Publisher Health

Polycystic ovary syndrome (PCOS) is a pervasive endocrine disorder that affects millions of women globally, impacting their hormonal balance, fertility and overall well-being. It is notoriously difficult to treat, with widely varying symptoms and mysterious, complex underlying causes. Researchers at the University of Chicago recently unveiled a potential new PCOS treatment that may improve multiple PCOS symptoms by regulating body systems and reducing inflammation.
Recently published results demonstrate the promise of this novel therapeutic approach that uses mesenchymal stem cell-derived extracellular vesicles (EVs), also known as exosomes: tiny, free-floating packages of molecules released by stem cells.
“Current PCOS treatments merely address the symptoms, and the most common treatments — oral contraceptives — do not address patients’ struggles with infertility,” said Hang-Soo Park, PhD, staff scientist at UChicago and the study’s first author. “Our approach represents a paradigm shift from symptom management to treating the underlying causes. We hope this will prove more effective in the long term and allow patients to have children if they wish to do so.”
The group had previously published findings that mesenchymal stem cells (MSCs) — adult cells that can differentiate into multiple cell types for healing and regeneration — can secrete factors that can help reverse the symptoms of PCOS, but it was unclear what those factors were. The latest study identifies the EVs they release as the therapeutic components.
The researchers found that MSC-derived EVs lowered the activity of genes that contribute to the overproduction of androgen hormones — a hallmark of PCOS. Based on this finding, the scientists injected the EVs into mouse models of PCOS, where they helped stabilize some of the metabolic irregularities often associated with the disorder, such as high glucose levels. The EVs can be injected into either blood vessels or directly into the mice’s ovaries, and in both cases, they actually restored ovarian function.
“Our study demonstrates the resilience of the ovaries under EV treatment, offering renewed hope for women battling PCOS-related fertility issues,” said Park.
The researchers believe an immune signaling protein called IL-10, known for its anti-inflammatory properties, may play a key role in the healing they observed. The EVs may serve as delivery vehicles that stabilize IL-10 and ferry it to target cells, increasing the molecule’s effectiveness in reducing inflammation and driving restorative processes.

Researchers at the University of Arizona Cancer Center discovered a new class of iron-targeting compounds that hamper the proliferation of cultured malignant cells in a laboratory setting. The results of the study were published in the Journal of the American Chemical Society.
“Cancer cells are what we call ‘addicted’ to iron, and so we are making compounds that are able to interfere with the availability of iron in cancer cells,” said Elisa Tomat, PhD, professor in the Department of Chemistry and Biochemistry at the UArizona College of Science and member of the UArizona Cancer Center.
The discovery could lead to the development of broad-spectrum, anticancer drugs that target iron metabolism.
The team has been working with Tech Launch Arizona, the university’s commercialization arm, with the goal of licensing the technology to a company that will move it into the marketplace. A patent application is pending.
Iron is the most abundant transition metal in the human body and, according to Tomat, plays a crucial role in tumor progression and metastasis. Cancer cells rely on several iron-dependent processes to sustain their rapid proliferation rates and therefore have a higher demand for this element compared with normal cells.
Tomat said the research team’s challenge was capturing iron within malignant cells yet keeping it available to the rest of the body. To do so, they targeted intracellular iron with compounds that are activated only after cellular uptake.
“As chemists, we can design and synthesize molecules that are able to bind iron only under certain conditions and not throughout the body,” Tomat said. “We’ve been working on various approaches toward this type of chemistry; we call these prochelator approaches because the chelator is the compound that binds the metal ion. The prochelator is the compound we designed to become activated only upon undergoing a certain reaction that occurs in cells.”
The research was inspired by a “common reagent,” a compound that is employed in laboratories worldwide to assess the ability of drug candidates to inhibit the proliferation of cultured mammalian cells.
“Because iron is such a fundamental player that is important in many cancer types, and this high demand for iron is a general characteristic of malignancy, I’ve been interested in this strategy for a number of years,” said Tomat, who has been exploring iron chelators and their role in tumor progression for more than 10 years.
“We’re excited about this new strategy because we think this class of molecules can be further modified to optimize the properties and improve the antiproliferative activity and really become a way for us to impact the iron availability in malignant cells and halt cancer growth.”

