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Hematopoietic Stem Cells | Hematopoiesis | Properties & Functions

September 4th, 2022 2:07 am

Hematopoietic Stem Cells: In living organisms, a specialized system that consist of blood and its progenitors are referred to as the hematopoietic system.

In particular, this system is made up of cells with specialized functions such as the red blood cells (for carrying oxygen to tissues), white blood cells (for immune defense against pathogens, and foreign agents), platelets (for blood clotting), macrophages and lymphocytes (also for immune defense).

However, many of the said blood cells are temporary and need to be replaced with new ones continuously. But fret not because a single cell can solve the problem!

Every day, almost billions of new blood cells are synthesized within the body with each coming from a specific progenitor cell called the hematopoietic stem cell.

How to pronounce Hematopoietic Stem Cells?

What is Hematopoiesis?

The formation of all kinds of blood cells including creation, development, and differentiation of blood cells is commonly known as Hematopoiesis or Haemopoiesis.

All types of blood cells are generated from primitive cells (stem cells) that are pluripotent (they have the potential to develop into all types of blood cells).

Also referred to as hemocytoblasts, hematopoietic cells are the stem cells that give rise to blood cells in hematopoiesis.

Where Does Hematopoiesis Occur?

In a healthy adult, hematopoiesis occurs in the bone marrow and lymphatic tissues, where 1000+ new blood cells (all types) are generated from the hematopoietic stem cells to main the steady-state levels.

Where Are Hematopoietic Stem Cells Found?

They can also be found in the umbilical cord and in the blood from the placenta.

Who Discovered Hematopoietic Stem Cells?

It was long believed that the majority of hematopoiesis occurs during ontogeny (origination and development of organism) and that the mammalian hematopoietic system originated from the yolk sac per se.

Functions of Hematopoietic Cells

As alluded to earlier, blood cells and blood cell components are formed in a process called hematopoiesis.

Coming from the Greek words hemato and poiesis which mean blood and to make respectively, hematopoiesis occurs in the bone marrow and is responsible not only for the synthesis but also the multiplication, and differentiation of blood cells.

Shown below is a diagrammatic illustration of the different blood cell types that hematopoietic cells can give rise to:

Clinical uses of Hematopoietic Stem Cells

The mammalian blood system showcases the equilibrium between the functions of hematopoietic stem cells. Intensive studies have already shown the structures and molecules that control these stem cells, but the exact picture of the underlying molecular mechanisms is still unclear.

Above everything else, it is important to note that such issues are not just of academic interest but can also be relevant in devising future novel methods of diagnosing and treating various diseases associated with cells.

Key References

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Canadian Blood Services Stem Cells for Life

September 4th, 2022 2:07 am

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From optimized stem cell transplants to CAR T cell therapy: Advancing options for cancer, HIV and more – City of Hope

September 4th, 2022 2:07 am

City of Hope recently shared significant news at the 24th Annual AIDS Conference about a patient treated in 2019 whose HIV has been in remission. The man had been living with HIV for 31 years before coming to City of Hope with another grave diagnosisacute myeloid leukemia.One of the best hopes for long-term remission of acute myeloid leukemia (AML) is a stem cell transplant, and City of Hope has one of the nations leading transplant programs, having performed more than 17,000 transplants since 1976. In addition, the institution is at the forefront of using transplants to treat older adults with blood cancers, including increasing efficacy and safety in those over 60 and those with comorbidities, like the then 63-year-old City of Hope patient with HIV. The research was presented by Jana K. Dickter, M.D., City of Hope associate clinical professor in the Division of Infectious Diseases.

City of Hope hematologist Ahmed Aribi, M.D., assistant professor in the Division of Leukemia, prepared the patient for an allogeneic blood stem cell transplant with a chemotherapy-based, reduced-intensity regimen developed for treatment of older patients with blood cancers. Reduced-intensity chemotherapy makes the transplant more tolerable for older patients and reduces the potential for transplant-related complications from the procedure.

Aribi and his team worked with City of Hopes Unrelated Donor BMT Program directed by Monzr M. Al Malki, M.D. to find a donor who was a perfect match for the patient and had the rare genetic mutation, homozygous CCR5 Delta 32, which is found in just 1 to 2% of the general population.

People who have this mutation have a resistance to acquiring HIV. CCR5 is a receptor on CD4+ immune cells, and most strains of HIV use that receptor to enter and attack the immune system. But the CCR5 mutation blocks that pathway, which stops HIV from replicating.

After this successful transplant for both AML and HIV, the patient has been in remission for HIV since stopping ART in March 2021. While this outcome has happened in three other patients, the City of Hope patient was both the oldest to undergo a transplant with HIV and leukemia and go into remission for both. He had also lived with HIV the longest 31 years.

The City of Hope patient is another major advancement. It demonstrates that research and clinical care developed and led at City of Hope are changing the meaning of an HIV diagnosis for patients across the United States and the world, said John Zaia, M.D., director of City of Hopes Center for Gene Therapy, Aaron D. Miller and Edith Miller Chair for Gene Therapy and a leader in HIV research. City of Hope remains at the forefront of clinical research that changes peoples lives for the better.

When I was diagnosed with HIV in 1988, like many others, I thought it was a death sentence. I never thought I would live to see the day that I no longer have HIV. City of Hope made that possible, and I am beyond grateful. The City of Hope patient

The story above is one significant example of several important advances being made at City of Hope in the care of people with HIV. When many centers still treated patients with low-intensity, noncurative treatment approaches for HIV-related lymphoma, City of Hope challenged that paradigm by demonstrating that autologous transplantation could be used to cure patients who would otherwise die.

More recently, City of Hope is leveraging its leadership in CAR T cell therapya groundbreaking treatment currently used to rally the bodys natural defenses against cancer and exploring its potential in tandem with another advance, City of Hopes vaccine for cytomegalovirus (CMV).

In a proof-of-concept study, funded by theCalifornia Institute for Regenerative Medicine, lab models demonstrated that the combination therapy could recognize and eliminate HIV without serious toxicity to cells in the virus host. In cultured human cells, the CAR T cells killed cells tagged with the gp120 protein, and kept killing them, without significant signs of risking damage to healthy cells. In a mouse model for HIV/AIDS, high doses of the dual-action CAR T cells followed by the CMV vaccine were successful in controlling HIV, and even nestled into the bone marrow, indicating potential for treatment to keep working over the long term.

In addition to achieving breakthrough outcomes in cancer and HIV, City of Hope has been recognized as the seventh "Best Hospital" for cancer in the nation according to U.S. News & World Report's 2022-23 Best Hospitals: Specialty Ranking. This marks the first time the cancer treatment center has cracked the top 10 of the U.S. News & World Report annual rankings and the 16th consecutive year it has been distinguished as one of the nation's elite cancer hospitals. It was also rated as high performing in four cancer surgery specialties: lung, colon, prostate and ovarian cancers.

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Devastation over death of schoolgirl, 11, who hoped she was beating cancer – Leicestershire Live

September 4th, 2022 2:07 am

A litle girl who thought she was winning a long battle against an aggressive form of cancer has died, leaving her family devastated. Libby Jones, 11, had neuroblastoma and it was throughout her body from her jaw to her knees.

She bravely underwent months of surgery, radiotherapy, chemotherapy and even a stem cell transplant that - doctors thought - was working to beat the cancer. The treatment included a seven-hour operation to remove the main tumour from her ribs, CoventryLive reported.

In June this year, the Nuneaton family received the news they had prayed and waited for with medics suggesting she would be clear of cancer by Christmas. But their joy was short lived and turned to devastation when, just weeks later on August 11, Libby became unwell and was taken back into hospital.

READ MORE: Violence flares during India v Pakistan cricket street celebrations in Belgrave, Leicester

Her family received the heartbreaking news that the cancer was back. It had moved to her brain and was even more aggressive than before.

Days later they were told the cancer was incurable and no further treatments were available. Libby returned home on August 18 and passed away on August 24.

A GoFundMe page has been set up to give the former Milby Primary School pupil the 'send off she deserves'. On the page, entitled 'Please help Libby have the send off she deserves', it says: "We desperately want to give Libby the send-off she deserves and Mara, Megan and Logan deserve this.

"If you can find it within your heart to be able to donate even 1 it really would make a difference."

So far, almost 2,500 has been raised in memory of Libby. Arrangements have been made for her funeral and it will take place on Monday, September 5, at 9.30am at the Heart of England Crematorium in Eastboro Way, Nuneaton.

The funeral procession will pass Higham Lane School at around 9.10am and then Milby Primary School at 9.20am. Tributes have been paid to Libby online. One person wrote: "Sad news - heaven has a beautiful angel."

Another wrote: "Such sad news - fly high angel." To donate to the GoFundMe page click here.

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Scientists unlock the key to immortality in jellyfish – Syfy

September 4th, 2022 2:07 am

Humans fear death so much that some of us would willingly trade our immortal souls if such a thing exists and become vampires for a chance to keep wandering the world a little longer. You can quench your thirst for vampire lore with the upcoming Vampire Academy series (streaming on Peacock Sept. 15), but in the meantime jellyfish might be teaching us how to live forever without needing to drink the blood of unsuspecting mortals.

Weve known for some time that Turritopsis dohrnii, otherwise known as the immortal jellyfish, was out there living its best life over and over again by intermittently switching between its adult and larval stages. When the stresses of being an adult become too much for it to bear, it simply turns back the clock to become a juvenile and starts the whole process over again. While disease or predation can and does end the life of individual jellies, they dont succumb to the same biological ticking clock as the rest of us.

While weve been able to observe this behavior in immortal jellyfish, so far it has been unclear what biological mechanisms contribute to their everlasting life. Now, scientists from the Department of Biochemistry and Molecular Biology at the University of Oviedo have identified the genes responsible, opening the door to future research. Their findings were published in the Proceedings of the National Academy of Sciences.

