Category Archives: Molecular Medicine

Newswise A multi-disciplinary, One Health approach to cancer research is necessary to guide society in reduction of toxic substances, as well as regulation of chemical impacts on the environment and public health, according to an editorial published recently in Issue II of Annals of Research in Oncology.

This medical-scientific journal is published by Editor in Chief Professor Antonio Giordano, M.D., Ph.D., Director and Founder of Sbarro Institute for Cancer Research and Molecular Medicine, and the Sbarro Health Research Organization (SHRO), at Temple University. The editorial by Prof. Philip Landrigan, Director of the Global Public Health Programme, highlights the relationship between environmental issues and childhood cancer cases, which have been growing rapidly over the past 50 years.

Landrigan's editorial moves towards the new scientific paradigm known as One Health, by which is meant the indissoluble intertwining of three factors: human health, animal health and environmental health as interconnected and dependent on each other.

In particular, Landrigan emphasises the link between environment and cancer in paediatric subjects, underlining the lack of scientific models that consider the use of chemicals with undesirable effects on human health, which are not carefully studied, and the consequent increase in oncological cases in paediatrics. In fact, there is evidence that environmental exposure, in particular to manufactured chemicals, are a major cause of childhood cancer. The National Cancer Institute currently directs about 1% of its funding towards research into environmental causes of paediatric cancers.

Landrigan's hope is to identify new scientific models based on epidemiological and toxicological studies to address the rising incidence of childhood cancer, a major challenge for society and the cancer and public health communities.

Original post:
One Health Approach Is Necessary to Address Rising Environmental Causes of Childhood Cancers - Newswise

LAUSANNE, Switzerland & SAN FRANCISCO--(BUSINESS WIRE)--Amazentis, a spin-off of the Swiss Federal Institute of Technology (EPFL) pioneering scientific breakthroughs in cellular health and nutrition, announced today that the peer-reviewed journal Aging Cell published new pre-clinical results showing the joint health benefits of gut microbiome postbiotic Urolithin A (UA). This is the first time a compound has been shown to improve mitochondrial health in an experimental model of osteoarthritis (OA).

This study showed that treatment with Amazentis proprietary Urolithin A, Mitopure, significantly improved mitochondrial health in human cartilage cells taken from both healthy and OA knee joints. And it showed that supplementation with Mitopure for eight weeks protected against osteoarthritis disease progression in an experimental model.

These findings highlight Mitopures benefits for joint and mitochondrial health. Mitopure works by supporting the cells ability to renew their powerplants, the mitochondria, during the aging process. This change is associated with age-related problems in various tissues, including osteoarthritis.

Previous research has shown Mitopure can improve mitochondrial health and muscle function in both older and middle-aged human populations. This new paper extends these benefits to cells in key joints such as the knee. Osteoarthritis is the most common age-related joint disorder, characterized by degradation of cartilage and other tissues, severe pain, and impaired mobility.

There are currently no effective solutions to treat osteoarthritis, a condition that is painful and limits the mobility of hundreds of millions of older people around the world. We tested Urolithin A in preclinical models of osteoarthritis and showed it has potential to both reduce inflammation and improve mitochondrial health, suggesting it may be a promising solution to support joint health and quality of life during aging, says Martin Lotz MD, lead author on the paper and Professor of Molecular Medicine at Scripps Research in California, USA.

This study is important and exciting as it shows, for the first time, that Urolithin A can increase mitochondrial health in living joint tissue, says Davide DAmico, first author on the paper and R&D Group Leader with Amazentis. It highlights the important role of mitophagy in maintaining healthy functioning joints throughout life.

In this study, Mitopure showed two key beneficial effects on cartilage cells from both healthy donors and OA patients:

The second part of the study focused on the effect of supplementing Mitopure for 2 months on an experimental pre-clinical model of osteoarthritis. This model mimics the same symptoms experienced by people suffering from osteoarthritis, i.e. progressive cartilage damage, increased pain and inflammation.

"It was great to collaborate with Scripps Research to expand the body of evidence on the health applications of Urolithin A into joint health. Its exciting to see a compound and mechanism of action that is benefiting both muscle and joints. We remain committed to delivering products that are clinically proven to have a meaningful impact on peoples health says Chris Rinsch, CEO and co-founder of Amazentis.

The new results are significant because they add to growing evidence of the benefits of Mitopure on age-related conditions. Recent studies showed that Mitopure can improve mitochondrial health and counteract age-related muscle function decline in both healthy elderly and middle-aged overweight subjects. Together, the latest research supports a combined beneficial action of Urolithin A in both muscle and joints.

Doi: 10.1111/acel.13662

About AmazentisAmazentis is an innovative life sciences company employing todays leading research and clinical science to develop the next generation of products targeting mitochondrial health for advanced nutrition. Amazentis has previously published its research on Mitopure Urolithin A in top peer reviewed scientific journals including Nature Medicine (doi:10.1038/nm.4132), Nature Metabolism (doi: 10.1038/s42255-019-0073-4), JAMA Network Open (doi:10.1001/jamanetworkopen.2021.44279), Cell Reports Medicine (Doi: 10.1016/j.xcrm.2022.100633) and European Journal of Clinical Nutrition (https://doi.org/10.1038/s41430-021-00950-1). The company has a global strategic partnership with Nestl Health Science to expand the health applications of Mitopure linked to mitochondrial and cellular health. For more information on Amazentis, please visit http://www.amazentis.com.

