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Intranasally Administered Small Peptide That Blocks COVID-19 Spike Protein Interaction with ACE-2 Shows Success in COVID-19 Therapy in Mouse Model

In a study published online on January 11, 2021 in the Journal of Neuroimmune Pharmacology, mouse models with COVID-19 showed positive results when a small peptide was introduced nasally. The peptide proved effective in reducing fever, protecting the lungs, improving heart function, and reversing “cytokine storm”--a condition in which an infection triggers the immune system to flood the bloodstream with inflammatory proteins. The researchers also report success in preventing the disease from progression. The open-access article is titled “ACE-2-interacting Domain of SARS-CoV-2 (AIDS) Peptide Suppresses Inflammation to Reduce Fever and Protect Lungs and Heart in Mice: Implications for COVID-19 Therapy.” "This could be a new approach to prevent SARS-CoV-2 infection and protect COVID-19 patients from breathing problems and cardiac issues," said Kalipada Pahan, PhD, the Floyd A. Davis Professor of Neurology at Rush University Medical Center and a Research Career Scientist at the Jesse Brown VA Medical Center, both in Chicago, understanding the mechanism is proving important to developing effective therapies for COVID-19." Many COVID-19 patients in the intensive care unit (ICU) suffer from cytokine storm that affects lungs, heart, and other organs. Although anti-inflammatory therapies such as steroids are available, very often these treatments cause immunosuppression. "Because SARS-CoV-2 binds to angiotensin-converting enzyme 2 (ACE2) for entering into the cells, we have designed a hexapeptide corresponding to the ACE2-interacting domain of SARS-CoV-2 (AIDS) to inhibit the binding of virus with ACE-2," Dr. Pahan said. "AIDS peptide inhibits cytokines produced by only SARS-CoV-2 spike protein, not other inflammatory stimuli, indicating that AIDS peptide would not cause immunosuppression.

Mental Health Research Funder “1907 Research” Announces Three Recipients of Its Inaugural 1907 Trailblazer Award; $120,000 Two-Year Grants to Support Pioneering, Early-Career Mental Health Researchers: Benjamin Bartelle, Laura Lewis, & Katherine Scangos

On January 5, 2021, the mental health research funder 1907* Research, Inc., announced the recipients of its first annual 1907 Trailblazer Awards. The two-year grants, valued at over $120,000 each, were awarded to three promising scientists to pursue groundbreaking mental health research proposals. The awards went to: Dr. Benjamin Bartelle (photo bottom), from Arizona State University, for his proposal "Accessing Neuroimmunity with a Domesticated Zika Virus." Dr. Bartelle's fellowship is generously sponsored by the Kissick Family Foundation; Dr. Laura Lewis (photo bottom), from Boston University, for her proposal "Linking Sleep, Cerebrospinal Fluid Flow, and Inflammation, in Depression;” and Dr. Katherine Scangos (photo bottom), from the University of California, San Francisco, for her proposal "Using Direct Cortical and Subcortical Neural Recordings to Uncover Principles of Network Dynamics Underlying Depression Symptom Severity in Major Depression." "The three early-career researchers we have chosen to support are truly exceptional in their ambition and innovation. Tackling psychiatric disease and mental illness through neuroscience needs new thinking, and this is exactly what our incoming Fellows are bringing," says Dr. Anil Seth, Professor of Cognitive and Computational Neuroscience at the University of Sussex (UK) and member of the 1907 Research Advisory Board which selected the inaugural 1907 Trailblazer Award Fellows.

Remarkable Results: UCSF Case Study of Personalized Electro-Stimulation of Select Brain Regions for Treatment of Severe Depression Suggests That “Even the Most Severe Depression Is a Brain-Circuit Disease” That Can Be Nudged Back into a Healthy State

