Biology & Medicine News and Discussions

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Nuclei on the move for muscle self-repair
https://medicalxpress.com/news/2021-10- ... epair.html
by Instituto de Medicina Molecular
Muscle is known to regenerate through a complex process that involves several steps and depends on stem cells. Now, a new study led by researchers at the Instituto de Medicina Molecular João Lobo Antunes (iMM; Portugal) and the University Pompeu Fabra (UPF Barcelona; Spain) and published today in the scientific journal Science, describes a new mechanism for muscle regeneration after physiological damage relying on the rearrangement of nuclei. This protective mechanism opens the road to a broader understanding of muscle repair in physiology and disease.
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Research reveals potential new strategy to combat urinary tract infections
https://medicalxpress.com/news/2021-10- ... inary.html
by Baylor College of Medicine

Identifying the dynamic events occurring during urinary tract infections (UTI) has revealed a new potential strategy to combat this condition, considered the most common type of infection. Researchers at Baylor College of Medicine and Washington University School of Medicine have discovered that the sequence of events taking place during UTI sustains a delicate balance between the responses directed at eliminating the bacteria and those minimizing tissue damage that may occur in the process.

The NRF2 pathway stood out as a key contributor to this balance, by regulating both the potential damage to tissues and the elimination of bacteria. Treating an animal model of UTI with the FDA-approved, anti-inflammatory drug dimethyl fumarate (DMF), a known NRF2 activator, reduced tissue damage and bacterial burden, opening the possibility that DMF could be used to manage this condition in the future. The study appears in the journal Cell Reports.

"Urinary tract infections are not only common, but typically recurrent and tend to give rise to antibiotic-resistant bacteria, a serious medical concern," said corresponding author Dr. Indira Mysorekar, E. L. Wagner Endowed Professor of Medicine- infectious diseases at Baylor, previously at Washington University School of Medicine.
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2 Blood Pressure Meds Recalled For Possibly Containing A Cancer-Causing Substance
Source: NPR

Two types of blood pressure medication made by the company Lupin Pharmaceuticals are being recalled because they may contain high levels of a substance that could cause cancer. The Food and Drug Administration said late last week that Lupin is voluntarily recalling certain dosages of irbesartan tablets and irbesartan and hydrochlorothiazide tablets.

Both are used to treat hypertension, or high blood pressure, and were distributed in 30- and 90-count bottles nationwide. The company found that certain batches of those drugs were "above the specification limit for the impurity N-nitrosoirbesartan," which could cause cancer in humans. It says it's received no reports of illness that appear to be related to this issue, but is acting out of an abundance of caution. It's recalling:

All batches of irbesartan tablets USP 75mg, 150mg and 300mg. All batches of irbesartan and hydrochlorothiazide tablets USP, 150mg/12.5mg and 300mg/12.5mg. Lupin says it received four reports of illness from irbesartan and none from irbesartan and hydrochlorothiazide between October 2018 (when the first of these affected batches were shipped from the manufacturing site) and the end of September 2021.

It discontinued the marketing of both drugs in January of this year. Here's what to do Lupin advises patients prescribed the drugs to continue taking their medication and contact their pharmacist, physician or medical provider for advice "regarding an alternative treatment."...
Read more: https://www.npr.org/2021/10/20/10476589 ... rothiazide
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Discovery of a potential new therapy for inflammatory arthritis
https://medicalxpress.com/news/2021-10- ... ritis.html
by University Health Network

In a paper published today in the journal Science Translational Medicine, researchers at the Schroeder Arthritis Institute, part of University Health Network (UHN) in Toronto, have made a discovery that could lead to new treatments for axial spondyloarthritis (SpA), a painful and debilitating form of arthritis which affects 1-2% of Canadians and causes inflammation in the spine, joints, eyes, gut and skin.

"We currently have very few therapeutic options for the majority of patients living with SpA and this is a devastating disease that directly impacts quality of life," says Dr. Nigil Haroon, a rheumatologist, Co-Director of the spondylitis program and senior author on the paper.

"Although several treatments including biologic drugs have been approved for SpA, 40-50 % of patients do not respond to any treatments and develop severe pain and abnormal new bone formation," says Dr. Akihiro Nakamura, first author on the paper and a spondylitis fellow and Ph.D. candidate in Dr. Haroon's lab. "So, there is a desperate need to find new treatments that are effective and cover all of the clinical symptoms of SpA."

The study focuses on the role of the Macrophage migration inhibitory factor (MIF), which functions as a protein that induces an inflammatory or immune response in the body. Until now, the role that MIF plays in the disease progression of SpA was unknown.

