has been confirmed that AuNPs bind to bacterial DNA and show bactericidal and bacteriostatic properties.173,174 Some studies show that Au nanocomposites can kill MRSA and P. aeruginosa through photothermal effects and could promote wound closure.150,175

Compared with gold and silver, copper is less expensive and more easily available. CuNPs are considered the best candidates for developing future technologies for the management of infectious and communicable diseases.49 Cai et al developed a CuNP-embedded hydrogel that accelerated wound healing and showed effective antibacterial capacity against both gram-positive and gram-negative bacteria as well as great photothermal properties.176

Inorganic non-metal nano-materials have been also considered potential antimicrobial agents owing to their intrinsic anti-infection effects.177 Based on the unique structural and physio-chemical properties of carbon nanomaterials, a research team prepared a carbon nanofiber platform that inhibits the growth of E. coli and MRSA.178 In this study, CuNPs and ZnNPs were asymmetrically distributed in carbon NFs grown on an activated carbon fiber substrate using chemical vapor deposition (CVD). The carbon NFs platform inhibited the growth of gram-positive and gram-negative bacterial strains with superior efficiency than simple metal NPs. Another study showed that carbon nanotubes can be used to prepare wound-repairing bandages with infection-preventing properties.179

The natural organic biomaterial chitosan and its derivatives are popular in biomedicine. Chitosan possesses good biocompatibility, antimicrobial properties, and low immunogenicity.180 Using nanobiotechnology, Ganji et al fabricated a nanofiber with chitosan-encapsulated nanoparticles loaded with curcumin for wound dressing. The electrospun chitosan-based nanofiber inhibited the growth of E. coli and MRSA by 98.9% and 99.3% in infected wounds in mice.50 Another type of chitosan nanofiber also showed potential in wound care owing to its antibacterial and re-epithelialization-promoting effects.181 Antibiotic-loaded chitosan nanofibers have also been used for local drug delivery and wound treatment.182 Other metalorganic framework nanorods have also shown bacterial inhibition in infectious wounds.183 Dias et al developed a series of soluble potato starch nanofibers sized 70264 nm. They incorporated carvacrol during the synthesis of the potato starch nanofibers, and the obtained nanocomposites showed great anti-pathogenic activity against S. aureus, E. coli, L. monocytogenes, and S. typhimurium, highlighting their potential as agents for wound dressing.184

With respect to organic nano-materials, anti-infection approaches focus on natural antibacterial compounds such as chitosan and its derivatives. Further, owing to the bactericidal effects of metals, metal-organic frameworks are also used. Given that metal NPs are associated with the potential risks of metal deposition, organic nano-antimicrobial materials, especially natural macromolecules with antibacterial properties, may become useful for wound dressing.

Biofilm, which are made up of surface-attached groups of microbes, are considered to be the primary cause of chronic wounds owing to their role in antibiotic resistance.141,185187 Most biofilms are formed on the surface of wounds. However, some special biofilms can get implanted into the deep layers of skin tissue, making traditional diagnose and treatment challenging.188 The clinical treatment of biofilms in wounds involves wound cleansing with polyvinylpyrrolidone or hydrogen peroxide, debridement, refashioning of wound edges, dressing, and the topical or general administration of antibiotics.189 With further insights into the mechanisms of biofilm formation and developments in nanobiotechnology, nanomaterials effective for biofilm therapy have been developed.

Nanomaterials based on metals or metal oxides are widely used against wound biofilms, including silver, copper, gold, titanium, zinc oxide, magnesium oxide, copper oxide, and iron oxide.190,191 Owing to the small size of these particles, metal or metal oxide NPs can move across bacterial membranes and rupture them. They can destroy enzyme activity and the respiratory chain in bacteria. It has been demonstrated that Ag NPs and silver oxide NPs are the most effective against microbial biofilms.192,193 Abdalla et al functionalized nano-silver with lactoferrin and incorporated them in a gelatin hydrogel, generating a dual-antimicrobial action dressing for infectious wounds and maximizing the anti-biofilm property of silver.194

Chitosan, bacterial cellulose (BC) and other natural antimicrobials have been modified using nanotechnology to treat wound biofilms. Owing to the positive charge on the polymeric chain of chitosan, chitosan NPs easily adhere to the negatively charged microbial membrane, triggering changes in permeability and preventing biofilm formation.195 Zemjkoski et al obtained chitosan NPs through gamma irradiation and encapsuled them into BC to form BC-nChiD hydrogels with excellent anti-biofilm potential. These hydrogels could provide a 90% reduction in viable biofilms and a 65% reduction in biofilm height.196 Mahtab reduced the amount of bacteria in a planktonic condition by treating bacterial biofilms with photodynamic therapy using curcumin encapsulated into silica NPs. After exposure to blue light, ROS was produced owing to the photodynamic properties of silica NPs. The ROS damaged biofilms, and the curcumin released prevented bacterial growth.197

The size of nanoparticles can be controlled, and they have a large specific area, can penetrate bacterial membranes, and show bactericidal properties. Hence, nanotechnology has great potential in destroying biofilms and treating infectious chronic wounds. In addition to providing nanoparticles with anti-infection properties, nanotechnology could also be used to provide a platform for antibiotics, enhance their solubility, prolong their half-life, and reduce the required treatment dose.

Due to its superiority with respect to tissue engineering, cell-based therapy is extensively used for chronic wound treatment.198201 Stem cells derived from bone marrow, the umbilical cord, and adipose and cutaneous tissue can differentiate into various tissue types and modulate cell migration, collagen deposition, re-epithelialization, and tissue remodeling.198,202205 Nanofibers prepared using electrostatic spinning are widely used for scaffolding. Mao et al prepared polycaprolactone nanofibrous scaffolds and combined collagen with bioactive glass NPs (CPB nanofibrous scaffold). The CPB nanofibrous scaffold exerted positive effects as a cell-carrying system containing epithelial progenitor cells (EPCs). The EPC-carrying CPB bioactive complex promoted wound healing by enhancing cell proliferation, granulation tissue formation, re-epithelialization, and cell adhesion (Figure 3).206 Khojasteh et al found that curcumin-carrying chitosan/poly(vinyl alcohol) nanofibers can carry pad-derived mesenchymal stem cells and show excellent curcumin release and improve cell adhesion and proliferation, indicating that they could be useful in wound dressings.207 Kaplan et al produced an injectable silk nanofiber hydrogel embedded with BMSCs. The nanofiber hydrogel maintained the stemness of the BMSCs, successfully carrying them to the target site and promoting wound healing through increased angiogenesis and collagen deposition.57

Figure 3 Schematic of a CPB/EPC construct that promotes wound healing. CPB enhances cell proliferation, collagen deposition, and EPC differentiation via the Hif-1/VEGF/SDF-1 pathway. This results in the rapid vascularization and healing of full-thickness wounds.

Notes: Reprinted from: Wang C, Wang Q, Gao W et al. Highly efficient local delivery of endothelial progenitor cells significantly potentiates angiogenesis and full-thickness wound healing. Acta Biomaterialia. 2018;69:156169. doi:10.1016/j.actbio.2018.01.019.206 2018 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. With permission from Elsevier. Available from: https://www.sciencedirect.com/science/article/abs/pii/S1742706118300308#f0060.

Usually, cell therapy in wound care is performed using micrometer-scale carriers as cell sizes fall in the range of microns. With the development of nanotechnology, an increasing number of nanofibers and NPs are being developed for cell therapy aimed at treating chronic wound given the excellent pro-differentiation, stemness-holding, and immunoregulation properties of the nanocomposites.

As an important component of the extracellular matrix, collagen mediates communication between cells, provides a scaffold for cell migration and adhesion, and plays a role in chronic wound healing.4 Some nanobiotechnology-based platforms have been used for collagen modulation. Sun et al loaded N-acetyl cysteine onto graphene oxide (GO) NPs to enable scarless wound healing (Figure 4).208 In their study, GO NPs decreased collagen metabolism and improved the balance between collagen formation and degradation, thus allowing the wound to heal without scarring. In another study by the same group, a polyamide nanofiber-based multi-layered scaffold was found to promote wound healing by encouraging the uniform arrangement of collagen.209 Krian et al synthesized a 3-D biomatrix with nanotized praseodymium that promotes collagen function via the stabilization of native collagen. Their rare-earth metal nanoparticles thus showed potential applications in wound care.210

Figure 4 Wound healing effect of a scaffold based on GO NPs.

Notes: Adapted from: Li J, Zhou C, Luo C et al. N-acetyl cysteine-loaded graphene oxide-collagen hybrid membrane for scarless wound healing. Theranostics. 2019;9(20):58395853. doi:10.7150/thno.34480.208 The author(s). Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.

In chronic wound treatment, deposited collagen acts as a natural scaffold for cells, and therefore, modulating collagens is synonymous with re-establishing tissue structure in the wound area. As a result, collagen-modulating nano-systems have mainly been used for accelerating tissue repair. However, the studies by Suns group are inspirational and demonstrate that this approach should also be utilized for developing chronic wound treatments that decrease scarring.

Despite the availability of dozens of commercial wound-care products, bionic systems have not yet been adopted for wound healing. There is an urgent need for smart wound-healing systems that can respond to the stimuli (temperature, pH, glucose, enzyme, etc.) at the site of the chronic wound area.211,212 Through developments in nanobiotechnology, NPs with stimuli-response characteristics have received great attention. Gong et al synthesized a nanozyme consisting of poly(acrylic acid)-coated Fe3O4 NPs (pFe3O4) and then combined them with GO to produce pFe3O4@GO NCs. The pFe3O4@GO NCs could react with glucose and function as a self-supplying H2O2 nanogenerator at the wound site, allowing the chemodynamic treatment of wound infections.157 Some researchers developed photoactive electrospun nanofibers using cellulose acetate, polyethylene oxide, methylene blue, and three-layered cellulose acetate/polyethylene oxide/silk fibroin/ciprofloxacin. The nanofibers could produce ROS after light irradiation at 635 nm, accelerating the healing of infectious wounds by inhibiting S. aureus, K. pneumoniae, and P. aeruginosa biofilms.213 Zhang et al developed a hybrid hydrogel with MnO2 nanosheets. The injectable MnO2 nanosheet hydrogel could perform thermogenesis under 808-nm laser irradiation, eliminating ROS and inflammation and promoting wound repair.214 Overall, nano-structures functionalized using stimuli-response properties could simulate the biological, chemical, and physical characteristics of natural skin, enabling tissue regeneration in refractory wounds.

Given the elucidation of mechanisms and physiological changes associated with wound healing, sensors that allow real-time monitoring of wound repair have been developed.215217 A complex smart wound-monitoring wound dressing has also been invented.218 This dressing contains a nanofiber membrane made of chitosan/collagen, and promotes proliferation and regeneration by upregulating extracellular matrix secretion and promoting integrin/FAK signaling. Olivo et al added AgNPs to a fiber-based membrane monitor to increase the active surface area in the sensor, improving the detection sensitivity for biomarkers in the wound area.219 In order to avoid secondary wound damage caused by dressing changes, Jiang et al created bacterial cellulose-based membranes with aminobenzeneboronic acid-modified gold nanoclusters (A-GNCs), which could be used for treating wounds infected with multidrug-resistant bacteria.220 A-GNCs emit bright orange fluorescence under UV light, and the intensity of this fluorescence decreases with the release of A-GNCs. This allows healthcare professionals to determine when the dressing needs to be replaced. In the past few years, dressings that can monitor the status of chronic wounds in real-time have been tested. However, this field is relatively new, and current research on nanotech-based systems for monitoring chronic wounds is scarce.

Along with advances in nanobiotechnology research, several new nanosystems have advanced from the laboratory investigation stage to the clinical trial stage. Table 4 lists some clinical trials that have tested nano-therapies for wound healing. As early as 2014, Lopes et al investigated the cost-effectiveness of using nanocrystalline silver for treating burns. Their study showed that AgNPs provided faster wound healing than traditional silver sulfadiazine, requiring fewer dressing changes and reducing the human resource burden.221 Meanwhile, some clinical trials tested the use of nano-products for treating chronic wounds (Table 4). Although metal NPs were typically used for antimicrobial therapy, one clinical trial studied the efficacy and safety of autologous nano-fat combined with platelet-rich fibrin for treating refractory diabetic foot wounds. However, overall, there were few clinical trials examining the applications of nanoplatforms in chronic wound care, likely owing to inadequate previous research on biocompatibility. Moreover, few doctors participated in research on nanotechnology-based chronic-wound treatment, and hence, several clinical requirements were ignored or misunderstood.

