Study examines role of metabolites in disease treatment

Phillip Owens, PhD
Photo Credit: Andrew Higley/UC Marketing + Brand

Each year, about 200,000 people in the United States are diagnosed with a bulge in the lower part of the aorta, the main artery in the body, called an abdominal aortic aneurysm (AAA).

New research from the University of Cincinnati examines the role a particular metabolite plays in the development of AAA and could lead to the first treatment of the condition.

The research was published in the journal Circulation.

“We started the study by examining whether AAA patients themselves had an increase in trimethylamine N-oxide (TMAO).  We examined an American and Swedish cohort with 354 human samples, and we compared those AAA patients to 1,775 control subjects,” says Phillip Owens, PhD, co-first author of the study along with Tyler Benson, PhD, both of the Division of Cardiovascular Health and Disease in the UC College of Medicine. “We started going into animal models after that, looking at what happens when we feed a high choline diet which leads to higher production of TMAO.”

Choline, found in a variety of foods with the richest sources being meat, fish, poultry, dairy and eggs, is processed into the organic compound TMAO when meat is digested by the bacteria in the gut.

Study reveals how treatment-resistant prostate cancer provides its own hormonal fuel

A new study from Washington University School of Medicine in St. Louis shows how prostate cancer creates its own hormonal fuel supply in response to anti-testosterone therapy. The study further suggests a strategy to block this process and potentially improve therapy options for treatment-resistant prostate cancer. Shown is a thin slice of a human prostate tumor. The dark staining throughout reveals the presence of histone acetylation promoting cholesterol production. Cholesterol is required to make testosterone, which fuels tumor growth.
Image Credit: Nupam Mahajan/School of Medicine

A new study in mice, led by researchers at Washington University School of Medicine in St. Louis, explains how prostate cancer senses a drop in testosterone levels due to common anti-hormone therapy and then begins making cholesterol — a necessary precursor to testosterone — to generate its own testosterone to fuel tumor growth. The study also points to a possible drug combination that may stop the cancer from feeding its own growth.

Healthy prostate cells do not produce testosterone, so the research provides long-sought answers to questions about how prostate cancer cells adapt to testosterone-deprivation therapy, a common therapeutic option, by developing an ability to supply their own hormonal fuel. Further, the research reveals that treating these aggressive prostate tumors with inhibitors that block aspects of the hormonal fuel supply chain slows tumor growth in mice. These findings suggest a novel treatment strategy for prostate cancer that has become resistant to the common anti-testosterone therapy abiraterone.

The study also may help explain why Black men are at higher risk of developing prostate cancer and tend to develop more aggressive forms of the cancer than white men of European ancestry.

Women feel the pain of losses more than men when faced with risky choices

Evaluating risk - are women more risk averse than men?
Photo Credit: Oleksandr Pidvalnyi

Women are less willing to take risks than men because they are more sensitive to the pain of any losses, they might incur than any gains they might make, new research from the University of Bath School of Management shows.

Published in the British Psychological Society’s British Journal of Psychology, the study – “Gender differences in optimism, loss aversion and attitudes toward risk" - also finds that men are ‘significantly’ more optimistic than women, making them more willing to take risks.

Researcher Dr Chris Dawson, associate professor in business economics at the University of Bath School of Management, said the findings were significant and could help explain sex-specific outcomes in different employment sectors, and in financial markets.

‘It is widely acknowledged that men, across many domains, take more risks than women. These differences in how the sexes view risk can have significant effects,” Dr Dawson says.

‘For instance, differences between the sexes in risk taking can explain why women are less likely to be entrepreneurs, are underrepresented in high-paying jobs and upper management, and less likely to invest their wealth in equities markets than men. Despite these important implications, we still know very little about why women take fewer risks than men.

Modified lactic acid bacteria provide faster wound healing

The lactic acid bacteria, or Limosilactobacillus reuteri, is genetically modified to produce the chemokine CXCL12 (ILP100-Topical). 
Photo Credit: Martina Sjaunja

Complicated, hard-to-heal wounds are a growing medical problem and there are currently only two drugs approved with proven efficacy. In a new study on humans, researchers at Uppsala University show that treatment with a specific type of modified lactic acid bacteria works well and has a positive effect on the healing of wounds.

