Anti-diabetic drugs could lower risk of primary and secondary brain cancer

Photo Credit: Tesa Robbins

Diabetic patients who take anti-diabetic drugs - known as glitazones – long term had a lower risk of primary and secondary brain cancer compared with diabetic patients on other medications, new research led by the University of Bristol has found.

The study, published in BMJ Open, suggests these drugs could be repurposed to prevent brain metastasis in cancer patients who are at high risk of secondary cancers, if the current research is supported by future studies.

PPAR- α agonists (fibrates) and PPAR γ agonists (glitazones) drugs are clinically important due to their widespread safe use to treat high cholesterol (hyperlipidemia) and diabetes.  Previous studies have suggested that fibrates and glitazones may have a role in brain tumor prevention. Given the drug's safety and cost, they have the potential to be repurposed to prevent brain cancers and reduce the risk of secondary tumors by stopping tumor growth.

Using primary care records from the UK GP database Clinical Practice Research Datalink (CPRD), which contains data from a network of over 2,000 GPs from more than 670 practices across the UK, the researchers examined if this theory could be supported.

Mice study suggests metabolic diseases may be driven by gut microbiome, loss of ovarian hormones

Mice that received fecal implants from donors that had their ovaries removed gained more fat mass and had greater expression of liver genes associated with inflammation, Type 2 diabetes, fatty liver disease and atherosclerosis. The findings may shed light on the greater incidence of metabolic dysfunction in postmenopausal women. The team members included, from left: molecular and integrative physiology professor Erik R. Nelson; Kelly Swanson, the director of the Division of Nutritional Sciences and the Kraft Heinz Endowed Professor in Human Nutrition; and animal sciences professor Brett R. Loman.
  Photo Credit: Fred Zwicky

The gut microbiome interacts with the loss of female sex hormones to exacerbate metabolic disease, including weight gain, fat in the liver and the expression of genes linked with inflammation, researchers found in a new rodent study.

The findings, published in the journal Gut Microbes, may shed light on why women are at significantly greater risk of metabolic diseases such as obesity and Type 2 diabetes after menopause, when ovarian production of female sex hormones diminishes.

“Collectively, the findings demonstrate that removal of the ovaries and female hormones led to increased permeability and inflammation of the gut and metabolic organs, and the high-fat diet exacerbated these conditions,” said Kelly S. Swanson, the director of the Division of Nutritional Sciences and the Kraft Heinz Endowed Professor in Human Nutrition at the University of Illinois Urbana-Champaign who is a corresponding author of the paper.  “The results indicated that the gut microbiome responds to changes in female hormones and worsens metabolic dysfunction.”

Stopping the awakening of leukemia stem cells to prevent relapse

Acute Myeloid Leukemia
Image Credit: National Cancer Institute

Why myeloid leukemias start to grow again after chemotherapy has killed the bulk of cancerous cells, and how growth may be blocked by repurposed drugs, may have been solved by new research.

The bone marrow of Acute Myeloid Leukemia (AML) patients contains a rare population of leukemic stem cells (LSCs) that do not grow and, therefore, are not killed by chemotherapy.

However, after treatment, these cells start to grow and produce AML cells, but it has until now been unclear as to what kick-starts this process.

In a new study, published in Nature Communications, experts from Newcastle University, the University of Birmingham and the Princess Maxima Centre of Pediatric oncology, studied single cells from patients with t(8;21) AML to investigate what made the rare LSCs grow.

Long COVID linked to persistently high levels of inflammatory protein: a potential biomarker and target for treatments

"We hope that this could help to pave the way to develop therapies and give some patients a firm diagnosis," -Benjamin Krishna
Photo Credit: Annie Spratt

SARS-CoV-2 triggers the production of the antiviral protein IFN-γ, which is associated with fatigue, muscle ache and depression. New research shows that in Long COVID patients, IFN-y production persists until symptoms improve, highlighting a potential biomarker and a target for therapies.

A University of Cambridge-led study identifies the protein interferon gamma (IFN-γ) as a potential biomarker for Long COVID fatigue and highlights an immunological mechanism underlying the disease, which could pave the way for the development of much needed therapies, and provide a head start in the event of a future coronavirus pandemic. 

The study, published today in Science Advances, followed a group of patients with Long COVID fatigue for over 2.5 years, to understand why some recovered and others did not. 

