Category Archives: Molecular Medicine

It was the juice that tipped him off. At lunch, caro de A.T. Pires found the flavor of his grape juice muted, flattened into just water with sugar. There was no grape goodness. I stopped eating lunch and went to the bathroom to try to smell the toothpaste and shampoo, says Pires, an ear, nose and throat specialist at Hospital IPO in Curitiba, Brazil. I realized then that I couldnt smell anything.

Pires was about three days into COVID-19 symptoms when his sense of smell vanished, an absence that left a mark on his days. On a trip to the beach two months later, he couldnt smell the sea. This was always a smell that brought me good memories and sensations, Pires says. The fact that I didnt feel it made me realize how many things in my day werent as fun as before. Smell can connect to our emotions like no other sense can.

As SARS-CoV-2, the virus responsible for COVID-19, ripped across the globe, it stole the sense of smell away from millions of people, leaving them with a condition called anosmia. Early in the pandemic, when Pires juice turned to water, that olfactory theft became one of the quickest ways to signal a COVID-19 infection. With time, most people who lost smell recover the sense. Pires, for one, has slowly regained a large part of his sense of smell. But thats not the case for everyone.

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About 5.6 percent of people with postCOVID-19 smell loss (or the closely related taste loss) are still not able to smell or taste normally six months later, a recent analysis of 18 studies suggests. The number, reported in the July 30 British Medical Journal, seems small. But when considering the estimated 550 million cases and counting of COVID-19 around the world, it adds up.

Scientists are searching for ways to hasten olfactory healing. Three years into the COVID-19 pandemic, researchers have a better idea of how many people are affected and how long it seems to last. Yet when it comes to ways to rewire the sense of smell, the state of the science isnt coming up roses.

A method called olfactory training, or smell training, has shown promise, but big questions remain about how it works and for whom. The technique has been around for a while; the coronavirus isnt the first ailment to snatch away smell. But with newfound pressure from people affected by COVID-19, olfactory training and a host of other newer treatments are now getting a lot more attention.

The pandemic has brought increased attention to smell loss. If we have to provide a silver lining, COVID is pushing the science at a speed thats never happened before, says Valentina Parma, an olfactory researcher and assistant director of the Monell Chemical Senses Center in Philadelphia. But, she cautions, we are really far from a solution.

Compared with sight or hearing, the sense of smell can seem like an afterthought. But losing it can affect people deeply. Your world really changes if you lose the sense of smell, in ways that are usually worse, Parma says. The smell of a babys head, a buttery curry or the sharp salty sea can all add emotional meaning to experiences. Smells can also warn of danger, such as the rotten egg stench that signals a natural gas leak.

As an ear, nose and throat doctor, Pires recalls a deaf patient who lost her sense of smell after COVID-19 and enrolled in a clinical trial that he and colleagues conducted on smell training. She worked in a perfumery company her sense of smell was crucial to her job and her life. At the first appointment, she said, with tears in her eyes, that it felt like she wasnt living, Pires recalls.

Unlike the cells that detect color or sound, the cells that sense smell can replenish themselves. Stem cells in the nose are constantly pumping out new smell-sensing cells. Called olfactory sensory neurons, these cells are dotted with molecular nets that snag specific odor molecules that waft into the nose. Once activated, these cells send messages through the skull and into the brain.

Because of their nasal neighborhood, olfactory sensory neurons are exposed to the hazards of the environment. They may be covered with a little layer of mucus, but theyre sitting out there being constantly bombarded with bacteria and viruses and pollutants and who knows what else, says Steven Munger, a chemosensory neuroscientist at the University of Florida College of Medicine in Gainesville.

Exactly how SARS-CoV-2 damages the smell system isnt clear. But recent studies suggest the viruss assault is indirect. The virus can infect and kill nose support cells called sustentacular cells, which are thought to help keep olfactory neurons happy and fed by delivering glucose and maintaining the right salt balance. That attack can inflame the olfactory epithelium, the layers of cells that line parts of the nasal cavity.

Once this tissue is riled up, the olfactory sensory neurons get wonky, even though the cells themselves havent been attacked. After an infection and ensuing inflammation, these neurons slow down the production of their odor-catching nets, a decrease that could blind themselves to odor molecules, scientists reported in the March 17 Cell.

With time, the inflammation settles down, and the olfactory sensory neurons can get back to their usual jobs, researchers suspect. We do think that for post-viral smell disorders, the most common way to recover function is going to be spontaneous recovery, Munger says. But in some people, this process doesnt happen quickly, if ever.

Thats where smell training comes in.

One of the only therapies that exists, smell training is quite simple a good old-fashioned nose workout. It involves deeply smelling four scents (usually rose, eucalyptus, lemon and cloves) for 30 seconds apiece, twice a day for months.