Zeroing in on what makes the immortal jellyfish special required a comparison of their genome with that of a close relative. Scientists compared their DNA with that of Turritopsis rubra, a jellyfish which is similar to the immortal jelly but, importantly, cannot regenerate. By comparing the genomes, they were able to identify specific sequences which the immortal jelly uses to revert from its adult medusa stage back to its larval stage, a process known as transdifferentiation.

The comparison revealed genes involved in DNA replication and repair, telomere maintenance, stem cell production, communication between cells, and reduction of the oxidative cellular environment, according to a press release from the University of Oviedo. All of those processes are associated with the healthy, or unhealthy, aging of humans.

The findings suggest there isnt one thing which allows immortal jellyfish to avoid the reaper. Instead, aging is akin to a series of locked doors, each of which needs a specific genetic key. Only by having the whole set of keys can you travel backward along the aging corridor. While most animals are strapped to a biological tram which only moves in one direction, their cells becoming what they are destined to be and then remaining that way, immortal jellyfish can coax their cells into becoming whatever they need to be no matter what stage of life they are in.

Researchers were careful to note that there are no immediate applications pertaining to human aging. Dont expect to visit your local department store and find immortal jellyfish face cream or dehydrated polyp powder promising to make you young. However, they did note that a better understanding of how immortal jellyfish control their cellular states could provide an avenue for tackling aging-related diseases.

What we have learned about the immortal jellyfish could lead to extended lifespan and, importantly, higher quality of life in old age, but its unlikely well be able to revert to our prepubescent stages like they do. When you stop to think about it, would you really want to even if you could? Immortality sounds nice, but at what cost?

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Forge Biologics Reports Positive Clinical Data on Brain Development and Motor Function from the RESKUE Novel Phase 1/2 Gene Therapy Trial in Patients…

September 4th, 2022 2:07 am

COLUMBUS, Ohio--(BUSINESS WIRE)--Forge Biologics, a gene therapy-focused contract development and manufacturing organization, today announced that Maria Escolar, M.D., Chief Medical Officer, will present preliminary clinical data on the treatment of its first patient in the RESKUE Phase 1/2 clinical trial for FBX-101, the Companys novel gene therapy for the treatment of patients with Krabbe disease. The data will be presented on August 31, 2022, at the annual symposium of the Society for the Study of Inborn Errors of Metabolism (SSIEM) in Freiburg, Germany.

RESKUE is the first-in-human clinical trial where subjects are administered FBX-101, an Adeno-Associated Virus (AAV) systemic gene replacement strategy, after full myeloablation and umbilical cord blood transplantation. Clinical data support preclinical observations that this approach may lessen many of the immune challenges previously observed with systemic AAV gene delivery and can create a novel approach for extending the delivery of gene replacement strategies to target metabolic diseases amenable to UCBT. The first patients data from the RESKUE clinical trial demonstrate that intravenous FBX-101 following UCBT has been safe and well tolerated through Day 180. Notably, the data demonstrate an absence of humoral immune response against the vector and significantly increased GALC enzyme activity. Through Day 180, the patient exhibited improved motor activity and normal brain development compared to previously reported transplanted patients with Krabbe disease.

Krabbe disease is a rapidly fatal neurodegenerative disorder. While early transplant can help patients, they inevitably develop motor disease. FBX-101, a systemic AAV therapy administered after hematopoietic stem cell transplantation, was well tolerated in the first patient and the initial clinical data support normal brain development during this period of rapid myelination, and normal gross motor function," stated Dr. Escolar. "The increased GALC levels and ablated immune response achieved in this transplant environment may represent a paradigm shift in the treatment of patients with Krabbe disease and for the field of gene therapy. We are excited by results thus far and we look forward to continuing this trial.

We are thrilled with Forges commitment to get this much-needed therapy into a clinical trial, said Stacy Pike-Langenfeld, Co-Founder and President of KrabbeConnect.

We're deeply grateful for this progress toward better treatments for patients suffering from Krabbe disease thanks to the dedication of the team at Forge, said Anna Grantham, Leukodystrophy Care Network Director of Hunters Hope Foundation.

Dr. Escolars poster, Intravenous FBX-101 (AAVrh10.hGALC) following hematopoietic stem cell transplantation increases GALC activity, improves gross motor function, and maintains brain development in Krabbe patients in the RESKUE Phase 1/2 Clinical Trial, will be available virtually for all symposium attendees and displayed in the main poster hall throughout the course of the conference. The poster walk will take place on Wednesday, August 31, 2022, from 18:45-20:15 CET. For more details on the symposium, please visit: https://www.ssiem.org/

About Krabbe Disease

Krabbe disease is a rare, neurodegenerative disease affecting about 1-2.5 in 100,000 people in the U.S. and is inherited in an autosomal recessive manner. Krabbe disease is caused by loss-of-function mutations in the galactocerebrosidase (GALC) gene, a lysosomal enzyme responsible for the breakdown of certain types of lipids such as psychosine. Without functional GALC, psychosine accumulates to toxic levels in cells. The psychosine toxicity is most severe in the myelin cells surrounding the nerves in the brain and in the peripheral nervous system, eventually leading to the death of these cells and loss of motor function. The disease initially manifests as physical delays in development, muscle weakness and irritability and advances rapidly to difficulty swallowing, breathing and cognitive problems, and vision and hearing loss. Early onset or Infantile Krabbe disease cases usually results in death of patients by the age of two years, while later onset or Late Infantile patients usually die by the age of six. Although bone marrow transplant is the current standard of care for treating the central nervous system in patients with Krabbe disease, patients continue to develop peripheral nervous system disease that eventually results in death. Currently, 10 states in the USA are approved to try and identify babies with Krabbe disease as part of newborn screening programs.

About FBX-101

Forge developed FBX-101 to treat patients with Infantile Krabbe disease. FBX-101 is an adeno-associated viral serotype rh10 (AAVrh10) gene therapy that is typically delivered after a hematopoietic stem cell transplant. FBX-101 delivers a functional copy of the GALC gene to cells in both the central and peripheral nervous system. FBX-101 has been shown to functionally correct the central and peripheral neuropathy and correct the behavioral impairments associated with Krabbe disease, as well as to drastically improve lifespan in animal models of the disease. This approach has the potential to overcome some of the immunological safety challenges observed in traditional AAV gene therapies and extend the duration of gene transfer.

About Forge Biologics

Forge Biologics is a hybrid gene therapy contract manufacturing and clinical-stage therapeutics development company. Forges mission is to enable access to life changing gene therapies and help bring them from idea to reality. Forges 200,000 square foot facility utilizes 20 cGMP suites in Columbus, Ohio, the Hearth, to serve as its headquarters. The Hearth is a custom-designed cGMP facility focused on AAV manufacturing and can host end-to-end manufacturing services to accelerate gene therapy programs from preclinical through clinical and commercial stage manufacturing. By taking a patients-first approach, Forge aims to accelerate the timelines of these transformative medicines for those who need them the most. To learn more, visit http://www.forgebiologics.com.

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Menin Inhibitors Have Potential to Become the Next Class of Targeted Therapy in AML – Targeted Oncology

September 4th, 2022 2:07 am

The acute myeloid leukemia (AML) treatment landscape has a novel class of agents coming down the pipeline. Menin inhibitors that targetNMP1mutations andKMT2A and KMT2Arrearrangements have been showing early promise in terms of efficacy and safety in multiple clinical trials.

Success with menin inhibition was first shown in preclinical models.NMP1andKMT2A/KMT2Aralterations cause the complex and upregulation of transcription factors that are essential for leukemogenesis to activate, and menin inhibitors can block this activation.

We think when those processes are active. Myeloid cells become stuck in a dedifferentiated state, and that promotes leukemia growth. In preclinical studies, use of these menin inhibitors against acute leukemia cells with NMP1 mutations, as well as those characterized byKMT2Arearrangements, leading to apoptosis and cell death via induction of what we thought was similar to a clinical differentiation syndrome, said Eunice S. Wang, MD, in an interview with Targeted Oncology.

Early findings have now been reported from first-in-human studies of menin inhibitors in patients with AML, showing encouraging efficacy and safety. First, in the COMET-001 study (NCT04067336), KO-539 showed early biologic activity in patients with relapsed AML. The agent also demonstrated unique pharmacokinetic characteristics that could lead to clinical benefit. Notably, some patients in the study hadKMT2Armutations.1

In the AUGMENT-101 (NCT04065399) study, SNDX-5613 achieved promising antileukemia activity in patients with heavily-pretreated KMT2A and NMP1-mutated acute leukemia, along with acceptable safety.2

In the interview, Wang, chief of the Leukemia Service at Roswell Park Comprehensive Cancer Center, discussed the growing use of menin inhibitors in AML and clinical trial research further supporting the treatment strategy.

TARGETED ONCOLOGY: Can you talk aboutNPM1mutations, KMT2A/KMT2Ar rearrangements in AML?

Wang: In acute myeloid leukemia, NMP1-mutated disease comprises about one-third of all newly diagnosed cases, particularly in patients under the age of 60. Patients who have rearrangements in the MLL gene, now known as the KMT2Ar gene have a prevalence of about 5% to 10%. Those patients are associated with an intermediate adverse prognosis and have translocation of 2 genes;1 that is located on the 11th chromosome, and 1that's located on a different chromosome. These rearrangements can occur with about 80 different chromosome partners and can occur not only in patients with AML, but in a small percentage of patients that have pediatric acute leukemias as well as acute lymphocytic leukemia.

Before the in-human trials that are happening, what was shown preclinically with the use of menin inhibitors in AML?

Menin inhibitors are targeted agents that block the binding of the protein menin to a complex epigenetic entity, which is based on the MLL or KMT2A gene. The interaction between menin and this KMT2A complex leads to activation of the complex and upregulation of transcription factors that are essential for leukemogenesis. Blocking that activation with a targeted protein inhibitor of menin allows that complex to be inactive, thereby downregulating some of the transcriptional processes that lead to the underlying leukemia.

We think when those processes are active, myeloid cells become stuck in a dedifferentiated state, and that promotes leukemia growth. In preclinical studies, use of these menin inhibitors against acute leukemia cells with NMP1 mutations as well as those characterized by KMT2A rearrangements lead to apoptosis and cell death via induction of what we thought was similar to a clinical differentiation syndrome.