About MitopureMitopure is a highly pure form of Urolithin A; a bioactive dietary metabolite that is produced by gut bacteria after eating certain foods, such as the pomegranate, though it is difficult for most people to get enough of this specialized nutrient from food alone. Mitopure has been shown to improve mitochondrial function by stimulating mitophagy, a process by which aging and damaged mitochondria are cleared from the cell, making way for healthy mitochondria to grow. Mitopure has been favorably reviewed by the U.S. Food and Drug Administration (FDA) and deemed safe following a GRAS (generally recognized as safe) filing. Mitopure has been extensively evaluated pre-clinically and clinically to support its use in humans for nutritional supplementation. For more information, please visit http://www.mitopure.com.

About TimelineTimeline is brought to you by the inventors of Mitopure. This novel, science-first nutrition brand was developed by Amazentis on the belief that uncompromising research can unlock a new class of clinically validated nutritional products to optimize cellular health. For more information, please visit http://www.timelinenutrition.com.

Related Linkshttps://www.amazentis.com

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New Study shows Urolithin A (Mitopure) Improves Mitochondrial Health, Reduces Joint Cartilage Damage and Alleviates Pain in Osteoarthritis - Business...

STOCKHOLM, July 7, 2022 /PRNewswire/ --The primary endpoints of safety and tolerability were met in the open-label investigator-initiated Phase II clinical trial GADinLADA, in which the diabetes vaccine Diamydwas administered directly into the lymph node of 14 patients aged 30 to 70 years with the autoimmune form of diabetes called LADA (Latent Autoimmune Diabetes in Adults). Analyses also showed a positive immunological response to the treatment and the clinical course appears promising with all individuals remaining insulin-independent 12 months after treatment.

"These results are very encouraging and the next step is together with collaborators and authorities evaluate the regulatory requirements to get the diabetes vaccine Diamyd approved as a disease-modifying therapy in individuals diagnosed with LADA", says Ulf Hannelius, CEO of Diamyd Medical.

All patients in the trial were followed for twelve months after their first injection. The topline results showed that the safety was good with no treatment-related severe adverse events. The treatment was well tolerated by the trial participants, all of whom completed the study with no drop-outs. The immunological analyses showed a similar response to the treatment as has been shown in previous trials in individuals with recent-onset type 1 diabetes, with a clear GAD-specific immune response evident in both circulating antibodies and cell-based reactions.

The clinical course appears positive with all 14 individuals remaining insulin-independent after 12 months of follow-up. The endogenous insulin production, measured as mixed-meal stimulated C-peptide, declined on average only 10% over 12 months.

"The GADinLADA trial has been successful, and treatment with three intralymphatic injections of Diamyd has been well received by the LADA patients," says PhD Ingrid K Hals, Sponsor's representative of the trial. "We will present the results from this trial at the upcoming international Europen Association for the Study of Diabetes (EASD) conference in Stockholm in September and we look forward to evaluating together with Diamyd Medical the next steps to make this important treatment available for individuals diagnosed with LADA."

Of the 14 LADA patients included in the trial, half carry the HLA haplotype DR3-DQ2 that is associated with a positive clinical response to Diamyd treatment in individuals recently diagnosed with type 1 diabetes. For the 7 individuals carrying HLA DR3-DQ2, endogenous insulin production (stimulated C-peptide) decreased on average by 8 % over the 12 month study period, while in the 7 individuals not carrying HLA DR3-DQ2, it declined by 13 %. GAD-stimulated cell proliferation showed a decrease in proliferation between 5 and 12 months for the HLA-DR3-DQ2 group while a comparable decrease was not observed for the group negative for HLA DR3-DQ2, reflecting the patterns seen in recent-onset type 1 diabetes.

The results will be presented at the upcoming EASD conference to be held in Stockholm on September 19-23, 2022. The accepted abstract is entitled "Early effects of treatment with intralymphatic administration of rhGAD65 in LADA appear similar to those observed in type 1 diabetes", and will be presented as an oral abstract on September 20, 2022, as part of the session "OP 10 Beta cells: protecting what is precious".

About the GADinLADA trialThe main aim of the trial was to evaluate the safety of three intralymphatic injections of Diamyd in patients with LADA (Latent Autoimmune Diabetes in Adults). The patients were recruited in Norway at the Norwegian University of Science and Technology (NTNU), Dept. of Clinical and Molecular Medicine, in Trondheim, in collaboration with St. Olavs Hospital, University Hospital in Trondheim, and in Sweden at the Center for Diabetes, Akademiskt specialistcentrum, an academic specialist unit run in collaboration between Stockholm County's healthcare area, Karolinska Institutet and Karolinska University Hospital. The patients included in the trial were between 30 and 70 years old, diagnosed with LADA within the last 18 months and were not yet on insulin therapy. The Sponsor of the trial has been the Norwegian University of Science and Technology with Ingrid K Hals, PhD, as Sponsor's representative. Diamyd Medical has contributed with study drugs, expertise and some financial support for immunological analyses and determination of HLA haplotypes.

About LADALatent Autoimmune Diabetes in Adults represents close to 10% of patients diagnosed with type 2 diabetes. LADA is characterized by an ongoing autoimmune destruction of the insulin-producing beta cells, a process similar to that of type 1 diabetes, but slower. Although research categorizes LADA as autoimmune diabetes, the disease is still in most cases treated according to the guidelines for type 2 diabetes. LADA patients are usually not insulin dependent at diagnosis, but for most patients, insulin therapy is required within a few years of diagnosis.