In one study, 40 people who had smell disorders came away from the training with improved smelling abilities, on average, compared with 16 people who didnt do the training, olfactory researcher Thomas Hummel and his colleagues reported in the March 2009 Laryngoscope.

Since then, the bulk of studies has shown that the method helps between 30 and 60 percent of the people who try it, says Hummel, of Technische Universitt Dresden in Germany. His view is that the method can help some people, but it does not work in everybody.

One of the nice things is that there are no harmful side effects, Hummel says. Thats the charming side of it. But to do the training correctly takes discipline and stamina. If you dont do it regularly, and you give up after 14 days, this is futile, he says.

Pires in his recent trial had hoped to speed up the process, which usually takes three months, by adding four more odors to the regimen. For four weeks, 80 participants received either four or eight smells. Both groups improved, but there was no difference between the two groups, the researchers reported July 21 in the American Journal of Rhinology & Allergy.

Its not known how the technique works in the people it seems to help. It could be that it focuses peoples attention on faint smells; it could be stimulating the growth of replacement cells; it could be strengthening some pathways in the brain. Data from other animals suggest that such training can increase the number of olfactory sensory neurons, Hummel says.

Overall, this nose boot camp may be a possible approach for people to try, but big questions remain about how it works and for whom, Munger says. In my view, its very important to be up front with patients about the very real possibility this therapy may not lead to a restoration of smell, even if they and their doctor feel it is worth trying, he says. I am not trying to discourage people here, but I also think we need to be very careful not to give unwarranted promises.

Smell training doesnt come with harmful biological side effects, but it can induce frustration if it doesnt work, Parma says. In her practice, I have been talking to a lot of people who say, I did it every day for six months, twice a day for 10 minutes. I met in groups with other people, so we kept each other accountable, and I did that for six months. And it didnt work for me. She adds, I would want to address the frustration that this induces in patients.

Other potential treatments are coming under scrutiny, such as steroids, omega-3 supplements, growth factors and vitamins A and E, all of which might encourage the recovery of the nasal epithelium.

More futuristic remedies are also in early stages of research. These include epithelial transplants designed to boost olfactory stem cells, treatments with platelet-rich plasma to curb inflammation and promote healing, and even an electronic nose that would detect odor molecules and stimulate the brain directly. This cyborg-smelling system takes inspiration from cochlear implants for hearing and retinal implants for vision.

For many people, the sense of smell is appreciated only after its gone, Parma says, an apathy thats illustrated in stark terms by a recent study of about 400 people. The vast majority of respondents nearly 85 percent would rather give up their sense of smell than sight or hearing. About 19 percent of respondents said they would prefer to give up their sense of smell than their cell phone. The survey results dramatically illustrate the negligible value people place on their sense of smell, researchers wrote in the March Brain Sciences.

Even as a doctor who treats people with smell loss, Pires has a newfound fondness for a good whiff. Having lost it for a while made me appreciate it even more.

Continued here:
COVID-19 gave new urgency to the science of restoring smell - Science News Magazine

The National Institutes of Health has awarded Wayne State University Assistant Professor Shengyi (Iris) Sun, Ph.D., a three-year, $1.18 million grant to investigate the role of endoplasmic reticulum-associated degradation in regulating the biogenesis of the liver protein fibrinogen, a key factor in bleeding disorders and liver diseases.

The study could advance understanding of conformational diseases associated with protein misfolding.

Protein is one of the most important building blocks of our body. Our bodies are made up of thousands of different proteins, each with a specific function, Dr. Sun said. When we make the proteins, just like in a factory, mistakes happen and defective products need to be examined and eliminated. Our research investigates the mechanism mediating such protein quality control process, and how this mechanism is linked to various human diseases, for example, liver diseases.

Dr. Sun is a principal investigator in the Center for Molecular Medicine and Genetics, and the Department of Biochemistry, Microbiology and Immunology.

Novel mechanism underlying fibrinogen biogenesis in the endoplasmic reticulum, is funded by the NIHs National Institute of Diabetes and Digestive and Kidney Diseases.

A large number of human diseases are now recognized as conformational diseases, caused by protein misfolding and subsequent aggregation, she said. One example is hepatic fibrinogen storage disease, where the underlying cause is the endoplasmic reticulum, or ER retention and aggregation of fibrinogen mutants, leading to liver damage, hypofibrinogenemia and excessive bleeding. However, the molecular events underlying the biogenesis and quality control of both wildtype and mutant fibrinogen in the ER remain unknown.

Fibrinogen is essential for hemostasis. Its aberrant biogenesis is directly linked to bleeding disorders and liver diseases.