Targeted neuromodulation tailored to individual patients' distinctive symptoms is an increasingly common way of correcting misfiring brain circuits in people with epilepsy or Parkinson's disease. Now, scientists at the University of California (UC) San Francisco's (UCSF’s) Dolby Family Center for Mood Disorders have demonstrated a novel personalized neuromodulation approach that--at least in one patient--was able to provide relief from symptoms of severe, treatment-resistant depression within minutes. The approach is being developed specifically as a potential treatment for the significant fraction of people with debilitating depression who do not respond to existing therapies and are at high risk of suicide. "The brain, like the heart, is an electrical organ, and there is a growing acceptance in the field that the faulty brain networks that cause depression--just like epilepsy or Parkinson's disease--could be shifted into a healthier state by targeted stimulation," said Katherine Scangos (photo), MD, PhD, Assistant Professor of Psychiatry and Co-Director of the TMS & Neuromodulation Program at UCSF, and Assistant Professor of Psychiatry and Clinical Psychiatry at UCSF’s Dolby Center for Mood Disorders, and the lead and corresponding author of the new study. "Prior attempts to develop neuromodulation for depression have always applied stimulation in the same site in all patients, and on a regular schedule that fails to specifically target the pathological brain state. We know depression affects different people in very different ways, but the idea of mapping out individualized sites for neuromodulation that match a patient's particular symptoms had not been well explored." In a case study published online on January 18, 2021 in Nature Medicine, Dr.

Once-in-a-Lifetime Event: Free Virtual Precision Medicine World Conference (PMWC 2021) (January 25-27) on COVID-19 Pandemic Will Feature 50 World-Class Speakers, Including Anthony Fauci & Leroy Hood; Free Registration Ends January 25

The Precision Medicine World Conference 2021 (PMWC 2021) (January 25-27) will be a free virtual conference focusing on almost all aspects of the grievous COVID-19 pandemic and featuring a panoply of world-class experts presenting a wide variety of critical viewpoints. The deadline for free registration for this extraordinary virtual conference is January 25 and may be achieved at the following link (https://www.pmwcintl.com/covid/#register). The spectacular lineup of 50 renowned speakers includes Anthony Fauci, Leroy Hood, Carl June, Eric Topol, Laura Esserman, and the leading vaccine scientists from Moderna, Pfizer, Johnson & Johnson, & the University of Oxford, among a host of other luminaries. This is truly a once-in-a-lifetime science/medicine/health conference not to be missed. The COVID-19 pandemic makes it necessary for leading experts from across disciplines and geographies to come together to jointly address the challenges we are facing when coping with the disruptive effects that the SARS-CoV-2 pandemic is having on our healthcare system and our society as a whole. The tasks upon us are enormous and include scaling diagnostics, tackling COVID-19 within existing healthcare systems, building health data platforms that support COVID-19 focused health care, accommodating clinical trials in the era of COVID-19, and developing functional vaccines and therapeutics. PMWC 2021 will touch upon these critical developments and ongoing activities, while also including the regulatory and investment sides that influence clinical advancements. Remember, the deadline for free registration is Friday, January 22. Links to the registration site, the conference program, and the conference web site are provided below.

Diet High In Omega-3 Fatty Acids Helps Arctic Ground Squirrels Stay Warmer During Hibernation and Also Increases Their Amounts of Brown Fat

By feeding arctic ground squirrels special diets, researchers have found that omega-3 fatty acids, common in flax seed and fish oil, help keep the animals warmer in deep hibernation. In a University of Alaska Fairbanks-led study, researchers fed ground squirrels either a diet high in omega-3 fatty acids or a normal laboratory diet, and measured how the animals hibernated afterward. Researchers found that the omega-3 diet helped the animals hibernate a little warmer than normal without negatively affecting hibernation. The omega-3 diets also increased the amount of a heat-producing fat, called brown adipose tissue, the animals pack on. The discovery could add more understanding about how hibernation works and why animals eat certain types of foods. The study was published online on January 14, 2021 in Scientific Reports. The open-access article is titled “Omega 3 Fatty Acids Stimulate Thermogenesis During Torpor in the Arctic Ground Squirrel.” "Arctic ground squirrels have an innate ability to withstand harsh sub-zero temperatures for an incredible amount of time," says Monica Mikes, who at the time of the study was an undergraduate researcher at UAF and a scholar in the university's Biomedical Learning and Student Training program. Mikes, who also co-designed the study, noted that the animals are able to take their body temperature below freezing. How hibernators regulate body temperature has fascinated researchers for over a century. The type of fat they eat might have something to do with that. Recent studies have found that omega-3s can affect metabolism in non-hibernating animals. Because wild hibernators are known to eat diets rich in omega-3 foods, the researchers wanted to know if those animals benefited from eating those diets.