About Diamyd MedicalDiamyd Medical develops precision medicine therapies for Type 1 Diabetes. The diabetes vaccine Diamyd is an antigen-specific immunotherapy for the preservation of endogenous insulin production. Significant results have been shown in a large genetically predefined patient group in a large-scale meta-analysis as well as in the Company's European Phase IIb trial DIAGNODE-2, where the diabetes vaccine was administered directly into a lymph node in children and young adults with recently diagnosed type 1 diabetes. DIAGNODE-3, a confirmatory Phase III trial is on-going. A vaccine manufacturing facility is being set up in Ume for the manufacture of recombinant GAD65, the active ingredient in the therapeutic diabetes vaccine Diamyd. Diamyd Medical also develops the GABA-based investigational drug Remygen as a therapy for regeneration of endogenous insulin production and to improve hormonal response to hypoglycaemia. An investigator-initiated Remygen trial in individuals living with type 1 diabetes for more than five years is ongoing at Uppsala University Hospital. Diamyd Medical is one of the major shareholders in the stem cell company NextCell Pharma AB as well as in the artificial intelligence company MainlyAI AB.

Diamyd Medical's B-share is traded on Nasdaq First North Growth Market under the ticker DMYD B. FNCA Sweden AB is the Company's Certified Adviser; phone: +46 8-528 00 399, e-mail: [emailprotected]

For further information, please contact:Ulf Hannelius, President and CEOPhone: +46 736 35 42 41E-mail: [emailprotected]

This information was brought to you by Cision http://news.cision.com

https://news.cision.com/diamyd-medical-ab/r/promising-topline-results-for-intralymphatic-diamyd--in-patients-with-lada,c3598517

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Promising topline results for intralymphatic Diamyd in patients with LADA - PR Newswire

Wilmington, Delaware, United States, Transparency Market Research Inc.: Transparency Market Research (TMR) has published a new report titled, Blood Group Typing Market - Global Industry Analysis, Size, Share, Growth, Trends, and Forecast, 2018 to 2026. According to the report, the global blood group typing market was valued at US$ 1,500.0 Mn in 2017 and is projected to reach US$ 3,556.0 Mn by 2026, expanding at a high CAGR of 10.3% from 2018 to 2026. Increase in blood transfusion rate across the world is anticipated to fuel the global blood group typing market during the forecast period.

North America and Europe are expected to dominate the global market during the forecast period. The market in these regions is primarily driven by the increase in government initiatives and a highly structured health care industry. The market in Europe is projected to expand at a high growth rate of 10.1% from 2018 to 2026. The market in Asia Pacific is expected to expand at a rapid pace during the forecast period. The market in Asia Pacific is anticipated to expand at a high CAGR of 10.7% from 2018 to 2026. The blood group typing market in Latin America is likely to expand at a moderate growth rate during the forecast period.

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Increase in preference for PCR-based technique to boost market

In terms of technique, the PCR-based segment is projected to account for a dominant share of the global blood group typing market during the forecast period. The segment is anticipated to expand at a CAGR of 10.6% from 2018 to 2026. Dominance of the segment is attributed to the increasing preference for PCR-based technique because of rising incidence of major chronic diseases such as aplastic anemia, sickle cell anemia, leukemia, and traumatic injuries, resulting increase in blood transfusion rate in countries across the globe.

Additionally, increasing the usage of PCR-based technique in the detection of rare type of blood group is a key factor that is expected to fuel the segment. The microarray-based segment held a major share of the market, following the PCR-based segment, due to increasing awareness about this technique. Assay-based technique and massively parallel technique segments accounted for around 30.0% share of the global blood group typing market, in terms of revenue, in 2017.

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Consumables segment dominates the market

The report offers detailed segmentation of the global blood group typing market based on product, technique, test, and end-user. In terms of product, the market has been classified into instrument (automated, semi-automated, and manual), consumables (reagent, test kits, antisera, others), and services. The consumables segment is estimated to hold a leading share of the global market during the forecast period. Higher share held by the segment is attributed to the constant development of new molecular diagnostic test kits and reagents, which reduces the turnaround time required for results, and increase in number of blood transfusions, globally, every year are key factors fueling the consumables segment.

Antibody screening test & ABO blood test: Top two test employed for blood group typing

In terms of test, the antibody screening test segment is projected to hold a dominant share of global blood group typing market by the end of the forecast period. The segment is likely to expand at a CAGR more than 10.0% between 2018 and 2026. Major factor responsible for the dominance of this segment is the rise in incidence of transfusion transmitted infections (TTIs), especially in lower-middle income and low-income countries. The ABO blood test segment held a major share, following the antibody screening test, due to increasing utilization of this test for blood grouping. HLA typing and antigen segments accounted for around 30.0% share of the global blood group typing market, in terms of revenue, in 2017.

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Hospital segment to expand at significant CAGR

Based on end-user, the hospital segment accounted for a leading share of the global blood group typing market in 2017. It is projected to gain market share by the end of 2026. The segment is anticipated to expand at a CAGR of 10% during the forecast period due to the large patient population undergoing surgical procedures in hospitals requiring blood transfusion, and increasing emphasis on blood grouping and patient testing. Clinical laboratories was a prominent segment, following the hospital segment, of the market in 2017. This is due to the rise in number of clinical laboratories for blood grouping and screening. This, in turn, is likely to drive the clinical laboratories segment during the forecast period.

North America to be highly lucrative market for blood group typing market

The blood group typing market in North America is driven by high percentage of active and voluntary blood donors in the U.S. and Canada, increasing number of blood transfusions per year in the region, and various blood transfusion policies being implemented regarding safety and testing of blood for infectious diseases. This, in turn, is further boosting the demand for blood grouping instruments and kits and reagents in North America. Moreover, a large number of players in the U.S. are focusing on R&D in order to introduce new products. The U.S. is an early adopter of innovative products, as most pharmaceutical products are first launched in the country. This is likely to boost the market in the country in the near future.