This application, with parallel physiological and biochemical studies, will establish a direct link between endoplasmic reticulum-associated degradation and fibrinogen biogenesis, uncover novel mechanisms underlying protein aggregation and inclusion bodies in the ER, and advance our understanding of disease pathogenesis and therapeutic approaches associated with protein misfolding and aggregation in general, Dr. Sun said.

Her co-investigators are University of North Carolina at Chapel Hill scientist Matthew Flick, Ph.D., and Michigan State University scientist James Luyendyk, Ph.D.

The award number for this NIH grant is R01DK128077.

Link:
Dr. Sun lab wins R01 from National Institutes of Health to study liver proteins - Wayne State University

-- Annual From Laboratory to Clinic conference, held at Trinity College, Oxford University, explores latest discoveries in immunology and molecular medicine ---- PAS002 is a proprietary DNA vaccine construct encoding GlialCAM --

MIAMI BEACH, Fla., Aug. 18, 2022 (GLOBE NEWSWIRE) -- Pasithea Therapeutics Corp. (Nasdaq: KTTA) (Pasithea or the Company), a biotechnology company focused on the research and discovery of new and effective treatments for psychiatric and neurological disorders, today announced it will present the preclinical proof of concept study results of its tolerizing vaccine program in multiple sclerosis (MS) on August 30th at the international conference From Laboratory to Clinic: Medicine after COVID held at Trinity College, Oxford University, United Kingdom.

From Laboratory to Clinicis an annual translational research conference established in 1984 that brings together basic scientists, clinicians, and industry researchers to explore how the latest discoveries in immunology and molecular medicine can be applied to improve clinical medicine. During the Symposium, Pasitheas Chairman, National Academy of Sciences Professor Lawrence Steinman, will be giving the opening keynote lecture. Other speakers will include Dr. Carola Vinuesa, Professor at the Francis Crick Institute in London; Dr. Gali Alter, Professor of medicine at Harvard Medical School; Dr. Jeffrey Ravetch, Professor and head of the Laboratory of Molecular Genetics and Immunology at the Rockefeller University and Dr. Anne Schaefer, Vice-chair of Neuroscience at the Icahn School of Medicine at Mount Sinai.

We look forward to presenting our data at this important international conference alongside other world recognized leading authorities in immunology and immunotherapy. The study results support the Companys commitment to the program and move us further along our path to uncover new and effective treatments for neurological disorders, said Dr. Tiago Reis Marques, Chief Executive Officer of Pasithea.

Conference details.

About Pasithea Therapeutics Corp.

Pasithea Therapeutics Corporation is a U.S. biotechnology company focused on the research and discovery of new and effective treatments for psychiatric and neurological disorders. With an experienced team of experts in the fields of neuroscience and psychopharmacology, Pasithea is developing new molecular entities for the treatment of psychiatric and neurological disorders. Pasithea is also focused on addressing the needs of patients currently suffering with mental illness by providing access to IV ketamine infusions both in clinics and in-home settings.

Forward Looking Statements

This press release contains statements that constitute forward-looking statements. Forward-looking statements are subject to numerous conditions, many of which are beyond the control of the Company. While the Company believes these forward-looking statements are reasonable, undue reliance should not be placed on any such forward-looking statements, which are based on information available to the Company on the date of this release. These forward-looking statements are based upon current estimates and assumptions and are subject to various risks and uncertainties, including, without limitation, those set forth in the Companys filings with the SEC. Thus, actual results could be materially different. The Company undertakes no obligation to update these statements whether as a result of new information, future events or otherwise, after the date of this release, except as required by law.

Pasithea Therapeutics Corp. Company ContactDr. Tiago Reis MarquesChief Executive OfficerE: tiago@pasithea.com

Pasithea Therapeutics Corp. Investor RelationsLisa M. WilsonIn-Site Communications, Inc.T: 212-452-2793E: lwilson@insitecony.com

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Pasithea Therapeutics to Present Results of Tolerizing Vaccine Program at Prestigious International Immunotherapy Conference - GlobeNewswire

In a series of articles published in Nature Genetics, researchers used data from the SPARK (Simons ... [+] Powering Autism Research) to show differences in genetic influences among people all along the autism spectrum.

In a series of articles published in Nature Genetics, researchers used data from the SPARK (Simons Powering Autism Research) to show differences in genetic influences among people all along the autism spectrum.

Autism is a spectrum and includes individuals with profound autism who often have cognitive differences or epilepsy, as well as talented and exceptional individuals in specific areas. In addition, we are now appreciating that the genetic contributions to different phenotypes vary in terms of the genes involved; when those genes are activated during brain development; and how common some of the genetic variants are in the population, said Wendy Chung, M.D., Ph.D., a board-certified clinical and molecular geneticist with Columbia University's Department of Pediatrics.