Table 4 List of Clinical Trials for Nanobiotechnology-Based Wound Treatment

As nanobiotechnology has developed, nano-sized biomaterials have been widely applied for treating chronic wounds. This review article highlights that the application of nanotechnology in chronic wound treatment has, so far, largely focused on scaffold construction, anti-infection treatment, and substance delivery.34,45,47,130,147

In scaffold systems, nanobiotechnology provides both materials and techniques for managing chronic wounds. Electrospinning, a nanotechnique, allows the production of biomimetic structures that mimic the natural skin and help in healing refractory wounds.50 Furthermore, some nano-scaffolds promote cell adhesion and migration by mimicking the construction of natural tissues, thus promoting chronic wound healing. Nevertheless, there is further scope to improve the quality of natural nano-biomaterials and the biocompatibility of synthetic nano-biomaterials to increase their application.

Dozens of metal NPs, and especially AgNPs, have been used in antimicrobial therapy for chronic wounds.163 However, metal deposition can cause DNA and cell damage. Hence, nanomaterials that prevent infection without causing toxicity are required. Further effort should be made to decrease the accumulation of heavy metals. Alternatively, nanocomposites without metal elements should be adopted more often in the future.

To overcome the ever-changing environment of the skin during chronic wound healing, several wound-monitoring and stimuli-responsive biomaterials have been developed.58,157,218 By leveraging specific characteristics, such as the photothermal effect, chemo-dynamic effect, fluorescence, and thermo-sensitivity, more nano-biomaterials that can be used in stimuli-responsive and dynamic monitoring systems for wound care should be developed. Most studies on wound healing have focused on migration-promoting effects, antimicrobial activity, and substance delivery. However, few nanotech-based multifunctional smart systems, such as smart dressings that show specific responses to stimuli, have been developed. Researchers in this field should work towards developing smart systems based on the mechanisms of disunion in chronic wounds, which could effectively demonstrate the potential of nanobiotechnology in promoting chronic wound repair.

Despite the decades-long history of nanotechnology research, few products and therapies based on nanobiotechnology have become available commercially or entered the clinical trial phase. One reason for this is that most basic nanotech research on chronic wound healing is performed in rodent models, such as C57BL/6 mice or SpragueDawley rats, even though the skin structure and chronic wound healing processes differ between rodents and humans.222 The wound healing effects observed in primates, such as humans, may not be as good as those in rats and mice. Meanwhile, the cost of nano-materials and processing platforms required for large-scale preparation also hinder the clinical translation of nanotechnologies.

During the past few years, numerous nano-materials and techniques have been used to repair chronic wounds. This review summarizes some nanobiotechnology-based systems and nanoplatform designs that can be used for treating chronic wounds. It highlights that a smart dressing for chronic wounds that allows real-time monitoring and has stimuli-responsive abilities is one possible direction for the future of nano-wound-repairing systems. We hope this review motivates the development of more sophisticated wound management systems based on nanobiotechnology in the future.

The authors acknowledge the support from the National Natural Science Foundation of China (81974289, 81772094), the Key Research and Development Program of Hubei Province (grant number 2020BCB031), the Guangdong Basic and Applied Basic Research Foundation (2019B1515120043), the international cooperation research project of Shenzhen, the international cooperation research project of Shenzhen (GJHZ20190822091601691), and the Key Project of Basic Research of Shenzhen (JCYJ20200109113603854).

The authors report no conflicts of interest in relation to this work.

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Applications in Chronic Wound Healing | IJN - Dove Medical Press

Nanorobots are electromechanical devices comprised of components that are within the nanometer size range. Within medicine, nanorobotic applications have been successfully used for a variety of microbiological, hematological, surgical and dental applications, to name a few.

The nanobots market global size accounted for USD 5.3 billion in 2021 and is expected to reach around USD 21.45 billion by 2030, expected to register growth at a CAGR of 16.8% from 2022 to 2030.

What is Biomedical Nanorobots?

As compared to industrial robots that were originally developed to automate routine and dangerous tasks, biomedical robots are highly specialized and miniature devices that must be capable of performing precise tasks within the human body. Recent advancements in nanotechnology and materials science have therefore promoted the development of both micro- and nanorobots for a wide range of biomedical applications.

Whereas the traditional power sources for industrial robots that require large power supplies and/or battery storage capabilities, both micro- and nanorobots will typically depend on chemically powered motors for their energy needs. To this end, these motors acquire energy by converting locally supplied fuels, such as oxygen or glucose within the body, to propel themselves towards different cellular structures. Nanorobots can also rely on externally powered motors based on either magnetic or ultrasound technology to drive their motion.

One of the most challenges that biomedical researchers have faced during the miniaturization of robotic systems has been the optimization of nanolocomotion. Recent developments in this field have demonstrated the ability of both micro- and nanorobots to efficiently propel themselves through complex biological media or narrow blood vessels. Furthermore, once these microscopic robots have penetrated through these areas, researchers have successfully developed ways in which these devices can collect and remove tissue biopsy samples, obtain detailed images, release active agents at predetermined locations and perform localized diagnoses.

Key market players

Report Scope of theNanobots Market

USD 21.45 Billion

Segments covered in the report

By Type

By Application

By Type of Manufacturing

By End User

Regional Segment

Nanomedicine segment is expected to dominate the application segment of the nanobots market

Based on application, the nanobots market is segmented into nanomedicine, biomedical and other applications. The Nanomedicine segment is expected to dominate the global nanobots market by holding more than 36% of the overall market. Nanobots are widely used in nanomedicine due to the increasing healthcare applications of nanobots. The large market share of this segment is attributed to the large level of commercialization in the healthcare sector for drug delivery, in vivo imaging, active implants, in vitro diagnostic, biomaterial, and drug therapy.

Additionally, increasing innovations in the field of cancer treatment related to the specific target are also contributing to the growth of nanobots market. The biomedical applications segment accounted for the second-largest market share of the overall nanobots marketplace.

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Fundamental Knowledge on Nanobots - Bio-IT World

Using nanoparticles to deliver cancer drugs offers a way to hit tumors with large doses of drugs while avoiding the harmful side effects that often come with chemotherapy. However, so far, only a handful of nanoparticle-based cancer drugs have been FDA-approved.

A new study from MIT and Broad Institute of MIT and Harvard researchers may help to overcome some of the obstacles to the development of nanoparticle-based drugs. The teams analysis of the interactions between 35 different types of nanoparticles and nearly 500 types of cancer cells revealed thousands of biological traits that influence whether those cells take up different types of nanoparticles.

The findings could help researchers better tailor their drug-delivery particles to specific types of cancer, or design new particles that take advantage of the biological features of particular types of cancer cells.

We are excited by our findings because it is really just the beginning we can use this approach to map out what types of nanoparticles are best to target certain cell types, from cancer to immune cells and other kinds of healthy and diseased organ cells. We are learning how surface chemistry and other material properties play a role in targeting, says Paula Hammond, an MIT Institute Professor, head of the Department of Chemical Engineering, and a member of MITs Koch Institute for Integrative Cancer Research.

Hammond is the senior author of the new study, which appears today in Science. The papers lead authors are Natalie Boehnke, an MIT postdoc who will soon join the faculty at the University of Minnesota, and Joelle Straehla, the Charles W. and Jennifer C. Johnson Clinical Investigator at the Koch Institute, an instructor at Harvard Medical School, and a pediatric oncologist at Dana-Farber Cancer Institute.

Cell-particle interactions

Hammonds lab has previously developed many types of nanoparticles that can be used to deliver drugs to cells. Studies in her lab and others have shown that different types of cancer cells often respond differently to the same nanoparticles. Boehnke, who was studying ovarian cancer when she joined Hammonds lab, and Straehla, who was studying brain cancer, also noticed this phenomenon in their studies.

The researchers hypothesized that biological differences between cells could be driving the variation in their responses. To figure out what those differences might be, they decided to pursue a large-scale study in which they could look at a huge number of different cells interacting with many types of nanoparticles.

Straehla had recently learned about the Broad Institutes PRISM platform, which was designed to allow researchers to rapidly screen thousands of drugs on hundreds of different cancer types at the same time. With instrumental collaboration from Angela Koehler, an MIT associate professor of biological engineering, the team decided to try to adapt that platform to screen cell-nanoparticle interactions instead of cell-drug interactions.

Using this approach, we can start thinking about whether there is something about a cells genotypic signature that predicts how many nanoparticles it will take up, Boehnke says.

For their screen, the researchers used 488 cancer cell lines from 22 different tissues of origin. Each cell type is barcoded with a unique DNA sequence that allows researchers to identify the cells later on. For each cell type, extensive datasets are also available on their gene expression profiles and other biological characteristics.

On the nanoparticle side, the researchers created 35 particles, each of which had a core consisting of either liposomes (particles made from many fatty molecules called lipids), a polymer known as PLGA, or another polymer called polystyrene. The researchers also coated the particles with different types of protective or targeting molecules, including polymers such as polyethylene glycol, antibodies, and polysaccharides. This allowed them to study the influence of both the core composition and the surface chemistry of the particles.

Working with Broad Institute scientists, including Jennifer Roth, director of the PRISM lab, the researchers exposed pools of hundreds of different cells to one of 35 different nanoparticles. Each nanoparticle had a fluorescent tag, so the researchers could use a cell-sorting technique to separate the cells based on how much fluorescence they gave off after an exposure of either four or 24 hours.

Based on these measurements, each cell line was assigned a score representing its affinity for each nanoparticle. The researchers then used machine learning algorithms to analyze those scores along with all of the other biological data available for each cell line.

This analysis yielded thousands of features, or biomarkers, associated with affinity for different types of nanoparticles. Many of these markers were genes that code for the cellular machinery needed to bind particles, bring them into a cell, or process them. Some of these genes were already known to be involved in nanoparticle trafficking, but many others were new.

We found some markers that we expected, and we also found much more that has really been unexplored. We're hoping that other people can use this dataset to help expand their view of how nanoparticles and cells interact, Straehla says.

Particle uptake

The researchers picked out one of the biomarkers they identified, a protein called SLC46A3, for further study. The PRISM screen had shown that high levels of this protein correlated with very low uptake of lipid-based nanoparticles. When the researchers tested these particles in mouse models of melanoma, they found the same correlation. The findings suggest that this biomarker could be used to help doctors identify patients whose tumors are more likely to respond to nanoparticle-based therapies.

Now, the researchers are trying to uncover the mechanism of how SLC46A3 regulates nanoparticle uptake. If they could discover new ways to decrease cellular levels of this protein, that could help make tumors more susceptible to drugs carried by lipid nanoparticles. The researchers are also working on further exploring some of the other biomarkers they found.

This screening approach could also be used to investigate many other types of nanoparticles that the researchers didnt look at in this study.

The sky is the limit in terms of what other undiscovered biomarkers are out there that we just haven't captured because we haven't screened them, Boehnke says. Hopefully its an inspiration for others to start looking at their nanoparticle systems in a similar manner.

The research was funded, in part, by SPARC funding to the Broad Institute, the Marble Center for Cancer Nanomedicine at the Koch Institute, and the Koch Institute Support (core) Grant from the National Cancer Institute.

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How different cancer cells respond to drug-delivering nanoparticles - MIT News

Nanorobots Marketare also utilised in the maintenance and assembly of complex systems. Nanorobotics widespread use in the medical field is also propelling market revenue growth. In individuals with sickness or weakened immunity, nanorobots can act as antiviral or antibody agents. In addition to cancer detection and treatment, the technique is also being employed in gene therapy.

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A nano robot is a new technology for designing, programming, and controlling nanoscale robots. Nanorobots are capable of doing specified jobs with components that are on the nanometer size (10-9 meters). Nanorobots are capable of diagnosing certain types of cancer and serve a critical role in human pathogen protection and treatment.Biomedicalinstrumentation, pharmacokinetics, surgical procedures, diabetes monitoring, and other healthcare services can all benefit from nano robots. Data Bridge Market Research analyses that the nanorobots market was valued at USD 7739.19 in 2021 and is further estimated to reach USD 19576.43 million by 2029, and is expected to grow at a CAGR of 12.23% during the forecast period of 2022 to 2029.

Some of the major players operating in the nanorobots market are

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NanorobotsMarket Dynamics

Drivers

In the healthcare industry, advances in molecular robot technology are increasingly being used to execute complex tasks and eliminate human error.

Recent research in DNA nanotechnology supports the use of nanorobots inregenerative medicineon a big scale which is further anticipated to contribute to the market growth.

Nanotechnology will be used in the medical field to aid in the detection and treatment of diseases such as diabetes.

Opportunities

In addition, the growing application areas of microscopes and incorporation of microscopy with spectroscopy are further estimated to provide potential opportunities for the growth of the nanorobots market in the coming years.

GlobalNanorobotsMarket Scope and Market Size

The nanorobots market is segmented on the basis of type and application. The growth amongst these segments will help you analyze meager growth segments in the industries and provide the users with a valuable market overview and market insights to help them make strategic decisions for identifying core market applications.