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Trend of strategic alliance with local companies to strengthen distribution network and expand geographic presence

The global blood group typing market is fragmented, owing to the presence of several small- and large-scale companies. However, the market is dominated by a few major players with strong global presence. The report provides profiles of leading players operating in the global blood group typing market. Key players in the market include Grifols, S. A., Bio-Rad Laboratories, Inc., Merck KGaA, Ortho Clinical Diagnostics, QUOTIENT LIMITED, BAG Health Care GmbH, Immucor, Inc., Beckman Coulter, Inc. (Danaher Corporation), Agena Bioscience, Inc., Rapid Labs Ltd, and Novacyt Group.

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Transparency Market Research, a global market research company registered at Wilmington, Delaware, United States, provides custom research and consulting services. Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insights for thousands of decision makers. Our experienced team of Analysts, Researchers, and Consultants use proprietary data sources and various tools & techniques to gather and analyze information.

Our data repository is continuously updated and revised by a team of research experts, so that it always reflects the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in developing distinctive data sets and research material for business reports.

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Blood Group Typing Market: Increase in Blood Transfusion Rate Across the World to Drive the Market - BioSpace

Photo of Dr. Daniel Goldberg courtesy of Washington University

Dr. Daniel Goldberg, a professor of molecular microbiology at Washington University School of Medicine in St. Louis, recently received one of the highest honors bestowed in the science community: He was elected to the National Academy of Sciences, a nonprofit society of distinguished scholars to whose ranks their peers add scientists for outstanding research contributions.

Goldberg, the David M. and Paula L. Kipnis Distinguished Professor in the schools Division of Infectious Diseases, is internationally known for his work in advancing drug development for malaria treatments. By studying the basic biology of malaria parasites, he identified a group of proteins called plasmepsins that play a key role in the parasites ability to live inside red blood cells. He also identified several compounds that inhibit these plasmepsins and is exploring whether they can be developed as drugs.

What excites me most about my work is the scientific odyssey that I get to undertake with each of the really talented young people in the lab, Goldberg says. Sharing in their discoveries, as well as their scientific and personal development, is the greatest privilege of the job.

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In addition to identifying new targets for antimalarial drug development, Goldberg and his team found a toxin that the malaria parasite puts out into the patients bloodstream to cause leaky blood vessels, which are a hallmark of severe malaria. We have figured out how this molecule works, which gives us a clear idea of how to treat these terrible malaria complications, he says. Malaria is a parasitic infection that kills over 600,000 people a year, mostly children in Africa. We desperately need new treatments.

Goldberg has served in many roles at the university, including as a past co-director of the Division of Infectious Diseases, as director of the medical scientist training program and as a member of the executive council of the Division of Biology and Biomedical Sciences, according to a university press release. He is a fellow of the American Association for the Advancement of Science, the American Society of Clinical Investigation and the American Association of Physicians. His many honors include the American Society for Biochemistry and Molecular Biologys prestigious C.C. and Alice Wang Award in Molecular Parasitology. He also was a Howard Hughes Medical Institute Investigator for 20 years.

Goldberg is one of 120 newly elected U.S. members of the National Academy of Sciences and the only Washington University faculty member elected to the academy this year. Im pleased that my scientific colleagues regard my work highly, he says. It gives Washington University more recognition as a great place to do scientific research.

Washington University School of Medicine, 660 S. Euclid Ave., St. Louis, medicine.wustl.edu

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Professor at Washington University School of Medicine in St. Louis Elected to National Academy of Sciences - Ladue News

Wilmington, Delaware, United States, Transparency Market Research Inc.: Eye-related disorders are expanding at an accelerated pace across the globe. One of the most common disorders of the eyes is dry eye disease. The growing geriatric population and the increasing screen time among individuals have resulted in the rising cases of dry eye diseases. According to numerous studies, the incidence of dry eye diseases is between the ranges of 8 percent to 34 percent. Hence, these factors have influenced the growth structure of the dry eye disease market considerably and will continue to influence during the forecast period of 2017-2025.

When an individual suffers from dry eye disease, his/her eyes do not produce enough tears. Dry eye also occurs when one is not able to maintain a normal layer of tears for coating the eyes. The common symptoms of dry eye disease are redness, stringy mucus, blurry vision, pain, difficulty reading, or not able to sit before the computer for long hours, etc. Dry eye disease is of two types: aqueous deficiency dry eye disease and evaporative dry eye disease.

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The prominent risk factors for eye diseases are diabetes, refractive surgeries, aging, consumption of certain medications, etc. Anti-inflammatory drugs, cyclosporine, artificial tears, lifitegrast, secretagogue, punctal plugs, and others are some vital treatment types for eye diseases.

The players indulge in research and development activities for expanding the growth landscape of the dry eye disease market. The players invest in these activities to find new treatments for dry eye diseases. These activities help in strengthening the revenue cycle of the global market, eventually increasing the growth rate. Mergers, acquisitions, joint ventures, and partnerships also form an important part of the dry eye disease market growth structure. These collaborations assure expansion of the treatment types in other regions and significantly impact the growth trajectory.

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According to the TMR experts, the market for dry eye disease is prognosticated to expand at 4.5 percent CAGR during the forecast period of 2017-2025. In the context of valuation, the plasma protein therapeutics market is estimated to reach a valuation of US$ 7,780 mn by 2025 and was valued at US$ 5045.2 mn in 2016.

Anti-Inflammatory Drugs to Reign Supreme in Terms of Demand

The use of anti-inflammatory drugs for treating dry eye diseases has increased exponentially over the years. Research activities revolving around anti-inflammatory drugs are increasing extensively, ultimately leading to an increase in the development of new drugs. These factors will influence the growth of the dry eye disease market to a considerable extent. The anti-inflammatory drugs segment is expected to dominate in terms of revenue and demand, whereas the artificial tears segment may emerge as the second-largest growth-contributing segment.