Can you discuss the AUGMENT-101 study?

The AUGMENT study was the first-in-human evaluation of a menin inhibitor in patients with relapsed and refractory acute leukemias characterized by NMP1 mutations and KMT2A gene rearrangements.This study enrolled dozens of patients with very refractory disease that had failed multiple lines of therapy including allogeneic stem cell transplantation.

The menin inhibitor SNDX-5613 was given twice a day at both escalating dose characterizations and then also at fixed doses based on the initial dose-finding cohort results of the AUGMENT-101 study. Findings presented at the American Society of Hematology Annual Meeting 2021 demonstrated in the 50 evaluable patients with an NMP1 mutation or KMT2A rearrangement, an overall response rate of approximately 50%. The complete remission and incomplete account recovery rate was about 24%,and in patients who did achieve a response of which they were 9, the duration of response in those patients lasted over a year.

The major side effects of the AUGMENT-101 study and the dose-limiting toxicity of the drug were found to be QTC prolongation, which occurred in about 10% or 12% of individuals. Few individuals had evidence of serious differentiation syndrome. This first-in-human study of the first-in-class menin inhibitor demonstrated impressive efficacy as monotherapy in the select biological subgroups of patients, particularly in patients who had failed multiple lines of prior therapy.

The COMET-001 study of a novel menin inhibitor is ongoing in relapsed or refractory AML. Can you discuss this study?

The COMET-001 study is a first-in-human study of a different menin inhibitor, KO-539. This agent was initially evaluated in a dose escalation phase and then an expansion phase. The expansion phase has evolved 2 doses of the drug and is evaluating the agent specifically in patients who hadNMP1mutation, as well asKMT2Arearrangements.

To date, the early data on that trial presented in 2020 at the ASH meeting demonstrated tolerability and efficacy in patients both withKMT2Amutation orNMP1rearrangement. There have been incidences of differentiation syndrome which have been observed, and further results of this agent will be updated in the ASH 2022 meeting, for which we're eagerly awaiting the outcomes.

The fact that these 2 menin inhibitors have demonstrated evidence of clinical activity to date has spurred active interest in vetted inhibitors as a class of agents. There currently are at least 3 or 4 other menin inhibitors that have shown promising efficacy in preclinical models, which are now moving forward in the early-phase testing in patients with these 2 biological alterations.

What are some other agents that are coming down the pipeline in AML?

I think that the menin inhibitors as a class have the promise to be the next class of targeted therapies for acute myeloid leukemia. We've seen since 2017, the advent of multiple mutations specific agents for this disease, including FLT3 inhibitors and IDH1/IDH2 inhibitors. We're now moving towards more mutational-directed therapy with agents that are showing efficacy, not only in NMP1- and KMT2A-altered patients, but also potentially in patients that have the dreadedp53mutation.

We're looking forward to having agents that are already established in the field and for novel combinations of targeted therapy with chemotherapy backbones, whether they be intensive, 7 + 3, or non-intensive venetoclax-based/hypomethylating regimens. Looking into the future, we see combined therapy moving into the upfront setting for some of these mutational subsets. We also see the advent of additional targeted therapy moving forward for additional subsets of this disease. More and more, we are moving towards better drugs, better targeting, and improved personalization or individualization of therapy for both the patient as well as the patient's disease.

REFERENCES:

1. Wang ES, Altman JK, Pettit K, et al. Preliminary data on a phase 1/2A first in human study of the menin-KMT2A (MLL) Inhibitor KO-539 in patients with relapsed or refractory acute myeloid leukemia.Blood. 2020;136(suppl 1:7-8. doi:10.1182/blood-2020-134942

2. Stein EM, Aldoos I, DiPersio JF, et al. Safety and efficacy of menin inhibition in patients (pts) with MLL-rearranged and NPM1 mutant acute leukemia: A phase (Ph) 1, first-in-human study of SNDX-5613 (AUGMENT 101).Blood. 2021;138(suppl 1):699. doi:10.1182/blood-2021-146944

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Wanted murder suspect John Belfield believed to still be in the UK as two more arrested over death of Thomas Campbell – The Manc

September 4th, 2022 2:07 am

News

128 new homes in Ancoats have been approved by Manchesters planning committee in the first of a new council housing development project.

Manchester City Council explains that the green light given to the first phase of the new This City development will include 118 apartments across two buildings, alongside 10 townhouses which will have either three or four bedrooms.

The apartments will be a mix of 27 one-bedroom and 91 two-bedroom homes.

30% of the homes will be made available at the Manchester Living Rent, which is capped at theGovernmentsLocal Housing Allowance rate and is therefore affordable to residents on housing benefit, according to the Council.

This will increase the number of homes available to people on lower incomes in the citycentre, while the remainder will be available at market rent.

The development bringsback into use a Brownfield site bound byRodney Street, Jersey Street,WadefordClose, and Butler Street on the border ofAncoatsand Miles Platting.

As well as the homes sitting in a highlysustainable location close to the citycentre, which give residents the option of walking, cycling, and using public transportto access local servicesand employment, the town houses will also eachincludea parking spacewith electricvehiclecharging points, andprivategardens to the rear.

Therell also be plenty of space for bicycle parking, and the addition of The Mobility Hub a new concept thatthe Council says will centraliseand reduce the need for onsite car parking, as well as limiting traffic in the widerneighbourhood.

Read more: Manchester pledges to build 36,000 homes before 2032 in new housing strategy

32 million will be invested in the widerpublicrealm, and a greening scheme will also see Ancoatsbecome alow-carbon sustainableneighbourhood with a focus on active travel, walking, and cycling routes.

1,500 homes are expected to be deliveredinthis area in the coming years as the final phase of the regeneration ofAncoats, the Council confirms.

Its great tosee the first This City siteoutof theblocks and delivering the homes that we know Manchester people need, said Cllr Bev Craig Leader of Manchester City Council.

Our intention is to scale up development to at least 500 homes per year and at least 20percent of these will be made available at the Manchester Living Rent delivering high quality, affordable housing for families on lower incomes.

This is a really exciting time forAncoatsand the beginning of thecompletionofa regenerationjourneyspanning two decades.

Featured Image Manchester City Council

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15 foods to boost the immune system – Medical News Today

September 4th, 2022 2:06 am

A healthful, balanced diet plays a vital role in staying well. The following foods may help to boost the immune system:

Blueberries contain a type of flavonoid called anthocyanin, which has antioxidant properties that can help boost a persons immune system. A 2016 study noted that flavonoids play an essential role in the respiratory tracts immune defense system.

Researchers found that people who ate foods rich in flavonoids were less likely to get an upper respiratory tract infection, or common cold, than those who did not.

Dark chocolate contains an antioxidant called theobromine, which may help to boost the immune system by protecting the bodys cells from free radicals.

Free radicals are molecules that the body produces when it breaks down food or comes into contact with pollutants. Free radicals can damage the bodys cells and may contribute to disease.

Despite its potential benefits, dark chocolate is high in calories and saturated fat, so it is important to eat it in moderation.

Turmeric is a yellow spice that many people use in cooking. It is also present in some alternative medicines. Consuming turmeric may improve a persons immune response. This is due to the qualities of curcumin, a compound in turmeric.

According to a 2017 review, curcumin has antioxidant and anti-inflammatory effects.

Salmon, tuna, pilchards, and other oily fish are a rich source of omega-3 fatty acids.

According to a 2014 report, long-term intake of omega-3 fatty acids may reduce the risk of rheumatoid arthritis (RA).

RA is a chronic autoimmune condition that occurs when the immune system mistakenly attacks a healthy part of the body.

Broccoli is another source of vitamin C. It also contains potent antioxidants, such as sulforaphane. For these reasons, it is a good choice of vegetable to eat regularly to support immune system health.

Sweet potatoes are rich in beta carotene, a type of antioxidant that gives the skin of the potatoes its orange color.

Beta carotene is a source of vitamin A. It helps to make skin healthy and may even provide some protection against skin damage from ultraviolet (UV) rays.

Spinach may boost the immune system, as it contains many essential nutrients and antioxidants, including:

Vitamins C and E can help support the immune system.

Research also indicates that flavonoids may help to prevent the common cold in otherwise healthy people.

People use ginger in a variety of dishes and desserts, as well as in teas.

According to a review, ginger has anti-inflammatory and antioxidative properties and is likely to offer health benefits. However, more research is necessary to confirm whether or not it can effectively prevent illness.

Garlic is a common home remedy for the prevention of colds and other illness.

One review looked at whether taking garlic supplements containing allicin reduced the risk of getting a cold.

The group of participants taking a placebo had more than double the number of colds between them than those taking the garlic supplements. However, the researchers concluded that more research is necessary to determine whether or not garlic can help to prevent colds.

Green tea contains only a small amount of caffeine, so people can enjoy it as an alternative to black tea or coffee. Drinking it may also strengthen the immune system.

As with blueberries, green tea contains flavonoids, which may reduce the risk of a cold.

Kefir is a fermented drink that contains live cultures of bacteria that are beneficial for health.

Initial research suggests that drinking kefir may boost the immune system. According to a 2017 review, various studies have shown that regular consumption of kefir can help with:

The majority of the research that supports this was carried out on animals or in a laboratory. Researchers need to perform additional studies to understand how kefir may prevent disease in humans.

Sunflower seeds can make a tasty addition to salads or breakfast bowls. They are a rich source of vitamin E, an antioxidant.

In the same way as other antioxidants, vitamin E improves immune function. It does this by fighting off free radicals, which can damage cells.

Almonds are another excellent source of vitamin E. They also contain manganese, magnesium, and fiber.

A small handful or a quarter of a cup of almonds is a healthful snack that may benefit the immune system.

Oranges and kiwis are an excellent source of vitamin C, which is the vitamin that many people turn to when they feel a cold developing.

While scientists are still not sure exactly how it helps, vitamin C may reduce the duration of common cold symptoms and improve the function of the human immune system.