Type

On the basis of type, the nanorobots market is segmented into microbivore nano robots, respirocyte Nano robots, clottocyte Nano robots, cellular repair Nanorobots and others. The others segment is further sub segmented into Nano swimmers and bacteria powered robots.

Application

On the basis application, the nanorobots market is segmented into nano medicine, biomedical, mechanical and other applications.

NanorobotsMarket Regional Analysis/Insights

The nanorobots market is analysed and market size insights and trends are provided by country, type and application as referenced above. The countries covered in the nanorobots market report are U.S., Canada and Mexico in North America, Germany, France, U.K., Netherlands, Switzerland, Belgium, Russia, Italy, Spain, Turkey, Rest of Europe in Europe, China, Japan, India, South Korea, Singapore, Malaysia, Australia, Thailand, Indonesia, Philippines, Rest of Asia-Pacific (APAC) in the Asia-Pacific (APAC), Saudi Arabia, U.A.E, South Africa, Egypt, Israel, Rest of Middle East and Africa (MEA) as a part of Middle East and Africa (MEA), Brazil, Argentina and Rest of South America as part of South America.

North America dominates the nanorobots market due to the rise in the adoption of nano robotics technology. Furthermore, the presence of sophisticated healthcare infrastructure will further boost the growth of the nanorobots market in the region during the forecast period. Asia-Pacific is projected to observe significant amount of growth in the nanorobots market due to the rise in the attention of the manufacturers.

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Nanorobots Market to close to USD 19576.43 million with CAGR of 12.23% during the forecast period to 2029 - Digital Journal

An image of the neutrobot at work SWNS

White blood cells have been made into a kind of micro-robot that could treat and prevent life threatening illnesses, according to scientists in China.

The tiny, laser-guided machines are made from white blood cells called neutrophilsand are set, the scientists think, to revolutionize medicine.

Named neutrobots, they can deliver drugs to precise locations in the body after being directed by laser beams. Other devices developed to perform similar tasks contain synthetic materials which in several instances have triggered serious immune responses and biological rejection.

The neutrophil microcrafts can be remotely activated by light and then navigated to the target position along a designated route, said project leader Dr. Xianchuang Zheng, of the Institute of Nanophotonics at Jinan University, China.

In experiments on the tails of zebrafish, the Chinese team used an incredibly impressive and precise laser called a scanning optical tweezers (SOTs) to perform three potential applications with the neutrobots.

SOTs point a highly focused beam to hold and move microscopic and sub-microscopic particles in a manner similar to tweezers, and were used with the help of the neutrobots for cell therapy, targeted nanomedicine, and removal of debris or organic waste that can trigger disease.

SIMILAR: Protein Motors Can Swim Around Wounds to Kill Bacteria And Deliver Lifesaving Drugs

Additionally, the neutrobots could carry payloads directly to a tumor, blood clot, or infection.

By integrating the non-invasive manipulation of optical tweezers and innate immunologic function of neutrophils, the proposed microcraft provides new insight for the construction of native medical microdevices for precision medicine, Dr. Zheng said.The neutrophil microcraft can be activated or recovered in a controlled manner and the migration is fully steerablejust like driving a vehicle.

The zebrafish have high blood circulation to their tails, allowing the neutrophils to be clearly identified through fluorescence labelling.

Its significantly less scary than other nanobot medical applications being developed elsewhere, like these miniscule crabs theorized as agents to dispose of tumors, clear clogged arteries, or stop internal bleeding.

Ordinary neutrophils are often slow and go in the wrong direction, part of why the development of micro-robotics has steered more towards artificial solutions.

Maneuvers of the neutrobots include remote activation by SOTs at a desired time and locationprecisely navigated to achieve a designed route and speed.

Not only do medical microrobots currently in development require injections or the consumption of capsules to get them inside an animal or person, but researchers have found the objects trigger immune reactions in small animals, resulting in their removal before they can perform their jobs.

CHECK OUT: For the First Time, Researchers Use Healthy Stem Cells for Future Type 1 Diabetes Cure

The study in the journal ACS Central Science is the first time they have been guided with lasers in living animals. The light-driven microrobot could be moved up to a velocity of 1.3 microns a secondthree times faster than a neutrophil naturally moves.

In one test, a neutrobot was moved through a blood vessel wall into the surrounding tissue. Another picked up and transported a plastic nanoparticle, showing its potential for carrying medicine. When one was pushed toward red blood cell debris, it engulfed the pieces.

It seems pure science fiction, but could become standard of care.

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Microscopic Robots Made from White Blood Cells Could Treat and Prevent Life-Threatening Illnesses - Good News Network

New York, United States Report Ocean published the latest research report on the Nano Therapy market. In order to comprehend a market holistically, a variety of factors must be evaluated, including demographics, business cycles, and microeconomic requirements that pertain precisely to the market under study. In addition, the Nano Therapy market study demonstrates a detailed examination of the business state, which represents creative ways for company growth, financial factors such as production value, key regions, and growth rate.

Key Companies Covered in theNano TherapyResearch areNanosphere Inc., Cristal Therapeutics, DIM, NanoMedia Solutions Inc., Luna, Nanobiotix, Sirnaomics Inc., Selecta Biosciences Inc., NanoBioMagnetics.n.nu, Nanospectra Biosciences Inc., Tarveda Therapeutics, Parvus Therapeutics, CytImmune Science Inc., Nanoprobes Inc., NanoBio Corporation, Smith and Nephewand other key market players.

TheNano Therapymarket revenue was $$ Million USD in 2016, grew to $$ Million USD in 2022, and will reach $$ Million USD in 2030, with a CAGR of % during 2022-2030.

The Centers for Medicare and Medicaid Services data estimates that the U.S. national healthcare expenditure surpassed US$ 4.1 trillion in 2020 and is forecast to reach US$ 6.2 trillion by 2028. According to the Commonwealth Fund, the U.S. expended nearly 17% of gross domestic product (GDP) on healthcare in 2018. Switzerland was the second-highest-ranking country, expending 12.2%. In addition, New Zealand and Australia devote only 9.3%.Request To Free Sample of This Strategic Report:-https://reportocean.com/industry-verticals/sample-request?report_id=mai284010

According to the U.S. Bureau of Labor Statistics, employment in healthcare fields is forecast to grow 16% from 2020 to 2030, much quicker than the standard for all occupations, counting about 2.6 million new jobs. This estimated growth is mainly due to an elder population, showing to greater demand for healthcare services. The median annual wage for healthcare practitioners and technical fields (such as registered nurses,0020physicians and surgeons, and dental hygienists) was US$ 75,040 in May 2021, which was greater than the median annual wage for all occupations in the economy of US$ 45,760.

Market Overview

Nano therapy is a branch of nanomedicine that involves using nanoparticles to deliver a drug to a given target location in the body so as to treat the disease through a process known as targeting.

GlobalNano TherapyMarket Development Strategy Pre and Post COVID-19, by Corporate Strategy Analysis, Landscape, Type, Application, and Leading 20 Countries covers and analyzes the potential of the global Nano Therapy industry, providing statistical information about market dynamics, growth factors, major challenges, PEST analysis and market entry strategy Analysis, opportunities and forecasts. The biggest highlight of the report is to provide companies in the industry with a strategic analysis of the impact of COVID-19. At the same time, this report analyzed the market of leading 20 countries and introduce the market potential of these countries.

Most important types of Nano Therapy products covered in this report are:Nanomaterial and Biological DeviceNano Electronic BiosensorMolecular NanotechnologyImplantable Cardioverter-Defibrillators

Most widely used downstream fields of Nano Therapy market covered in this report are:Cardiovascular DiseaseCancer TherapyDiabetes TreatmentRheumatoid ArthritisOthers

Top countries data covered in this report:United StatesCanadaGermanyUKFranceItalySpainRussiaChinaJapanSouth KoreaAustraliaThailandBrazilArgentinaChileSouth AfricaEgyptUAESaudi Arabia

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Chapter 1 is the basis of the entire report. In this chapter, we define the market concept and market scope of Nano Therapy, including product classification, application areas, and the entire report covered area.

Chapter 2 is the core idea of the whole report. In this chapter, we provide a detailed introduction to our research methods and data sources.

Chapter 3 focuses on analyzing the current competitive situation in the Nano Therapy market and provides basic information, market data, product introductions, etc. of leading companies in the industry. At the same time, Chapter 3 includes the highlighted analysisStrategies for Company to Deal with the Impact of COVID-19.

Chapter 4 provides breakdown data of different types of products, as well as market forecasts.

Different application fields have different usage and development prospects of products. Therefore, Chapter 5 provides subdivision data of different application fields and market forecasts.

Chapter 6 includes detailed data of major regions of the world, including detailed data of major regions of the world. North America, Asia Pacific, Europe, South America, Middle East and Africa.

Chapters 7-26 focus on the regional market. We have selected the most representative 20 countries from 197 countries in the world and conducted a detailed analysis and overview of the market development of these countries.

Chapter 27 focuses on market qualitative analysis, providing market driving factor analysis, market development constraints, PEST analysis, industry trends under COVID-19, market entry strategy analysis, etc.

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Key Points:Define, describe and forecast Nano Therapy product market by type, application, end user and region.Provide enterprise external environment analysis and PEST analysis.Provide strategies for company to deal with the impact of COVID-19.Provide market dynamic analysis, including market driving factors, market development constraints.Provide market entry strategy analysis for new players or players who are ready to enter the market, including market segment definition, client analysis, distribution model, product messaging and positioning, and price strategy analysis.Keep up with international market trends and provide analysis of the impact of the COVID-19 epidemic on major regions of the world.Analyze the market opportunities of stakeholders and provide market leaders with details of the competitive landscape.

Table of Content:

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Key Benefits for Industry Participants & Stakeholders

Key Questions Answered in the Market Report

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Nano Therapy Market 2022 Growth Is Expected To See Development Trends and Challenges to 2030 This Is Ardee - This Is Ardee

Artificial Intelligence (AI), cloud computing, 5G, and Nanotech in healthcare: How organizations are preparing best for the future

Automation, digitalization, and technological enablement are having a significant impact on several industries. The healthcare industry is not an exception. The healthcare delivery system in India is changing and is about to advance significantly. The pandemic has shown that healthcare organizations can become innovative, flexible, and resilient by utilizing tech-enabled business models that place data at the core.

Additionally, healthcare organizations quickly realize that no matter how technically advanced their services or products are, they will no longer be applicable. To produce not just an enhanced product or service but also a better healthcare experience, it is imperative to connect with users along the healthcare value chain, be they patients or physicians. Fortunately, technological progress has accelerated the process of change required for Indian healthcare to become digitally linked and shown promise for enhancing peoples healthcare experiences.

India has already begun developing a national digital framework to create a digital health ecosystem on a national scale. The market for digital healthcare in India was estimated to be worth INR 116.61 billion in 2018 and is projected to reach INR 485.43 billion by 2024, growing at a CAGR of 27.41 per cent. Adopting electronic health records for the whole population is one of the several steps made in that regard.

Healthcare organizations are quickly embracing innovative technology to change how care is delivered in the nation and benefit the healthcare ecosystem as a solution to address the problems that the countrys healthcare system is now facing. Here are a few new technologies that are changing things:

Artificial Intelligence (AI)

Artificial intelligence (AI), machine learning (ML), and digital representations of the human bodys physiology make it possible to anticipate the chance that chronic diseases will advance based on the decisions being made. By using these simulations, healthcare professionals can better comprehend options and therapies and their consequences on patient health outcomes and influence on related expenditures.

Additionally, AI is helping healthcare professionals manage illnesses holistically, better coordinate care plans, and help patients manage and adhere to their treatment regimens. Further, statistics indicate that administrative expenses account for 30% of healthcare expenditures. The bulk of these duties, such as keeping track of bills that need to be paid and maintaining records, may be automated with AI, considerably cutting expenses.

Cloud Computing

The collaboration between physicians, nurses, and departments has grown crucial as healthcare organizations throughout the nation transition to value-based care. Thanks to cloud computing, accessing patient information has gone from a sluggish and laborious procedure to a quick and easy process.

With cloud computing, data may be stored centrally and made accessible from any location at any time. In addition, cloud infrastructure allows users to adjust health data storage depending on the new patient volume. IoT-enabled devices are being offered to patients by a variety of healthcare providers. By connecting these devices to a healthcare providers cloud system, patient data may be swiftly delivered to the doctor. This makes for a quicker diagnosis and better treatment.

The 5G Network

Every aspect of healthcare has the potential to be improved by a 5G connection, particularly since the healthcare sector is still recovering from the ravages of the epidemic. Large data files and real-time, high-definition video may be transmitted over a fast network to handle telemedicine appointments. Patients may reach medical professionals more quickly and receive treatment more quickly thanks to the use of 5G, especially in remote places.