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Growing Awareness about Various Treatment Types to Increase Growth Prospects Considerably

Government and non-government initiatives are encouraging many individuals to diagnose and get treated for dry eye diseases. This factor will have a great impact on the growth of the dry eye disease market. Further, many companies in the dry eye disease market promote their products through effective strategies, ultimately contributing to the growth trajectory.

Accelerated FDA Approvals to Boost Growth of North Americas Dry Eye Disease Market

The approvals for new dry eye disease treatment drugs at a rapid pace will bring immense growth prospects for the dry eye disease market in North America. The Food and Drug Administration (FDA) is trying to speed up the approval process to provide good and effective dry eye disease treatment options to the citizens. Hence, this factor will help North Americas dry eye disease market to gain a larger growth share.

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Some well-entrenched players in the dry eye disease market are Sun Pharmaceutical Industries Ltd., Valeant Pharmaceuticals International, Inc., Otsuka Pharmaceutical Co., Ltd., TRB Chemedica International SA, Novartis AG, Johnson & Johnson, and Sentiss Pharma Pvt. Ltd.

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About Us

Transparency Market Research, a global market research company registered at Wilmington, Delaware, United States, provides custom research and business consulting services. Our exclusive blend of quantitative forecasting and trends analysis provides forward-looking insights for thousands of decision makers. Our experienced team of Analysts, Researchers, and Consultants use proprietary data sources and various tools & techniques to gather and analyze information.

Our data repository is continuously updated and revised by a team of research experts, so that it always reflects the latest trends and information. With a broad research and analysis capability, Transparency Market Research employs rigorous primary and secondary research techniques in developing distinctive data sets and research material for business reports.

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Dry Eye Disease Market: Increasing Awareness and the Booming Geriatric Population to Accelerate the Market Growth - BioSpace

image:For innate immune system activation against HIV-1, Scripps Research scientists have found that the protein PQBP1s recognition of incoming HIV-1 particles (depicted in red) is required for cGAS activation, a production of cGAMP (depicted in green), in human dendritic cells. Nuclei (Dapi) are depicted in blue. view more

Credit: Scripps Research

LA JOLLA, CA Human immunodeficiency virus 1, more commonly known as HIV-1, is known for its uncanny ability to evade the immune system. Scientists at Scripps Research and collaborators have now uncovered how our innate immune system the bodys first line of quick defense in attacking foreign invaders detects HIV-1, even when the virus is present in very small amounts.

The findings, published on July 8, 2022, in Molecular Cell, reveal the two-step molecular strategy that jolts the innate immune response into action when exposed to HIV-1. This discovery could impact drug development for HIV treatments and vaccines, as well as shape our understanding of how the innate immune response is implicated in other areas including neurodegenerative disorders such as Alzheimers.

This research delineates how the immune system can recognize a very cryptic virus, and then activate the downstream cascade that leads to immunological activation, says Sumit Chanda, PhD, professor in the Department of Immunology and Microbiology. From a therapeutic potential perspective, these findings open up new avenues for vaccines and adjuvants that mimic the immune response and offer additional solutions for preventing HIV infection.

The innate immune system is activated before the adaptive immune system, which is the bodys secondary line of defense that involves more specialized functions, such as generating antibodies. One of the innate immune systems primary responsibilities is recognizing between self (our own proteins and genetic material) and foreign elements (such as viruses or other pathogens). Cyclic GMP-AMP synthase (cGAS) is a key signaling protein in the innate immune system that senses DNA floating in a cell. If cGAS does detect a foreign presence, it activates a molecular pathway to fight off the invader.

However, because HIV-1 is an RNA virus, it produces very little DNA so little, in fact, that scientists have not understood how cGAS and the innate immune system are able to detect it and distinguish it from our own DNA.

Scripps Research scientists discovered that the innate immune system requires a two-step security check for it to activate against HIV-1. The first step involves an essential protein polyglutamine binding protein 1 (PQBP1) recognizing the HIV-1 outer shell as soon as it enters the cell and before it can replicate. PQBP1 then coats and decorates the virus, acting as an alert signal to summon cGAS. Once the viral shell begins to disassemble, cGAS activates additional immune-related pathways against the virus.

The researchers were initially surprised to find that two steps are required for innate immune activation against HIV-1, as most other DNA-encoding viruses only activate cGAS in one step. This is a similar concept to technologies that use two-factor authentication, such as requiring users to enter a password and then respond to a confirmation email.

This two-part mechanism also opens the door to vaccination approaches that can exploit the immune cascade that is initiated before the virus can start to replicate in the host cell, after PQBP1 has decorated the molecule.

While the adaptive immune system has been a main focus for HIV research and vaccine development, our discoveries clearly show the critical role the innate immune response plays in detecting the virus, says Sunnie Yoh, PhD, first author of the study and senior staff scientist in Chandas lab. In modulating the narrow window in this two-step process after PQBP1 has decorated the viral capsid, and before the virus is able to insert itself into the host genome and replicate there is the potential to develop novel adjuvanted vaccine strategies against HIV-1.

By shedding light on the workings of the innate immune system, these findings also illuminate how our bodies respond to other autoimmune or neurodegenerative inflammatory diseases. For example, PQBP1 has been shown to interact with tau the protein that becomes dysregulated in Alzheimers disease and activate the same inflammatory cGAS pathway. The researchers will continue to investigate how the innate immune system is involved in disease onset and progression, as well as how it distinguishes between self and foreign cells.