One study, Integrating de novo and inherited variants in 42,607 autism cases identifies mutations in new moderate effect genes, was published in Nature Genetics today, on August 18, 2022. Researchers analyzed the DNA of almost 43,000 people with autism, including 35,000 participants from the SPARK autism research study.

To better understand the full spectrum of autism genes, the researchers analyzed 19,843 participants ... [+] with autism, along with one or both of their biological parents, and found that roughly 20% of people with autism have de novo genetic variants that affect the function of the associated gene. Nearly 70% of this genetic contribution can be attributed to known autism or neurodevelopmental disorder genes. However, this means that although known autism-associated genes are responsible for most de novo variants, others are still to be identified.

It is widely known that autism is heritable. Still, previous studies have primarily identified autism genes with de novo variants (DNV), which occur spontaneously in germ cells before conception that are not inherited. These variants are also implicated in other neurodevelopmental disorders (NDDs). Most genetic variants of this type associated with autism have profound effects on the brain in those individuals when they occur. However, according to a study by NCBI, only 20% of individuals with autism have this type of genetic variant.

For many years, we have known from twin studies that there must be inherited genetic variants that lead to autism, but we have not been able to identify individual genes until now systematically, said lead author Pamela Feliciano, Ph.D. SPARKs scientific director. We have identified a group of genes associated with autism that can include inherited variants, which begin to explain a different part of the autism spectrum.

To better understand the full spectrum of autism genes, the researchers analyzed 19,843 participants with autism, along with one or both of their biological parents, and found that roughly 20% of people with autism have de novo genetic variants that affect the function of the associated gene. Nearly 70% of this genetic contribution can be attributed to known autism or neurodevelopmental disorder genes. However, this means that although known autism-associated genes are responsible for most de novo variants, others are still to be identified.

The researchers added 22,764 individuals with autism and 236,000 people without autism from the general population. This meta-analysis identified 60 autism genes whose contribution to autism is largely driven by the rare inherited loss of function (LOF) variants transmitted by parents who do not have cognitive differences or autism. Of these genes, five have not previously been implicated in neurodevelopmental conditions.

Individuals with autism who carry inherited variants in these moderate effect genes are less likely to have cognitive differences than people with autism who take LOF variants in well-established autism genes, such as CHD8 and SCN2A.

Most parents who passed down these genetic variants in our study do not have cognitive differences or autism, but we know that these genes are associated with autism because we find that children with autism more frequently inherit these variants. Therefore, we hypothesized that people with autism with these inherited genetic variants are less likely to have seizures and cognitive differences than those with de novo genetic variants. So far, our data strongly support[s] this hypothesis, said Dr. Feliciano.

A second study also published in Nature Genetics, Rare coding variation provides insight into the ... [+] genetic architecture and phenotypic context of autism, led by a team of investigators supported by the Simons Foundation Autism Research Initiative (SFARI) and the Autism Sequencing Consortium (ASC), performed analyses on genetic data from 20,627 people with autism, with new genetic data derived primarily from SPARK.

A second study also published in Nature Genetics states, Rare coding variation provides insight into the genetic architecture and phenotypic context of autism. This study was led by a team of investigators supported by the Simons Foundation Autism Research Initiative (SFARI) and the Autism Sequencing Consortium (ASC). They performed analyses on genetic data from 20,627 people with autism, with new genetic data derived primarily from SPARK.

The team developed new methods to discover gains and losses of DNA, or copy number variants (CNVs), from exome sequencing and strategies to integrate data from these CNVs with other classes of de novo and rare inherited variants identified 72 genes associated with autism. Most evidence came from de novo variants, with smaller but significant contributions from rare inherited variants. The researchers then combined data from the autism studies with a large dataset of 31,000 families in which the child was diagnosed with developmental delay or other neurodevelopmental conditions. These analyses discovered 373 genes associated with these diverse neurodevelopmental outcomes, allowing the team to identify genes more associated with autism than other neurodevelopmental conditions and vice versa. In addition, they found that genes associated predominantly with developmental delay tend to be important in early neuronal development. In contrast, autism genes tend to play a role in more mature neurons.

The studys senior author, Michael Talkowski, Ph.D., director, Center for Genomic Medicine at Massachusetts General Hospital and member of the Broad Institute, noted that the scale of the data collections from SPARK, the ASC and other sources as well as the newly developed methods has allowed us to explore the relative contribution of the diverse classes of genetic variants that contribute to a continuum of neurodevelopmental variability across these datasets. These analyses suggested that most genes identified play a role very early in brain development. However, the genes with higher mutation rates in autism displayed slightly greater enrichment in more mature excitatory neurons.