Nanotech

Utilizing nanotechnology has given the healthcare sector new opportunities. Researchers and scientists use this technology to improve medical imaging, target tumours, and medication delivery systems. Additionally, the technique reduces costs, speeds up DNA sequencing, and provides scaffolding for tissue regeneration or wound healing. Further, artery obstructions are being removed by nanobots or micro-scale robots, as are quick biopsies of worrisome cancerous tumours.

The healthcare sector is anticipated to strengthen in 2022, thanks to groundbreaking discoveries and technologies. Most of the significant modifications are still in the future!

This article will examine the main medical technology developments and changes anticipated for the medical industry shortly.

The focus is often on lowering the cost, increasing access to healthcare services, and identifying and treating problems sooner rather than later. The US healthcare industry is expanding quickly; by 2026, the national healthcare products value is predicted to reach USD 6 trillion. Its never too late to prepare for the many available healthcare possibilities. Make sure to use digital technology to increase revenue, and staff productivity, achieve better financial results, and improve patient care.

Artificial intelligence (AI) technology has advanced quickly in recent years, and this trend will persist in 2022. Among the various sectors that gain from AI, medicine mainly uses it for accurate illness diagnosis and detection, albeit this is not the only use. IBM Watson, for instance, is one of the AI systems already accessible for use in business and healthcare.

Computed Tomography Scan Analysis

The demand for computed diagnostic professionals (radiologists) has significantly grown since the COVID-19 epidemic struck the worlds population.

AI-powered technology could provide a solution. AI systems can quickly evaluate CT images from hundreds of patients, identifying pneumonia patterns brought on by COVID-19 and informing physicians of these. That would make up for the lack of qualified labour in this industry.

Before our eyes, innovative ideas are taking shape. For instance, a deep learning model for imaging COVID-19 was developed to recognize COVID-19 patterns in CT images automatically. The Microsoft-sponsored InnerEye research project is another promising endeavour for processing computed tomography scans. Even though accuracy has significantly increased, radiologists are still hesitant to entrust the digital mind with crucial choices. AI cannot be held responsible for a poor diagnosis or ineffective course of therapy. Instead, the expert who decided to employ AI must pay for their error and take every precaution to limit the adverse effects while maximizing this digital health trend.

Because of this, most cutting-edge clinics employ AI as an additional tool rather than a stand-alone diagnostic or therapeutic method. It is excellent for validating current diagnoses or enhancing research data that has been gathered conventionally.

Machine Learning in Biopharma and Medtech

The pharmaceutical sector will effectively capitalize on technological advancements in healthcare by utilizing AI to discover new medications. A group of British and Japanese scientists filed a patent for the first medicinal molecule created by AI in January 2020. The drug will be used to treat obsessive-compulsive disorder after it passes muster for testing on humans.

AI-enhanced lab research has also led to the discovery of other intriguing formulations since late 2021, including some potential treatments for uncommon and extremely severe ailments. Numerous cutting-edge studies, such as molecular modelling and simulation of chemical reactions in multi-factor settings, leverage AI and machine learning approaches to support chemical experiments and therapeutic medication development.

Since many tests may be carried out electronically, this method enables scientists to reduce the number of expensive onsite experiments using reagents and high-tech lab equipment. It also hastens the discovery of critical scientific innovations.

Automating Hospital Workflows using Robotics

Startups from all over the world will pour hundreds of millions of dollars into creating AI projects in 2022, including various forms of robotic systems, which may enable them to reduce the cost of recruiting trained medical personnel. The intention is to assist medical facilities that already have a severe shortage of nurses and clinicians as a result of the COVID-19 pandemic, which has put the entire healthcare system under unprecedented strain, rather than to replace people with machines, which would lead to unemployment and a decline in social standards. Learn more about creating medical HR software to assist HR professionals in addressing the U.S. medical workforce problem.

Innovative enterprises should keep in mind the medical communitys restrictions on AI-driven software, its capabilities, and its applications as they work to realize these lofty goals. Modern medicine has countless applications for robotic assistance and automated systems, including cleanliness, surgery, remote diagnostics, etc. However, the healthcare systems top goals will always be the well-being of medical personnel and the effective treatment of patients.

In light of this, robotic and AI-driven technologies will be employed to support current procedures rather than replace them, resulting in a potent fusion of the present and the future. Daring projects combined with sound regulation are a prominent trend in the digital health sector. It will enable physicians to utilize cutting-edge technology fully, learn to apply it in satisfying and secure ways, and steer clear of any pitfalls.

Symptom Checker Chatbots

Chatbots are computer programs with artificial intelligence (AI) support (often not true AI but powerful algorithms) that engage in meaningful conversations that resemble those between humans using voice, text, or option-based input.

Every area, including healthcare and medical consultancy, is seeing a rise in their use. These solutions, available around-the-clock online or via mobile devices, can provide preliminary medical diagnoses and health advice based on input and complaints from a patient. Chatbots can also be connected with unique patient portals for hospitals and clinics. When human medical assistants are unavailable, they can assist patients with their health issues and worries, even in acute situations (such as disaster-induced overloads of call centres, peak or non-operation hours, etc.)

These chatbots can aid patients in determining their subsequent actions and motivate them to seek professional medical advice when necessary. Care must be exercised, though, since it may result in inaccurate self-diagnosis and disinformation.

Globalization of AI Requirements in Healthcare

Ten recommendations that can serve as the foundation for the creation of GMLP have been developed by a powerful coalition of the U.S. FDA, Health Canada, and the United Kingdoms Medicines and Healthcare products Regulatory Agency (MHRA) (Good Machine Learning Practice). These guidelines will help programmers and AI engineers create secure medical equipment, software, and systems powered by artificial intelligence and machine learning (AI/ML) components. This shows that governments take the potential and hazards posed by AI exceptionally seriously and would want to regulate the use of AI in healthcare practices as soon as feasible.

Adoption of AI-backed Technologies

The main drawback of the advancement in artificial intelligence technology is that hackers will use it to target medical systems and steal secured healthcare information, rather than only to save human lives or help medical personnel with their everyday responsibilities. One of the growing dangers to the security of medical technology in 2022 and beyond is sophisticated malware with AI capabilities.

Which medical technology solutions are in jeopardy? Almost everything could have weak security or security flaws, such as wireless systems in hospitals, clinics, or health centres, EMR/EHR solutions, IoT, and computer-aided healthcare provider and health insurance company systems. Intricate phishing and social engineering assaults can also target clients and staff members.

Hackers may use this feature to simulate personal identities as part of next-generation super-personalized social engineering and phishing campaigns, which have the potential to be as dangerous and deceptive as ever before due to AIs growing capacity to mimic photorealistic 3D faces or organically sounding voices. This necessitates installing high-end data protection methods that can mitigate any hazards by hacker techniques aided by AI.

Despite all the technological safeguards and healthcare providers knowledge, statistics on data breaches show a sharp rise over the previous ten years, with infractions peaking in 20202021. These data breaches impact thousands of patients around the US. Hopefully, healthcare organizations will focus more on data security and their digital ecosystems in 2022. Healthcare cybersecurity is quickly emerging as a popular technological topic this decade.

How to Prevent Data Breaches in Healthcare?

The security of medical records, which is governed by HIPAA and EDI in the healthcare industry, is a top priority for the US government.

Every healthcare professional should follow a few effective procedures:

Facial Recognition With Masks

Face recognition technology, which permits approved access for medical professionals to mobile devices or workstations, rose to popularity due to its ease.

Deep learning facial recognition algorithms must be used in the COVID-19 pandemic to distinguish staff members wearing masks. Specific sources claim that some businesses have already achieved 99.9% accuracy in the face recognition of people wearing masks.

Nanotechnology may still seem like science fiction, yet it is steadily influencing our daily lives. By the end of 2021, fantastic news about the creation of tiny, organic robots that can reproduce themselves will reach every part of the globe. Therefore, it is realistic to anticipate that 2022 will bring forth several significant advancements in the nanomedicine sector. Early investments are welcome in the burgeoning nanomedicine industry.

Here is a brief explanation of what nanomedicine is: it uses nanoscale (microscopically small) materials and objects, like biocompatible nanoparticles, nanoelectronic devices, or even nanorobots, for specific medical uses and manipulations, like the diagnosis or treatment of living organisms. The injection of a group of nanorobots into a humans blood vessels might be utilized as a possible hunter for cancer cells or viruses, for instance. This method is anticipated to effectively combat a wide range of cancers, rheumatoid arthritis, and other hereditary, oncologic, or auto-immune illnesses on a cellular level (or even become an ultimate solution to them).

Even though the IoMT will not be a novel concept by 2022, this industry will experience exponential growth. Every one of the several digital health developments in this sector has excellent applications for healthcare professionals and has the potential to save billions of dollars.

Apps for remote health monitoring and wellness will continue to grow in popularity in 2022. You may discover a decent number of professional (and many other semi-professionals) mobile applications for healthcare and health in the GooglePlay or iTunes libraries.

Some mobile applications can connect to wearables like pulsometers or fitness trackers to use the information gathered by the sensors attached to your body to report or evaluate your health problems, including blood pressure, body temperature, pulse, and other metrics.

Autonomous nursing robots or self-moving smart gadgets can substantially assist by minimizing the tasks linked to supply management or sanitary maintenance that medical professionals must perform.

Different types of robots can work in various hospital-based settings and jobs, protecting human workers from infection risks or stress from the extreme burden imposed on many US hospitals by a COVID-19 patient overflow. An Italian hospital, for instance, employed robot nurses during a COVID-19 severe epidemic. These clever assistants were utilized to remotely check patients blood pressure and oxygen saturation levels because they are two critical indicators of their present state of health. Those levels might decline quickly, necessitating emergency intervention for the patient. This drastically decreased the requirement for nurses to visit patients in person.

Healthcare systems primarily concentrate on elements within their area of expertise: quality and price of medical services while generating risk assessments and accumulating illness data. However, they represent the very beginning. Before patients feel symptoms and seek the help of physicians, a host of other less apparent circumstances impact them.

Initial health problems are caused by factors other than a lack of care. Their origins are deeper; they are found in social, environmental, and demographic contexts that are rarely taken into account in the context of conventional clinical diagnoses.

Medical institutions mainly handle symptoms and offer advice on lifestyle modifications, having a minimally significant influence on treatment results (between 10% and 20%). In addition, between 80% and 90% of health outcomes are determined by non-medical variables. The term social determinants of health refers to these elements (SDOH).

In 2022, healthcare providers will approach SDOH with greater caution than ever before and carefully review patients medical histories, taking into account details that were overlooked in earlier years.

Doctors will shift from treating symptoms to prediction and prevention based on patients SDOH predisposition to particular diseases to stop the advancement of dangerous health concerns and reduce individual medical expenditures.

More implant-related options and technology will hit the global and American healthcare markets in 2022. This offers dramatically improved regenerative medicine effectiveness, patient rehabilitation, and a solution for many disabilities previously thought to be incurable.

Increasing the Use of 3D Bioprinting

By 2027, it is anticipated that the medical industrys volume of 3D printing potential will surpass $6 billion. Even if 3D printing biocompatible implants is not a novel technique in 2022, new materials and more advanced prosthetic methods will make this technology more dependable and available to a more extensive range of patients. In particular, it is anticipated that advancements in 3D bioprinting technology would improve the following areas:

Neural Implants

In 2022, effective options for brain-computer implants are anticipated to debut. Neuralink plans to begin inserting its devices into human brains at least in 2022. More businesses, groups, initiatives, and startups are preparing to market their neuro-implants for various medical requirements, including regaining functional independence in patients with multiple forms of paralysis or blindness.

For instance, it was stated that by the end of 2021, a team of scientists had implanted a microelectrode array (a penny-sized implant) into the visual brain of a blind individual, enabling her to recognize several letters and shapes. Although there is still a long way to go, brain implants potential to help people with various disabilities seems to have a genuinely fantastic and promising future.

Healthcare businesses will employ an exponentially growing number of data sources, and the volume of gathered healthcare data (including patient records, DICOM files, and medical IoT solutions) will also rapidly increase. Medical service providers will seek contemporary platforms, such as data fabrics, to combine and handle massive amounts of dispersed and structured data.

It will be among the tasks to build safe multi-cloud solutions capable of transporting significant amounts of data to manage, store, and mine it for valuable insights and to link siloed data with the healthcare systems.

Healthcare payers and providers frequently have interests that clash. The standard of their collaborative work decreases when both sides take absolutist positions. Patients, therefore, do not get the care they need. They are frequently mistreated, have to wait longer, and pay more.

Both payers and providers should embrace a value-oriented mindset and work toward group goals rather than individual success. All parties must understand that they are working for the same purposeproviding high-end healthcare to the publicand that if either suffers losses, the other will no longer support them. All organizations involved in the healthcare sector will hopefully try their utmost to learn how to collaborate in 2021. They will concentrate on delivering complete care, move from settling disagreements to cooperation, and communicate information to support successful decision-making.