In addition to Yoh and Chanda, authors of the study, Recognition of HIV-1 Capsid Licenses Innate Immune Response to Viral Infection, include Na Rae Ahn and Heather Curry of Scripps Research; Joao I. Mamede of Northwestern University and Rush University Medical Center; Gianguido C. Cianci, Lacy M. Simons, Judd F. Hultquist and Thomas J. Hope of Northwestern University; Derrick Lau, Andrew Tuckwell and Till Bocking of the University ofNew South Wales; Maria T Sanchez-Aparicio and Adolfo Garcia-Sastre of the Icahn School of Medicine at Mount Sinai; Joshua Temple and Yong Xiong of Yale University; Nina V. Fuchs and Renate Konig of Paul-Ehrlich-Institute; Stephanie Gambut of Rush University Medical Center; Laura Riva of Calibr; and Xin Yin of the Harbin Veterinary Research Institute.

Funding was provided by NIAID of the National Institutes of Health, the Gilead Sciences Research Scholars Program in HIV and the German Research Foundation.

About Scripps Research

Scripps Research is an independent, nonprofit biomedical institute ranked the most influential in the world for its impact on innovation by Nature Index. We are advancing human health through profound discoveries that address pressing medical concerns around the globe. Our drug discovery and development division, Calibr, works hand-in-hand with scientists across disciplines to bring new medicines to patients as quickly and efficiently as possible, while teams at Scripps Research Translational Institute harness genomics, digital medicine and cutting-edge informatics to understand individual health and render more effective healthcare. Scripps Research also trains the next generation of leading scientists at our Skaggs Graduate School, consistently named among the top 10 US programs for chemistry and biological sciences. Learn more atwww.scripps.edu.

Recognition of HIV-1 Capsid Licenses Innate Immune Response to Viral Infection

8-Jul-2022

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Immune system uses two-step verification to defend against HIV - EurekAlert

When she was in her 30s, Molly Cassidy was handed a death sentence. Traditional treatments failed to fight the aggressive head and neck cancer that was running rampant through her body. Doctors were out of options, until a clinical trial at the University of Arizona Health Sciences offered a glimmer of hope and, eventually, a second chance at life thanks to immunotherapy.

Immunotherapy is a treatment that uses a person's own immune system to fight cancer, while molecular therapies use drugs and other substances to target specific molecules involved in disease progression. In Cassidys case, she received a personalized cancer vaccine in combination with an immunotherapy drug that helps the immune system fight certain kinds of cancer, and it worked. A year after the UArizona Cancer Center clinical trial ended, there were no traces of cancer left in her body.

Researchers and physician-scientists are increasingly using precision medicine to develop new cell- and gene-based therapeutical options for diseases, building on the idea that the most effective defense against health issues is the bodys natural immune system. At UArizona Health Sciences, the Center for Advanced Molecular and Immunological Therapies, or CAMI, is being developed to advance knowledge of the immunology of cancers, infectious diseases and autoimmune conditions to develop novel strategies for the diagnosis, prevention and treatment of diseases.

Immunotherapy is one of the most promising approaches to cancer treatment, as it has the potential to sidestep the effects of therapies that can compromise patients long-term health and wellness. But cancer isnt the only target researchers, including bioengineer Michael Kuhns, PhD, have in their sights.

Bioengineers solve fundamental problems with technologies that can have many applications, said Dr. Kuhns, associate professor in the UArizona College of Medicine Tucson and member of the BIO5 Institute. If you can make something run more efficiently in certain circumstances for example, make T cells in the immune system more effective at combating a particular disease then the only limit to immunotherapy is your imagination.

Dr. Kuhns research in the Department of Immunobiology focuses on engineering chimeric antigen receptors, or CARs, a relatively new type of gene therapy. He built a biomimetic five-module chimeric antigen receptor, or 5MCAR, to direct killer T cells to target and destroy autoimmune T cells. When tested in a non-obese diabetic mouse model, the 5MCAR T cells recognized and destroyed pathogenic T cells, effectively preventing Type 1 diabetes.

The Center for Advanced Molecular and Immunological Therapies will focus on developing precision therapies that stimulate or suppress the immune system to fight diseases including cancers, infectious diseases and autoimmune conditions.

This technology has clear implications for autoimmune disease, but also for cancer, said Dr. Kuhns, who serves on the 21-member CAMI Advisory Committee. This technology emerged from basic science, is taking hold in the laboratory and is showing promise to go to the clinic. This is a prime example of what we can do.

CAMI will build on UArizona Health Sciences expertise in basic science, translational medicine and investigator-initiated clinical trials to advance immunotherapies research in four areas: cancer, infectious diseases, autoimmune diseases and real-time immune system monitoring.

Other examples of potential research include identifying biomarkers for response to immunotherapy that may help determine the precise drugs to fight specific cancers in individual patients, understanding individual immune responses to autoimmune diseases such as lupus, rheumatoid arthritis or Crohns disease, and creating ways to analyze immune health at the cellular level to identify how individuals might respond to a disease and to predict their health outcomes.

CAMI will serve as the anchor for an innovation district that aims to differentiate Phoenix from other emerging life sciences hubs, establishing the Phoenix Bioscience Core as a center of cell and gene therapy research, startup activity and corporate engagement. Its location is expected to facilitate strong connections with partners such as Arizona State University, Northern Arizona University, the Mayo Clinic and the Translational Genomics Research Institute, among others.

We expect CAMI to be nothing short of a national biomedical research hub, said Michael D. Dake, MD, senior vice president for UArizona Health Sciences. CAMI will be a beacon for people who are involved in this type of research to work, collaborate and engage on the Phoenix Bioscience Core.

The research will take place in connected buildings that are being designed to include laboratories to support translational research, clinical research space and startup incubator space to create a synergistic environment for commercialization opportunities. Student education will be prioritized in learning spaces dedicated to academic programs that will allow CAMI faculty and researchers to mentor and train the next generation of scientists.

