Biology & Medicine News and Discussions

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New study reveals hundreds of new drug targets to combat tuberculosis
https://medicalxpress.com/news/2022-05- ... losis.html
by Rockefeller University
Tuberculosis is a stubborn disease, born of yet more stubborn microbes. While many bacterial infections resolve within days of starting antibiotics, tuberculosis often refuses to budge for around six months, and in some cases, may never release its vice grip on the human body. It claimed 1.5 million lives in 2020, second only to COVID-19 among infectious diseases.

Now, a new study in Nature Microbiology maps the methods by which Mycobacterium tuberculosis (Mtb) bacteria shrug off antibiotics, revealing hundreds of drug targets that could strip this pathogen of its notorious resistances. The scientists also identified a class of existing antibiotics that may be particularly effective against one prominent strain in Southeast Asia.

"Examining how current drugs affect bacterial physiology, and how the bacterium subverts this, is part of our long-term goal of developing better treatment combinations," says Rockefeller University's Jeremy Rock, head of Laboratory of Host-Pathogen Biology. "This study is the tip of the spear getting us into that realm."

A genome-wide view of Mtb

The researchers started out with a simple question. "We just wanted to know all of the genes involved in Mtb's resistance to different antibiotics," says Nick Poulton, a graduate student in Rock's lab and coauthor on the study. The team developed a platform based on the CRISPR gene knockdown tool that scoured the Mtb genome, pitting the bacteria against common antibiotics to quantify how the absence or presence of each gene impacted the efficacy of existing drugs.
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U.S. Health Outpaced by Other Countries, as Journal Looks for Root Causes
May 31, 2022

Introduction:
(EurekAlert) Health and mortality in the U.S. continue to rank poorly compared to peer nations, and a new supplemental issue to The Journals of Gerontology, Series B: Psychological Sciences and Social Sciences titled “Why Does Health in the U.S. Continue to Lag Behind?” features papers that analyze the reasons for the downward trends.

In 2010, according to the journal, life expectancy at birth in the U.S. was a full year lower than the average of 27 European Union countries; in the subsequent decade, the shortfall doubled, and the COVID-19 pandemic has widened the gap.

Even the most affluent U.S. states — those characterized by dynamic gig economies with many highly skilled workers — exhibit outcomes that are on par or lag national averages of other high-income countries. Chronic disease and disability levels are also generally higher in the U.S. compared to many other peer countries.

The supplemental issue was guest edited by Neil K. Mehta, PhD, of The University of Texas Medical Branch, Mikko Myrskylä, PhD, of the Max Planck Institute for Demographic Research, and the late Robert F. Schoeni, PhD, of the University of Michigan.

“There’s no simple answer,” Mehta said. “The issue touches on the many complicated factors with a focus on social and behavioral factors. The U.S. has lagged behind for some time, but over the last decade it’s gotten a lot worse. Even though the U.S. has fared poorly compared to other countries, we are falling even further behind.”
Read more here: https://www.eurekalert.org/news-releases/954447
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weatheriscool
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New type of triterpenes discovered
https://phys.org/news/2022-06-triterpenes.html
by University of Tokyo

A collaborative effort has revealed a new type of triterpene, a group of organic compounds which are an important source of many medicines. Until now, all triterpenes were believed to be derived from squalene, itself a type of triterpene. However, for the first time, researchers witnessed biosynthesis of triterpenes in fungi without the use of squalene. This important discovery opens up a whole new world of possibilities for pharmaceutical science.

Triterpenes are organic compounds which are abundantly found in animals, plants, microorganisms and even us. About 20,000 different triterpenes have been found and they are widely used in cosmetics, food supplements and, most importantly, medicine, thanks to their anti-inflammatory, anti-cancer, anti-diabetic and other valuable properties. Until now, all known triterpenes were thought to be generated from a common precursor or source, squalene.

However, as revealed in Nature, a collaborative effort among the University of Tokyo and KEK in Japan, Wuhan University in China and Bonn University in Germany, has found a new type of triterpenes that doesn't require squalene.

"Nobody could have imagined this happening in nature. This is the discovery of a new biosynthetic machine," explained Professor Ikuro Abe from the Graduate School of Pharmaceutical Sciences at the University of Tokyo.
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This parasite will self-destruct: Researchers discover new weapon against drug-resistant malaria
https://phys.org/news/2022-06-parasite- ... laria.html
by University of Melbourne
A new method to combat malaria, which sees the disease turn against itself, could offer an effective treatment for the hundreds of millions of people infected globally each year as the efficacy of current antimalarial drugs weakens.

