Biology & Medicine News and Discussions

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New discovery about diabetes may reduce the risk of organ failure
https://medicalxpress.com/news/2021-10- ... ilure.html
by Aarhus University
A new research result from Aarhus University and the Steno Diabetes Center Aarhus has identified how diabetes affects stem cells residing in muscle to form fat and connective tissue. According to the researchers, the discovery has major clinical perspectives.

The cells that researchers from Aarhus University and the Steno Diabetes Center Aarhus have found are located in the skeletal muscle, but also in a many other organs. They are responsible for creating fat and scar tissue. Unhealthy skeletal muscle with an accumulation of connective tissue (fibrosis) and fat cells (called adipogenesis in medicine) damage the muscle's function.

In this study, the researchers have studied how type 2 diabetes alters the skeletal muscles. They discovered that both fibrosis and fatty tissue are formed in the muscles.

"One characteristic of e.g. diabetes is that the tissue becomes filled with fat and scar tissue," says Jean Farup.

Huge potential

He therefore believes that the clinical perspective can be huge, because the cells are found all over the body, and because many diseases are associated with exactly this build-up of fat and scar tissue in the skeletal muscle and other organs.

"With the help of studies of gene expression at single cell level, we've simply found the fibrosis-forming and fat-accumulating cells in the skeletal muscle," he explains.

The researchers also uncovered how gene expression occurs in an unhealthy cell compared to a healthy cell. Once they had identified the cells, they examined how the cells changed in a person with type 2 diabetes.
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New computer modelling could boost drug discovery
https://phys.org/news/2021-10-boost-drug-discovery.html
by Queen's University Belfast
Scientists from Queen's University Belfast have developed a computer-aided data tool that could improve treatment for a range of illnesses.

The computer modeling tool will predict novel sites of binding for potential drugs that are more selective, leading to more effective drug targeting, increasing therapeutic efficacy and reducing side effects.

The data tool or protocol will uncover a novel class of compounds—allosteric drugs in G protein-coupled receptors (GPCRs).

GPCRs are the largest membrane protein family that transduce a signal inside cells from hormones, neurotransmitters, and other endogenous molecules. As a result of their broad influence on human physiology, GPCRs are drug targets in many therapeutic areas such as inflammation, infertility, metabolic and neurological disorders, viral infections and cancer. Currently over a third of drugs act via GPCRs. Despite the substantial therapeutic success, the discovery of GPCR drugs is challenging due to promiscuous binding and subsequent side effects.

Recent studies point to the existence of other binding sites, called allosteric sites that drugs can bind to and provide several therapeutic benefits. However, the discovery of allosteric sites and drugs has been mostly serendipitous. Recent X-ray crystallography, that determines the atomic and molecular structure, and cryo-electron microscopy that offers 3D models of several GPCRs offer opportunities to develop computer-aided methodologies to search for allosteric sites.
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New ribosome-targeting antibiotic acts against drug-resistant bacteria

by University of Illinois at Chicago
https://medicalxpress.com/news/2021-10- ... teria.html
A new study published in Nature reports on a new antibiotic that binds to the ribosome of bacterial cells and stops drug-resistant pathogens from making mice sick.

Co-authored by researchers from the University of Illinois Chicago, the study not only shows the potential of the drug—called iboxamycin—to one day help humans who are ill because of antibiotic-resistant bacteria, but also identifies how the drug overcomes the most widespread mechanism of resistance to this class of antibacterials.

The drug—a synthetic oxepanoprolinamide, which is a novel class of antibacterial drugs—was developed and tested in animals by study co-authors from Harvard University.

The Nature study, "A synthetic antibiotic class overcoming bacterial multidrug resistance," reports that iboxamycin was powerfully effective at fighting both gram-negative and gram-positive drug-resistant bacteria in mouse models.
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Detector advance could lead to cheaper, easier medical scans
https://phys.org/news/2021-10-detector- ... dical.html
by Cristina Deptula, UC Davis
Researchers in the U.S. and Japan have demonstrated the first experimental cross-sectional medical image that doesn't require tomography, a mathematical process used to reconstruct images in CT and PET scans . The work, published Oct. 14 in Nature Photonics, could lead to cheaper, easier and more accurate medical imaging.