There is not a field with more explosive growth than immunotherapy. There is rapid growth in research investment and increased formation of academic and industry partnerships around the world, Dr. Dake said said during a Tomorrow is Here Lecture Series presentation in Phoenix. My hopes are that CAMI is going to provide opportunities to accelerate the development and delivery of revolutionary treatments for the management of cancer, autoimmune and infectious diseases.

We are going to see diversification of drug classes and different types of combination therapies, delivery mechanisms and monitoring, he added. Going forward, I think were going to see a wide array of therapies that are going to be vastly different than any past generations ever had. Suffice it to say, in the future, pills and syringes are going to be obsolete.

Read more:
CAMI Set to Transform Immunotherapy Field Through Research - University of Arizona

* WHO provides technical support to the study on investigating seroprevalence of SARS-CoV-2 and dengue infections in Sri Lankan childrenFri, Jul 8, 2022, 12:23 pm SL Time, ColomboPage News Desk, Sri Lanka.

July 08, Colombo: Sri Lanka too experienced a rapid rise in number of cases and deaths, with the community spread of the Delta variant of the SARS-CoV -2 virus. However, deaths were predominantly seen among adults, with children rarely developing severe disease, as observed in other countries.

Sri Lanka experienced two massive COVID-19 outbreaks due to the Alpha and Delta variants of the SARS-CoV -2 virus, resulting in a large number of individuals being infected in the community. It was estimated that surveillance of SARS-CoV-2 with the Real-time polymerase chain reaction (RT-PCR) testing alone may underestimate the true prevalence of the disease by tenfold. Therefore, conducting a seroprevalence study remained an option for Sri Lanka to determine prevalence of SARS CoV-2 specific antibodies due to infection or vaccines in the country.

Seroprevalence studies help understand the true extent of an outbreak and provide valuable insights in to efforts that help project the trend of future outbreaks, and their transmission dynamics. However, in Sri Lanka, a majority of infections was reported in adults, most of whom experienced more severe and symptomatic infections. On the other hand, true infection rates among children in the country were not clearly known. One of the reasons for this could be limited PCR testing in children, largely because they do not show symptoms following infection with SARS-CoV-2 virus. Also, infection rates could be very different across districts, based on the intensity of transmission reported in different geographical regions.

Considering the above, the Allergy Immunology and Cell Biology Unit, Department of Immunology and Molecular Medicine, University of Sri Jayewardenepura and the Ministry of Health supported by WHO Country Office for Sri Lanka planned a study on seroprevalence of SARS-CoV-2 infections and dengue infections in Sri Lankan children.

In order to submit the study protocol to WHOs Ethical Review Committee, a joint review of study protocols was undertaken by the Unity trial desk of WHO Headquarters, the SEA Regional Office and the WHO country office for Sri Lanka. After revising the study protocol based on WHO recommendations, investigators submitted the finalized protocol to the Regional Review Committee.

The proposed study will help Sri Lanka determine the proportion of children who have been infected with COVID-19 and also with dengue, by studying the presence of antibodies to these viruses in children of different age groups. Additionally, it will determine genetic associations that predispose children to severe disease of dengue. Further, the study will provide information that will help understand how COVID-19 and dengue have spread geographically in the Sri Lankan population.

The seroprevalence in this study will be determined by biological assays, which are both qualitative and quantitative (ELISA, Luminex). The patient data will be collected on clinical features, clinical disease severity and complications.

The findings of this investigation will be used to inform public health response to COVID-19. Specifically, it can provide estimates of otherwise unrecognized SARS-CoV-2 infection in the population, as well as likely susceptibility of the population to further epidemic peaks. The findings may also supplement other supportive evidence used to inform decision-making about vaccine prioritization for target groups, based on demonstrated susceptibility by age groups.

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Sri Lanka : WHO provides technical support to the study on investigating seroprevalence of SARS-CoV-2 and dengue infections in Sri Lankan children -...

Summary: Targeting the GAT3 protein in the thalamus could help block and prevent long-term damage following brain injury.

Source: Gladstone Institute

For days, and even years, after someone suffers a stroke or traumatic brain injury, they have an increased risk of developing epilepsy.

Now, researchers at Gladstone Institutes discovered that star-shaped cells called astrocytes in the thalamus play a key role in making mice with brain injuries susceptible to seizures.

The team also analyzed human post-mortem brain tissue and showed that the same cells identified in mice might be altered in the thalamus of people affected by brain injury and stroke.

The findings,published in the journalScience Translational Medicine,suggest that targeting a protein in these cells could prevent the long-term damage that follows brain injury.

In the aftermath of brain injuries, the thalamus has been relatively understudied compared to other brain regions, saysJeanne Paz, PhD,an associate investigator at Gladstone and senior author of the new study. Im hoping this is just the beginning of many new lines of research about how important this region is in determining how we can help the brain be resilient to consequences of injuries.

A Cascade of Inflammation Deep in the Brain

At the time of a stroke or traumatic brain injury, many cells at the site of the injury die almost immediately. Inflammatory cells and molecules begin to gather, cleaning up the dead cells and molecular debris. In the thalamus, an area deep in the center of the brain that may be far from the site of injury, cells called astrocytes become activated, leading to a cascade of inflammatory changes.

Previous studies from the teamhave shown, in rodent models, that activation of astrocytes in the thalamus is a common consequence of brain injury. However, astrocytes also play key roles that support neurons, including controlling their connections and providing them with nutrients.

In this study, the scientists wanted to determine whether the activation of astrocytes in the thalamus helps the brain recover, leads to additional damage, or has both positive and negative effects.

Astrocytes are so important to the brain that you cant just get rid of them to treat disease, says Frances Cho, a graduate student at Gladstone and UC San Francisco (UCSF), and the first author of the new study. We needed to determine whether we could separate the damaging actions of activated astrocytes from their protective actions.

