Publisher Health

Researchers at UVA Cancer Center have unveiled important new insights into how hormones known as androgens act on our cells — and the discovery could boost efforts to develop better treatments for prostate, ovarian and breast cancers.
The findings shed light on how androgens interact with their receptors inside cells to affect gene activity. This process is important in both healthy cells and certain cancers. Hormone therapy for prostate cancer, for example, aims to reduce the amount of androgen in the body, or to stop it from fueling the cancer cells. However, the approach does not work for some men, and for others it eventually fails. So scientists are eager to better understand how our cells — and cancer — interact with androgen.
“Our study reveals a new mechanism for how androgen regulates communication within prostate cancer cells,” said Bryce M. Paschal, PhD, of the University of Virginia School of Medicine’s Department of Biochemistry and Molecular Genetics. “Anti-androgen therapies continue to be the cornerstone for prostate cancer therapy. The better we understand how androgens work, the better clinicians will be positioned to understand why it fails, and how even better therapies can be designed.”
Androgen and Cancer
In a new paper in the scientific journal Nature Communications, Paschal and his colleagues describe how a complex signaling system regulates androgen receptor activity. The system, they found, uses a “writer” and a “reader” to modify cellular proteins — sort of like how a computer reads and writes information.
Scientists have appreciated the importance of these modified proteins, but understanding just how they influence the androgen receptors has been difficult. One key to the regulation process, found by Paschal and his SOM team, is an enzyme, Parp7, produced by the PARP7 gene. Parp7 is part of a family of enzymes involved in important cellular functions including DNA repair.
Certain cancer drugs already target certain Parp enzymes; these drugs are used to treat prostate, ovarian and breast cancers in patients who have mutations in DNA-repair genes. And while androgens are usually discussed in the context of prostate cancer, androgens may be important in ovarian and breast cancer as well.
Paschal’s new findings offer fresh insights into these Parp drugs and could lead to improved treatments that help patients get the best outcomes. Further, Paschal and his team found lower levels of Parp7 in prostate cancer that has spread to other parts of the body than in the initial tumors. That may suggest that a reduction in Parp7 is associated with the progression of the disease, the researchers say.
With their new androgen insights, Paschal and his colleagues have provided scientists with important new directions to explore in the battle against prostate and other cancers.
“Our next steps will be to use preclinical models to determine the role this pathway plays in prostate cancer progression, and whether inhibition of the pathways slows disease,” Paschal said. “We are very excited by what we have learned thus far. Our study emphasizes there is still so much to be learned, and that basic science plays a critical role in defining the molecular context for enzyme and drug action. ”
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Materials provided by University of Virginia Health System. Note: Content may be edited for style and length.

Ro, the parent company of Roman, the brand that is best known for delivering erectile dysfunction and hair loss medication to consumers, announced on Wednesday that it would acquire Modern Fertility, a start-up that offers at-home fertility tests for women.The deal is priced at more than $225 million, according to people with knowledge of the acquisition who spoke on condition of anonymity because the information was not public. It is one of the largest investments in the women’s health care technology space, known as femtech, which attracted $592 million in venture capital in 2019, according to an analysis by PitchBook.Modern Fertility was founded in 2017 with its flagship product: a $159 finger prick test that can estimate how many eggs a woman may have left, which can help determine which fertility method might be best.“We essentially took the same laboratory tests that women would take in an infertility clinic and made them available to women at a fraction of the cost,” said Afton Vechery, a founder and chief executive of Modern Fertility, noting that her own test at a clinic set her back $1,500.The company now also sells an at-home test, available at Walmart, to help track ovulation, as well as standard pregnancy tests and prenatal vitamins.Ro, which was founded in 2017 with a focus on men’s health and was valued in March at about $5 billion, has in recent years expanded into telehealth, including delivering generic drugs by mail. In December, Ro acquired Workpath, which connects patients with in-home care providers, like nurses.The global digital health market, which includes telemedicine, online pharmacies and wearable devices, could reach $600 billion by 2024, according to the consulting firm McKinsey & Company. And yet, by one estimate, only 1.4 percent of the money that flows into health care goes to the femtech industry, mirroring a pattern in the medical industry, which has historically overlooked women’s health research.“Gender bias in health care research methods and funding has really contributed to sexism in medicine and health care,” said Sonya Borrero, director of the Center for Women’s Health Research and Innovation at the University of Pittsburgh. “I think we’re seeing again — gender bias in the venture capital sector is going to exactly shape what gets developed.”That underinvestment was part of the reasoning behind the acquisition, said Zachariah Reitano, Ro’s chief executive. The company developed a female-focused online service in 2019 called Rory.“We’re going to continue to invest hundreds of millions of dollars over the next five years into women’s health,” Mr. Reitano said, “because ultimately I think women’s health has the potential to be much larger than men’s health.”