For people trying to avoid the sugar in fruit, red bell peppers are an excellent alternative source of vitamin C.

Stir-frying and roasting both preserve the nutrient content of red bell peppers better than steaming or boiling, according to a study on cooking methods.

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The powerful supplement that could enhance your immune response to bacteria and viruses – Express

September 4th, 2022 2:06 am

Clarissa said: Also called the queen of mushrooms and the mushroom of immortality, reishi has an abundance of health benefits and is associated with longevity. As the mushroom with one of the highest concentrations of beta-glucans, it has powerful immune-boosting and immune-modulating properties. It increases natural killer cell activity, helps to fight infections and displays anti-cancer effects. It is known to exert anti-inflammatory effects on the body and has been shown to positively impact the gut microbiome, further supporting healthy immunity. Reishi even displays natural anti-histamine activity, making it one of the top natural supplements for those dealing with hay fever.

Alongside its immune-supportive effects, reishi is considered one of the best supplements for stress, anxiety and sleep. Stress can deplete immunity, so reducing stress levels may also help to support your defences. DIRTEAs Reishi extract powder (29.99 from http://www.dirteaworld.com) is particularly rich in active components, highly bioavailable and stirs easily into hot water. I like to add a drop of honey to mine.

Chaga

Chaga is another functional mushroom with incredible health benefits.

Clarissa said: It has the highest antioxidant potential of all natural foods, with just one teaspoon of DIRTEAs Chaga extract powder (29.99 from http://www.dirteaworld.com) containing more antioxidants than 600 blueberries. These antioxidants dramatically reduce oxidative stress and systemic inflammation, which helps to support immune activity. It is also associated with anti-cancer benefits. Mixed into hot water it has a pleasant, earthy flavour, a little like coffee. It can also be added to other hot drinks and smoothies.

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Long COVID: How researchers are zeroing in on the self-targeted immune attacks that may lurk behind it – The Conversation Indonesia

September 4th, 2022 2:06 am

For almost three years, scientists have raced to understand the immune responses in patients who develop severe COVID-19, with an enormous effort aimed at defining where healthy immunity ends and destructive immunity begins.

In the early days of the COVID-19 pandemic, much attention focused on reports of harmful inflammation and so-called cytokine storms dangerous immune overreactions that can lead to tissue damage and death in patients with severe COVID-19. It wasnt long before researchers began to identify antibodies that target the patients own body rather than attacking SARS-CoV-2, the virus the causes COVID-19.

Those studies revealed that patients with severe COVID-19 share some of the key traits of chronic autoimmune diseases diseases in which the patients immune systems chronically attack their own tissues. Scientists have long suspected and sometimes even documented links between viral infection and chronic autoimmune diseases, but the research remains murky. However, the COVID-19 pandemic has offered an opportunity to better understand potential connections between these conditions.

As an immunologist and member of an interdisciplinary team of physicians and scientists investigating the intersection between COVID-19 and autoimmunity, I have been working to understand the origins of these untamed antibody responses and their long-term effects. Led by Ignacio Sanz, a specialist in investigating the immune dysfunctions that underlie autoimmune diseases like lupus, our group has long suspected that these misdirected immune responses may follow patients well after recovery and could even contribute to the debilitating set of symptoms commonly referred to as long COVID-19.

Our new study, published in the journal Nature, helps shed light on these questions. We now know that in patients with severe COVID-19, many of the developing antibodies responsible for neutralizing the viral threat are simultaneously targeting their own organs and tissues. We also show that self-directed antibodies can persist for months or even years in those suffering from long COVID-19.

As researchers like us continue to study COVID-19, our understanding of the link between antiviral immunity and chronic autoimmune disease is rapidly evolving.

Its easy to assume that your immune system is laser-focused on identifying and destroying foreign invaders, but that isnt the case at least under some circumstances. Your immune system, even in its healthy state, contains a contingent of cells that are fully capable of targeting and destroying your own cells and tissues.

To prevent self-destruction, the immune system relies on an intricate series of fail-safes that are collectively termed self-tolerance to identify and eliminate potentially traitorous immune cells. One of the most important steps in this process occurs as the immune system builds up its arsenal against a potential threat.

When your immune system first encounters a pathogen or even a perceived threat such as a vaccine that resembles a virus it rapidly recruits B cells that have the potential to become antibody-producers. Then, any of these naive B cell recruits naive being a technical term used in immunology that demonstrate an ability to competently attack the invader are put into a boot camp of sorts.

Here, the cells are trained to better recognize and combat the threat. The training period is intense and mistakes are not tolerated; B cells with any discernible potential for misdirected attacks against their host are killed. However, like any training process, this buildup and mobilization takes time typically a week or two.

So, what happens when the threat is more immediate when someone is quite literally fighting for their life in an intensive care unit?

Researchers now know that under the stress of severe viral infection with SARS-CoV-2, that training process collapses. Instead, it is replaced by an emergency response in which new recruits with little training are rushed into battle.

Friendly fire is the unfortunate result.

Our teams new work reveals that in the heat of battle with severe COVID-19, the same antibodies responsible for fighting the virus are uncomfortably prone to targeting a patients own tissue. Importantly, this effect seems mostly restricted to severe disease. We identified the cells that produce these rogue antibodies much less frequently in patients with mild forms of the illness whose immune responses were more measured.

So, does that mean that everyone who gets severe COVID-19 develops an autoimmune disorder?

Fortunately, no. By following patients after their infection has resolved, we have found that months later, most of the concerning indications of autoimmunity have subsided. And this makes sense. Though we are identifying this phenomenon in human COVID-19, researchers studying these emergency immune responses for more than a decade in mice have determined that they are mostly short-lived.

Mostly being the operative word.

Although most people fully recover from their run-in with the virus, up to 30% have not returned to normal even three months after recovery. This has created a group of patients who are experiencing what is known as post-acute sequelae of COVID-19, or PASC the technical terminology for long COVID-19.

With debilitating symptoms that can include the long-term loss of taste, smell or both, general fatigue, brain fog and a variety of other conditions, these patients have continued to suffer and are rightfully looking for answers.

An obvious question for researchers who are studying these patients is whether the same self-targeted antibodies that are emerging in severe COVID-19 are lingering in those who suffer from long COVID-19. They are. Our new study makes clear that newly developed self-antibodies can persist for months. Whats more, in work currently under development and not yet peer-reviewed, we find that these responses are not restricted to those recovering from severe illness, and are readily identifiable in a large subset of long COVID-19 patients who had recovered from more mild illness as well.

Just as it was in the race to better understand the causes of acute disease earlier in the pandemic, we researchers are now working to get a more complete understanding of the cells and antibodies directing this self-attack for months and years following the resolution of infection.

Are they directly contributing to the symptoms long COVID-19 sufferers are experiencing? If so, are there therapeutic interventions that could blunt or eliminate the threats they pose? Are long COVID-19 patients at increased risk for the development of true, chronic autoimmune diseases in the future? Or, is all of this just a red herring a temporary quirk of the immune system that will resolve on its own?

Only time and continued work in this critical area will tell.

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New research: Cancer-fighting viruses can boost body’s immune response – The Indian Express

September 4th, 2022 2:06 am

Can a virus help the body fight back against cancer and boost the immune system to tackle the disease better? A new study published in the journal Cancer Cell suggests that the bodys immune capacity against cancer to recognise and destroy cancer cells can be boosted by using oncolytic viruses. Oncolytic viruses (OVs) are viruses that selectively target and kill cancer cells while sparing normal ones. The study notes that these viruses also enhance the immune systems ability to recognise and terminate cancer cells.

Although long theorised, the research into oncolytic virotherapy picked up only in the 1960s. Of late, there have been several trials looking at different viruses for cancer treatment.

The latest study focused on the virus known as myxoma and it found that T-cells infected with myxoma virus can lead to a type of cancer cell death not previously observed.

The research claims to uncover an unexpected synergy between T-cells and MYXV (myxoma virus) to bolster solid tumor cell autosis that reinforces tumor clearance.

Autosis is a form of cell destruction that is useful against solid tumors, which are seen as treatment-resistant.

Myxoma can target and kill cancer cells directly, but using myxoma-equipped T-cells works well as cancerous cells in the vicinity of those targeted are also destroyed. This process is called bystander killing.

The study makes the case that immunotherapy combined with virotherapy holds potential to seek and destroy cold tumors that fly under the immune systems radar.

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Five Natural Immune-Boosting Treatments to Try This Flu Season – Boston magazine

September 4th, 2022 2:06 am

Guides

This cold and flu season, dont just douse yourself in hand sanitizer. Fight germs with local treatments designed to boost the bodys natural defenses.

Illustration by Jeannie Phan

For a Spin in an Infrared SaunaThe Indoor Oasis

From soaking up the sun on your favorite beach down on the Cape to perfecting the camel pose in your weekly hot yoga class, youre not afraid to break a sweat. Put your tolerance for heat to good use at the Indoor Oasis in Newton, where you can book 20- and 40-minute sessions in a private infrared sauna. Unlike a traditional sauna, which uses steam to warm the air, infrared models rely on heat lamps or light panels to raise your body temperaturepromising to ease joint pains, increase circulation, and (according to some studies) help you ward off the common cold in the process.

theindooroasis.com.

For IV TherapyVita Hydration + Wellness

Not one to panic at the sight of a needle? The trendy IV-powered services at this Worcester-based wellness center should suit you just fine. In particular, the teams Immunity drip is packed with vitamins B and C as well as the mineral zinc to help naturally strengthen your immune system and boost energy. Right arm or left?

vitahydrationandwellness.com.

For Red-Light TherapyRestore Hyper Wellness

Skin-care enthusiasts, take note: Red-light therapy isnt just known to strengthen the bodys disease-fighting resources. Some research suggests that the non-invasive treatmentwhich stimulates production of cell-repairing nitric oxide by harnessing the power of low-intensity LEDsmay combat wrinkles, scars, and sun damage, too. Give it a go at Restore Hyper Wellness. With locations in Newton and Hingham (and new spots on the way in Woburn and Dedham), the spas single-user red-light therapy rooms are prime spots for donning your sunglasses and basking in the scarlet glow.

restore.com.