Focus on the Thalamus

Paz, Cho, and their collaborators hypothesized that activated thalamic astrocytes might play a role in some of the longer-term symptoms of brain injuryincluding an increased risk of seizures and sleep problems. So, rather than study mice with brain injuries, the team initially tested the consequences of activating thalamic astrocytes in otherwise healthy animals.

They found that just activating thalamic astrocytes was enough to cause altered patterns of brain activity similar to those seen after injury, and made the mice susceptible to seizures.

When the researchers then analyzed the molecular properties of the activated astrocytes, in collaboration with the team ofAnna Molofsky, MD, PhD,at UCSF, they discovered that these cells lost a protein called GAT3, which is responsible for regulating the levels of a specific inhibitory neurotransmitter molecule.

As a result, the neighboring neurons were exposed to too much of the neurotransmitter, which resulted in neuronal hyperexcitability and susceptibility to seizures.

We wondered, if the loss of GAT3 in thalamic astrocytes caused neuronal dysfunction, could boosting the level of this protein solve the problem and restore the neurons function? says Paz, who is also an associate professor at UCSF.

To answer this question, the team collaborated withBaljit S. Khakh, PhD,and his group at UCLA who had developed a tool to increase GAT3 specifically in astrocytes. Remarkably, increasing levels of GAT3 specifically in thalamic astrocytes was enough to prevent neuronal hyperexcitability and increased seizure risk caused by activated astrocytes.

The team next tested whether the results held true in mice with brain injuries. Increasing levels of GAT3 in the thalamic astrocytes of these mice also reduced the risk of seizure and the rate of mortality.

These activated astrocytes are quite different in many ways than astrocytes that are not activated, so it was surprising we could pinpoint a single molecular change that we could target to prevent the consequences of brain injury, says Cho.

A Potential Therapeutic

Samples of human thalamus are rarely collected during post-mortem brain biopsies. But, in collaboration withEleonora Aronica, MD, PhD,and her group at the University of Amsterdam, the researchers were able to obtain a small number of post-mortem thalamus samplesthree from individuals with no known brain injuries, three from people who had had a stroke, and four from people with traumatic brain injury.

The post-mortem brains with stroke and traumatic brain injury seemed to have lower levels of GAT3 in their thalamic astrocytes, just as we had seen in the mouse model, says Cho.

We hope that with increased attention to the thalamus, it will become more routine to collect thalamus samples from post-mortem biopsies in the future.

The researchers hope to continue collecting longer-term data on both mice and humans to study the time course of astrocyte activation in the thalamus after brain injury.

Since these changes to the thalamus occur after the initial brain injury, there is a window of time in which clinicians might be able to intervene to stop or reverse themand prevent the increased risk of developing epilepsy, says Paz.

Other authors are Yuliya Voskobiynyk, Allison Morningstar, Bryan Higashikubo, and Agnieszka Ciesielska of Gladstone; Ilia Vainchtein and Francisco Aparicio of UCSF; Diede Broekaart, Jasper Anink, Erwin van Vliet and Eleonora Aronica of University of Amsterdam; and Xinzhu Yu of UCLA.

Funding: The work was supported by funding from the National Institute of Neurological Disorders and Stroke (F31 NS111819, R01 NS096369, R01 R01NS121287, R00 NS078118, R35 NS111583), the National Institute of Mental Health (DP1 MH104069, DP2 MH116507, R01 MH119349), the National Cancer Institute (P30 CA082103), the National Science Foundation (1144247), a UCSF Discovery Fellowship, the Department of Defense (EP150038, EP190020), a Gladstone Institutes Animal Facility grant (RR18928), Pew Charitable Trusts, an EU Seventh Framework Programme EPITARGET grant (602102), an EU Horizon 2020 Research and Innovation Programme Marie Sklodowska-Curie grant (722053), and the Dutch Epilepsy Foundation (project 16-05).

Author: Julie LangelierSource: Gladstone InstitutesContact: Julie Langelier Gladstone Institutes Image: The image is in the public domain

Original Research: Open access.Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents by Jeanne Paz et al. Science Translational Medicine

Abstract

Enhancing GAT-3 in thalamic astrocytes promotes resilience to brain injury in rodents

Inflammatory processes induced by brain injury are important for recovery; however, when uncontrolled, inflammation can be deleterious, likely explaining why most anti-inflammatory treatments have failed to improve neurological outcomes after brain injury in clinical trials. In the thalamus, chronic activation of glial cells, a proxy of inflammation, has been suggested as an indicator of increased seizure risk and cognitive deficits that develop after cortical injury.

Furthermore, lesions in the thalamus, more than other brain regions, have been reported in patients with viral infections associated with neurological deficits, such as SARS-CoV-2. However, the extent to which thalamic inflammation is a driver or by-product of neurological deficits remains unknown.

Here, we found that thalamic inflammation in mice was sufficient to phenocopy the cellular and circuit hyperexcitability, enhanced seizure risk, and disruptions in cortical rhythms that develop after cortical injury.

In our model, down-regulation of the GABA transporter GAT-3 in thalamic astrocytes mediated this neurological dysfunction. In addition, GAT-3 was decreased in regions of thalamic reactive astrocytes in mouse models of cortical injury.

Enhancing GAT-3 in thalamic astrocytes prevented seizure risk, restored cortical states, and was protective against severe chemoconvulsant-induced seizures and mortality in a mouse model of traumatic brain injury, emphasizing the potential of therapeutically targeting this pathway.

Together, our results identified a potential therapeutic target for reducing negative outcomes after brain injury.

Read more from the original source:
Pathway Deep in the Brain Makes It Resilient After Injury - Neuroscience News