The University of Melbourne-led research published today in Science has identified an anti-malarial compound, ML901, which inhibits the malaria parasite but does not harm mammalian—human or other mammals'—cells.

Co-lead author Professor Leann Tilley, from the Bio21 Institute at the University of Melbourne, said the ML901 compound effectively made the parasite the agent of its own demise, underpinning it potency and selectivity.

"ML901 works by an unusual reaction-hijacking mechanism," Professor Tilley said.

"Imagine a stealth weapon that can be used to launch a self-destruct attack on your vehicle—slamming on the brakes and cutting the engine. ML901 finds a particular chink in the machinery that the malaria parasite uses to generate the proteins needed to reproduce itself and stops it doing so.

"While there is much work to be done to fine-tune what we've discovered, these results are really encouraging in the search for new antimalarials."
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Repurposing cancer drug to treat neuroinflammation
https://medicalxpress.com/news/2022-06- ... ation.html
by Karolinska Institutet
The repurposing of FDA-approved drugs for alternative diseases is a faster way of bringing new treatments into the clinic. Researchers at Karolinska Institutet in Sweden have repurposed a cancer drug for treatment of neuroinflammatory diseases such as multiple sclerosis. A novel drug carrier was also developed to facilitate drug delivery to target myeloid cells. These pre-clinical findings are described in a paper in the journal EMBO Reports.

Microglia are an organ-specific type of macrophage in the central nervous system. In the majority of chronic neurodegenerative disease conditions, such as amyotrophic lateral sclerosis (ALS), Alzheimer's disease and chronic multiple sclerosis (MS), dysfunctional microglia play an important role. Modifying the activation of these disease-promoting microglia is an attractive therapeutic principle.

"The biotechnology industry has realized the potential for microglia-targeting strategies, and at least 20 new companies have started during recent years," says Professor Bob Harris at the Center for Molecular Medicine, Karolinska University Hospital and the Department of Clinical Neuroscience, Karolinska Institutet. "Compared to novel drug discovery programs that can take 20 years before a new medicine is approved, using existing prescribed drugs can halve that time."

The researchers used in silico drug screening to identify candidates for microglial modulation and selected a Topoisomerase 1 (TOP1) inhibitor for further study. TOP1 was highly expressed in neuroinflammatory conditions both in mice and in tissues from MS patients, and TOP1 inhibition using camptothecin (CPT) and its FDA-approved analog topotecan (TPT) reduced inflammatory responses in microglia and macrophages in in vitro cultures, as well as ameliorating neuroinflammatory diseases in vivo.
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Researchers find epigenetic changes during pregnancy may contribute to the development of asthma

by University of Chicago Medical Center
https://medicalxpress.com/news/2022-06- ... sthma.html
Asthma is a chronic condition that affects 25 million people in the United States. Having a mother with asthma is an important risk factor and a new study may explain why. A team of researchers at the University of Chicago have found striking epigenetic differences in the airway cells of patients with asthma who have asthmatic mothers, compared to patients whose mothers never had asthma. The research was published on June 6 in Proceedings of the National Academy of Sciences.

Carole Ober, Ph.D., and her research team have spent years examining genetic influences that contribute to the development of asthma, including epigenetic factors. Epigenetics refers to changes in how genes are expressed that are not directed by changes or mutations in the DNA sequence itself. Instead, gene activity can be turned on or off by the attachment of small chemical structures such as methyl groups to DNA. Many environmental factors are known to impact DNA methylation patterns, including the in-utero environment.

In the study, the team found different DNA methylation patterns in epithelial cells of the lower airways of asthmatic adults with asthmatic mothers compared to those whose mothers did not have asthma.
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Stem cell research reveals detailed genetic roadmap of glaucoma
https://medicalxpress.com/news/2022-06- ... admap.html
by University of Melbourne
A new, detailed genetic roadmap of glaucoma—the world's leading cause of irreversible blindness—will help researchers develop new drugs to combat the disease, by identifying potential target areas to stall or reverse vision loss.

The research, one of the largest and most detailed stem cell modeling studies reported for any disease, is published today in Cell Genomics.

By comparing stem cell models of the retinal ganglion cells of people with Primary Open Angle Glaucoma to those without the disease, more than 300 novel genetic features of these cells were uncovered.