Exosomes from Diabetics Contain Higher Levels of miR-20b-5p and Suppress Wound Healing, As Does miR-20b-5p Alone; Exosomes Loaded with miR-20b-5p Inhibitors May Accelerate Wound Healing in Diabetics, Author Suggest

Scientists at the Tongji University School of Medicine, in Shanghai, People’s Republic of China, have shown that microRNA-20b-5p (miR-20b-5p) is overexpressed in exosomes from patients with diabetes, and that these exosomes, or miR-20b-5p by itself, can act to inhibit cutaneous would healing in diabetic patients. In a mouse model and in cultured human fibroblasts, the scientists showed that miR-20b-5p may inhibit wound healing by suppressing fibroblast function by suppressing vascular endothelial growth factor A (VEGFA) expression. The researchers said that fibroblasts are able to readily internalize serum-derived exosomes and are essential mediators of wound healing, owing to their ability to promote collagen synthesis and localized remodeling of diverse tissue types. VEGFA is a known critical regulator of wound healing, tissue remodeling, and collagen production. Impaired VEGFA signaling activity is believed to be a key cause of disrupted wound healing in diabetic foot ulcers, and several studies have shown VEGFA to be associated with fibroblasts. In their current work, the scientists identified VEGFA as a miR-20b-5p target gene such that when its expression was suppressed, fibroblast function and wound repair were adversely impacted. The scientists suggested that exosomes loaded with inhibitors of miR-20b-5p might prove useful in accelerating would healing in diabetics. The article was published on January 14, 2021 in the International Journal of Nanomedicine, Published by Dove Press. The open-access article is titled “Inhibition of Circulating Exosomal miRNA-20b-5p Accelerates Diabetic Wound Repair.”

Innocan Pharma Successfully Completes Large-Scale Production of Exosomes

On January 14, 2021, Innocan Pharma Corporation (CSE: INNO) (FSE: IP4) (OTC Pink: INNPF), headquartered in Israel, announced the successful completion of a large-scale production of exosomes. Innocan's cannabidiol (CBD)-Loaded Exosome (CLX) Therapy project led by Professor Daniel Offen (https://www.danioffenlab.com/prof-dani-offen), PhD, demonstrates the capability of having reliable large-scale production of exosomes and is an important milestone in the CLX Therapy development process. Innocan managed to perform the production of trillions of exosomes in a short period of time in a 3-dimensional bioreactor, and that may lead to economic large-scale exosome production for the CLX. This achievement is expected to pave the way for larger tests and studies. "Innocan is now one of a few public companies in the exosome's science field. Although we are still in the development stage of the CLX platform, large-scale exosome production capabilities are a significant proof of advantage and capability for Innocan, as part of the path to commercialization," said Iris Bincovich, Founder and CEO of Innocan. Innocan Pharma, together with Tel Aviv University and Professor Offen and his team, are developing a new revolutionary cell therapy-based technology, loaded with CBD (cannabidiol), designed to target coronavirus infected lung cells and central nervous system diseases. The CLX Therapy holds the potential to provide a highly synergistic effect of anti-inflammatory properties and help in the recovery of infected lung cells. This product is planned to act as a "guided missile" to the infected lungs, combining the cell-healing properties of exosomes and the anti-inflammatory properties of CBD.