Finally, two other studies (Antaki et al., 2022, Warrier et al., 2022) appearing in a recent issue of Nature Genetics analyzed the SPARK datasets. These two studies used the ASC and SPARK whole genomes, exomes, and single nucleotide polymorphism (SNP) genotypes to determine the contributions of multiple genetic factors to ASD, including de novo mutations, inherited rare variants, common polygenic variants, and sex. The study by Antaki et al. found that different forms of genetic contributors are associated with various ASD symptoms and that the wide variety of clinical presentations of individuals across the autism spectrum can be explained by the combinations of hereditary factors they carry. Antaki also found that genetic contributors to ASD influence behavior in all family members, including parents and typically developing siblings.

Jonathan Sebat, Ph.D., professor of psychiatry and cellular and molecular medicine at UCSD and senior author on Antaki et al., said, The spectrum of symptom severity in ASD is attributable to a spectrum of genetic influence. People who meet diagnostic criteria for autism may have the most genetic factors for autism, but these types of factors are present to varying degrees in all of us. So we are all somewhere on a continuum.

Together, the four papers provide new insights into the genetic basis of autism, a condition so ... [+] varied in its characteristics that it has been difficult to understand its neurobiological basis. Although researchers have yet to identify the fuller picture of brain molecules and pathways that underlie autism, these new studies will lead the way toward an improved understanding of this complicated and common condition.

Together, the four papers provide new insights into the genetic basis of autism, a condition so varied in its characteristics that it has been difficult to understand its neurobiological basis. Although researchers have yet to identify the fuller picture of brain molecules and pathways that underlie autism, these new studies will lead the way toward an improved understanding of this complicated and common condition.

There are so many new genes and insights into neurodevelopment to be pursued from these findings.

Read more:
New Study Identifies How A Group Of Genes Are Linked To Behavioral Conditions - Forbes

A variant typical of the Finnish population that protects against heart diseases was identified in the FinnGen genomic study coordinated by the University of Helsinki. The risk of developing heart diseases is roughly one-fifth lower in carriers of the variant compared to the population on average.

The protective effect of the newly discovered variant against coronary heart disease is likely to be caused by the below-average arterial stiffness of variant carriers.

The variant in question is located in the MFGE8 gene that produces a protein called lactadherin, which is known to affect the process of arterial stiffening. The results indicate that the variant inhibits the function of the lactadherin protein. However, further studies are needed to ascertain this.

The findings, published in the Communications Biology journal on 17 August 2022, are based on a FinnGen dataset comprising more than 260,000 Finnish biobank sample donors.

Discovery made possible by the FinnGen research dataset

Cardiovascular diseases remain the most common cause of death worldwide. In Finland too, one-third of all deaths are caused by cardiovascular diseases.

In the recently published study, genomic variation between individuals with coronary heart disease and other study subjects was compared in the FinnGen dataset. The results exposed 38 genetic loci associated with a risk of coronary heart disease, of which four, including the MFGE8 gene, were previously unknown.

Hundreds of genetic factors affecting the risk of developing cardiovascular diseases have already been identified. However, the number of known variants that reduce the risk of disease and directly indicate the active gene, like the MFGE8 variant, is relatively low,says Doctoral Researcher Sanni Ruotsalainen from the University of Helsinkis Institute for Molecular Medicine Finland, who carried out the study.

Identifying the link between MFGE8 and coronary heart disease is a good example of the special benefits the Finnish population offers to genetic research. The variant in question is 70 times more common in Finland than in the overall European population, which is why it has not been observed in previous similar gene studies elsewhere. The variant is found in roughly 5.5% of Finns, with slightly higher frequency in eastern Finland than in western parts of the country.

A protective effect against coronary heart disease opens up perspectives in drug development

The variant was also found to have an effect on the age of onset of coronary heart disease. Carriers of the protective variant suffered a myocardial infarction or were diagnosed with coronary heart disease on average 18 months later than the rest of the population.

In terms of developing new drug therapies, variants that reduce the risk of developing diseases are particularly interesting, says the studys principal investigator, Professor Samuli Ripatti from the University of Helsinki.

For example, PCSK9 inhibitors, the next-generation cholesterol drugs already in use, have been developed on the basis of a similar observation. This new finding introduces a new mechanism of action alongside cholesterol that protects against cardiovascular diseases.

Our findings also demonstrated that the MFGE8 variant did not increase the risk of any other disease. Therefore, a drug molecule mimicking the functioning of the gene could make it possible to develop entirely novel therapies for the prevention of cardiovascular diseases, Ripatti notes.