The findings are the result of a national collaboration led by Professor Alex Hewitt (Centre for Eye Research Australia, University of Melbourne and University of Tasmania), Professor Alice Pébay and Dr. Maciej Daniszewski (University of Melbourne) and Ms Anne Senabouth and Professor Joseph Powell (Garvan Institute of Medical Research).

Professor Hewitt, who is Head of Clinical Genetics at CERA, says the study will lead to a better understanding of the mechanisms that damage retinal ganglion cells and lead to the onset of glaucoma.
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Rapid Ebola diagnosis may be possible with new technology
https://medicalxpress.com/news/2022-06- ... ology.html
by Washington University School of Medicine
A new tool can quickly and reliably identify the presence of Ebola virus in blood samples, according to a study by researchers at Washington University School of Medicine in St. Louis and colleagues at other institutions.

The technology, which uses so-called optical microring resonators, potentially could be developed into a rapid diagnostic test for the deadly Ebola virus disease, which kills up to 89% of infected people. Since it was discovered in 1976, Ebola virus has caused dozens of outbreaks, mostly in central and west Africa. Most notable was an outbreak that began in 2014 and killed more than 11,000 people in Guinea, Sierra Leone and Liberia; in the U.S., the virus caused 11 cases and two deaths. A rapid, early diagnostic could help public health workers track the virus' spread and implement strategies to limit outbreaks.

The study—which also involved researchers from the University of Michigan, Ann Arbor, and Integrated Biotherapeutics, a biotech company—is published June 8 in Cell Reports Methods.

"Any time you can diagnose an infection earlier, you can allocate health-care resources more efficiently and promote better outcomes for the individual and the community," said co-first author Abraham Qavi, MD, Ph.D., a postdoctoral researcher at Washington University. "Using a biomarker of Ebola infection, we've shown that we can detect Ebola infection in the crucial early days after infection. A few days makes a big difference in terms of getting people the medical care they need and breaking the cycle of transmission."
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New drug delivery system releases therapeutic cargo only when bacteria are present
https://phys.org/news/2022-06-drug-deli ... teria.html
by Kevin Stacey, Brown University

A team of Brown University researchers has developed a new responsive material that is able to release encapsulated cargo only when pathogenic bacteria are present. The material could be used to make wound dressings that respond quickly to burgeoning infections, but only deliver medication on demand.

The development is particularly relevant in the face of the global antibiotic resistance crisis, the researchers say, as the material could help to fight infections while also addressing the problem of resistance.

"We've developed a bacteria-triggered, smart drug-delivery system," said Anita Shukla, an associate professor in Brown's School of Engineering, who led the material's development. "Our hypothesis is that technologies like this, which reduce the amount of drug that's required for effective treatment, can also reduce both side effects and the potential for resistance."

The new material, described in the journal ACS Applied Materials and Interfaces, is a hydrogel—a hydrated polymer network. Hydrogels are highly biocompatible, and can be used to encapsulate a range of nanoparticles or small molecule therapeutics. They are often used in wound dressings. "Smart" or responsive hydrogels are emerging as promising platforms for drug delivery. They can be made to respond to the localized environment—speeding or slowing the release of medication in response to temperature, pH or other factors.
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New delivery method allows slow-release of broader array of peptide drugs in the body
https://phys.org/news/2022-06-delivery- ... array.html
by University of Michigan

A new study from the University of Michigan describes one of the first entirely new drug delivery microencapsulation approaches in decades.

Microencapsulation in biodegradable polymers allows drugs such as peptide therapeutics to be released over time in the body.

Peptides are molecules in the body that are composed of short chains of amino acids, and include messengers, growth factors and well-known hormones such as insulin. Because of their larger size and structure, peptide drugs are rarely given by mouth and must be injected. Microencapsulation is one way to decrease the time needed between injections.

One slow-release delivery method for peptide drugs is to encapsulate them within the type of resorbable polymers often used as dissolving sutures, said study co-author Steven Schwendeman, professor of pharmaceutical sciences and biomedical engineering.

However, development of polymer dosage forms for delivery of certain peptide drugs has been difficult because the currently available methods to microencapsulate the peptide molecules in the polymer require organic solvents and complex manufacturing.

"The Schwendeman group discovered about 10 years ago that peptides can bind and enter the polymer spontaneously from water to microencapsulate the peptide very simply without organic solvent," Schwendeman said.
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