Researchers at the National Institutes of Health found that living in an area with high levels of particulate air pollution was associated with an increased incidence of breast cancer. The study, published in the Journal of the National Cancer Institute, is one of the largest studies to date looking at the relationship between outdoor air pollution, specifically fine particulate matter, and breast cancer incidence. The research was done by scientists at the National Institute of Environmental Health Sciences (NIEHS) and the National Cancer Institute (NCI), both part of NIH.
The researchers saw that the largest increases in breast cancer incidence was among women who on average had higher particulate matter levels (PM2.5) near their home prior to enrolling in the study, compared to those who lived in areas with lower levels of PM2.5. Particulate matter is a mixture of solid particles and liquid droplets found in the air. It comes from numerous sources, such as motor vehicle exhaust, combustion processes (e.g., oil, coal), wood smoke/vegetation burning, and industrial emissions. The particulate matter pollution measured in this study was 2.5 microns in diameter or smaller (PM2.5), meaning the particles are small enough to be inhaled deep into the lungs. The Environmental Protection Agency has a website known as Air Now where residents can enter their zip code and get the air quality information, including PM2.5 levels, for their area.
“We observed an 8% increase in breast cancer incidence for living in areas with higher PM2.5 exposure. Although this is a relatively modest increase, these findings are significant given that air pollution is a ubiquitous exposure that impacts almost everyone,” said Alexandra White, Ph.D., lead author and head of the Environment and Cancer Epidemiology Group at NIEHS. “These findings add to a growing body of literature suggesting that air pollution is related to breast cancer.”
The study was conducted using information from the NIH-AARP Diet and Health Study, which enrolled more than 500,000 men and women between 1995-96 in six states (California, Florida, Pennsylvania, New Jersey, North Carolina, and Louisiana) and in two metropolitan areas (Atlanta and Detroit). The women in the cohort were on average about 62 years of age and most identified as being non-Hispanic white. They were followed for approximately 20 years, during which 15,870 breast cancer cases were identified.
The researchers estimated annual average historical PM2.5 concentrations for each participant’s residence. They were particularly interested in air pollution exposures during a period of 10-15 years prior to enrollment in the study, given the length of time it takes for some cancers to develop. Most previous studies have assessed breast cancer risk in relation to air pollution around the time of study enrollment and did not consider past exposures.
“The ability to consider historic air pollution levels is an important strength of this research,” said Rena Jones, Ph.D., senior author and principal investigator of the study at NCI. “It can take many years for breast cancer to develop and, in the past, air pollution levels tended to be higher, which may make previous exposure levels particularly relevant for cancer development.”
To consider how the relationship between air pollution and breast cancer varied by the type of tumor, the researchers evaluated estrogen receptor-positive (ER+) and -negative (ER-) tumors separately. They found that PM2.5 was associated with a higher incidence of ER+ breast cancer, but not ER-, tumors. This suggests that PM2.5 may affect breast cancer through an underlying biologic pathway of endocrine disruption. ER+ tumors are the most common tumors diagnosed among women in the United States.
The authors note that the study was limited in its ability to explore any differences in the relationship between air pollution and breast cancer across the different study areas. They suggest future work should explore how the regional differences in air pollution, including the various types of PM2.5 women that women are exposed to, could impact a woman’s risk of developing breast cancer.