Long COVID continues to affect millions of people globally and is placing a major burden on health services. An estimated 1.9 million people in the UK alone (2.9% of the population) were experiencing self-reported Long COVID as of March 2023, according to the ONS. Fatigue remains by far the most common and debilitating symptom and patients are still waiting for an effective treatment.

Researchers reveal mechanism of drug reactivating tumor suppressors

Mechanism of methylated-histone inhibitor valemetostat
Researchers revealed the mechanism of the cancer drug valemetostat and established its efficacy in treating adult T-cell leukemia/lymphoma (ATL).
Illustration Credit: ©2024 Makoto Yamagishi, The University of Tokyo

Researchers have revealed the mechanism of a drug shown to be effective in treating certain types of cancer, which targets a protein modification silencing the expression of multiple tumor suppressor genes. They also demonstrated in clinical trials the efficacy of the drug in reducing tumor growth in blood cancer. The findings could lead to longer-term treatments for the disease and therapies for other types of cancer with similar underlying causes.

A team of researchers from the University of Tokyo and their collaborators focused on therapies targeting H3K27me3, a modification on a DNA-packaging histone protein, which plays a large role in regulating gene expression. The modification occurs when methyl groups, each consisting of three hydrogen atoms bonded to a single carbon atom (CH3), are added to the protein in a process called methylation.

The modification, also referred to as being epigenetic (a heritable change in gene function that occurs without altering the sequence of the DNA), has been tied to the repression, or reducing the expression, of tumor suppressor genes, with the accumulation of the methylated histones around the genes.

Possible trigger for autoimmune diseases discovered

 One of the great mysteries of immunology: the function of B cells (green) in the thymus gland was previously unknown. Researchers have now been able to show that the immune cells help to prevent T cells from attacking the body.
Image Credit: Jan Böttcher, Thomas Korn / TUM

Immune cells must learn not to attack the body itself. A team of researchers from the Technical University of Munich (TUM) and the Ludwig Maximilian University of Munich (LMU) has discovered a previously unknown mechanism behind this: other immune cells, the B cells, contribute to the "training" of the T cells in the thymus gland. If this process fails, autoimmune diseases can develop.

In children and adolescents, the thymus gland functions as a "school for T cells". The organ in our chest is where the precursors of those T cells that would later attack the body's own cells are discarded. Epithelial cells in the thymus present a large number of molecules that occur in the body to the future T cells. If any of them reacts to one of these molecules, a self-destruction program is triggered. T cells that attack the body's own molecules remaining intact and multiplying, on the other hand, can cause autoimmune diseases.

New mechanism discovered

In Nature, the team led by Thomas Korn, Professor of Experimental Neuroimmunology at TUM and a Principal Investigator in the SyNergy Cluster of Excellence, and Ludger Klein, Professor of Immunology at LMU’s Biomedical Center (BMC), describe another previously unknown mechanism behind this.

In addition to the precursors of T cells, the thymus gland also contains other immune cells, the B cells. They develop in the bone marrow but migrate to the thymus in early childhood. "The function of B cells in the thymus gland has been a mystery that has puzzled immunologists for many years," says Thomas Korn. The researchers have now been able to show for the first time that B cells play an active role in teaching T cells which targets not to attack.

False Alarm of the Immune System during Muscle Disease

Prof. Claudia Günther (left) from Dresden and Prof. Eva Bartok (right) from Bonn are jointly investigating the connection between myotonic dystrophy and autoimmune diseases.
Photo Credit: © Universitätsklinikum Dresden & Universitätsklinikum Bonn

Researchers at the University Hospitals of Dresden and Bonn of the DFG Transregio 237 and from the Cluster of Excellence ImmunoSensation2 at the University of Bonn have made progress clarifying why patients with myotonic dystrophy 2 have a higher tendency to develop autoimmune diseases. Their goal is to understand the development of the disease, and their research has provided new, potential therapeutic targets. The results of the study have now been published in the renowned journal Nature Communications.

Myotonic dystrophy 2 (DM2) is a form of muscular dystrophy, a disease that leads to progressive muscle degeneration. It is caused by the expansion of a repetitive DNA sequence containing multiple CCTG bases in the CNBP gene. In general, the sequence of nucleobases in the DNA carries the genetic information. Patients suffer from muscle weakness that is more pronounced in the area of the muscles close to the trunk, as well as sustained muscle stiffness and pain. Although DM2 occurs in roughly one out of 10,000 people in Germany, there are no targeted therapies. In initial studies, Prof. Claudia Günther and her team at the Carl Gustav Carus University Hospital at the Technical University of Dresden also observed that patients with DM2 suffer more from autoimmune diseases with an increased production of antibodies in the blood than the general population. However, the underlying mechanism for these symptoms was previously unknown.