Labour’s Andy Slaughter has called on the prime minister to give NHS nurses “more than an insulting 1% pay rise”.He raised the case of Jenny McGee, a nurse who treated the PM for Covid, who is leaving the NHS and has criticised the handling of the pandemic.Boris Johnson spoke of his “own huge personal debt” to nurses, and said started salaries had been raised, and “many more nurses” has been recruited.PMQs: As it Happened in text, images and video

Researchers from Case Western Reserve University have identified a potential new approach to better controlling epileptic seizures.
Lin Mei, professor and chair of the Department of Neurosciences at the Case Western Reserve School of Medicine, who led the new study in mouse models, said the team found a new chemical reaction that could help control epileptic seizures.
Their findings were recently published in The Journal of Clinical Investigation.
Epilepsy is a neurological disorder in which abnormal brain activity causes seizures or periods of unusual behavior, sensations and sometimes loss of awareness.
A human brain contains about 86 billion nerve cells, also known as neurons. Eighty percent of them — known as excitatory neurons — send messages to bundles of nerves that control muscles, typically calling on them to do something. In a healthy brain, activity that excitatory neurons inspire is managed by the remaining 20% of nerve cells, called inhibitory neurons.
“This balance between excitatory and inhibitory neurons is absolutely important for everything that we do,” Mei said. “When the balance is tilted, so that excitatory neurons are super active, there will be a problem. It’s highly likely there will be epilepsy.”

Blocked blood vessels in the brains of stroke patients prevent oxygen-rich blood from getting to cells, causing severe damage. Plants and some microbes produce oxygen through photosynthesis. What if there was a way to make photosynthesis happen in the brains of patients? Now, researchers reporting in ACS’ Nano Letters have done just that in cells and in mice, using blue-green algae and special nanoparticles, in a proof-of-concept demonstration.
Strokes result in the deaths of 5 million people worldwide every year, according to the World Health Organization. Millions more survive, but they often experience disabilities, such as difficulties with speech, swallowing or memory. The most common cause is a blood vessel blockage in the brain, and the best way to prevent permanent brain damage from this type of stroke is to dissolve or surgically remove the blockage as soon as possible. However, those options only work within a narrow time window after the stroke happens and can be risky. Blue-green algae, such as Synechococcus elongatus, have been studied previously to treat the lack of oxygen in heart tissue and tumors using photosynthesis. But the visible light needed to trigger the microbes can’t penetrate the skull, and although near-infrared light can pass through, it is insufficient to directly power photosynthesis. “Up-conversion” nanoparticles, often used for imaging, can absorb near-infrared photons and emit visible light. So, Lin Wang, Zheng Wang, Guobin Wang and colleagues at Huazhong University of Science and Technology wanted to see if they could develop a new approach that could someday be used for stroke patients by combining these parts — S. elongatus, nanoparticles and near-infrared light — in a new “nano-photosynthetic” system.
The researchers paired S. elongatus with neodymium up-conversion nanoparticles that transform tissue-penetrating near-infrared light to a visible wavelength that the microbes can use to photosynthesize. In a cell study, they found that the nano-photosynthesis approach reduced the number of neurons that died after oxygen and glucose deprivation. They then injected the microbes and nanoparticles into mice with blocked cerebral arteries and exposed the mice to near-infrared light. The therapy reduced the number of dying neurons, improved the animals’ motor function and even helped new blood vessels to start growing. Although this treatment is still in the animal testing stage, it has promise to advance someday toward human clinical trials, the researchers say.
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Materials provided by American Chemical Society. Note: Content may be edited for style and length.