In this study, researchers observed that the expression of MIF and its receptor CD74, is increased in the blood and tissues of pre-clinical models. They also found that human neutrophils (a type of white blood cell that induces the immune system's response) from SpA patients secreted higher concentrations of MIF, compared to healthy individuals. This, in turn, drives other cells to cause more inflammation.
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Novel computational pipeline could help repurpose cancer drugs for rare diseases
https://medicalxpress.com/news/2021-10- ... -rare.html
by University of Pittsburgh

By combining computational and experimental approaches, University of Pittsburgh School of Medicine and Prairie View A&M University researchers identified cancer drugs that show promise for treating pulmonary hypertension, or PH, a rare and incurable lung disease.

Published today in Science Advances, the study used a new algorithm to identify candidate cancer drugs for PH. Two of these compounds improved markers of the disease in human cells and rodents. The findings support broader use of this drug-repurposing platform for other non-cancerous conditions that don't yet have effective treatments.

"Repurposing drugs can cut down the time and cost of developing treatments for rare diseases, which historically don't receive much investment into research and drug development," said senior author Stephen Chan, M.D., Ph.D., professor of medicine and director of the Vascular Medicine Institute at Pitt and UPMC. "Pulmonary hypertension is an example of a rare disease where there is an unmet need for new treatments, given its devastating consequences. We developed this pipeline to rapidly predict which drugs are effective for PH and get these treatments to patients faster."

Pulmonary hypertension is a type of high blood pressure that occurs in the vessels that transport blood from the heart to the lungs. As the disease progresses and the heart must strain harder against these high pressures, it can lead to heart failure, multi-organ dysfunction and death. PH affects people of all ages but hits young women more often than men.

One of these young women is Allison Dsouza, a 24-year-old nurse who not only lives with the condition herself but also treats PH patients in the UPMC Lung Transplant Program. She was diagnosed with PH as a high school senior after she started having trouble walking to her car and doing hobbies like horseback riding. According to Dsouza, she was the sickest patient with the highest lung pressures that her doctors had seen.
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Nature-inspired coatings could power tiny chemistry labs for medical testing and more
https://phys.org/news/2021-10-nature-in ... istry.html
by Lynsey Mellon, University of Toronto
A newly developed coating that allows for certain liquids to move across surfaces without fluid loss could usher in new advances in a range of fields, including medical testing.

This new coating—created in the DREAM (Durable Repellent Engineered Advanced Materials) Laboratory, led by University of Toronto Engineering Professor Kevin Golovin—was inspired by the natural world.

"Nature has already developed strategies to transport liquids across surfaces in order to survive," says Mohammad Soltani, researcher in the DREAM Laboratory and lead author of a new paper recently published in Advanced Functional Materials.

"We were inspired by the structural model of natural materials such as cactus leaves or spider silk. Our new technology can directionally transport not only water droplets, but also low surface tension liquids that easily spread on most surfaces."

The innovation has important implications for microfluidics, a field where small quantities of liquids are transported within tiny channels, often less than a millimetre wide. This technique has many applications, one of them being to miniaturize the standard analytical tests that are currently preformed in chemical laboratories.
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Novel approach to treating type 2 diabetes shows prolonged normal blood sugar levels after a single one-time procedure
https://medicalxpress.com/news/2021-10- ... sugar.html
by American Technion Society

A novel approach to treating type 2 diabetes is being developed at the Technion. The disease, caused by insulin resistance and reduction of cells' ability to absorb sugar, is characterised by increased blood sugar levels. Its long-term complications include heart disease, strokes, damage to the retina that can result in blindness, kidney failure, and poor blood flow in the limbs that may lead to amputations. It is currently treated by a combination of lifestyle changes, medication, and insulin injections, but ultimately is associated with a 10-year reduction in life expectancy.

Led by Professor Shulamit Levenberg, Ph.D. student Rita Beckerman from the Stem Cell and Tissue Engineering Laboratory in the Technion's Faculty of Biomedical Engineering presents a novel treatment approach, using an autograft of muscle cells engineered to take in sugar at increased rates. Mice treated in this manner displayed normal blood sugar levels for months after a single procedure. The group's findings were recently published in Science Advances.