The healthcare sector is already seeing the effects of the vast diversity, universality, and growth of digital communication channels. A brand-new channel for distributing medical data is telehealth. It entails delivering healthcare services remotely through the Internet, videoconferencing, streaming services, and other communication technologies. Long-distance education for patients and medical professionals is included in telehealth. Telehealth has achieved widespread acceptance and has evolved into a regular procedure in 2021. Modern clinics already counsel their patients electronically. This kind of communication will replace conventional internal dialogues and receive full regulatory permission in the upcoming years.

With the introduction of 5G wireless, telehealth will expand rapidly and be universally adopted shortly.

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Artificial Intelligence (AI), Cloud Computing, 5G, And Nanotech In Healthcare: How Organizations Are Preparing Best For The Future - Inventiva

IntroductionPotassium Channels Structure and Function

K+ channels are membrane proteins that facilitate the selective potassium ion flow under an electrochemical gradient. Besides the voltage-dependent gating, K+ channels are activated by several intracellular and extracellular stimuli,13 including extracellular and intracellular pH, kinases, SUMOylation, G protein-coupled receptors, stretch, and lipid regulation among others.1,2,4 These channels can be grouped into three major families according to their subunit structure: the Kv (voltage-gated K+ channel), Kir (inwardly rectifying K+ channel), and K2P (two-pore K+ channels)1,2,4 (see Figure 1AC). K+ channels need four pore-forming domains, which together, generate a functional and selective ion pathway. Thus, the Kv and Kir channels need four subunits to form a functional pore in a tetramer architecture.2,4 On the other hand, the K2P family forms a functional channel in a dimer architecture (see Figure 1C).1,5 For each K+ channel, subunit is also clearly identifiable in this pore-forming P domain, characterized by the amino-acid signature GYG that confers the high selectivity to K+ ions observed in potassium channels.6 The Kv channels present a topology model with six transmembrane domains (TM1-6) and one pore-forming domain (P) (Figure 1A). This Kv family represents the most numerous K+ channel group, with 40 genes encoding for K+ subunits in humans. The transmembrane domain (TM4) into Kv channels present positive charged amino acids (Arg and Lys) which act as voltage sensors generating the channel opening in response to changes in voltages7,8 (Figure 1A).

Figure 1 Schematic structure of potassium channels. Lateral view of monomers of a (A) voltage-gated potassium channel (Kv), (B) inward rectifier potassium channel (Kir) and (C) two-pore domain potassium channel (K2P), showing the transmembrane segments, the cap and their corresponding pore-forming loops (P-loops).

For the Kir channel family, each subunit has one P domain and two transmembrane domains (Figure 1B), and this family is integrated by 15 different genes grouped into 7 subfamilies (Kir1.x to Kir7.x), identified in mammals.24 Kir potassium channels present a gating governed by a voltage-dependent blocked process by Mg2+ and polyamines.3,4 Moreover, the gating voltage-dependence for Kir channels defines their characteristic K+ inward rectification (movement into the cell).3,4

K2P family has a two-pore forming domain and four transmembrane domains, whose subunits assemble as dimers (Figure 1C). Fifteen different genes found in mammals encode these family subunits and are grouped into 6 subfamilies according to their homology and functional properties.1,5,9,10 The K2P channels are voltage-independent and highly modulated channels, playing key roles in the maintenance of the resting membrane potential in the cells. These channels are recognized as the leak or background potassium channels.1,5

Cancer condition is a major non-infectious public health problem and affects millions of people worldwide. Cancer is also the second most common cause of death after cardiovascular disease, with 10.0 million deaths (9.9 million excluding nonmelanoma skin cancer) in 2020,11 with estimated 28.4 million cases in 2040, a 47% rise from 2020.11 The Americas accounts 20.9% of cancer incidence and 14.2% of mortality worldwide,11 and for Latin America and the Caribbean region, it has been estimated that 1.7 million cancer cases will be diagnosed by 2030, whereas more than one million of the cases will die per year.12 Currently, more than 100 types of cancer have been identified, being breast (24.5%), colorectal (9.4%), lung (8.4%), cervix (6.5%), and thyroid (4.9%) most frequent types of cancer in women.11 Meanwhile, lung cancer (14.3%), prostate (14.1%), colorectal (10.6%), stomach (7.1%) and liver (6.3%) are the most common type of cancers among men.11

In recent years, ion channels, and particularly potassium (K+) channels, have emerged as relevant molecular targets for the development of cancer treatments.1316 The association between potassium (K+) channels and cancer disease is mainly due to the participation of those proteins in the cancer progression mechanisms.13,1618 Potassium channels are complex proteins that form selective pores for K+ conduction in biological membranes, which are critical in K+ homeostasis, cell volume regulation, setting of resting membrane potentials, the neurotransmitters release, and regulating the excitability of neurons and muscle tissue.1,2,19

For instance, overexpression of different potassium channels, such as Kv, Ca2+-activated (KCa), ether go-go human (hEag), ATP-sensitive (KATP), and K2P has been reported in prostate cancer cells, colon, lung, breast, and other organs.20 It has been hypothesized that there is a relationship between K+ channel overexpression and the generation and growth of malignant tumors,14,17,18,21 being involved in cell proliferation, apoptosis, and differentiation.14,18,21 Studies performed with pharmacological drugs that specifically block K+ channels have shown antitumor effects by inhibiting tumor growth directly or enhancing the effectiveness of chemotherapeutics or cytotoxic drugs as a combined therapeutical strategy.18,22 On the other hand, several studies have exhibited the impact of Kv channels (Eag1, HERG, and Kv1.3), Kir (Kir3.1), and Ca2+-activated potassium channels (KCa1.1 and KCa3.1) in cancer cell proliferation and their association with tumorigenesis process in patients and animal models.17,18,2123

A relatively minor amount of research has focused on the relationship between K2P channels and cancer.18,24 Those studies suggested that TASK-3 is involved in tumor formation in several types of human cancer.14,18,24,25 Moreover, other investigations showed that breast cancer cells metastatic properties depend on TASK-3 expression levels.20

By contrast, the Kir channels have been related to different cancer conditions, such as lung, gastric, prostate, stomach, breast, and choroid plexus.2632

The Kv channel is the most numerous K+ channel family, playing relevant functions in various cellular and physiological processes.2 Additionally, these channels have been implicated in cancer hallmarks, such as cell proliferation, cancer progression, and migration14,15,3335 (Figure 2 and Table 1).

Table 1 Potassium Channels Associated with Cancer

Figure 2 Roles of K+ channels in cancer hallmarks. Cellular processes associated with changes in expression and increased activity of the two-pore domain K+ channel (K2P), the inward rectifier K+ channel (Kir), and the voltage-gated K+ channel (Kv) in cancer. K+ channels structure in ribbon representation were generated with the PDB 6RV2, 7s5z and 7wf4.

The Kv1.1 (KCNA1) channel is relevant for potassium transport in the central nervous system and kidney.36,37 Moreover, it is overexpressed in cervical cancer tissues and medulloblastoma.38,39 Additionally, the Kv1.1 depletion suppressed growth, proliferation, migration and invasion of HeLa cells.38

Kv1.3 channels also have been reported as overexpressed in the breast, lung, colon, prostate, pancreas, smooth muscle, skeletal muscle, and lymph node of some types of cancers.4044 However, its relevance as a therapeutic target has been evidenced in glioblastoma, melanoma, and pancreatic adenocarcinoma models,4547 where Kv1.3 suppression induces apoptosis.

Another related channel is Kv1.5. This channel shows a correlated expression pattern with glioma entities and malignancy grades, with a high expression in astrocytomas, moderate in oligodendrogliomas, and low in glioblastomas.48 For the Kv1.5 channel, an overexpression was detected in some gastric cancer cell lines.49 Furthermore, Kv1.5 plays a role in the activation and proliferation of cells in the immune system, is remodeled during carcinogenesis, and has shown an abundance that inversely correlates with clinical aggressiveness in human non-Hodgkin lymphomas.50 In the same way that Kv1.3, this channel is overexpressed in human smooth muscle tumors.40 Kv1.5 has been involved in tumor cell proliferation of gastric cancer cells, where this channel is overexpressed.49

The expression of the Kv2.1 channel recently was reported to be higher in the metastatic prostate cancer cells (PC3), and their blockade with stromatoxin-1 or siRNA significantly inhibits the migration of malignant prostate cancer cells.51 This channel as Kv1.4, Kv4.2, Kv7.1 and large-conductance Ca2+-activated K+ channel (BKCa) also showed a high expression in the CD133+ subpopulation of SH-SY5Y neuroblastoma cells.52

Increased levels of Kv3.4 channel expression were identified in OSCC (oral squamous cell carcinoma).53 In addition, the expression and clinical significance of this channel in the development and progression of head and neck squamous cell carcinomas was reported.54 The Kv3.4 and Kv3.1 are known as oxygen sensors, and their function in hypoxia has been well investigated.55 These channels, Kv3.1 and Kv3.4, are tumor hypoxia-related channels involved in cancer cell migration and invasion in A549 and MDA-MB-231 cells (lung and breast cancer models, respectively).55

Another set of experiments showed a varied expression of Kv4.1 mRNA depending on the tumor stage in human breast cancer tissues.56 Recent studies have demonstrated that Kv4.1 channels are expressed in the human gastric cancer cell lines.57 Moreover, the suppression of Kv4.1 induces a G1-S transition blockade affecting the cell cycle progression.57

Interestingly, together with the expression profile of Kv7.1 in neuroblastoma cells,52 this channel was also found to be up-regulated in human colonic cancer cells.58 Conversely, Kv7.1 and Kv7.5 expression in vascular cancers was reported to be down-regulated.59 In this case, the proposed role of Kv7 channels is related to cell proliferation rather than controlling vascular tone.59

A particular case is a Kv9.3 channel, an electronically silent subunit, which forms heterotetramers with Kv2.160. The Kv2.1/Kv9.3 heterotetramers are overexpressed in colon carcinoma, lung adenocarcinoma, and cervical adenocarcinoma cells.60,61 Moreover, the knockdown of Kv9.3 inhibits proliferation in colon carcinoma and lung adenocarcinoma models.60

The Ether go-go (Eag (hERG); Kv10.1) K+ channel expression is typically restricted to the adult brain and the heart, but it has been detected in several cancer cell lines and tumor tissues from patients,62,63 showing it to influence cell proliferation. This channel is overexpressed in 71% of tumors and cancer cell models of neuroblast, glial, liver, lung, breast, ovary, cervix, prostate, gastrointestinal tract, myeloid leukemia, and retinoblastoma.34,6368 The Kv10.1 channel suppression generates apoptosis, inhibition of cell proliferation, and decrease in cancer cell migration.63,6972 Additionally, the inhibition of Kv10.1 channels sensitizes the mitochondria of tumor cells to antimetabolic treatments, improving the efficacy of the metabolic inhibitors.73

Kv11.1 is overexpressed in leukemia, ovarian, lung, pancreatic, colorectal, and breast cancer cells, among others.7479 The Kv11.1 channels have a key role in the cell cycle, acting as regulators for apoptosis and cell proliferation in cancer cells.74,7981 However, blockers of Kv11.1 channels also retard the cardiac repolarization.80

Another subgroup of potassium channels involved in cancer corresponds to the calcium-activated potassium channels. These channels are activated by rise in cytosolic calcium ions, allowing the K+ ion to flow under an electrochemical gradient. As a member of this subgroup, the KCa1.1 channel is overexpressed in prostate, glia, breast, pancreas, and endometrium cancer cell types.8286 KCa1.1 channel regulates the proliferation and migration of prostate cancer condition.83 In breast cancer, KCa1.1 channel overexpression has been associated with advanced tumor stage, cell proliferation, and poor prognosis.87

On the other side, the KCa3.1 (intermediate conductance Ca2+-activated K+ channel) is overexpressed in 32% of glioma patients and correlates with poor patient survival.88 In addition, these channels are overexpressed in breast cancer, non-small cell lung cancer, melanoma, leukemia, renal and hepatocellular carcinoma.8994 The inhibition of KCa3.1 channel activity reduces the cancer cell motility, proliferation and induces apoptosis.91,94,95

A less associated channel to a cancer condition corresponds to KCa2.3 (SK3), with a report of overexpression in melanoma cell lines, and their knockdown led to plasma membrane depolarization and decreased cell motility.96

The Kir channel family is integrated by 15 different genes grouped into seven subfamilies. Among these channels, different subunits have been associated with cancer conditions (Kir2.1, 2.2, 3.1, 3.4, 4.1, 6.1, 6.2)26,27,2932,94 (Figure 2 and Table 1).