Communications Biology

Cells

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Original post:
New gene variant that protects against coronary heart disease uncovered - EurekAlert

image:Quentin Vanhaelen, PhD, of Insilico Medicine will present on the Company's AI-powered target discovery platform PandaOmics at the 9th annual Aging Research and Drug Discovery conference. view more

Credit: c/o Insilico Medicine

The 9th annual Aging Research and Drug Discovery Conference, happening Aug. 29-Sept. 2 at the University of Copenhagen, will feature researcher Quentin Vanhaelen, PhD from Insilico Medicine discussing the Companys artificial intelligence target discovery platform, PandaOmics. The platform has been validated through numerous drugs in development, including thefirstAI-discovered and AI-designed drug for idiopathic pulmonary fibrosis,currently in Phase I trials. Vanhaelen is one of over 70academic and industry leaders in longevity speaking at the event, and will describe theprogress that PandaOmics has made since Insilico launched it in 2020.

PandaOmics uses aging as an important biomarker, sifting through trillions of data points from clinical trials, research grants, and omics data samples, including transciptomics, genomics, epigenomics, and proteomics. The system identifies where aging and disease intersect and how aging contributes to poorer health. Researchers have used PandaOmics to predict ninemolecular targets for new drugs that can combat aging as well as aging-associated diseases including Alzheimers, Parkinsons, cirrhosis, and rheumatoid arthritis.

Vanhaelen will discuss the possibilities of developing dual-purpose drugs using AI, and talk about how the PandaOmics platform works using data to discover where age-associated and non-age-associated diseases overlap, and evaluating targets' therapeuticpotential by ranking them for druggability and safety. And Vanhaelen will talk about the benefits of an AI approach, which allows scientists to make these discoveries in record time. The nine novel dual-purpose aging and disease targets were discovered and published in less than two months.

Identifying ways to identify and treat aging is one of the many topics being explored relative to expanding human lifespan and healthspan at the ARDD. The conference, founded by Insilico Medicine founder and CEO Alex Zhavoronkov, PhD, brings together experts in longevity to share breakthroughs, collaborate, and advance aging research.

This conference was designed to create the worlds first platform for the pharmaceutical industry to actively engage in and incorporate the latest discoveries in credible aging research into every aspect of their internal R&D strategy, says Zhavoronkov.

Vanhaelen has been working with Insilico since 2016 and holds a PhD in theoretical physics from the University of Brussels. He founded a consultancy company called Insilicoscreen on the analysis of signaling pathways dynamics that was acquired by Insilico Medicine and his research interests includetheories of aging, signaling pathways activation, modeling of dynamical systems, and applications of deep learning techniques for drug discovery.

He will present on PandaOmics on September 2, 7:40-8pm EST.

About the ARDD

The 9th annual Aging Research and Drug Discovery (ARDD) conference brings together leading academic and industry speakers in aging research with prominent startups, venture capitalists, and editors of industry journals. The event will be held virtually and in person at the University of Copenhagen Aug. 29-Sept. 2.

Details and registration: http://www.agingpharma.org/

About Insilico Medicine

Insilico Medicine, a clinical stage end-to-end artificial intelligence (AI)-driven drug discovery company, is connecting biology, chemistry, and clinical trials analysis using next-generation AI systems. The company has developed AI platforms that utilize deep generative models, reinforcement learning, transformers, and other modern machine learning techniques to discover novel targets and to design novel molecular structures with desired properties. Insilico Medicine is delivering breakthrough solutions to discover and develop innovative drugs for cancer, fibrosis, immunity, central nervous system (CNS) diseases and aging-related diseases.

For more information, visit http://www.insilico.com

For media inquiries, contact media@insilicomedicine.com

News article

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Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.

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Insilico Medicine presents on AI for drug discovery at 9th Annual Aging Research and Drug Discovery Conference - EurekAlert

Summary: DKT, a Japanese herbal remedy containing ginger, pepper, ginseng, and maltose, reduced symptoms of colitis in mice, a new study reports.

Source: RIKEN

Zhengzheng Shi and colleagues at the RIKEN Center for Integrative Medical Sciences (IMS) in Japan report the effects of a common herbal remedy on colitis, one of two conditions that comprise inflammatory bowel disease (IBD).

Published inFrontiers in Immunology, the study shows that DKTa standard formula containing ginger, pepper, ginseng, and maltosereduced the severity of colitis in lab mice by preventing the characteristic imbalance in gut microbes and by increasing levels of immune cells in the colon that fight inflammation.

Colitis is a chronic inflammation of the colon, characterized by an imbalance ingut bacteriaand an abnormal immune response. Prevalence has doubled over the last 20 years, and its currently a global health concern, particularly in Europe and North America. Although treatments are numerous, they are only partially effective.