New research found the most common form of breast cancer presents differing metabolic signatures in the blood of African American women with estrogen receptor-positive breast cancer compared with non-Hispanic white women. The scientists also identified a protein — negative elongation factor complex E — that was linked with higher mortality rates among African American women with estrogen receptor-positive breast cancer.
The findings, published online by Nature Scientific Reports, may help explain some of the molecular processes driving higher rates of the disease — especially more aggressive forms of it — in African American women. ER-positive breast cancer accounts for about 70%-80% of all breast cancer cases, and African American women are 40% more likely to die from it than white women, said Zeynep Madak-Erdogan, a professor of nutritional sciences and of food science and human nutrition at the University of Illinois Urbana-Champaign and co-author of the paper.
Ashlie Santaliz-Casiano, a then-graduate student at the university, was the first author of the study. Madak-Erdogan, the corresponding author, oversaw the project along with Jonna Frasor, a professor of physiology and biophysics at the U. of I. Chicago; and Dr. Kent F. Hoskins, a professor of medicine in the UIC College of Medicine and director of the UIC Familial Breast Cancer Program. Researchers at Northwestern University, Northwestern Memorial Hospital and Northeastern University were partners on the project.
“Overall, we are pretty good at managing the disease, early diagnosing cases with mammography and treating them with drugs that were developed several decades ago,” Madak-Erdogan said.
“Although the tumors are often caught at earlier stages, patients from lower-income neighborhoods such as Chicago’s South Side are more likely to have poor outcomes. That suggests there are some biological factors driving these differing effects,” she said.
The study population included African American women and non-Hispanic white women ages 20-79 who were recruited at three hospitals in the Chicago area in 2018-19.
The team collected blood samples from 102 patients who were newly diagnosed with ER-positive breast cancer in stages 1-3, and 148 healthy women served as the control group. The samples were collected from control group participants at the time they enrolled in the study and from the patients with ER-positive breast cancer prior to breast surgery or other cancer treatment.

When humans or animals get infected, the body’s immune system tries to not only clear the infection but also build up a memory of the pathogen that caused it. So, when the pathogen comes around again for possible reinfection, the body has an army of memory T cells that can recognize and destroy it. These T cells are a critical part of immunological memory, and an important component of efficient vaccines.
Now, researchers at the University of Missouri are one step closer to making the T cell army stronger. In a recent study, conducted in the Roy Blunt NextGen Precision Health building, the researchers found that by manipulating one molecular signaling pathway in the T cells that participate in clearing influenza virus in the lungs, the strength and longevity of immunological memory produced can be improved.
This finding can potentially support the future development of more effective vaccines and therapeutics to combat influenza and other respiratory infections with the ultimate goal of increasing the body’s immunological memory, which can both prevent and lessen the severity of infections and reinfections.
Emma Teixeiro and Mark A. Daniels, associate professors in the MU School of Medicine, led the NIH-funded study, which involved unique mouse models of influenza infection.
“Immunologists like myself have always wondered why T cells in the lungs after influenza infection disappear so quickly,” Teixeiro said. “This research can help us solve that problem by increasing the amount of T cells that can fight against infection. In this study, we have identified novel ways to improve the generation and long-term maintenance of protective immunity against influenza, and that is by manipulating a molecular target known as the IKK2/NFkB signaling pathway.”
Teixeiro added that T cells can recognize parts of viruses that do not mutate, so if researchers can better understand how to strengthen the T cells and extend the timeframe when they can do their job appropriately, the body’s immune system will ultimately be better suited to fight against infection and lessen the severity.
While the influenza virus was the focus of this particular study, gaining knowledge of the underlying molecular mechanisms and signaling pathways that regulate memory in tissues can be helpful to improve therapeutics for patients with cancer, autoimmunity or other respiratory infections.
“By unveiling the biochemical and molecular secrets of these T cells, we can provide valuable information to other scientists who work on optimizing vaccine strategies,” Teixeiro said. “The good news is there are already clinical treatments that do target this particular pathway we identified, so this study is a big step in the right direction, but we still have a long way to go.”
“IKK2/NFkB signaling controls lung resident CD8+ T cell memory during influenza infection” was recently published in Nature Communications. Coauthors on the study include Curtis J. Pritzl, Dezzarae Luera, Karin M. Knudson, Michael J. Quaney, Michael J. Calcutt and Mark A. Daniels.