For Salt TherapyScituate Salt Cave

We all know that filling our bellies with too much high-sodium food can wreak havoc on our kidneys and blood pressure. But spending time in the company of 30,000 pounds of Himalayan pink salt, which has anti-inflammatory properties? Thats another story. At this recently opened spot in Scituate, you can book 45-minute sessions in your choice of two salt caveseach designed to help you relax while you inhale the mineral-rich air (and rid your airways of any illness-causing intruders while youre at it).

scituatesaltcave.com.

For Lymphatic DrainageG2O Spa + Salon

Charged with producing infection-battling white blood cells, the lymphatic system is a critical component of your bodys immune response. Give it the attention it deserves with G2Os 60-minute body lymphatic drainage treatment, during which a technician moves a vacuum-like device over the back, legs, and abdomen to help alleviate any swelling or blockages in the system that may affect its performance, as well as reduce everyday annoyances like bloating and fatigue.

g2ospasalon.com.

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Study raises concerns about the effectiveness of the monkeypox vaccine – STAT

September 4th, 2022 2:06 am

A new study is raising concerns about the effectiveness of the monkeypox vaccine being used in the United States and other parts of the world.

The work, which has not yet been peer-reviewed, found that two doses of the vaccine induced relatively low levels of neutralizing antibodies against the monkeypox virus, and those antibodies had poor neutralizing capacity.

The researchers noted the so-called correlates of protection what is needed, in terms of immune system weaponry, to be protected against monkeypox are not known. Still, the evidence of low levels of neutralizing antibodies raises questions about how much protection is generated by two doses of the vaccine, marketed as Jynneos in the U.S. and made by the Danish manufacturer Bavarian Nordic.

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At this moment it is unclear what the relatively low [monkeypox virus] neutralizing titers mean for protection against disease and transmissibility, the researchers, from Erasmus Medical Center in Rotterdam, the Netherlands, wrote.

But one of the senior authors of the paper said what is clear is that people being administered this vaccine ought to be cautious about assuming they are protected against infection.

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The expectation is not that this will provide sterilizing immunity, said Marion Koopmans, who heads Erasmus department of viroscience, referring to the type of immunity that will block infection.

Koopmans added that controlling the outbreak will require a suite of transmission-reducing tools, including isolation of cases, tracing and quarantining of contacts, and vaccination of people who have been exposed to the virus or are at high risk of exposure.

Inger Damon, who heads the division of high-consequence pathogens and pathology at the Centers of Disease Control and Prevention, said that studying how much protection the vaccine offers is critical, especially given that many of the people contracting it may be becoming infected via exposure of mucus membranes to infectious lesions. Mucus membranes are more delicate than skin, potentially allowing a larger dose of virus to infect an exposed individual.

I think this is something that we have to very carefully follow, and we need to really be very forthright in helping the community who is at risk to understand what the limitations of our knowledge is, Damon told STAT earlier this week in an interview.

On Friday, she said Koopmans had shared the data in the study with the CDC before it was posted online.

Foundational to all of this will be to understand the progression of disease and the immune response to disease with the different routes of infection that we believe we are seeing, Damon said in an email. This is complicated, and will require concerted, coordinated, and collaborative efforts to find the right solutions to stop the spread of disease. Good health communications, and effective harm reduction messages are going to be integral.

The Erasmus study suggests, among other things, that a one-dose regimen seems to be inadequate to induce protection.

The second vaccination is important for reaching detectable antibody levels, as individuals in a single-shot regimen hardly developed antibody responses four and eight weeks after vaccination, the researchers wrote.

The study also casts a shadow over the recent decision by the U.S. government and others to stretch vaccine supplies by giving people one-fifth of a regular dose and to do so by intradermal (into the skin) rather than subcutaneous (under the skin) injection. Intradermal administration, which requires smaller doses to be protective, has been shown to be effective in other disease outbreaks with other types of vaccine.

The decision to use this dose-sparing approach which allows up to five people to be vaccinated with the amount of vaccine normally used for one was largely based on a small study that compared immune responses generated by two fractional doses given intradermally to two full doses given subcutaneously. They were deemed to be comparable.

But Koopmans and her colleagues saw another result in an earlier Erasmus study that tested fractional doses of a bird flu vaccine using the same vaccine backbone as the Bavarian Nordic product.

Jynneos uses a modified vaccinia virus called MVA, the same attenuated virus formerly used to vaccinate against the now-eradicated smallpox to teach the immune system to be on guard for monkeypox, a related virus.

The same MVA backbone was used in an experimental vaccine to protect against H5N1 bird flu. There, the two fractional doses generated lower amounts of antibodies than the full doses did, the researchers reported.

This same trial indicates that dose-sparing has a negative effect on the serological outcome of vaccination, they wrote.

It should be noted that in that trial, the fractional doses were administered by intramuscular injections, not intradermal. Koopmans said the group is planning to test whether intradermal vaccine administration would improve results, once it has been cleared to conduct the study.

Asked if she thought public health authorities should rethink giving fractional doses of monkeypox vaccine, she wrote: I think it requires testing.

So does Michael Osterholm, director of the University of Minnesotas Center for Infectious Diseases Research and Policy. Osterholm thought the move to fractional dosing was made too quickly, based on too little data.

I realize in a public health crisis, sometimes you have to make decisions with imperfect information, he said after reading the Erasmus study. But this is the kind of data that I think everyone needs to take a step back now and say: What does this mean for what were doing right now?

They dont have a lot of other tools, he acknowledged. But at the same time, if the tool youre using isnt adequate to do the job, then you have to consider that. Do we need to go back to full dose?

Osterholm and others expressed concern that people getting the vaccine will conclude they have a level of protection that they may not have.

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Returning to Football After COVID-19 Infection – Louisiana State University

September 4th, 2022 2:06 am

BATON ROUGE - A first-of-its-kind study conducted in collaboration with LSUs School of Kinesiology, LSU Athletics, Pennington Biomedical Research Center and Our Lady of the Lake researched how the immune system of elite student-athletes responded to the COVID-19 virus.

New collaborative study shows LSU Football players bounced back quickly from COVID-19 following the CDC's recommended amount of isolation time.

Photo: LSU Athletics

The football players who were diagnosed with COVID-19 were able to have their immune system back to its baseline after the CDC-recommended isolation. This is in stark contrast with older adults with comorbidities, who tend to be more at riskfor serious side effects and symptoms, and even death.

When COVID-19 really started moving out of control, we met with Neil Johannsen, an exercise physiologist at LSU, and the athletic trainers Derek Calvert and Jack Marucci, and we discussed what we could do to make sure our athletes remained healthy. We especially wanted to make sure that athletes were not at risk for secondary infections when they came back from isolation, said Guillaume Spielmann, associate professor in LSU's School of Kinesiology.

When the idea started for the research, we discussed why not turn something negative into a positive, and assist with the research to find some answers. If we can do things to understand the virus better, lets do it, said Jack Marucci, LSUs Director of Athletic Training. The student-athletes were willing to be a part of it.

During that time at the start of the COVID pandemic, the CDC had recommended 14 days of isolation.

There was a lot unknown during this time. We are looking at a population that are extremely close to each other during plays and during games. We wanted to make sure that since they are literally face-to-face with other players, that their salivary defenses, their oral defenses were pretty much intact and that that part of their immune system was not affected by the disease; that there were no long-lasting effects of the disease, Spielmann said.

Saliva samples were collected from 29 student-athletes in 2020, before a COVID vaccine. Fourteen were COVID positive and 15 had no history of infection. Of the 14, only six reported mild symptoms from the virus, the other eight were asymptomatic throughout the isolation period.

Salivary immunity is extremely important to ensure that people dont contract secondary infections, so when athletes are coming back we need to make sure they are as healthy as can be. We found that the isolation period was sufficient to restore the athletes salivary immunity to the level seen in non-infected players, Spielmann said.

These findings suggested the student-athletes could safely return to practice and play football without a risk of secondary infection; that their immune system wasnt at risk when playing the close contact sport.

I was worried a bit about long-haulers and other more significant outcomes like the concerns for the development of myocarditis. Engaging in athletic activities at an elite level can be stressful on the body and you would want to arm yourselves with the best scientific information to help understand potential outcomes. This data helped to validate some of these decisions that were made. Providing a safe environment for your student-athletes is paramount and this helped that process along, said Shelly Mullenix, LSU's Senior Associate Athletics Director for Health & Wellness.

For this study, three graduate students also participated in the research. Their research is now published in Scientific Reports.

This kind of access is unique in Division I sports. You typically dont have access to football players, so the fact that we have access is hugely instrumental as well, Spielmann said. LSU is a great place for this field.

I think this COVID research is something that we are really proud to be a part of and contribute to finding answers to such a devastating virus, Marucci said.

Spielmann, an immunologist, researches the impact of stress on the immune system of elite and tactical athletes, including astronauts and fire fighters.But this study isnt the first for Spielmann and LSU Athletics. They have worked together to study psychological and physiological health, along with performance measures in other student-athletes and sports teams.A new study will take a closer look at female athletes mental, physiological and immune resilience to stress. Funded by a grant from the Wu Tsai Foundation, this collaborative research led by Tiffany Stewart at Pennington Biomedical and Spielmann will include participation from 50 LSU female athletes.

These groups also work together as part of the healthcare partnership with Our Lady of the Lake. Our Lady of the Lake has committed $170 million over the next 10 years for academics- and athletics-focused initiatives. Dr. Catherine O'Neal, Chief Medical Office of Our Lady of the Lake said this partnership allows for increased collaboration and research between LSU and Our Lady of the Lake, as well as Pennington Biomedical Research Center.