Muscle cells are among the main targets of insulin, and they are supposed to absorb sugar from the blood. In their study, Prof. Levenberg's group isolated muscle cells from mice and engineered these cells to present more insulin-activated sugar transporters (GLUT4). These cells were then grown to form an engineered muscle tissue, and finally transported back into the abdomen of diabetic mice. The engineered cells not only proceeded to absorb sugar correctly, improving blood sugar levels, but also induced improved absorption in the mice's other muscle cells, by means of signals sent between them. After this one treatment, the mice remained cured of diabetes for four months—the entire period they remained under observation. Their blood sugar levels remained lower, and they had reduced levels of fatty liver normally displayed in type 2 diabetes.
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Scientists make breakthrough in understanding how penicillin works
https://phys.org/news/2021-10-scientist ... illin.html
by University of Sheffield
The mechanism which allows β-lactam antibiotics, including penicillin, to kill MRSA has been revealed for the first time.

An international team of researchers led by the University of Sheffield discovered that β-lactam antibiotics kill MRSA (Methicillin Resistant S. aureus) by creating holes in the cell wall which enlarge as the cell grows, eventually killing the bacteria.

The growth of these holes leads to failure of the cell wall and death of the bacteria, something which the scientists now plan to exploit in order to create new therapeutics for antibiotic resistant superbugs.

It was previously known that β-lactam antibiotics work by preventing cell wall growth, but exactly how they kill has remained a mystery until now.

Professor Simon Foster, from the University of Sheffield's School of Biosciences, said: "Penicillin and other antibiotics in its class have been a centrepiece of human healthcare for over 80 years and have saved over 200 million lives. However, their use is severely threatened by the global spread of antimicrobial resistance.

"Concentrating on the superbug MRSA, our research revealed that the antibiotics lead to the formation of small holes that span the cell wall that gradually enlarge as part of growth-associated processes, eventually killing the bacteria. We also identified some of the enzymes that are involved in making the holes.

"Our findings get to the heart of understanding how existing antibiotics work and give us new avenues for further treatment developments in the face of the global pandemic of antimicrobial resistance."
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Sharpest images ever reveal the patchy face of living bacteria
https://phys.org/news/2021-10-sharpest- ... teria.html
by University College London
The sharpest images ever of living bacteria have been recorded by UCL researchers, revealing the complex architecture of the protective layer that surrounds many bacteria and makes them harder to be killed by antibiotics.

The study, published today in Proceedings of the National Academy of Sciences and done in collaboration with scientists at National Physical Laboratory, King's College London, University of Oxford and Princeton University, reveals that bacteria with protective outer layers—called Gram-negative bacteria—may have stronger and weaker spots on their surface.

The team found that the protective outer membrane of the bacteria contains dense networks of protein building blocks alternated by patches that do not appear to contain proteins. Instead, these patches are enriched in molecules with sugary chains (glycolipids) that keep the outer membrane tight.

This is an important finding because the tough outer membrane of Gram-negative bacteria prevents certain drugs and antibiotics from penetrating the cell: this outer membrane is part of the reason why antimicrobial resistance of such bacteria (including A. baumannii, P. aeruginosa, and enterobacteriaceae such as Salmonella and E. coli) is now considered a greater threat than that of Gram-positive bacteria such as resistant S. aureus (well known as MRSA).
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Deterioration of brain cells in Parkinson's disease is slowed by blocking the Bach1 protein, preclinical study shows
https://medicalxpress.com/news/2021-10- ... sease.html
by Medical University of South Carolina
Parkinson's disease (PD) is the most common neurodegenerative movement disorder, afflicting more than 10 million people worldwide and more than one million Americans. While there is no cure for PD, current therapies focus on treating motor symptoms and fail to reverse, or even address, the underlying neurological damage. In a new study, researchers at the Medical University of South Carolina (MUSC) have identified a novel role for the regulatory protein Bach1 in PD. Their results, published on Oct. 25 in the Proceedings of the National Academy of Sciences, showed that levels of Bach1 were increased in postmortem PD-affected brains, and that cells without Bach1 were protected from the damages that accumulate in PD. In collaboration with vTv Therapeutics, they identified a potent inhibitor of Bach1, called HPPE, that protected cells from inflammation and the buildup of toxic oxidative stress when administered either before or after the onset of disease symptoms.

"This is the first evidence that Bach1 is dysregulated in Parkinson's disease," said Bobby Thomas, Ph.D., professor of Pediatrics in the College of Medicine and the SmartState COEE Endowed Chair in Pediatric Neurotherapeutics.

In PD, brain cells that produce the chemical messenger dopamine begin to die as the disease progresses, resulting in tremors and other disruptions to motor function. Additionally, as we age, neurons accumulate damage through inflammation and the buildup of toxic oxidative stress.
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