Steps to ensure safety and mitigate the spread of COVID-19 have had some unintended consequences on the management of chronic conditions such as high blood pressure, a leading cause of heart disease and health disparities in the United States. COVID-19 has disproportionately affected people from different racial and ethnic groups, those who are from under-resourced populations and communities that face historic or systemic disadvantages. Discussions and research are ongoing to address what many experts label as long-existing inequities in the U.S. health system, according to information published today in the Journal of the American Heart Association, an open access journal of the American Heart Association.
“Media coverage has examined how and why COVID-19 is disproportionately impacting communities of color to some degree. However, it is critical that we continue to examine and explain the degree to which the pandemic has widened the divide among race/ethnic and class groups in the U.S. and exposed the systemic and institutional cracks in our health care system in terms of health care equity for people who are under-represented and populations that face disadvantages,” said Adam Bress, Pharm.D., M.S., lead author of the paper, an associate professor of population health science in the Division of Health System Innovation and Research at the University of Utah School of Medicine in Salt Lake City and an investigator at the VA Salt Lake City Health Care System. “COVID-19 has also reminded us that when we design interventions, it is important to consider health equity from the beginning rather than as an afterthought.”
A panel of frontline clinicians, researchers and leaders from diverse backgrounds recently convened virtually at the 4th Annual University of Utah Translational Hypertension Symposium to discuss how the pandemic has worsened inequities in blood pressure control and to highlight the environmental and socioeconomic factors contributing to disparities within the health care system, as well as strategies to help close the gap going forward.
The group also discussed the latest research on trends in hypertension care and effective ways to improve outcomes, and this study reflects a comparison on hypertension statistics before and during the COVID-19 pandemic outlined in previously published research.
One large nationwide study of over 50,000 adults indicated the number of people maintaining healthy blood pressure levels had been declining even prior to the pandemic, with lack of health insurance and access to health care being key factors. High blood pressure in this study was defined as greater than 140/90 mm Hg (the current American Heart Association guidelines define high blood pressure as 130/80 mm Hg). The research showed that from 2017-2018, only 22% of uninsured people in the study had healthy blood pressure levels, compared to 40-46% of the people who had some form of health insurance. Additionally, among the people who had not seen a health care professional in the previous year, only 8% had their blood pressure under control, compared to 47% of those who reported seeing a health care professional. The results also indicated Black adults were 12% less likely to have healthy blood pressure levels compared to white adults.
One nationally representative audit of practices in the U.S. shows that during the second quarter of 2020, new health care visits for the purpose of managing high blood pressure, both in-person and virtual, decreased by 39% compared to the same quarter in 2018 and 2019. A dangerous decrease in hospitalizations due to heart attacks, strokes and heart failure since COVID-19 was noted in another study of hospitalizations, yet it also found a 20% increase in out-of-hospital deaths during the same time period.

A new article from Liverpool ocular researchers demonstrates that small uveal (intraocular) melanomas are not always harmless, as the current paradigm suggests.
Instead, a reasonable proportion of them have molecular genetic alterations, which categorises them as highly metastatic tumours. The article recommends that they should not be observed but rather treated immediately, to improve patients’ chances of survival.
The paper shows that uveal melanoma patients with small tumours, when treated within a certain time frame in Liverpool, do indeed have improved outcomes.
The study was undertaken by researchers at Liverpool Ocular Oncology Centre based at Liverpool University Hospitals NHS Foundation Trust, the Liverpool Ocular Oncology Research Group (LOORG) at the University of Liverpool and with Professor Bertil Damato, formerly of Liverpool and now based at the Ocular Oncology Service at Moorfields Eye Hospital, London.
First author Dr Rumana Hussain, of Liverpool Ocular Oncology Centre, said: “Uveal melanoma is a potentially lethal disease, with a 50% mortality rate from metastatic disease. However, traditionally, small lesions have been monitored rather than treated as it was considered that these are less likely to cause metastatic spread and that local treatment does not influence outcome.
“Liverpool is one of the only ocular oncology centres in the world that offers prognostic biopsies to all of its melanoma patients, and we have therefore collected a large molecular genetic cohort of small tumours. This is the first study to show that over a quarter of these smaller uveal melanomas have lethal genetic mutations, and suggests that we may be able to influence patient survival and mortality outcomes with earlier treatment of these small melanomas. This will cause a massive shift in the approach to such patients, both in terms of management of their primary tumour, but also in terms of the consideration of prognostic biopsies in small ocular cancers.”
The Liverpool Ocular Oncology Research Group’s mission is to conduct high quality basic, translational and clinical research into the pathogenesis and treatment of adult ocular tumours that will improve patient care and survival.
Together with Dr Helen Kalirai, Professor Sarah Coupland leads the basic science and translational research portfolio, in addition to being a diagnostic Consultant Pathologist at the Liverpool University Hospitals Foundation Trust. Sarah leads one of the four NHSE supra-regional Ophthalmic Pathology services, and has led the molecular oncology prognostication service for around 10 years. Professor Heinrich Heimann leads the clinical research portfolio of the LOORG and heads the Liverpool Ocular Oncology Centre.
Professor Sarah Coupland said: “Since the early 1990s it was clear that uveal melanomas could be divided into differing genetic prognostic groups. This has become even more definitive through studies such as The Cancer Genome Atlas Uveal Melanoma study, to which LOORG significantly contributed. These past analyses, however, were based mainly on large tumours, and very few genetic investigations have been undertaken on small uveal melanomas, which erroneously have all been labelled as ‘safe’. Our study using a unique collection of tiny intraocular biopsies of small uveal melanomas with follow-up clinical data, shows that they too can be broken down into ‘good’ and ‘bad’ tumours. Instead of watching the latter, they can be treated earlier and thereby increase significantly the chance of cure for these patients.”
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Materials provided by University of Liverpool. Note: Content may be edited for style and length.