This has led some researchers to take a closer look at traditional herbal medicines that originated in China, and are now commonly used in Japan and other Asian countries.

Daikenchuto (DKT) is a formula containing specific amounts of ginger, pepper, ginseng, and maltose, and is one of 148herbal medicinescalled Kampo, which have been developed in Japan and are often prescribed by doctors to treat a variety of illnesses.

Previous research has hinted that DKT might be useful for treating colitis, but evidence, particularly at themolecular level, has been lacking. Thus, Shi and the team of researchers at RIKEN IMS led by Naoko Satoh-Takayama conducted a detailed examination of its effects on a mouse model of colitis.

Colitis was induced in mice using dextran sodium sulfate, which is toxic to the cells that line the colon. When these mice were given DKT, their body weights remained normal, and they had lower clinical scores for colitis. Additional analysis revealed much less damage to the cells lining the colon.

Having thus shown that DKT does indeed help protect against colitis, the researchers proceeded to analyze the gut microbiome of the mice and expression levels of anti-inflammatory immune cells.

Gut microbiomes contain numerous bacteria and fungi that aid in digestion and help the immune system.

Colitis is associated with an imbalance in thesegut microbiota, and analysis showed that a family of lactic acid bacteria were depleted in the colitic mice of this study. Also depleted was one of their metabolites, a short-chain fatty acid called propionate.

Treating the model mice with DKT restored much of these missing bacteriaparticularly those from the genus Lactobacillusand levels of propionate were normal.

Colitis is also associated with an abnormal immune response that causes the characteristic intestinal inflammation.

When the team looked at innate intestinal immune cells, they found that levels of a type called ILC3 were lower in the untreated colitic mice than in the DKT-treated colonic mice, and that mice engineered to lack ILC3 suffered more and could not benefit from DKT treatment.

This means that ILC3s are critical for protecting against colitis and that DKT works by interacting with them. Lastly, qPCR analysis indicated that these important immune cells had receptors for propionate, called GPR43, on their surface.

Daikenchuto is commonly prescribed to prevent and treat gastrointestinal diseases, as well as for reducingintestinal obstructionafter colorectal cancer surgery, says Satoh-Takayama.

Here we have shown that it can also alleviate intestinal diseases likecolitisby rebalancing Lactobacillus levels in the gut microbiome. This likely helps reduce inflammatory immune responses by promoting the activity of type 3 innate lymphoid cells.

Author: Press OfficeSource: RIKENContact: Press Office RIKENImage: The image is in the public domain

Original Research: Open access.A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells by Zhengzheng Shi et al. Frontiers in Immunology

Abstract

A Japanese Herbal Formula, Daikenchuto, Alleviates Experimental Colitis by Reshaping Microbial Profiles and Enhancing Group 3 Innate Lymphoid Cells

Daikenchuto (DKT) is one of the most widely used Japanese herbal formulae for various gastrointestinal disorders. It consists ofZanthoxylum Fructus(Japanese pepper),Zingiberis Siccatum Rhizoma(processed ginger),Ginseng radix, and maltose powder. However, the use of DKT in clinical settings is still controversial due to the limited molecular evidence and largely unknown therapeutic effects.

Here, we investigated the anti-inflammatory actions of DKT in the dextran sodium sulfate (DSS)-induced colitis model in mice.

We observed that DKT remarkably attenuated the severity of experimental colitis while maintaining the members of the symbiotic microbiota such as family Lactobacillaceae and increasing levels of propionate, an immunomodulatory microbial metabolite, in the colon.

DKT also protected colonic epithelial integrity by upregulating the fucosyltransferase geneFut2and the antimicrobial peptide geneReg3g. More remarkably, DKT restored the reduced colonic group 3 innate lymphoid cells (ILC3s), mainly RORthigh-ILC3s, in DSS-induced colitis. We further demonstrated that ILC3-deficient mice showed increased mortality during experimental colitis, suggesting that ILC3s play a protective function on colonic inflammation.

These findings demonstrate that DKT possesses anti-inflammatory activity, partlyviaILC3 function, to maintain the colonic microenvironment.

Our study also provides insights into the molecular basis of herbal medicine effects, promotes more profound mechanistic studies towards herbal formulae and contributes to future drug development.

See the article here:
How a Japanese Herbal Medicine Protects the Gut Against Inflammatory Bowel Disease - Neuroscience News

Polio cases in Western nations are likely from imported cases of unvaccinated individuals visiting countries where polio has yet to be eradicated, says Dawn Bowdish, a professor of pathology and molecular medicine.

August 17, 2022

A rise in polio cases in Western countries has put the virus, which was eradicated in Canada nearly 30 years ago, back on the radar of health officials.