NIH study offers new clues into the causes of post-infectious ME/CFS

In-depth study finds brain, immune, and metabolic abnormalities linked to debilitating chronic disease.
Image Credit: John A Beal
(CC BY 4.0 DEED)

In a detailed clinical study, researchers at the National Institutes of Health have found differences in the brains and immune systems of people with post-infectious myalgic encephalomyelitis/chronic fatigue syndrome (PI-ME/CFS). They also found distinct differences between men and women with the disease. The findings were published in Nature Communications.

“People with ME/CFS have very real and disabling symptoms, but uncovering their biological basis has been extremely difficult,” said Walter Koroshetz, M.D., director of NIH’s National Institute of Neurological Disorders and Stroke (NINDS). “This in-depth study of a small group of people found a number of factors that likely contribute to their ME/CFS. Now researchers can test whether these findings apply to a larger patient group and move towards identifying treatments that target core drivers of the disease.”

A team of multidisciplinary researchers discovered how feelings of fatigue are processed in the brains of people with ME/CFS. Results from functional magnetic resonance imaging (fMRI) brain scans showed that people with ME/CFS had lower activity in a brain region called the temporal-parietal junction (TPJ), which may cause fatigue by disrupting the way the brain decides how to exert effort.

They also analyzed spinal fluid collected from participants and found abnormally low levels of catecholamines and other molecules that help regulate the nervous system in people with ME/CFS compared to healthy controls. Reduced levels of certain catecholamines were associated with worse motor performance, effort-related behaviors, and cognitive symptoms. These findings, for the first time, suggest a link between specific abnormalities or imbalances in the brain and ME/CFS.

Mitochondrial activation in transplanted cells promotes regenerative therapy for heart healing

Regenerative therapy to treat heart failure is more effective when the mitochondria of the regenerative cells are activated prior to treatment.
Image Credit: Gemini Advance

Heart failure stands as a leading cause of mortality worldwide, demanding advanced treatment options. Despite the urgency for more effective treatments, options for severe heart failure remain limited. Cell transplantation therapy has emerged as a promising ray of hope, as it can be used in regenerative therapy to heal the heart.

A research team led by Professor Yuma Yamada of Hokkaido University’s Faculty of Pharmaceutical Science has developed a technique to promote cardiac regeneration by delivering mitochondrial activators to cardiac progenitor cells. Their findings were published in the Journal of Controlled Release.

“Cardiomyocytes efficiently use the mitochondrial tricarboxylic acid cycle to produce large amounts of adenosine triphosphate from several substrates via oxidative phosphorylation (OXPHOS),” explains Yamada. “Based on the energy metabolism of cardiomyocytes, we hypothesized that activating the mitochondrial function of transplanted cells may improve the outcome of cell transplantation therapy.”

Could Ultra-Processed Foods Be the New ‘Silent’ Killer?

Hundreds of novel ingredients never encountered by human physiology are now found in nearly 60 percent of the average adult’s diet and nearly 70 percent of children’s diets in the U.S.
Photo Credit: Nico Smit

From fizzy drinks to cereals and packaged snacks to processed meat, ultra-processed foods are packed with additives. Oil, fat, sugar, starch and sodium, as well as emulsifiers such as carrageenan, mono- and diglycerides, carboxymethylcellulose, polysorbate and soy lecithin continue to strip food of healthy nutrients while introducing other ingredients that could also be detrimental to human health.

Hundreds of novel ingredients never encountered by human physiology are now found in nearly 60 percent of the average adult’s diet and nearly 70 percent of children’s diets in the United States.

While obesity and lack of physical activity are well recognized contributors to avoidable morbidity and mortality in the U.S., another emerging hazard is the unprecedented consumption of these ultra-processed foods in the standard American diet. This may be the new “silent” killer, as was unrecognized high blood pressure in previous decades.

Physicians from Florida Atlantic University’s Schmidt College of Medicine explored this hypothesis and provide important insights to health care providers in a battle where the entertainment industry, the food industry and public policy do not align with their patients’ needs. Their findings are published in a commentary in The American Journal of Medicine.