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#1 Best Way to Boost Your Immunity Against BA.5 Eat This Not That – Eat This, Not That

September 4th, 2022 2:06 am

Nature has thrown at us many challenges throughout our existence. This time around it is a novel coronavirus that has led to a global pandemic. When facing an infectious disease, like COVID-19, how healthy and robust our immune system is plays a pivotal role in how our body can defend itself from infection. With COVID-19, we've seen how it's adapted and transformed to survive and bypass our immune defenses. Therefore, having a healthy immune system that can quickly adapt and respond to such a threat is important. The newest transformation of COVID is known as variant BA.5. This omicron subvariant has become the predominant strain in the US as of July 2022. Its mutations have made it possible for it to infect people who are vaccinated and/or have had a recent COVID infection.

The healthier we areboth mentally and physicallythe easier we can adapt and respond to threats in our surroundings. A person in good physical health is more likely to outrun someone who is trying to do them harm than someone who is unhealthy. Unfortunately, we cannot outrun a threat like COVID no matter how healthy we are, but we can take steps to help our bodies protect themselves against possible infection. It requires all of our mental and physical health when facing a virus like COVID. Physical health is not only about having lean healthy muscle mass, but also having an immune system that can face the ever-changing threat of a mutating virus.Jimmy Salas Rushford, MD is a Medical Director Protocol Architect of FiTBodyMD.

As research continues to advance human immunity, the importance of polysaccharides obtained from natural edible sources has gained significant traction. Natural foods like mushrooms and fruits are filled with polysaccharides. One of the key factors in building a robust and healthy immune system is by maintaining a diet filled with natural whole foods and/or incorporating daily supplements.

Polysaccharides found in some sea weeds have shown promise for antiviral properties. Another promising supplement is AHCC which is a cultured extract from the roots of a Japanese mushroom. AHCC has been shown by numerous human clinical studies to help the body's immune system recognize and fight pathogens such as viruses and bacteria.

If we want to be ready for health threats like COVID, we should prepare our body to recognize and have the resources to fight infection before it gains access to our body and then outsmart those pathogens in order to prevent future infection.

In addition to ensuring we're taking the right supplement(s) to boost immunity, there are a few more steps we can take to protect ourselves from infection. In my experience, I've learned that it is better to do a few things extremely well than many things poorly. By concentrating on a few key points and making consistent habits, we can ensure the greatest results.

We've heard time and again that sleep is not only important to our mental health but to our physical health as well. It plays a huge role in how our body can protect itself from disease/infection. The National Sleep Foundation advises that healthy adults need between 7 and 9 hours of sleep per night. Research has shown that sleep deficiency is linked to many chronic health problems. Thus, adequate sleep is a must.

Rely on trusted sources and not just a Google search. When seeking out information to protect your health, find trusted and reliable sources of information such as a medical practitioner or information backed by medical institutions, practitioners, or research. For example, when searching for dietary modifications and supplement recommendations, look for sources backed by human clinical data and reputable researchers and institutions.

Vitamin D is another example of a nutrient that has been shown to boost immunity. Vitamin D's effect goes far beyond just helping our body with calcium homeostasis and bone health. Vitamin D also regulates many other cellular functions in your body. Its anti-inflammatory, antioxidant and neuroprotective properties support immune health, muscle function and brain cell activity.6254a4d1642c605c54bf1cab17d50f1e

Eating whole foods and achieving daily physical activity are of upmost importance in maintaining good health. The pandemic has helped us realize that physical health is only a part of the puzzle when preparing our bodies to fight COVID and future infections. Although our immune system is one that has evolved over millennia and is extremely complex, it only takes a few basic healthy routines to keep it in tip top shape. Let's start by eating whole foods and vegetables, choosing vitamins and supplements backed by reputable clinical data, achieving consistent physical activity and reducing our stress.

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Non-Hodgkin’s lymphoma: What is the cancer that Jane Fonda announced she has? – FOX 29 Philadelphia

September 4th, 2022 2:06 am

Jane Fonda announced on Friday that she is suffering from non-Hodgkin's lymphoma a type of cancer that can start anywhere in the body where lymph tissue is located. (Getty Images)

Two-time Academy Award winnerJane Fonda announced on Instagram on Friday that she's been diagnosed with a treatable form ofnon-Hodgkins lymphoma.

"So, my dear friends, I have something personal I want to share," the 84-year-old wrote.

"Ive been diagnosed with non-Hodgkins lymphoma and have started chemo treatments," Fonda also said.

Cancer occurs when cells in the body grow out of control, according to the American Cancer Society. Almost any cell in the human body can become cancerous and spread to other parts of the body, the same source also explained.

JANE FONDA ANNOUNCES CANCER DIAGNOSIS: VERY TREATABLE

But what is non-Hodgkins lymphoma, exactly?

Non-Hodgkin's lymphoma (NHL) is a type of cancer that begins in theimmune system.

Jane Fonda (Photo by Tommaso Boddi/WireImage )

The immune system helpsfight infection, but sometimes a cancer can start in the white blood cells called lymphocytes and cause non-Hodgkins lymphoma, the society added.

It is a general term that is used for many types of lymphoma that occurs most often in adults, per the association.

Approximately 2% of men and women will be diagnosed with non-Hodgkin's lymphoma at some point during their lifetime, according to the National Cancer Institute's data from 2017-2019.

The institute estimates that 763,401 people were living with non-Hodgkin's lymphoma in the United States in 2019.

"Lymphomas can start anywhere in the body where lymph tissue is found," according to the American Cancer Societys website.

Jane Fonda (Photo by Caroline McCredie/Getty Images for Chopard)

These include lymph nodes, which are small, bean-shaped structures that are connected by a network of lymphatic vessels.

They're located throughout the body, such as inside the chest and abdomen and pelvis. Lymph tissue is also found in the spleen, bone marrow, thymus, tonsils and digestive tract.

Symptoms include fever, night sweats and weight loss as well as a swelling of lymph nodes in the neck, armpit or groin, according to the Mayo Clinic.

Patients may feel persistent fatigue, coughing, shortness of breath or chest pain.

"The lymph system is made up mainly of lymphocytes, a type of white blood cell that helps the body fight infections," according to the American Cancer Societys website.

There are two types of lymphocytes: B cells or T cells.

Actress Jane Fonda is seen outside "GMA" on July 19, 2022 in New York City. (Photo by Raymond Hall/GC Images)

B cells help the body fight germs by creating antibodies which in turn help the body neutralize them.

"There are several types of T cells. Some T cells destroy germs or abnormal cells in the body," according to the American Cancer Society.

"Other T cells help boost or slow the activity of other immune system cells."

Although lymphoma can start in either type of cell line, B-cell lymphomas are most common.

Lymphocytes usually go through a life cycle, in which old lymphocytes die and then the body replaces them.

"In non-Hodgkin's lymphoma, your lymphocytes don't die, and your body keeps creating new ones," according to the Mayo Clinics website.

Jane Fonda is shown posing for a publicity shot in 1967. She wrote on Instagram this week that she "will not allow cancer to keep me from doing all I can, using every tool in my toolbox." (Bettmann/Contributor via Getty Images)

"This oversupply of lymphocytes crowds into your lymph nodes, causing them to swell."

Lymphomas also can be categorized by how fast they grow and spread to other parts of the body.

Some are known as "indolent," which means they grow and spread slowly, so they might not need to be treated when first diagnosed.

"The most common type of indolent lymphoma in the United States is follicular lymphoma," according to the American Cancer Society.

Aggressive lymphomas, however,grow and spread rapidly, so treatment is often started immediately.

"The most common type of aggressive lymphoma in the United States is diffuse large B cell lymphoma," per the American Cancer Society. "Regardless of how quickly they grow, all non-Hodgkin lymphomas can spread to other parts of the lymph system if not treated."

Eventually, they can also spread to other parts of the body.

STUDY SUGGESTS ALCOHOL AND SMOKING CAUSE ALMOST HALF OF GLOBAL CANCER DEATHS

The overall five-year relative survival rate for NHL is 73.8%, per the National Cancer Institute's 2012 to 2018 data.

Fonda posted on Instagram that she feels lucky because she has a "very treatable cancer" with an 80% survivable rate, although she did not specify the exact type she has.

Some people are more at risk for NHL, including those who take medications to depress the immune system and patients with certain viral infections, such as HIV or the virus that can cause mononucleosis known as Epstein-Barr virus, according to the Mayo Clinic.

The cancer is also associated with the bacteria Helicobacter pylori, which causes stomach ulcers as well as certain chemicals that are used to kill insects and weeds, per Mayo Clinic.

NEW STUDY SUGGESTS YOU SHOULD STOP EATING ULTRA-PROCESSED FOODS

And people over the age of 60 are at higher risk, although anyone can get the cancer, per Mayo Clinic.

"Im doing chemo for six months and am handling the treatments quite well and, believe me, I will not let any of this interfere with my climate activism," said Fonda, who is also an advocate for environmental issues.

Actress Jane Fonda is arrested during the "Fire Drill Friday" Climate Change Protest on October 25, 2019 in Washington, DC . (Photo by John Lamparski/Getty Images)

She was inspired bySwedish environmental activistGreta Thunberg in 2019, she said, to become an advocate for the climate change, starting "Fire Drill Fridays" to raise awareness of environmental challenges, according to her website.

She was arrested multiple times that year after organizing protests on the climate crisis inWashington, D.C, according to The New York Times.

Fonda posted on Instagram that she"will not allow cancer to keep me from doing all I can, using every tool in my toolbox, and that very much includes continuing to build this Fire Drill Fridays community and finding new ways to use our collective strength to make change."

LINK: Get updates and more on this story at foxnews.com.

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Whatever happened to the Botswana scientist who identified omicron then caught it? – NPR

September 4th, 2022 2:06 am

Sikhulile Moyo, the laboratory director at the Botswana-Harvard AIDS Institute and a research associate with the Harvard T.H. Chan School of Public Health, headed the team that identified the omicron variant. Leabaneng Natasha Moyo hide caption

Sikhulile Moyo, the laboratory director at the Botswana-Harvard AIDS Institute and a research associate with the Harvard T.H. Chan School of Public Health, headed the team that identified the omicron variant.

Sikhulile Moyo led the team of scientists that first identified the omicron variant of COVID-19 in November 2021. It's gone on to dominate the world. Moyo directs the laboratory for the BotswanaHarvard AIDS Institute and is a research associate with the Harvard School of Public Health.