It was never fully eradicated in countries like Afghanistan and Pakistan, and periodically there are parts of the world where if there was a disruption of their vaccine campaign, like a war, there might be local outbreaks, Dawn Bowdish,professor of pathology and molecular medicine, told the Toronto Star.

Polio cases in Western nations are likely from imported cases of unvaccinated individuals visiting countries where polio has yet to be eradicated, she explained.

The Public Health Agency of Canada will be testing wastewater across the country for any indication of the virus.

Its not totally unexpected to occasionally find this in the wastewater, but where its increasingly concerning now is because of the COVID pandemic and public resistance to vaccination there are going to be some people who are unprotected, she said.

According to Bowdish, because most Canadians are vaccinated against polio, there is a strong protection against the virus, she said.

Officials should focus on ensuring everyone is getting their routine vaccinations.

We want to make sure we really focus on the very young and anyone whos been missed for any reason, she says.

Link:
Why polio is back on the radar of Canadian health officials - Brighter World

Angela DeMichele, MD, MSCE, spoke about the I-SPY2 trial, which evaluates patients with early breast cancer who are treated with experimental neoadjuvant systemic therapy regimens.

At the 2022 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork spoke with Angela DeMichele, MD, MSCE, co-leader of the Breast Cancer Research Program, co-director of 2-PREVENT Breast Cancer Translational Center of Excellence, and Alan and Jill Miller Professor in Breast Cancer Excellence at Penn Medicine in Philadelphia, about the rationale of the phase 2 I-SPY2 platform trial (NCT01042379) investigating various experimental systemic therapy regimens in patients with early breast cancer presenting with various baseline characteristics and molecular subtypes. She highlighted how this protocol was instrumental in quickly and efficiently bringing novel therapies to patients, many of which have now been accepted as standard of care options in the space.

The I-SPY2 trial was designed over 10 years ago to evaluate new drugs in the early breast cancer setting. That was a novel idea back when we started because traditional drug development started in the metastatic setting. Its been borne out that that is somewhat misleading in terms of how drugs can ultimately help patients. By moving evaluation of drugs to an earlier setting, we can help patients earlier and cure more patients. The trial is a platform trial, which means that we set it up and continue to run drugs through the platform. We dont have to set up a new trial every time we want to evaluate a new drug. Weve evaluated almost 30 drugs now over the last 10 years, and some of those are now things that are standard of care, like PARP inhibitors and immunotherapy. We were able to show in patients who were starting neoadjuvant therapy that these drugs could improve patient outcomes. Those led to phase 3 trials that now have resulted in drugs being approved as standard of care.

Reference

Huppert LA, Rugo HS, Pusztai L, et al. Pathologic complete response (pCR) rates for HR+/HER2- breast cancer by molecular subtype in the I-SPY2 Trial. J Clin Oncol. 2022;40(suppl 16):504. doi:10.1200/JCO.2022.40.16_suppl.504

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Angela DeMichele, MD, MSCE, Assesses the Value of I-SPY2 for Neoadjuvant Treatment of Early Breast Cancer - Cancer Network

Would you like to contribute your creativity to an international team of scientists from various disciplines focusing on basic research in the area of molecular life sciences?

The European Molecular Biology Laboratory (EMBL) invites you to apply for PhD positions in Heidelberg, Barcelona, Grenoble, Hamburg, Hinxton (near Cambridge) and Rome.

Information about the PhD Programme and fellowships as well as research topics at EMBL can be found here.

We welcome candidates with diverse backgrounds, such as in Biology, Chemistry, Physics, Mathematics, Computer Science, Engineering and Molecular Medicine.

EMBL provides PhD students with a starting platform for a successful career in science by fostering early independence and interdisciplinary research. The enriching encounter of different nationalities, the friendly and collaborative atmosphere, and the passion for science is what unites EMBL s diverse staff and provides an ideal setting to forge long-lasting connections and make studying at EMBL a formative experience. Our PhD positions are fully funded and offer broad health care and pension benefits.

Learn more about the EMBL International PhD Programme and apply onlinehere: https://www.embl.org/about/info/embl-international-phd-programme/application/.

The deadline for submitting the online application is 4 October 2022. References must be submitted by 6 October 2022.

Interviews will take place in January - February 2023. Successful candidates would start their work at EMBL latest by mid of October 2023.

EMBL is a signatory of DORA. Find out how we implement best practices in research assessment in our recruitment processes here.

For further information, please contact EMBL Graduate Office via graduate-office@embl.org.

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Exciting PhD positions at the European Molecular Biology Laboratory (EMBL) job with EUROPEAN MOLECULAR BIOLOGY LABORATORY (EMBL) | 304753 - Times...