In several controlled preclinical models, the research team behind the new study has previously demonstrated accelerated wound healing after topical treatment (treatment on the skin) using lactic acid bacteria, or Limosilactobacillus reuteri, genetically modified to produce the chemokine CXCL12 (ILP100-Topical).

The researchers can now show data from the first clinical study on humans, in which the main objective was to establish safety and tolerability. Other objectives were to see clinical and biological effects on wound healing using traditionally accepted methods, as well as more exploratory and traceable measurements.

36 healthy volunteers were included in the study with a total of 240 induced wounds studied. The study’s design and methodology are described in more detail below.

Bacteria with a taste for inflammation could help protect against heart disease

Nacho Vivas, lab manager at the Rey Lab in the Bacteriology Department at the University of Wisconsin–Madison, checks on a group of germ-free mice inside a sterile lab environment on June 22, 2015. Research led by Federico Rey has found some microbes in the guts of humans and mice may help control the buildup of plaque in arteries, the leading cause of cardiovascular disease, by gobbling up a group of inflammatory chemicals before they can circulate in the body.
Photo Credit: Bryce Richter

Some microbes in the guts of humans and mice may help control the buildup of plaque in arteries, the leading cause of cardiovascular disease, by gobbling up a group of inflammatory chemicals before they can circulate in the body.

New research from the University of Wisconsin–Madison and collaborators around the world identified bacteria able to break down uric acid in the low-oxygen environment of the intestines and the specific genes that enable the process. They describe a new way in which gut microbes may influence our health and a potential avenue to treat gout or prevent heart disease.

Uric acid is a product of the breakdown in the human body of purines, a class of molecules that include those necessary for life, like adenine and guanine (two of the basic building blocks of DNA), and some that are life indulgences, like caffeine and theobromine (found in chocolate and tea leaves). Most uric acid is cleaned out by healthy kidneys, but about 30 percent of it spills into the gut. Too much uric acid leads to a painful condition called gout.

Bat-Borne Sarbecoviruses Spilled Over in Southeast Asia Pre-Pandemic

Elephant loggers bring in a timber harvest in Myanmar.
Photo Credit: Tierra Smiley Evans/UC Davis

A virus previously found only in bats was detected in the antibodies of people screened for exposure to sarbecoviruses between 2017 and 2020 in rural Myanmar in Southeast Asia, according to a study from the University of California, Davis and collaborators in Myanmar and Singapore. The work is published in the International Journal of Infectious Diseases.

Sarbecoviruses are a group of coronaviruses. This study found exposure to diverse sarbecoviruses, including some known to be closely related to SARS-CoV-2, such as RaTG13.

The study found that people were significantly more likely to have been exposed to sarbecoviruses if their livelihood involved working directly with or close to bats, such as logging, hunting or harvesting bat guano.

“This study provides new evidence that bat-borne coronaviruses can and do spill over to people, underscoring the importance of surveillance in high-risk rural areas, where humans and wildlife closely interact,” said lead author Tierra Smiley Evans, an epidemiologist and research faculty with the One Health Institute in the UC Davis School of Veterinary Medicine.

Zinc Transporter Has Built-in Self-regulating Sensor

Overall structure of a transmembrane ZIP zinc transporter protein determined by cryo-electron microscopy (cryo-EM) (left) and a schematic showing some of the functional features (right). A flexible loop (magenta) facing into the cell binds to zinc and folds to block the entry of more zinc when levels of this micronutrient get too high.
Illustration Credit: Courtesy of Brookhaven National Laboratory

Scientists at the U.S. Department of Energy’s (DOE) Brookhaven National Laboratory have determined the atomic-level structure of a zinc-transporter protein, a molecular machine that regulates levels of this crucial trace metal micronutrient inside cells. As described in a paper just published in Nature Communications, the structure reveals how the cellular membrane protein shifts its shape to move zinc from the environment into a cell, and temporarily blocks this action automatically when zinc levels inside the cell get too high.

