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.
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.
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."...
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.
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.
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.
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.
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."
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).
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.
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.
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.
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.
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.
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.
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.
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."
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."
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.
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.