A healthy lifestyle that involves moderate alcohol consumption, a healthy diet, regular physical activity, healthy sleep and frequent social connection, while avoiding smoking and too much sedentary behaviour, reduces the risk of depression, new research has found.
In research published today in Nature Mental Health, an international team of researchers, including from the University of Cambridge and Fudan University, looked at a combination of factors including lifestyle factors, genetics, brain structure and our immune and metabolic systems to identify the underlying mechanisms that might explain this link.
According to the World Health Organization, around one in 20 adults experiences depression, and the condition poses a significant burden on public health worldwide. The factors that influence the onset of depression are complicated and include a mixture of biological and lifestyle factors.
To better understand the relationship between these factors and depression, the researchers turned to the UK Biobank, a biomedical database and research resource containing anonymised genetic, lifestyle and health information about its participants.
By examining data from almost 290,000 people — of whom 13,000 had depression — followed over a nine-year period, the team was able to identify seven healthy lifestyle factors linked with a lower risk of depression. These were: moderate alcohol consumption healthy diet regular physical activity healthy sleep never smoking low-to-moderate sedentary behaviour frequent social connectionOf all of these factors, having a good night’s sleep — between seven and nine hours a night — made the biggest difference, reducing the risk of depression, including single depressive episodes and treatment-resistant depression, by 22%.
Frequent social connection, which in general reduced the risk of depression by 18%, was the most protective against recurrent depressive disorder.

The sequencing of the human genome promised a revolution in medicine, but scientists soon realized that a genetic blueprint alone does not show the body in action. That required understanding the proteome — all the proteins, expressed by our genes, forming the cellular machinery that performs the bulk of the body’s functions. Now, another set of molecules known as the lipidome — all the lipids in our bodies — is filling in more details of human physiology.
Lipids are a broad category of small, fatty or oily molecules, including triglycerides, cholesterol, hormones and some vitamins. In our bodies, they make up cell membranes, act as cellular messengers and store energy; they play key roles in responding to infection and regulating our metabolism.
Our genome is essentially stable. Our proteome, though influenced by our health and environment, is largely dependent on what’s encoded by our genes. In contrast, our lipidome can be directly altered, in part, by what we eat and which microbes live inside our gut, making it more malleable and perhaps more responsive to interventions. But the number and variety of lipid molecules — there are at least thousands — has made them hard to study.
“Lipids are very understudied,” said Michael Snyder, PhD, the Stanford W. Ascherman, MD, FACS Professor in Genetics. “They are involved in pretty much everything, but because they’re so heterogenous, and there are so many of them, we probably don’t know what most lipids really do.”
A new study from Snyder’s lab, published Sept. 11 in Nature Metabolism, is among the first to deeply dive into the human lipidome and track how it changes under healthy and diseased conditions, particularly in the development of Type 2 diabetes.
Indicators of health
More than 100 participants, including many at risk for diabetes, were tracked for up to 9 years, providing blood samples every three months when healthy and every few days during illness.

Parkinson’s disease, characterized by various motor dysfunctions, is the second most common neurodegenerative disorder in the world. It is known that specific gene mutations that are passed down through families are responsible for some cases of Parkinson’s disease. But now, researchers from Japan have found that this might open the doors to new therapies.
In a study published recently in EMBO Molecular Medicine, researchers from Tokyo Medical and Dental University (TMDU) have identified the cellular processes that likely lead to Parkinson’s disease in patients with mutations in a specificgene.
Motor disorders seen in Parkinson’s disease are caused by the death of cells that produce dopamine — an important molecule for cellular communication — in a brain region known as the substantia nigra. In this region, protein aggregates containing a protein known as alpha-synuclein form. However, the exact cause and the process remains unknown.
Researchers from TMDU decided to investigate these mechanisms in a familial form of Parkinson’s disease caused by mutations in CHCHD2, a gene encoding a specific domain containing two CHCHD2 proteins. To do this, they induced a CHCHD2 mutation in both cell cultures and mice.
“When we looked at normal CHCHD2 protein in cells, it was located in the mitochondria, which provides energy to the cell,” says lead author of the study Satoru Torii. “But the mutant CHCHD2 was expressed in a very different area — in the cell cytosol, where it recruited another protein known as casein kinase 1 epsilon/delta (Csnk1e/d) and led to the aggregation of phosphorylated alpha-synuclein and neurofilaments.”
Because the mutant CHCHD2 caused Parkinson’s disease-related pathology in cells, the researchers investigated its effects in mice using two different methods of expressing mutant CHCHD2. All mice with CHCHD2 mutation had motor impairments, and their brains showed mislocalized CHCHD2 and aggregated alpha-synuclein in the dopamine-producing cells of the substantia nigra. The same observations were made when the research team looked at a postmortem brain of a patient with Parkinson’s disease caused by a CHCHD2 mutation, and in laboratory cell cultures harvested from another patient.
“The most exciting finding for us was that, when we inhibited the associated protein Csnk1e/d, we saw motor improvements and fewer Parkinson’s disease-related symptoms in the Parkinson’s disease model mice, as well as less pathology in cells grown from a patient with a CHCHD2 gene mutation,” explains Shigeomi Shimizu, senior author of the study. “This suggests that it may be possible to delay — or even prevent — Parkinson’s disease development in people with this mutation.”
Given that there are currently no treatments that effectively slow or halt the progression of Parkinson’s disease, the findings of this study are very encouraging, especially for patients with CHCHD2 mutations. The results also improve our understanding of how Parkinson’s disease can develop in the brain and bring hope to all patients and their families.