The advance was made possible by development of new, ultrafast photon detectors, said Simon Cherry, professor of biomedical engineering and of radiology at the University of California, Davis and senior author on the paper.

"We're literally imaging at the speed of light, which is something of a holy grail in our field," Cherry said.

Experimental work was led by Sun Il Kwon, project scientist in the UC Davis Department of Biomedical Engineering and Ryosuke Ota at Hamamatsu Photonics, Japan, where the new photon detector technology was developed. Other collaborators included research groups led by Professor Yoichi Tamagawa at the University of Fukui, and by Professor Tomoyuki Hasegawa at Kitasato University.

The process of tomography is required to mathematically reconstruct cross-sectional images from the data in imaging that uses X-rays or gamma rays. In PET scans, molecules tagged with trace amounts of a radioactive isotope are injected and taken up by organs and tissues in the body. The isotope, such as fluorine-18, is unstable and emits positrons as it decays.
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Researchers invent chemical reaction that could accelerate drug discovery

by Laura Bailey, University of Michigan
https://phys.org/news/2021-10-chemical- ... overy.html
Medicines come from chemical reactions, and better chemical reactions lead to better medicines.

Yet, the most popular reaction used in drug discovery, called the amide coupling, makes an inherently unstable amide bond. Because the body excels at metabolizing medication, one of the most important and difficult goals of drug research is to invent metabolically stable molecules, so we can take one pill a day instead of every 15 minutes.

To that end, researchers at the University of Michigan College of Pharmacy hacked the popular amide coupling to produce a carbon-carbon bond instead of an amide. The carbon-carbon bond is the most prevalent bond arrangement in nature and in synthetic drugs, and it's also typically more stable than the amide bond, said Tim Cernak, assistant professor of medicinal chemistry and principal investigator of the study that appears online in the Angewandte Chemie International Edition.

The discovery of the carbon-carbon bond-forming reaction opens the door to more stable medicines, and is particularly applicable to biological probes and new medical imaging agents, Cernak said.
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Needle-free vaccine patches coming soon, say researchers and makers
https://medicalxpress.com/news/2021-10- ... ccine.html
by Lucie Aubourg

Effective vaccines, without a needle: Since the start of the COVID pandemic, researchers have doubled down on efforts to create patches that deliver life-saving drugs painlessly to the skin, a development that could revolutionize medicine.

The technique could help save children's tears at doctors' offices, and help people who have a phobia of syringes.

Beyond that, skin patches could assist with distribution efforts, because they don't have cold-chain requirements—and might even heighten vaccine efficacy.

A new mouse study in the area, published in the journal Science Advances, showed promising results.

The Australian-US team used patches measuring one square centimeter that were dotted with more than 5,000 microscopic spikes, "so tiny you can't actually see them," David Muller, a virologist at the University of Queensland and co-author of the paper, told AFP.
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Researchers show 'encrypted' peptides could be wellspring of natural antibiotics
https://phys.org/news/2021-11-encrypted ... otics.html
by University of Pennsylvania

While biologists and chemists race to develop new antibiotics to combat constantly mutating bacteria, predicted to lead to 10 million deaths by 2050, engineers are approaching the problem through a different lens: finding naturally occurring antibiotics in the human genome.

The billions of base pairs in the genome are essentially one long string of code that contains the instructions for making all of the molecules the body needs. The most basic of these molecules are amino acids, the building blocks for peptides, which in turn combine to form proteins. However, there is still much to learn about how—and where—a particular set of instructions are encoded.

Now, bringing a computer science approach to a life science problem, an interdisciplinary team of Penn researchers have used a carefully designed algorithm to discover a new suite of antimicrobial peptides, hiding deep within this code.

The study, published in Nature Biomedical Engineering, was led by Cesar de la Fuente, Presidential Assistant Professor in Bioengineering, Microbiology, Psychiatry, and Chemical and Biomolecular Engineering, spanning both Penn Engineering and Penn Medicine, and his postdocs Marcelo Torres and Marcelo Melo. Collaborators Orlando Crescenzi and Eugenio Notomista of the University of Naples Federico II also contributed to this work.