Possible Breakthrough in Producing Large Quantities of Potential Therapeutic Drug Compound (FR) Originally Found in Bacterium Colonizing Coralberry Plant; Compound Inhibits Gq Proteins and Has Shown Suggestive Effectiveness in Asthma and Certain Cancers

For some years, an active substance from the leaves of an ornamental plant has been regarded as a possible forerunner of a new group of potent drugs. So far, however, it has been very laborious to manufacture this substance in large quantities. That could now change as researchers at the University of Bonn (Germany) have identified a bacterium that produces the substance and can also be easily cultivated in the laboratory. The results were published online on January 8, 2021 in Nature Communications. The open-access article is titled “Thioesterase-Mediated Side Chain Transesterification Generates Potent Gq Signaling Inhibitor FR900359.” The coralberry (photo) currently once again adorns many living rooms. In winter, it bears bright red fruits, which make it a popular ornamental plant at this time of year in the Northern hemisphere. For pharmacists, however, it is interesting for a different reason: it contains an active substance that has emerged in recent years as a beacon of hope against asthma and certain types of cancer. Unfortunately, obtaining this substance, with the cryptic name FR900359 (abbreviated: FR), in larger quantities is rather laborious. Cultivating the plants in greenhouses takes many weeks; moreover, the yield can vary enormously depending on the specimen. Incidentally, the plants do not produce the active ingredient themselves, but have bacteria in their leaves that do it for them. "However, these only grow in the coralberry and cannot be cultivated in the laboratory," explains Max Crüsemann PhD, of the Institute of Pharmaceutical Biology at the University of Bonn. Manufacturing FR is a complex undertaking. The bacteria have a special assembly line for this purpose, in which a number of enzymes work hand in hand. The bacterial genetic makeup specifies how this assembly line must be set up.

How Plants Produce Defensive Toxins Without Harming Themselves; Researchers Elucidate Biosynthesis & Mode of Action of Diterpene Glycosides in Wild Tobacco

Plants produce toxic substances to defend themselves against herbivores. In a new study, scientists from the Max Planck Institute for Chemical Ecology in Jena and the University of Münster, both in Germany, were able to describe in detail the biosynthesis and exact mode of action of an important group of defensive substances, the diterpene glycosides, in wild tobacco plants. Diterpene glycosides allow plants to fend off herbivores. The study shows that these plant chemicals attack certain parts of the cell membrane. To protect themselves from their own toxins and to prevent their cell membranes from being damaged, tobacco plants store these substances in a non-toxic form, which is synthesized in a very particular way. Autotoxicity and the protection against it seem to play a greater role in the evolution of plant defenses than previously thought according to results published in the January 15, 2021 issue of Science (https://science.sciencemag.org/content/371/6526/255). The article is titled “Controlled Hydroxylations of Diterpenoids Allow for Plant Chemical Defense Without Autotoxicity.” Many plants produce chemical defenses to protect themselves against being eaten. Still little is known about what makes these substances toxic to their consumers. Researchers at the Max Planck Institute for Chemical Ecology and the University of Münster have now investigated how plants produce toxins and store them in their tissues without harming themselves. In particular, they wanted to know whether the mechanisms of autotoxicity and its prevention share similar mechanisms as the toxic characteristics that provide defense against herbivores. For their experiments, the scientists chose diterpene glycosides from Nicotiana attenuata plants, a wild tobacco species. "These substances occur at very high concentrations in the leaves of tobacco plants.

Cancer Research Reveals How Mutations in a Specific Gene (RUNX1) Cause Different Types of Cancers

Leading cancer experts at the University of Birmingham (UK) have solved a long-standing question of how various types of mutations in just one gene cause different types of diseases. A team of scientists at the University's Institute of Cancer and Genomic Sciences, led by Professor Constanze Bonifer, PhD, studied a gene known as RUNX1 (https://en.wikipedia.org/wiki/RUNX1) (image here is graphic reprentation of the RUNX1 protein), which is responsible for providing instructions for the development of all blood cells and is frequently mutated in blood cancers. The results of the team’s research has shown that the balance of cells types in the blood is affected much earlier than previously thought, which is particularly important for families that carry the mutant gene. The research, published online on January 4, 2021 in Life Science Alliance, opens up the possibility of identifying early changes in cells of patients carrying the mutation even before any disease manifests itself--increasing their chances of survival. The study, the culmination of four years of research, showed that while some types of RUNX1 mutations directly changed how other genes behaved in blood cells, not all did. In particular, the mutations that are inherited through families do not immediately affect the cells but instead change the roadmap (differentiation trajectory) they follow to become other cell types, such as platelets and white blood cells.

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