“Zinc is important for many biological activities, but too much can be a problem,” said Qun Liu, the Brookhaven Lab biophysicist who led the project. “During evolution, different organisms have evolved in many ways to regulate zinc. But no one has shown that a transporter that controls the uptake of zinc from the environment can regulate its own activity. Our study is the first to show a zinc transporter with such a built-in sensor.”

The research was conducted as part of Brookhaven Lab’s Quantitative Plant Sciences Initiative (QPSI). Using a bacterial version of a zinc transporter that shares essential features with zinc transporters in plants, the scientists gained key insights into how these proteins work. 

“This research is part of our effort to understand how micronutrients like zinc are taken up by plants so we can understand how to design plants that are better able to grow on marginal land for the production of bioenergy,” said Brookhaven Lab Biology Department Chair John Shanklin, a co-author on the paper.  

Alcohol consumption increases the risks of over 60 diseases

Photo Credit: Taylor Friehl

Alcohol consumption increases the risks of over 60 diseases in Chinese men, including many diseases not previously linked to alcohol, according to a new study by researchers from Oxford Population Health and Peking University, published in Nature Medicine.

Alcohol consumption is estimated to be responsible for about 3 million deaths worldwide each year, and it is increasing in many low- and middle-income countries such as China. The harmful effects of heavy drinking for certain diseases (such as liver cirrhosis, stroke and several types of cancer) are well known, but very few studies have systematically assessed the impact of alcohol use on an extensive range of diseases within the same population.

The study shows that alcohol use increases the risks of 61 diseases in men in China, including many non-fatal diseases not known to be alcohol-related due to limited previous evidence. The findings of this study demonstrate the influence that alcohol intake may have on the risk of disease in populations around the world.

The researchers used data from the China Kadoorie Biobank (CKB), a collaborative study of over 512,000 adults recruited during 2004-08 from ten diverse urban and rural areas across China. Study participants were interviewed about their lifestyle and behaviors, including detailed alcohol drinking patterns. About a third of men, but only 2% of women, drank alcohol regularly (ie at least once a week). The researchers comprehensively assessed the health effects of alcohol use on over 200 different diseases in men identified through linkage to hospital records over a period of about 12 years. Importantly, they also undertook a genetic analysis to clarify whether or not alcohol intake was responsible for causing disease.

Study: Ingestion of taurine delays aging

Treating mice with taurine led to increased lifespans and healthspans, a study in Science shows. Henning Wackerhage, Professor of Exercise Biology provided data on human test subjects hinting at similar mechanisms in humans.
Photo Credit: Andreas Heddergott / TUM

Taurine deficiency is one of the driving forces in the aging process of humans and animals. This is one of the results of a study which has now been published in the prestigious journal Science. Treatment with taurine extends the lifespan of mice by 10 percent. Monkeys that receive the treatment remain healthy for longer. It is not known whether these two results apply to humans. However, the study demonstrates a link between some age-related diseases and low taurine levels.

Treating mice with taurine led to increased lifespans and healthspans, a study in Science shows. Henning Wackerhage, Professor of Exercise Biology provided data on human test subjects hinting at similar mechanisms in humans.

Ancient herbivore’s diet weakened teeth leading to eventual starvation

Reconstruction of the rhynchosaur Bentonyx from the Middle Triassic of Devon, about 245 million years ago.
Illustration Credit: Reconstruction artwork by Mark Witton

A team of researchers from the University of Bristol have shed light on the life of the ancient reptile Rhynchosaur, which walked the earth between 250-225 million years ago, before being replaced by the dinosaurs.

Rhynchosaurs are a little-understood group of roughly sheep-sized ancient reptiles that thrived during the Triassic Period, a time of generally warm climates and tough vegetation.  

In the new study, the researchers studied specimens found in Devon and used CT scanning to see how the teeth wore down as they fed, and how new teeth were added at the backs of the tooth rows as the animals grew in size.

The findings, published today in Palaeontology, show that these early herbivores likely eventually starved to death in old age, the vegetation taking its toll on their teeth.

“I first studied the rhynchosaurs years ago,” said team-leader Professor Mike Benton from Bristol’s School of Earth Sciences, “and I was amazed to find that in many cases they dominated their ecosystems. If you found one fossil, you found hundreds.