Kir2.1 (KCNJ2) is overexpressed in 44.23% of small-cell lung cancer (SCLC) tissues, and it correlates with the clinical stage and chemotherapy response in SCLC patients. Additionally, the Kir2.1 knockdown in H69AR and H446AR cells inhibited cell growth and was sensitized to chemotherapeutic drugs by increasing cell apoptosis and cell cycle arrest.28 Kir2.1 channel also promotes the invasion and metastasis of human gastric cancer by enhancing MEKK2-MEK1/2-ERK1/2 signaling by interaction with Stk38.97

Similarly, Kir2.2 is found in human SCLC cells.31 Kir2.2 knockdown induced growth arrest and senescence by a mechanism involving reactive oxygen species (ROS) accumulation in cell lines derived from tissues of the prostate, stomach, and breast.98 Kir2.2 plays a role as an unconventional activator of RelA and increases the expression level of NF-B targets, including cyclin D1, matrix metalloproteinase (MMP)9, and vascular endothelial growth factor (VEGF)99 in cancer cells.

Another inward potassium channel associated with cancer is the Kir3.1 which is found within lymphocytes and in resected human pancreatic ductal adenocarcinoma (PDAC), overexpressed in 80% of tumor specimens. However, no associations were found between metastasis and Kir3.1 expression.26 On the other hand, the gene encoding the Kir3.1 channel was found to be aberrantly overexpressed in invasive breast carcinomas.100 In addition, the Kir3.1 overexpression correlates with lymph node metastasis, and this overexpression is greater in tumors with more than one positive lymph node.100

Kir3.1 gene overexpression is detected in tissue specimens from patients with non-small cell lung cancers (NSCLCs).101 In addition, the expression of Kir3.1 has been shown in tissue samples from approximately 40% of primary human breast cancers and in breast cancer cell lines.102

Also, the inwardly rectifying K+ channel Kir3.4 (KCNJ5 gene) (or GIRK4 channel) have been identified in adrenal aldosterone-producing adenomas (APAs), where several ion channel gain-of-function mutants are associated with the APA condition.29,103

In human brain tumors (low- and high-grade astrocytomas and oligodendrogliomas), mislocalization (redistribution) of the Kir4.1 channel has been reported and suggests a compromised buffering capacity of glial tumor cells.32 Furthermore, in human astrocytic tumors, Kir4.1 channel expression markedly increases with the pathologic grade of cancer104 and suggests that Kir4.1 activation could promote proliferation and inhibit apoptosis in the tumors.104

The subunits of ATP-sensitive Kir potassium channels (Kir6.1, Kir6.2) are highly expressed in leiomyoma cells.30 The estrogen-induced proliferation of the leiomyoma cells is inhibited by treatment with glibenclamide (KATP-channel inhibitor).30 These two channels are expressed in MDA-MB-231 cancer cells, and the cytostatic effect of glibenclamide is mediated through KATP channels (Kir6.1 and 6.2), associated with the inhibition of the G1-S phase progression.105 In hepatocellular carcinoma (HCC), the KCNJ11 (Kir6.2) gene was identified as a key dysregulated K+ channel and is associated with a poor prognosis in HCC patients.106 In agreement, the knockdown of Kir6.2 inhibited cell proliferation, promoted cell apoptosis, and reduced cell invasive capacity.106 The Kir6.2 overexpression was observed in cervical cancer cell lines and cervical tumor tissues.107 In particular, the increased Kir6.2 channel expression was observed in high-grade, poorly differentiated and invasive human cervical cancer biopsies.107 Moreover, an inhibitory effect of glibenclamide on the proliferation of cervical cancer cell lines is associated with Kir6.2 channel.107

Kir6.2 channel activity plays a critical role in the proliferation of glioma cells where the expression is greatly increased.108 Moreover, the treatment with tolbutamide (a Kir6.2 inhibitor) suppressed the proliferation of glioma cells and blocked the cell cycle.108 The Kir6.2 knockdown obtained a similar result in glioma cell proliferation.108

Finally, a less studied channel corresponds to Kir7.1 (KCNJ13) with a high expression linked to choroid plexus epithelium or choroid plexus tumors (CPTs)27,109,110 and it has been considered a sensitive and specific diagnostic marker for choroid plexus tumors.27,109,111

The two-pore domain K+ channels (K2P), encoded by the KCNK genes, are a family of fifteen members that form the leak or background channels.1,5,9 K2P channels display K+ outward rectifying currents, constitutively open, that control the neuronal excitability. Thus, activation of K2P channels stabilizes the cell membrane potential below the firing threshold, whereas the K2P channels inhibition facilitates membrane depolarization and cell excitability.

The K2P family can be divided into six subfamilies based on structural and functional properties.1,5,9 Regarding protein structure, each K2P channel subunit has four transmembrane domains (TM1-TM4) and two pore-forming domains (P1 and P2) (Figure 1C). Moreover, two subunits are required to form a functional channel.112,113 K2P channels display an exclusive extracellular cap domain formed by the extracellular loop that connects the first transmembrane domain and the first pore-forming sequence (TM1-P1 loop) (Figure 1C). The extracellular cap covers the upper selectivity filter (SF) pore,114 and this structure is responsible for the poor sensitivity of K2P channels to classical K+ channel blockers.114

From the K2P family, seven members are confirmed to be involved in cancer (TASK-1, TASK-2, TASK-3, TREK-1, TREK-2, TWIK-1, and TWIK-2)15,115120 (Figure 2 and Table 1). Among these, TASK-1 (K2P3, encoded by KCNK3 gene) has been detected in medulloblastoma and Ehrlich ascites tumor cells.121,122 Also, in MG63 osteosarcoma cells, the overexpression of TASK-1 was reported.118 Additionally, TASK-1 is overexpressed in a subset of non-small cell lung cancers, promoting proliferation and inhibiting apoptosis. TASK-1 knockdown enhances apoptosis and reduces the proliferation of lung cancer cell-line A549.123 In these cells, A549, the overexpression of TASK-1 promoted epithelial mesenchymal transition (EMT), a pivotal event in lung cancer cell invasion and metastasis.124 Moreover, the expression of TASK-1 has been associated with aldosterone production in both aldosterone-producing adenomas and normal adrenals.125

The second K2P channel associated with cancer is TASK-2 (K2P5; encoded by KCNK5 gene), a member of the TALK subfamily. TASK-2 plays a role in the proliferation of estrogen receptor positive breast cancer cells being highly upregulated in response to 17-estradiol (E2) in MCF-7 and T47D breast cancer cell lines.126,127 In these cells, the knockdown of the TASK-2 channel reduces the estrogen-induced proliferation of breast cancer cells.127 Also, the overexpression of TASK-2 has found in HPAF cells, a human pancreatic ductal adenocarcinoma cell line, but the role in cancer progression has not been further studied.128

Among the K2P channels, the most studied in cancer correspond to TASK-3 (TWIK-related acid-sensitive K+ channel 3). This channel has been shown to localize in both the plasma membrane and mitochondrial inner membrane.117 The TASK-3 channel overexpression occurs in several types of cancer, such as melanoma, ovarian carcinoma, and breast cancer.24,117,129132

Also, TASK-3 (KCNK9, located in chromosomal region 8q24.3) gene expression is enhanced by 1044% in human breast tumors and 35% in lung tumors.24 Additionally, overexpression of KCNK9 has been reported in over 90% of ovarian tumors.130 In most cases studied, TASK-3 is associated with the acquisition of malignant characteristics, including hypoxia resistance or serum deprivation conditions.24,25 Consistently, a monoclonal antibody (Y4) against the cap domain of TASK-3 inhibits the growth of human lung cancer xenografts and breast cancer metastasis in mice.133 Further studies showed that TASK-3 gene knockdown in breast cancer cells is associated with an induction of cellular senescence and cell cycle arrest.132 Furthermore, TASK-3 is overexpressed in colorectal cancers and gastric cancers.134136 In gastric adenocarcinoma cells, the TASK-3 gene knockdown causes changes in migration and reduces cell proliferation and viability by increasing apoptosis without ffecting cell cycle checkpoints.136

TASK-3 is highly expressed in melanoma,117,129,137 being identified in the inner mitochondrial membrane of melanocytes, WM35 and B16F10, and keratinocytes.117,129,137,138 In WM35 and A2058, human melanoma cells, the knockdown of TASK-3 resulted in compromised mitochondrial function, mitochondrial membrane depolarization, and reduced cell survival inducing apoptosis.139,140

Another K2P channel related to cancer is TREK-1 (K2P2, encoded by KCNK2). This channel has been shown to play a pro-proliferative role in the human prostate cancer cell-line PC3.116 In MG63 osteosarcoma cells, overexpression of TREK-1 was reported118 and it is correlated with the proliferation of the osteoblast cells.141 TREK-1 is also overexpressed in prostate cancer tissues142 and epithelial ovarian cancer.130 For TREK-1 channel, the exact role of cancer development is still unclear. However, TREK-1 overexpression is associated with a poor prognosis for patients with prostate cancer.142 In prostate cancer, inhibition or knockdown of TREK-1 inhibits proliferation by inducing cell cycle arrest at the G1/S checkpoint.142 On the other side, the treatment with TREK-1-blocking agents, such as curcumin, has shown reduced ovarian cancer cells proliferation and increased late apoptosis processes.130

Among the TREK subfamily, the TREK-2 channel (K2P10, encoded by KCNK10) was present in bladder cancer cell lines and contributed to cell cycle-dependent growth.119 The sixth K2P channel involved in cancer is TWIK-1 (K2P1, encoded by KCNK1). The TWIK-1 was detected as an upregulated channel in pancreatic ductal adenocarcinoma (PDAC) compared to normal tissue.115 Recently, TWIK-2 (K2P6, encoded by KCNK6 gene) was reported as a significantly overexpressed channel in breast cancer.120 Moreover, the overexpression of TWIK-2 increases the capacity of proliferation, invasion, and migration of breast cancer cells.120

The rational design and development of selective blockers is a dynamic field of study that includes diverse methods such as high-throughput screening, bioengineering techniques, and chemical modification, among others.143,144 Fortunately, we count on several software and computational tools that allow us to explore innovative approaches based on the molecular interaction of potassium channels structural data from the ligands and molecules, and the physicochemical and pharmacological properties of K+ channels interacting with drugs.

Some computational tools used for the rational design of specific modulators (blockers and activators) examine the three-dimensional structure of the target (K+ channels, in this case), previously solved by X-ray crystallography, cryoelectron microscopy145 or comparative modeling. Following this, it is necessary to study the binding sites and affinity of the ligand.143 This approach has been particularly helpful for the identification of ligands, targeting membrane proteins.146,147

Additionally, the multidisciplinary work among different areas, such as biochemistry, bioinformatics, bioengineering, medical chemistry, genomics, proteomics, and metabolomics, has contributed to the development of new computational tools for the rational design of ion channel modulators.143 Thus, the combinatory strategy including docking, virtual screening, de novo drug design, molecular simulations and the experimental validation by electrophysiological measures have allowed the development and a successful search for small modulators.146,147 For the K+ channels, a three-dimensional structure of representative K+ subunits (Kv, K2P, and Kir) has been reported, providing insights into how these channels can be used to design specific modulators for cancer treatment.