An international research team led by Professor Charles Gauthier from the Institut national de la recherche scientifique (INRS) has discovered a new molecule with potential to revolutionize the biosurfactant market. The team’s findings have been published in Chemical Science, the Royal Society of Chemistry’s flagship journal.
Surfactants are synthesized from petroleum and are the main active ingredient in most soaps, detergents, and shampoos. Biosurfactants, produced by bacteria, are safer and can replace synthetic surfactants.
Rhamnolipid molecules are some of the safest surfactants known and are particularly attractive, thanks to their biodegradability, minimal toxicity, and amenability to be produced from industrial waste. But there’s a problem. They are made using Pseudomonas aeruginosa, a pathogenic bacterium harmful to humans.
“If we want to fully gain the benefits of rhamnolipids, we need to grow these pathogenic bacteria on a huge scale. And because that’s a health risk, the industry is looking for alternatives,” explained Professor Gauthier. The molecules produced by these bacteria are usually mixed with other compounds or virulence factors, making them trickier to use.
To address the problem, the research team identified molecules that resemble rhamnolipids in Pantoea ananatis, a non-pathogenic bacterium. The team was then able to chemically synthesize these molecules, called ananatosides, in the laboratory, raising the possibility that they could be produced on a larger scale than using bacteria. The industry is already showing interest in these promising new biosurfactants.
A look at the structure
The new molecule comes in two different forms, A and B. Ananatoside A structure is described as closed, while B is open. The molecule A is closed in on itself to form a loop. The process that closes the loop is called lactonization, and it has also been achieved with rhamnolipids to create new molecules.

Researchers at Oregon State University have found a key new piece of the puzzle in the quest to use gene therapy to enable people born deaf to hear.
The work centers around a large gene responsible for an inner-ear protein, otoferlin. Mutations in otoferlin are linked to severe congenital hearing loss, a common type of deafness in which patients can hear almost nothing.
“For a long time otoferlin seemed to be a one-trick pony of a protein,” said Colin Johnson, associate professor of biochemistry and biophysics in the OSU College of Science. “A lot of genes will find various things to do, but the otoferlin gene had appeared only to have one purpose and that was to encode sound in the sensory hair cells in the inner ear. Small mutations in otoferlin render people profoundly deaf.”
In its regular form, the otoferlin gene is too big to package into a delivery vehicle for molecular therapy, so Johnson’s team is looking at using a truncated version instead.
Research led by graduate student Aayushi Manchanda showed the shortened version needs to include a part of the gene known as the transmembrane domain, and one of the reasons for that was unexpected: Without the transmembrane domain, the sensory cells were slow to mature.
“That was surprising since otoferlin was known to help encode hearing information but had not been thought to be involved in sensory cell development,” Johnson said.

Chronic exposure to second-hand smoke results in lower body weight and cognitive impairments that more profoundly affects males, according to new research in mice led by Oregon Health & Science University.
The study published today in the journal Environmental Health Perspectives.
“The hope is that we can better understand these effects for policymakers and the next generation of smokers,” said lead author Jacob Raber, Ph.D., professor of behavioral neuroscience in the OHSU School of Medicine. “Many people still smoke, and these findings suggest that that the long-term health effects can be quite serious for people who are chronically exposed to second-hand smoke.”
The research examined daily exposure of 62 mice over a period of 10 months. Researchers used a specially designed “smoking robot” that went through a pack of cigarettes a day in ventilated laboratory space at OHSU. The longest previous study of this kind lasted three months.
“Nobody has done this, ever. This study is unique,” Raber said. “It really gives you the ability to look at long-term effects.”
“This study more accurately replicates the human experience by daily exposing mice to cigarette smoke,” added senior author Glen Kisby, Ph.D., professor of pharmacology at Western University of Health Sciences in Lebanon, Oregon.