Having a hobby is linked to fewer depressive symptoms and higher levels of happiness, self-reported health and life satisfaction among people aged 65 and over, and this holds true across 16 countries on three continents, according to a new study led by UCL (University College London) researchers.
The study, published in the journal Nature Medicine, aimed to see if the benefits of hobbies were consistent in different national settings, and looked at data from 93,263 people aged 65 or over who had enrolled in five existing longitudinal studies in England, Japan, United States, China and 12 European countries.
Analysing data from participants spanning four to eight years, the researchers found that having a hobby was also linked to subsequent decreases in depressive symptoms and increases in happiness and life satisfaction, suggesting there might be a causal effect, although as an observational study it could not prove causality.
These results remained after adjusting for other factors such as partnership status, employment and household income.
The study found the benefits of having a hobby were relatively universal, with only small differences between countries.
Lead author Dr Karen Mak (UCL Institute of Epidemiology & Health Care) said: “Our study shows the potential of hobbies to protect older people from age-related decline in mental health and wellbeing. This potential is consistent across many countries and cultural settings.
“Of the four outcomes, life satisfaction was most strongly linked to hobby engagement. Hobbies may contribute to life satisfaction in our later years through many mechanisms, including feeling in control of our minds and bodies, finding a purpose in life, and feeling competent in tackling daily issues.

New research suggests that hospital electronic health records (EHRs) that are difficult to use are also less likely to catch medical errors that could harm patients.
As clinicians navigate EHR systems, alerts, reminders, and clinical guidelines pop up to steer decision making. Yet a common complaint is that these notifications are distracting rather than helpful. These frustrations could signal that built-in safety mechanisms similarly suffer from suboptimal design, suggests the new study. Researchers found that EHR systems rated as being difficult to operate did not perform well in safety tests.
“Poor usability of EHRs is the number one complaint of doctors, nurses, pharmacists, and most health care professionals,” says David Classen, M.D., the study’s corresponding author and a professor of internal medicine at University of Utah Health. “This correlates with poor performance in terms of safety.”
Classen likens the situation to the software problems that led to two deadly Boeing 737 MAX airplane crashes in 2018 and 2019. In both cases, pilots struggling to use the system foretold deeper safety issues.
“Our findings suggest that we need to improve EHR systems to make them both easier to use and safer,” Classen says. He collaborated on the study with senior author David Bates, M.D., at Brigham and Women’s Hospital and Harvard T.H. Chan School of Public Health, and scientists at University of California San Diego Health; KLAS Enterprises, LLC; and University of California, San Francisco.
The research appears in the September 11 issue of JAMA Network Open.
Experts estimate that as many as 400,000 people are injured each year from medical errors that occur in hospitals. Medical professionals predicted that widespread use of EHRs would mitigate the problem. But research published by Classen, Bates and colleagues in 2020 showed that EHRs failed to reliably detect medical errors that could harm patients, including dangerous drug interactions. Additional reports have indicated that poorly designed EHRs could be a contributing factor.