"The human body is a treasure trove of information, a biological dataset. By using the right tools, we can mine for answers to some of the most challenging questions," says de la Fuente. "We use the word 'encrypted' to describe the antimicrobial peptides we found because they are hidden within larger proteins that seem to have no connection to the immune system, the area where we expect to find this function."
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Nerves may be key to blocking abnormal bone growth in tissue
https://medicalxpress.com/news/2021-11- ... -bone.html
by UT Southwestern Medical Center
A UTSW study finds that cells called pericytes (green), which wrap around the outside of blood vessels, secrete nerve growth factor (NGF) to simulate elongation of nerves into soft tissue injury. That process is associated with abnormal bone growth during healing. Deletion of NGF or its receptor (TrkA) reduces aberrant nerve growth. Credit: UT Southwestern Medical Center

Blocking a molecule that draws sensory nerves into musculoskeletal injuries prevents heterotopic ossification (HO), a process in which bone abnormally grows in soft tissue during healing, UT Southwestern researchers reported in a study. The findings, published in Nature Communications, suggest that drugs currently being tested in clinical trials to inhibit this molecule for pain relief could also protect against this challenging condition.

"Heterotopic ossification is an incredibly debilitating condition for which we have no truly effective therapies," said study leader Benjamin Levi, M.D., Associate Professor of Surgery and in the Children's Medical Center Research Institute at UT Southwestern and the Charles and Jane Pak Center for Mineral Metabolism and Clinical Research. "To be able to prevent HO from occurring after an injury while also decreasing pain would be a substantial step forward."
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New technique may lead to safer stem cell transplants
https://medicalxpress.com/news/2021-11- ... lants.html
by Julia Evangelou Strait, Washington University School of Medicine
For hard-to-treat leukemias, lymphomas and other blood cancers, stem cell transplantation is the gold standard of care. The procedure involves replacing a patient's own blood-forming stem cells with a donor's stem cells, and in the process, eradicating cancer cells in the blood, lymph nodes and bone marrow.

But many patients with such deadly blood cancers are too fragile to undergo stem cell transplants. That's because a patient's stem cells first must be destroyed by intensive chemotherapy and sometimes total body radiation before a donor's stem cells are infused. This so-called conditioning regimen makes space for incoming donor stem cells, helps to remove cancer cells remaining in the body, and depletes the patient's immune system so it can't attack the donor's stem cells. However, toxicities and suppression of the immune system caused by conditioning regimens puts patients at high risk of infections, organ damage and other life-threatening side effects.

Now, studying mice, researchers at Washington University School of Medicine in St. Louis have developed a method of stem cell transplantation that does not require radiation or chemotherapy. Instead, the strategy takes an immunotherapeutic approach, combining the targeted elimination of blood-forming stem cells in the bone marrow with immune-modulating drugs to prevent the immune system from rejecting the new donor stem cells. With the new technique, mice underwent successful stem cell transplants from unrelated mice without evidence of dangerously low blood cell counts that are a hallmark of the traditional procedure. The data also suggested that such stem cell transplants can be effective against leukemia.
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Microbiome discovery may open new doors to development of treatments for gastrointestinal diseases
https://medicalxpress.com/news/2021-11- ... tinal.html
by Mike Fisher, University of Calgary
University of Calgary researchers probing the gut—"the inner tube of life"—have for the first time discovered specific factors in its workings that in the future may help improve treatment for patients facing gut damage or gastrointestinal disease.

The findings from Snyder Institute for Chronic Diseases researchers immediately improve the understanding of factors that help regulate the enteric nervous system, the system of nerves that control the gastrointestinal tract. Researchers can now explore novel ways to treat gastrointestinal disorders using approaches based on these new findings, though the transition to treatment is likely years away.

The study's findings may impact future treatments for gastrointestinal diseases and disorders such as irritable bowel syndrome, inflammatory bowel disease and slow transit constipation, among others.
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