Moreover, ion channels with limited background expression in normal tissues and strong overexpression in tumors due to their cell-surface accessibility constitute a preferential target for the development of antibody-based therapies.148152 Antibodies recognizing ion channels represent a strategy effective in modulation of ion channel activity. The mechanisms of action include direct block of ion permeation pathway, modulation of ion channel gating, and internalization and degradation upon surface clustering.152154 For example, systemic administration of specific mouse monoclonal antibodies generated in the human channel K2P9 (KCNK9) using its M1P1 loop fused into the Fc domain of IgG2a, effectively inhibits the growth of human lung cancer xenografts and murine breast cancer metastasis in mice.133 In addition, a specific monoclonal antibody which inhibits the function of highly oncogenic Kv10.1 potassium channel can effectively restrict cancer cell proliferation and reduce tumor growth in animal models with no significant side effects.155 However, currently, only one polyclonal antibody (BIL010t; Biosceptre) targeting a non-functional form of P2X7 (nfP2X7) has reached the level of clinical trials for the treatment of basal cell carcinoma.156,157

Other developing innovative strategies consist of the rational design of specific short peptides (less than 50 amino acid residues), which have acquired widespread interest as tools to address challenging proteinprotein interactions (PPIs).158,159 These short peptides can form complexes, and structures, mimicking critical motifs of proteins,160 which allow them to inhibit PPIs or functional activities with high specificity and affinity, emerging as a promising alternative to small molecules and biopharmaceuticals (>5000 Da). Furthermore, short peptides are easy to produce and modify161 and present low off-target side-effects given their higher specificity and reduced immunogenicity.161 All those attractive features make short peptides exceptional candidates to serve as therapeutics, even more considering that more than 100 peptide-based drugs are available in the market for AIDS, Cancer, and other medical conditions.162,163 Some examples of therapeutic drug-based peptides include oxytocin (8 aa), calcitonin (32 aa), teriparatide (34 aa), Fuzeon (36 aa, antiretroviral), corticotropin-releasing hormone (41 aa), and growth-hormone-releasing hormone (44 aa).159

Additionally, animal venoms are a natural and affluent source of peptides.164166 These peptide sources (from different animals such as cone snails, scorpions, sea anemones, snakes, spiders, among others) have been widely used as a starting point to develop toxin-based drugs, and some of them have currently reached clinical trials.165 Captopril was the first toxin-based drug approved for humans (1981). It is a nonapeptide that acts by blocking the angiotensin-converting enzyme (ACE) activity inhibiting the production of angiotensin II and was developed from Bothrops jararaca snake venom.167 Captopril is currently suitable and widely used for hypertension treatment.168 Among the different approved toxin-based drugs marketed, the ziconotide is obtained from cone snails, exenatide and lixisenatide are obtained from lizards. Bivalirudin and desirudin from leeches and Batroxobin and cobratide are purified from snake venoms.165 Desirudin, on the other hand, is a recombinant peptide derivated from snake. Other drugs (bivalirudin, enalapril, eptifibatide, exenatide, tirofiban, and ziconotide) are synthetic molecules from the same source.165

Currently, a large number of ionic channel blocking peptides (for Ca2+, K+ and Na+ channels) have been reported and obtained from different origin.166,169173 For instance, some peptides with antitumor effect are -hefutoxin 1 and analogues, APETx4, purpurealidin analogs, KAaH1 and KAaH2 among others.174177

There is no doubt that the specific short peptide blockers can inhibit the functional activity of K+ channels and show an antitumor effect, impacting the hallmark of cancer and representing a novel strategy for the rational design of new cancer drugs.

Compelling evidence indicates that the upregulation of the majority of K+ channels is associated with current cancer hallmarks (Figure 2 and Table 1). Thus, these channels have emerged as alternatives to develop new cancer treatments. K+ channel subunits are diverse and highly regulated proteins that respond to different stimuli. In different cancer conditions, where K+ channels are overexpressed, K+ channel blockers have been shown to reduce the tumorigenic properties and reverse the cancer progression in cell lines and animal models. However, K+ channels are critical regulators in several cellular and physiological processes; therefore, the search for selective K+ channel blockers becomes restrictive in developing future cancer treatments. Fortunately, the 3D structure of representative K+ channels178180 opens new possibilities for the rational design of highly selective K+ modulators.

The research for these highly selective potassium channel blockers must also include natural products (eg, plant extracts), bioinformatics search using the database (eg, Zinc181), venoms peptides, and the design of cyclic peptides (CPs) as modulators of proteinprotein interactions. Indeed, there is no doubt that rational design, search, and development might increase the therapeutic arsenal of drugs against cancer conditions associated with K+ channels. Nevertheless, the design, search, and development of selective K+ channel blockers remains a challenge that must be addressed in a multidisciplinary manner, including chemistry, bioinformatics, bioengineering, and biophysics groups.

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

This work was supported by Fondecyt 1191133 to WG and LZ, FIC-R BIP 40.027.577-0 Portafolio de servicios para la caracterizacin de blancos teraputicos para el tratamiento de cncer y enfermedades crnicas no transmisibles to WG and LZ. C.V. acknowledges the financial support of the National Fund for Science & Technology Development FONDECYT 1201147 and the BASAL Grant AFB180001 (CEDENNA) from the National Research and Development Agency (ANID), Government of Chile.

The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed in the funding section and report no conflicts of interest in relation to this work.

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41. Bielanska J, Hernndez-Losa J, Moline T, et al. Increased voltage-dependent K+ channel Kv1.3 and Kv1.5 expression correlates with leiomyosarcoma aggressiveness. Oncol Lett. 2012;4(2):227230. doi:10.3892/ol.2012.718

42. Comes N, Bielanska J, Vallejo-Gracia A, et al. The voltage-dependent K+ channels Kv1.3 and Kv1.5 in human cancer. Front Physiol. 2013;4:283. doi:10.3389/fphys.2013.00283

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Potassium Channels as a Target for Cancer Therapy & Research | OTT - Dove Medical Press

After the unexpected deaths of three animals on campus a horse, a rabbit and a ferret multiple sources have accused NC State of gross negligence. According to a United States Department of Agriculture (USDA) 2022 Inspection Report, the University has committed multiple violations of the federal Animal Welfare Act.

Furthermore, USDAs inspection at NC State in 2021 reported three specific violations pertaining to NC States mistreatment of animals. One of the violations, 3.127(a), mentioned that a pasture containing five horses had no shelter or shade of any type, despite the summer heat.

The violations of animal protection laws documented by federal inspectors at North Carolina State University (NCSU) are so severe that the school should lose its license to house and experiment on animals, said PETA Senior Vice President Kathy Guillermo in a statement.

NC State was inspected May 11, and it was found that three animals unexpectedly died one horse had urine scalding, and lack of quick action resulted in the horses euthanization. A veterinary student also improperly handled a rabbit, breaking its back, while another veterinary student prolonged surgery for a ferret. Both the rabbit and ferret were also euthanized.

Students are not being properly trained, and with all the animals dying and being hurt, it seems like a systematic problem, said PETA Vice President of Laboratory Investigations Dr. Alka Chandna.

These health problems are not being properly addressed, and the University has now received a complaint filed by a National Research Watchdog, SAEN, a non-profit watchdog that monitors U.S. research facilities.

A rabbit died of a broken back, a horse was euthanized after failure to receive veterinary care and a ferret died in connection to a botched surgery, said co-founder and executive director of SAEN, Animal Health Technician Michael Budkie in a press release. These deaths are made worse by NC States failure to investigate these deaths. This attempted cover-up by research administration is criminal.

Any research facility must have an animal care committee, also known as the Institutional Animal Care and Use Committee (IACUC). IACUC is responsible for evaluating and approving every research protocol, experiment or procedure that use live animals and making sure animals are taken care of in correspondence with the Animal Welfare Act.

The IACUC failed to investigate what was going on with injured animals, such as with the rabbit, horse and ferret recently, Chandna said.

The complaint from SAEN was written to Dr. Robert Gibbens, director of Animal Welfare Operations, USDA/APHIS/AC, discussing the violations that NC State has committed. In this complaint, Gibbens is urged to penalize the University $10,000 per infraction/per animal.

Most of the time, the fines are considered part of the cost of doing business, Budkie said in an interview. My opinion is that they are more concerned about the negative media intention that can come out of things like this than the fines.

In a statement, Mike Charbonneau, the director of communications and marketing at NC States College of Veterinary Medicine, said the euthanization of the horse was an isolated incident, and after this incident, the University is working with the USDA to ensure care of animals.

In an unfortunate, and isolated, incident, a team caring for a horse that was on campus to provide life-saving blood donations for sick horses didnt immediately recognize medical symptoms of a bladder stone, and when the condition was discovered and diagnosed, the decision was made to humanely euthanize the horse, Charbonneau said. Following this incident, we strengthened our procedures and requirements for daily health monitoring of all teaching and support animals.

While the statement Charbonneau offered referred to the horses euthanization, it failed to provide clarity on the unexpected deaths of the rabbit and ferret mentioned in the original inspection notes. When asked about the same, Charbonneau declined to give any further information.

According to Budkie, NC States first citation was for not performing investigations on animals after they were hurt or mishandled, leading to the death of the animals.

When the injuries occur, it is not being reported so the animals cant receive veterinary care, and the IACUC is not looking into it to find out what the problem is so procedures can be changed to keep injuries or mistakes from happening again, Budkie said.

Budkie also voiced his concerns that the University may have committed more violations than just those the inspections revealed.

There is no reason to assume that more things have not occured and just were not discovered by the inspector, Budkie said. When the inspector comes through, they only have one or two days to inspect everything.

According to Budkie, critical citations are rare, yet NC State has received several. One of these critical violations found after an inspection in August 2021, showed that five employees did not know who to call if there was a hurt or mishandled animal, revealing a lack of knowledge on what to do in a veterinary emergency.

We are talking about the workers, the animal technicians and the students, and they have not been trained that they need to inform a veterinarian if there is a problem, Chandna said. Students are not only injuring animals, but are handling them so poorly that they require euthanization. There's an issue in the classroom, and with the IACUC.

According to Charbonneau, the necessary changes have been made to ensure that animals are properly taken care of.

We continue to work with our partners at the USDA to ensure that all animals at the NC State College of Veterinary Medicine have the recommended level of shelter, food, water and medications as well as exceptional medical care, Charbonneau said. The compassionate treatment of all animals is at the heart of all we do, and its something clinicians, faculty, staff and students at the NC State College of Veterinary Medicine carefully train for and prioritize every day.

SAEN and PETA are urging NC State to make a change. Animals are suffering, hurting and dying due to the lack of care from the University, and if concrete change doesnt happen soon, its possible more animals will be mishandled and mistreated at the hands of faculty, staff and students.

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NC State commits multiple Animal Welfare Act violations, animals suffering and dying - N.C. State University Technician Online

The bacteriumStaphylococcus aureushas long been known to cause infections in humans, ranging from mild skin infections to pneumonia to more serious infections of the heart. In high-income countries, its the leading cause of a sometimes-fatal condition known as infective endocarditis, involving inflammation of the hearts valves or lining.

Now, in a new study, researchers at the University of Wisconsin School of Veterinary Medicine describe another way the bacterium can cause harm: by undermining the bodys ability to heal from those infections.

The findings may point the way toward improving treatment of infections withS. aureus, more commonly called a staph infection.

TheS. aureusbacteria produce small toxins, called superantigens, that bind to white blood cells and over-activate the immune system, which can cause complications for the circulatory system. Thestudy in rabbits, published recently in Science Advances, found that a superantigen called SEC (superantigen staphylococcal enterotoxin C) prevents injured blood vessels from healing. It also stops the formation of new branching blood vessels crucial to the wound repair process.

The role of many immune system molecules is to make the vessels around the infection more permeable, so they can enter and heal the infection, explains senior author Wilmara Salgado-Pabn, professor of pathobiological sciences. But when superantigens hyperactivate the immune system, your blood vessels can become leaky, leading to low blood pressure and organ dysfunction.

When an area of the body has suffered injury, it will form tiny branching blood vessels called capillaries, which send nutrients and oxygen to the damaged area. Using whats called the aortic root model, researchers sliced small sections of a rabbits aortic artery to imitate an injury. These ring slices were unable to form new capillaries in the presence of SEC, hindering the vascular system from healing the injury.

The model works well, says Salgado-Pabn, because it allows us to test capillary formation which can be complex in a laboratory environment, with all of the elements you would expect in the body.

Infective endocarditis disproportionately affects Black and Indigenous populations, as well as people predisposed to infection such as the elderly, people with diabetes and people who smoke.

The condition is responsible for high rates of in-hospital mortality, as it progresses very quickly and can go on to cause complications in other organs throughout the body, Salgado-Pabn says.

Over the last 50 years, treatment for infective endocarditis has remained largely unchanged, currently consisting of a six-week course of antibiotics or heart surgery to clear the infection. The new findings offer potential for developing new and better approaches.

You could not only neutralize the toxins vascular effects, but you could possibly treat patients to improve their vascular health, says Salgado-Pabn, whose work is supported by the National Institutes of Health. By strengthening a patients vascular health, you could proactively prevent the complications that lead to fatality.

Now that the lab has identified this new biological function, it is working to define the structures and molecules that are critical to the process, including identifying the molecules SEC interacts with and defining the cellular receptors that react to the toxins presence.

Maddie Arthur

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New understanding of 'superantigens' could lead to improved staph infection treatments - University of Wisconsin School of Veterinary Medicine

Veterinarian Dr. Rebecca Jackson was working in an Alberta mountain town a few summers ago when a patient came in showing signs of heatstroke.

The dog had just had a long day of hiking and was disoriented, vomiting, panting heavily, and "very, very weak," she recalled. "He had a high elevated heart rate, he had low blood pressure. His body temperature was elevated."

He was immediately put on intravenous fluids and wrapped in cool towels. Isopropyl alcohol was applied to his paw pads for an evaporative cooling effect. He was also given an anti-nausea injection to prevent any further dehydration through vomiting.

The story has a happy ending: The dog's body temperature came down and he made a full recovery, Jackson said.

But it's a reminder during these hazy, humid days of summerthat humans aren't the only ones feeling the heat pets are, too. And with even hotter days projected to come, veterinarians say it's important to take precautions and watch for signs of trouble in your furry family members.