About This Series

Over the next week, we'll be looking back at some of our favorite Goats and Soda stories to see "whatever happened to ..."

Moyo was disturbed to see the world's reaction to the more transmissible variant. Other nations closed off travel and trade with southern African countries, including Botswana, even as they discovered the variant was already within their own borders. In fact, it was subsequently found that the variant was circulating in the Netherlands a week before the announcement from Africa.

"How do you reward the countries that alert you of a potential dangerous pathogen with travel bans? My country was put on a red list, and I didn't feel good about that," Moyo told NPR.

NPR touched base with Moyo to see what he's been working on and thinking about since this landmark discovery.

This interview has been edited for length and clarity.

You discovered omicron. Did omicron discover you?

I got COVID. Funnily enough, the omicron discoverer gets omicron.

I had three days of very serious symptoms of COVID, and I had to stay at home. So I would say mild to severe, but not too severe.

Then I had long COVID. I had almost three months of difficulty trying to recover my lung volume, my breathing. Walking, I was fatigued. All of a sudden, the COVID made my [blood] sugar worse, and I had to change my diabetes doses. I had to step up my meds, because it was no longer controlling [my diabetes] the way it was.

These are the complications that come with COVID, while people think COVID is gone.

Do you think the world has made any progress in learning not to cast blame?

There was a global awakening. Those events around the omicron discovery showed us the triumph of science but the failure of global health policy.

While we suffered, we were a catalyst to make people aware of the value of global public health that we cannot be inward-looking, because the virus knows no borders.

You see the response to monkeypox is different than the response to COVID. No one is blacklisting anyone from the monkeypox-endemic areas.

Has your work changed because of this discovery are you and your lab collaborating more with scientists around the world?

Yes! We have established collaborations with the Africa CDC. We've established what is called the Pathogen Genomics Initiative, a network of labs that are working together, and we have a lot of demand for training.

I was named one of the TIME magazine's 100 most influential people of 2022. That gives us a voice to share our experiences but also access to a lot of collaborations that I never thought I would have. That is really pushing us forward.

Have you made more ground-breaking omicron discoveries?

Earlier this year, around April, May, there was the discovery of BA.4 and BA.5, and we detected them in Botswana a few days after South Africa detected them. And these are the variants that have taken over the world. Some of the questions have been: What's happening in southern Africa that [the region] is seemingly detecting more variants?

What is unique about southern Africa, especially Botswana and South Africa, is the ability to detect these variants in near real-time because of the pathogen genomic sequencing that has been established [examining DNA to identify it or see if it's changing]. We think it's not that they are not circulating elsewhere, but it's just that maybe we are looking deeper.

We are always doing pathogen genomic sequencing. The most resourced in the world, in terms of sequencing, is of course the U.K. and the United States, and many parts of Europe. But I think the systematic, real-time, sampling and sequencing [in southern Africa] has been very, very useful.

How has southern Africa become so good at finding new variants and subvariants?

Southern Africa was the hotspot for HIV. We have passed through difficult times. I think we have taken this to our advantage to find solutions for ourselves. With funding from PEPFAR and from other international agencies, U.S. institutes, some donors southern Africa began to implement pathogen genomics focusing on HIV.

Some of us were involved in setting up population-based sequencing to understand the movement of viruses, to characterize transmission dynamics and that has spilled out to malaria, to TB. And we used those technologies to quickly adapt to SARS-CoV-2. That has been the strength of southern Africa.

We're even thinking beyond COVID. We are preparing ourselves to be able to adapt for pathogen discovery. If a [new] outbreak happens, we should be able to quickly check within 24 to 36 hours what it is.

New subvariants seem to be getting better at reinfecting people. What does that mean moving forward?

BA.4 and BA.5 are masters in terms of evading the fury of the immune system. The subvariants were able to elicit an immune response, but magnitudes lower than what we saw before.

As the immunity wanes down, that's where my worry is: How far can we hold on with the current levels of immunity?

The vaccine immunity still provides some protection against severe disease. We know that you may get infected, but you may not get hospitalized with BA.4 and BA.5.

It may get a little bit rough. Many people are spending days at home and [developing] long COVID afterward.

What do you think needs to happen next?

Research, training and development cost a lot of money, but as cases go down, people forget that we need to make sure these systems are sustained. That's one of the challenges: Are we going to be able to sustain some of this innovation that we have developed over a very difficult time of our lives during COVID?

The virus is still finding some pathways to escape immune pressure.

And there's always a possibility of a more virulent variant?

The variant that is going to really dominate is a variant that would have a massive escape to antibody neutralization or to vaccine neutralization. Chances are low of that happening. But omicron taught us that anything can happen.

So we need to be very careful. We need to continue with surveillance, so that if we notice anything, we should be able to go back and say: Do we need to change the way we are doing things?

While I support loosening and going back to our lives [when cases are low], I also feel that's when you need to be more vigilant. When you see signs of wildfire starting, then you can try and put it out.

Melody Schreiber (@m_scribe) is a journalist and the editor of What We Didn't Expect: Personal Stories About Premature Birth.

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Whatever happened to the Botswana scientist who identified omicron then caught it? - NPR

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8 Health Benefits of Cabbage – Health Essentials

September 4th, 2022 2:06 am

Cabbage may not be the most attractive vegetable, but its full of nutritional goodness that can keep you feeling strong and healthy. From boosting your immune system to improving your digestion (sometimes with embarrassing results), cabbage and its health benefits deserve a place at your table.

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This common leafy green vegetable comes in a range of colors, shapes and sizes that you can use for soups, salads, sandwiches and more. Eat it raw or stir-fried to get the most benefit. Find it fermented in gut-healthy foods like sauerkraut and kimchi or chopped into coleslaw for a quick fix.

Cabbage is good for you. Its one of those foods that tastes better than it looks, and it has even more nutritional value than people expect, says registered dietitian Julia Zumpano, RD, LD. Plus, its versatile, affordable and easy to find.

Zumpano explores the benefits of eating cabbage and how it can boost your health.

Many people recognize cabbage for its bounty of fiber, vitamins and minerals. One cup of chopped, raw green cabbage is only 22 calories and delivers:

Cabbage is also a potassium-rich food, which can help lower high blood pressure, says Zumpano. The more we learn about cabbage, the better it promises to be.

Research shows leafy green vegetables, in general, are good for you, but we need more studies to understand how cabbage specifically affects your body. Zumpano says many people believe the nutritional value of cabbage means it can have any of the following benefits.

Some of cabbages health benefits are due to anthocyanins, which are naturally occurring antioxidants. Anthocyanins not only add color to your fruits (think blueberries) and vegetables, but may also reduce inflammation.

Chronic inflammation (long-term swelling) is associated with heart disease, cancer, rheumatoid arthritis and many other medical conditions. In animal studies, anthocyanins have been shown to help control inflammation.

We need more research, but one small human study showed that those who ate the most cruciferous vegetables had much lower inflammation levels than those who ate the least.

Vitamin C, also known as ascorbic acid, does a lot of work for your body. It helps make collagen and boosts your immune system. It also helps your body absorb iron from plant-based foods.

Packed with phytosterols (plant sterols) and insoluble fiber, cabbage can help keep your digestive system healthy and bowel movements regular. It fuels the good bacteria in your gut that protects your immune system and produces essential nutrients. Thats especially true when you eat fermented cabbage in kimchi or sauerkraut.

Cabbage can help you stay regular, says Zumpano. It can also help support safe and healthy weight loss.

Fiber is a nondigestible or absorbed carbohydrate, so it adds bulk to meals and takes space in your belly causing you to fill full faster and longer without ingesting carbs that youre absorbing.

The anthocyanins found in cabbage help with more than inflammation. Research suggests they add to the health benefits of cabbage by reducing your risk of heart disease. Scientists have found 36 different kinds of anthocyanins in cabbage, which could make it an excellent option for cardiovascular health.

Potassium is a mineral and electrolyte that helps your body control blood pressure. One cup of red cabbage can deliver a healthy amount of potassium as much as 6% of your recommended daily value. This could help lower your blood pressure, reducing your risk for heart disease.

Too much bad cholesterol, or LDL cholesterol, can cause heart problems if it builds up in your arteries. Cabbage contains two substances fiber and phytosterols (plant sterols) that compete with cholesterol to be absorbed by your digestive system. They wind up reducing your bad cholesterol levels and improving your health.

Vitamin K is essential to your well-being. Without it, youd be at risk of developing bone conditions like osteoporosis, and your blood wouldnt be able to clot properly. Enter cabbage, a great source of vitamin K. One cup provides 85% of the recommended daily value.

Vitamin K helps keep our bones strong and our blood clotting well, says Zumpano. Cabbage can give you that boost you need to make sure your levels are adequate, and your body stays protected against illness and disease. And you dont even need to eat that much cabbage to get great health benefits.

Early animal studies suggest that leafy green vegetables like cabbage have phytochemicals that may help protect against cancer. They contain antioxidants and plant compounds like glucosinolates. These sulfur-containing chemicals break down during the digestive process into substances that may help fight cancer cells and clear them from your body.

Excited to add more cabbage to your diet? Just be careful not to go overboard. To maximize its health benefits, increase your cabbage intake slowly and allow your body to adjust. Also, stay hydrated to reduce constipation, which can cause excess gas.

Cabbage might not be the best choice for a romantic night out since eating too much can cause diarrhea, flatulence or abdominal discomfort. It also contains substances that can interfere with medications like blood thinners or cause hypothyroidism, a condition where your thyroid doesnt create enough thyroid hormone and causes your metabolism to slow down.

In most cases, you can avoid side effects by eating cabbage as part of a healthy diet. Talk to your healthcare provider if you experience symptoms or have any concerns.

Cabbage belongs to the Brassica oleracea species of vegetable, along with broccoli, cauliflower, kale and Brussels sprouts. The most common type is green cabbage. But hundreds of other varieties exist in red, white and purple hues, with a range of textures and sizes.