Heatstroke may be top of mind for pet owners since it's something that humans can also suffer from. But burnt paws are actually a more common summertime injury and one that can be easy to overlook, said Jackson, an instructor at the University of Calgary's faculty of veterinary medicine.

Imagine walking barefoot across a sidewalk or beach on a hot summer day, and you get some idea of what our four-legged friends go through.

"We forget that they're very unique in that their paw pads are touching the ground as they walk," she said. "Black pavement in particular can attract a lot of heat and can cause burn injuries to those paw pads."

Severe burns on paw pads can be tough to heal because the surface of the pads is relatively avascular, meaning that it's lacking in blood supply. On very hot days, consider keeping your pet inside and walking them only in the early morning or late evening when temperatures are cooler, Jackson said.

If you're unsure, the American Kennel Club suggests placing the back of your hand on the asphalt on hot days; if you can't comfortably hold it there for 10 seconds, it's too hot for your pup's paws.

If you do take your pet out on a hot day, watch for signs of heatstroke, which happens when the body is unable to cope with external heat.

As humans, we regulate our body temperature in part through sweating: the evaporation of sweat from our skin's surface removes excess heat and cools us down. But our pets don't have sweat glands distributed throughout their body in the same way.

In dogs and cats, the sweat glands are mostly located in the paw pads. It's such a small surface area that it doesn't help much with temperature regulation, according to Dr. Sarah Machell, a licensed veterinarian and medical director of Vetster, a telehealth app that connects pet owners to veterinarians for virtual consults.

That's why our pets pant in the heat it's their way of cooling off.

"[Panting is] the only way that pets dogs, in particular, we see this in can really evaporate water from any surface to help lower body temperature," Machellsaid.

"So their capacity and their tolerance for heat is much, much less than humans."

To help your pets stay cool, make sure they have lots of access to shade and that any exercise taken on is very moderate and at a slow pace, Machellsaid. Keep them hydrated by carrying water bottles, taking frequent breaks and encouraging them to drink.

Specialized cooling bandanas and cooling vests can also keep your pets from getting overheated, Machellsaid.

Most pet owners know to never leave their pets alone in a car because of how fast temperatures can rise in the enclosed space. Machellrecommends planning ahead and taking a second person with you who can walk the dog while you pop into the store.

As with humans, it only takes a few degrees of difference in your pet's body temperature for the situation to tip intodangerous territory.

A normal body temperature for a dog is in the range of 37.5 C to 39.2 C. When it gets above 41 C, the possibility of heatstroke starts to be a significantconcern, and there is risk of multiple organ failure and death, said Dr. Matthew Richardson, a veterinarian at The Animal Clinic in Toronto and president-elect for the Ontario Veterinary Medical Association (OVMA).

The higher above that level it goes and the longer it is elevated, the more serious the consequences, he said.

According to the OVMA, the signs of heatstroke in pets can include:

While symptomsare fairly similar across pet species, there are some minor differences.

"In dogs, we will see vomiting and diarrhea as symptoms of heatstroke. In birds andreptiles, ittends to be a reduction in the production of fecal matter and a reduction in the amount that they want to eat," Richardson said.

If you think your pet is suffering from heatstroke, you should move them to a cooler setting and use cool not cold water and damp towels to try to lower their body temperature, according to the OVMA. If they are able, allow them to drink.Bring any pets suffering from heatstroke to aveterinarian as soon as possible, the OVMA says.

Pet owners should also be aware that some animals are more vulnerable to heatstroke than others. The Toronto Humane Society says these include animals with flat faces, such as pugs and Persian cats, as they can't pant as effectively; elderly pets; overweight pets; and those with heart or lung diseases.

A puppy would also be more prone to heatstroke than an adult dog, Richardson said.

Heat stress can also be an issue for indoor pets if there is a lack of air conditioning.

Machellsuggests having multiple locations for access to fresh water and adding ice cubes to water or even using a water fountain, since running water can sometimes be more appealing for pets.

For pets like birds and guinea pigs, make sure the cage is out of direct sunlight, and you could place a fan on them, Richardson said.

For small mammals, you can also try to create a special spot for them in their cage that will retain a cooler temperature for longer than regular bedding.

"If you can find a piece of stone, tile, granite, something like that that's cool and can stay in the shade so it stays cool you can put that in their cages," he said. "You can have this sort of cold area where they can go to try to find that cooler spot."

Have you ever had a dispute over ownership or custody of a pet? We want to hear from you for an upcoming story. Send an email to ask@cbc.ca.

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Pets are also feeling the heat this summer. Here's how you can protect them - CBC.ca

VIRGINIA BEACH, Va. - With temperatures as hot as they are, veterinarians say it's important to keep your pets inside to avoid heat stroke and other emergencies.

"Recently, we actually saved a police dog. He was working outside and his temperature went up to 107 degrees and we were very lucky...they brought him in immediately," said Dr. Julie Nelson, an emergency veterinarian at Bay Beach Veterinary Emergency Hospital in Virginia Beach.

The dog and its handler were also lucky because they were able to find a clinic to take the case.

Bay Beach's schedule for emergency doctors currently has numerous openings, particularly during overnight shifts No doctor on staff means pets could be turned away. It nearly happened on Monday of this week, the clinic tells News 3.

We did not have an emergency doctor overnight and most of the veterinary emergency hospitals in our community did not have emergency doctors overnight either so we did not have anywhere to send the patient. We did end up getting him taken care of, but, at the same time, its a really tough situation for people to be in," said Allison Rye, the Hospital Administrator at Bay Beach.

According to Blue Pearl an emergency veterinary hospital that operates across the country, with two locations in Hampton Roads the problem is nationwide due to a shortage of veterinarians and support staff.

A statement to News 3, from company spokesperson Laura Fourniotis, reads, "Over the past decade, there has been an increased generational interest in pet ownership, which was accelerated by a historic influx of pandemic pets. Adding to this, the industry is facing a national veterinary professional shortage. COVID-19 only exacerbated pre-existing issues in veterinary medicine, including burnout. Loss of qualified/experienced para-staff, clinicians, and leadership is notable across all aspects of the veterinary business. However, emergency and critical care medicine has seen the greatest attrition or movement of Associates. Many determined to take a break, to move to another role or another team/practice, or to leave the profession altogether. This trend is not yet slowing in 2022."

Fourniotis pointed News 3 to a study by Mars Veterinary Health that breaks down the numbers.

Rye says the staffing situation at Bay Beach and across the region is the worst she's seen since joining the clinic as a veterinary assistant in 2001.

"I think we had five or six 24-hour facilities locally. Now we have two," she said. "We do our best to cover the holes (in our schedule) that we can, but our doctors can only work so many hours in a week."

If the hospital is unable to take on a new patient, Dr. Nelson says her staff may refer the owner to another clinic outside the region.

It hurts us immensely to have to send them somewhere else, like all the way to Richmond. That is a two-hour drive to do in the middle of the night when their pet is having an emergency but when you dont have the doctor to take care of them, we have to do whats best for them," she told News 3.

But sometimes even those locations are already full too.

Dr. Nelson says the best thing for someone having an emergency with their dog, cat or another pet is to call ahead to make sure a hospital is accepting patients to avoid a wasted trip.

Also, if you think your pet might be sick, try to get in to see your regular veterinarian before it becomes an emergency.

And keep in mind if you do have to visit the ER, be patient and prepared to wait several hours in the event the doctor is working on another, higher priority case.

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Heat emergency with your pet? Don't be surprised if your ER visit requires a drive - News 3 WTKR Norfolk

Rep. Kurt Schrader would have to apply for a new license from state board led by wife of candidate who defeated him.

Oregon is a small state, prone to odd intersections of political lives. To wit:

U.S. Rep. Kurt Schrader, D-Canby, would have to apply for a new veterinarian's license from a state board led by the wife of the candidate who defeated him in the May primary.

State records show that Walter Schrader the congressman goes by his middle name, Kurt received a state veterinary license in 1977. Elected to Congress in 2008, Schrader has served as chair of the Veterinary Medicine Caucus.

But state records show that after 42 years, Schrader allowed his license to lapse in December 2019.

Schrader lost the May 17 Democratic primary to Terrebonne attorney Jamie McLeod-Skinner.

If Schrader wanted to resume his practice after he leaves office in January, he'd apply for a new license from the Oregon Veterinary Medicine Examining Board.

The board's interim executive director since December 2020 is Cass McLeod-Skinner. She's Jamie's wife.

Cass McLeod-Skinner is also the executive director of the Oregon Board of Chiropractic Examiners. She stepped into the additional work of leading the veterinary board after the previous executive director, Lori Maakinen, retired in December 2020.

State records show Cass McLeod-Skinner has a base pay of $119,899 and earned total compensation in the 2021 fiscal year of $120,109.

Gov. Kate Brown announced she plans to fill the veterinary board commission job and was accepting applications until the end of June. No announcement has been made on an appointment.

Schrader is paid $174,000 per year as a member of the U.S. House of Representatives. Starting next year, the paycheck will go to either Jamie McLeod-Skinner or Republican Lori Chavez-DeRemer, depending on the outcome of the November election.

You count on us to stay informed and we depend on you to fund our efforts.Quality local journalism takes time and money. Please support us to protect the future of community journalism.

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Oregon's a small world: Politics and vetting veterinarians - Portland Tribune

A cat treated for care at UC Davis Veterinary Hospital after the 2018 Camp Fire. (UC Davis School of Veterinary Medicine)

Discovery Could Change the Way Veterinarians Treat Wildfire-Injured Cats

Quick Summary

July 24, 2022 - By Trina Wood - Cats who suffered burns and smoke inhalation in urban California wildfires are at risk of forming deadly blood clots, according to a new study from researchers at the University of California, Davis, Veterinary Medical Teaching Hospital.The study, recently published in the journal Frontiers in Veterinary Science, follows up ona previous discoverythat showed cats injured in urban wildfires had a high incidence of heart problems.

Prior to these two papers, we didnt realize that cats impacted by urban wildfires were prone to forming clots, which can lead to sudden death, said lead co-author Ronald Li, associate professor of small animal emergency and critical care at UC Davis. This study will change the standard of care for rescued cats from these wildfires and hopefully save more lives.

Cats treated for their injuries from the 2018 Camp Fire in Paradise, California, were some of the models for this study. Researchers examined their platelets, the cells that circulate in blood and help stop bleeding or form blood clots. They found that cats with wildfire injuries had increased overactive platelets compared to healthy cats or cats with heart disease, in this case subclinical hypertrophic cardiomyopathy, or HCM. HCM is the most common cardiac disease in cats and causes a thickening of the heart muscle.

Cats with HCM are hypercoagulable, meaning they are more likely to form clots, explained lead co-author Ava Tan, a veterinary research fellow currently working in Lis laboratory. Thats why we used them as a control group to compare with cats in the wildfire group.

The platelets of wildfire-injured cats also released high amounts of microvesicles, microscopic membranous bubble-like structures filled with proteins, which are associated with cardiovascular disease and an elevated risk of clotting.

We found cats exposed to wildfire smoke and injuries are even more prone to throwing clots, showing a direct association between wildfire injuries, platelet response and clot formation, Tan said.

In addition to clot formation, platelets have a lot to do with overall cardiovascular health and disease. The study also led to the discovery of a novel receptor on cat platelets, Toll-Like-Receptor-4, that may play a role in clotting and could be the target for treatments developed in the future.

These results could lead to bigger health implications for our feline patients and highlight the important role that platelets play in linking inflammation with the coagulation system, Li said.

Wildfires pose a major risk for humans as well. Emergency room visits increase due to heart attack and strokes after wildlife exposure. Although the underlying mechanism isnt known in humans, this study in cats may shed light on systemic platelet activation, which plays a crucial role in mediating the likelihood of developing clots as a result of wildfire injuries.

This study opens a new door to looking at how wildfires impact cardiovascular health in humans, Li said.

The researchers were able to use blood samples collected from cats brought in for treatment from the Camp Fire, which have been used in these two studies to date. This study has also led to a third study, which is underway, to discover new cellular processes that may explain why feline platelets are so sensitive and prone to clotting, especially in cats with heart conditions or wildfire injuries. The data collected is critical to developing early treatment plans, Li said.

Other authors include veterinary cardiologists Joshua Stern, Catherine Gunther-Harrington and Ashley Sharpe; veterinary critical care specialists Yu Ueda, Steven Epstein and Satoshi Haginoya; and research associates Nghi Nguyen and Mehrab Hussain in the Li Comparative Platelet and Neutrophil Physiology Laboratory. The diagnostics and therapeutic management of feline burn victims reported in this study were funded through the UC Davis Veterinary Catastrophic Need Fund.This study also received funding through the Center for Companion Animal Health.Source: UC Davis

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Cats Injured in Wildfires at Risk of Deadly Blood Clots - Sierra Sun Times