Some forms of cabbage have subtle, delicate flavors, while others pack a peppery punch. Nutrition from cabbage comes from types like:

Cabbage is a versatile vegetable thats affordable, widely available and easy to prepare. Keep it whole and unwashed in the refrigerator until youre ready to eat it, recommends Zumpano. And when youre ready, it wont take long to find easy cabbage recipes that add a (healthy) zing to your diet and color to your plate.

Link:
8 Health Benefits of Cabbage - Health Essentials

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Identification of cervical squamous cell carcinoma feature genes and construction of a prognostic model based on immune-related features – BMC Women’s…

September 4th, 2022 2:06 am

Construction of CSCC gene co-expression network and screening of immune-related module

Firstly, the unqualified samples and genes in the TCGA-CESC dataset were removed based on hierarchical clustering, and 253 samples and 4,553 genes were reserved for WGCNA to build the gene co-expression network. =3 (scale-free R2=0.92) was selected as an optimal soft threshold to construct a scale-free network, and finally 15 gene modules were obtained (Table 1). Then, the correlation between the feature genes of each module and four immune-related features (Stromal, Immune, Estimate Scores, and Tumor Purity) was calculated. It was found that brown module was significantly associated with immune status, presenting Immune Score (r=0.88, P=1e-84), Stromal Score (r=0.46, P=1e-14), ESTIMATE Score (r=0.79, P=2e-55) and Tumor Purity (r=-0.82, P=1e-63) (Fig.1). Therefore, the brown module was included in the subsequent study.

The immune-related modules based on WGCNA

Enrichment analysis was performed on 330 genes in the brown module to reveal relevant biological function. The results showed that the genes were largely enriched in the functions and pathways related to immune signal activation and immunomodulation, such as response to interferon-gamma, positive regulation of immune response, adaptive immune response, regulation of cytokine production, myeloid leukocyte activation, regulation of response to biotic stimulus, T cell activation, inflammatory response, negative regulation of immune system process, Type II interferon signaling (IFNG), Lysosome, response to tumor necrosis factor, regulation of viral process, etc. (Fig.2AC).

Enrichment analysis of genes in the brown module. A P value distribution of the top 20 enriched pathways and biological processes in the brown module; B The P value clustering network of genes in the brown module, with the redder the node color is, the more significant P value is; C Network analysis of enriched terms of genes in the brown module. Different node colors indicate different functional or pathway clusters that nodes belong to

The brown module was known to be highly correlated with cellular immunity. In the present study, consensus clustering was conducted on tumor samples based on the expression patterns of genes in the brown module to identify different immune subtypes. Since the grouping was suboptimal when using K=3 as the clustering value, we selected K=3 to divide the samples into three groups (Fig.3AC). The samples obtained were named as cluster A (38 cases), cluster B (132 cases) and cluster C (84 cases). To better understand the immune patterns of the three subgroups, we explored the expression of genes in the brown module in the three subgroups (Fig.3D). The results showed that most of the genes in the brown module were down-regulated in the cluster B subgroup, while most of the genes were up-regulated in the other two subgroups, and the overall level of gene up-regulation in the cluster A subgroup was more evident than that in the cluster C subgroup. Therefore, we assumed that the three subgroups might represent different immune patterns, which was further verified by subsequent analysis.

Consensus clustering analysis of gene expression pattern in the brown module. A Cumulative distribution function (CDF) of consensus clustering when K=2~9; B Relative change of AUC of CDF curve when K=2~9; C Tracking plot results of consensus clustering when K=3; D Heat map of gene expression in different subtypes in the brown module

GSVA was done to explore the biological behaviors of the three tumor immune subtypes. Cluster A enriched in the pathways associated with immune deficiency and disease development, such as PRIMARY IMMUNODEFICIENCY, TYPE I DIABETES MELLITUS, INTESTINAL IMMUNE NETWORK FOR IGA PRODUCTION, ALLOGRAFT REJECTION, etc. Cluster B was enriched in pathways related to immunosuppressive biological processes. Cluster C was mainly enriched in pathways associated with cell adhesion, cytokine and cytotoxic activation pathways, including CYTOSOLIC DNA SENSING PATHWAY, CELL ADHESION MOLECULES CAMS, HEMATOPOIETIC CELL LINEAGE, CYTOKINE NATURAL KILLER CELL MEDIATED CYTOTOXICITY, CYTOKINE RECEPTOR INTERACTION, etc. (Fig.4). These results indicated that the three subtypes have different enrichments in biological pathways, and it was speculated that these subtypes may have different biological behaviors.

Heat maps of GSVA among different subtypes. Red: up-regulated pathways; green: down-regulated pathways

The analysis of cell infiltration in TME showed that there were differences in the contents of B cells, T cells, NK cells, monocytes and macrophages among the three subtypes (Fig.5A). ssGSEA results showed significant differences in CD8 T cells, CD4 T cells, Treg cells, macrophage MD, M1 and dendritic cell contents among the three subtypes (Fig.5B). To further verify the classification, ESTIMATE was used to calculate Stromal Score, ESTIMATE Score, Immune Score, and Tumor Purity based on mRNA data. These indicators were used to distinguish the high, low and medium immune groups. Compared with low immune cell infiltration group, the high immune cell infiltration group had lower Tumor Purity and higher Stromal Score, Immune Score and ESTIMATE Score. Therefore, Cluster A was defined as high immune group, Cluster B as low immune group, and Cluster C as medium immune group (Fig.5C). High immune group was significantly positively correlated with ESTIMATE Score, Immune Score and Stromal Score, but negatively correlated with Tumor Purity (Fig.5D). human leukocyte antigen (HLA) is an expression product of human major compatibility complex and is also a highly polymorphic allogeneic antigen [23]. In the present study, the correlation between immune cell infiltration and HLA family proteins in different subgroups was analyzed to verify the rationality of typing. The results demonstrated that the expression of HLA family gene was significantly downregulated in high immune group compared with in low immune group (Fig.5E). The above results indicated that there were differences in the immune cell infiltration, immune-related scores and HLA family protein expression among subtypes, which also provided support for the rationality of the typing.

Analysis of immune cell infiltration and immune-related indices in different tumor subtypes. A CIBERSORT analysis of differences in immune cell composition among different subtypes; B Differences in the abundance of each immune infiltrating cell among different subtypes; C Heat map of immune cell typing; D Violin plot of the differential analysis of Tumor Purity, ESTIMATE Score, Immune Score and Stromal Score among the three subtypes; E Differences in the expression of HLA family gene among different subtypes

Subsequently, a prognostic model was constructed based on the genes in the brown module. In the TCGA-CESC dataset, the samples with survival time less than 30days were excluded. Then, for the 330 genes in the brown module, a univariate regression analysis was conducted, and 46 genes significantly associated with prognosis were obtained with P<0.01 as the screening condition (Additional file 1: Table S1). Next, lasso and multivariate regression analyses were done on these 46 genes, and 8 feature genes were obtained finally, including ISCU, MSMO1, GCH1, EEFSEC, SPP1, RHOG, LSP1 and TCN2 (Fig.6A, Additional file 2: Table S2). HRs of MSMO1 and SPP1 were higher than 1, which were risk factors for CSCC prognosis, while HRs of ISCU, GCH1, EEFSEC, RHOG, LSP1 and TCN2 were lower than 1, which could be protective factors for CSCC prognosis. The risk scores were calculated based on these 8 feature genes, and the samples were classified into high-risk and low-risk groups. According to the heat map, the expression levels of GCH1, EEFSEC, SPP1, RHOG, LSP1 and TCN2 were decreased overall with the increase of risk score (Fig.6B). Based on the risk score distribution and survival time of the high/low-risk group samples, we found that the number of patients dying increased and the survival time decreased with the increase of risk score (Fig.6CD). Survival curves of the high/low-risk groups also demonstrated that patients in the low-risk group had a higher survival rate (Fig.6E). ROC curve demonstrated the reliability of the risk assessment model in predicting 1-, 3- and 5- year survival rates of samples, with AUC values of 0.8, 0.77 and 0.75 respectively (Fig.6F). Also, the expression statuses of the 8 genes were examined using qRT-PCR, whose results showed that ISCU was downregulated, while MSMO1, GCH1, EEFSEC were upregulated in the tumor tissues (Fig.6G). In addition, this study assessed the correlation between the prognostic model and immune cell infiltration. As a result, the risk score was significantly negatively correlated with 6 immune cells, including B_ cell, CD8_ T cell, CD4_ T cell, neutrophil, dendritic cell and macrophage (Fig.7AF). To verify whether the risk score could be considered as an independent prognostic indicator, univariate and multivariate Cox regressions were introduced based on risk score and clinical features of the samples. As observed in Fig.7GH, risk score could independently serve as prognostic factor. In conclusion, we constructed an 8-feature gene risk assessment model to predict the prognosis of patients with CSCC and proved the favorable predictive ability of this model and revealed the association between the model and cellular immunity.

Construction and assessment of a prognostic model for CSCC. A Forest map of the 8-prognostic feature genes, *P<0.05; B Heatmap of expression of the 8 prognostic feature genes in the high- and low-risk groups; C Risk score distribution of CSCC patients, with green representing the low-risk group and red representing the high-risk group; D Scatter plot of survival status of CSCC patients, with green and red dots representing survival and death, respectively; E KaplanMeier survival curve of the high- and low-risk groups; F ROC curves of the prognostic model predicting 1-, 3-, and 5-year overall survival of patients.; G qRT-PCR was used to measure the mRNA expressions of the feature genes

Correlation between risk score and infiltration degree of 6 immune cells. A Correlation between risk score and B_cell infiltration; B Correlation between risk score and CD4 T cell infiltration; C Correlation between risk score and CD8 T cell infiltration; D Correlation between risk score and dendritic cell infiltration; E Correlation between risk score and macrophage infiltration; F Correlation between risk score and neutrophil infiltration. GH Univariate and multivariate Cox regression for risk score and the clinical features

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Identification of cervical squamous cell carcinoma feature genes and construction of a prognostic model based on immune-related features - BMC Women's...

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