Giant step forward to help treat chronic wounds that affect millions

A team of international scientists has developed a more effective treatment for chronic wounds that does not involve antibiotics or silver-based dressings, but an ionized gas called plasma.

The treatment involves boosting the plasma activation of hydrogel dressings with a unique mix of different chemical oxidants that decontaminate and help heal chronic wounds.

University of South Australia physicist Dr Endre Szili, who led the study published this week in Advanced Functional Materials, describes the new method as “a significant breakthrough” that could revolutionize the treatment of diabetic foot ulcers, internal wounds and potentially cancerous tumors.

“Antibiotics and silver dressings are commonly used to treat chronic wounds, but both have drawbacks,” Dr Szili says. “Growing resistance to antibiotics is a global challenge and there are also major concerns over silver-induced toxicity. In Europe, silver dressings are being phased out for this reason.”

Widely used AI tool for early sepsis detection may be cribbing doctors’ suspicions

Image Credit: Scientific Frontline

When using only data collected before patients with sepsis received treatments or medical tests, the model’s accuracy was no better than a coin toss

Proprietary artificial intelligence software designed to be an early warning system for sepsis can’t differentiate high and low risk patients before they receive treatments, according to a new study from the University of Michigan.

The tool, named the Epic Sepsis Model, is part of Epic’s electronic medical record software, which serves 54% of patients in the United States and 2.5% of patients internationally, according to a statement from the company’s CEO reported by the Wisconsin State Journal. It automatically generates sepsis risk estimates in the records of hospitalized patients every 20 minutes, which clinicians hope can allow them to detect when a patient might get sepsis before things go bad.

“Sepsis has all these vague symptoms, so when a patient shows up with an infection, it can be really hard to know who can be sent home with some antibiotics and who might need to stay in the intensive care unit. We still miss a lot of patients with sepsis,” said Tom Valley, associate professor in pulmonary and critical care medicine, ICU clinician and co-author of the study published recently in the New England Journal of Medicine AI.

Targeting inflammation to tackle long covid

Illustration Credit: Gerd Altmann

Overactivation of the immune system leading to circulation of inflammatory proteins around the body contributes to the development of long covid, and could be targeted to provide treatments for patients, finds new research.

Cardiff University research has uncovered biological markers that could be targeted by repurposing medication to treat long covid.

The research conducted extensive analysis of plasma samples obtained from a large cohort of healthy post-covid individuals and non-hospitalized patients with long covid. They found that the complement system – a system that plays a crucial part of the immune system, consisting of a group of proteins that work together to enhance the function of antibodies and immune cells – was commonly overactivated in those with long covid.

“The covid-19 pandemic has left a global legacy of ill health, with long covid estimated to affect up to 1.9 million people in the UK. Long covid can last for months or years after the triggering infection and is associated with diverse symptoms including brain fog, chest pain, breathlessness, fatigue, and sensory problems. The causes of this disease remain largely unknown, emerging evidence suggests an important role for chronic inflammation."
Professor Paul Morgan 'Professor of complement biology, Division of Infection and Immunity

Scientists help discover new treatment for many cancers

UniSA/CCB Professor Greg Goodall, part of the team that made the landmark discovery.
Photo Credit: Courtesy of University of South Australia 

Australian scientists have made a major discovery that could underpin the next generation of RNA-based therapeutics, and lead to more potent and longer-lasting RNA-based drugs with an even wider array of potential uses.

In a paper published in the journal Nature, Peter MacCallum Cancer Centre scientists Vi Wickramasinghe and Linh Ngo and collaborator Greg Goodall at the University of South Australia and SA Pathology’s Centre for Cancer Biology, have described a new pathway that could help to overcome a major drawback of RNA-based therapeutics to date.

Currently these breakthrough therapeutics utilize mRNA – injectable genetic material that produces a desired therapeutic or vaccine effect, but they can also break down quickly once absorbed into the human body.

“It’s the linear shape of mRNA that makes it relatively unstable and lack durability inside the body and this has been a limiting factor in the potential application of RNA-based therapeutics for diseases such as cancer,” explains Dr Wickramasinghe, senior author on the paper.

Better diagnosis and treatment of cryptococcosis

Photo Credit: Courtesy of University of Cologne

Global guideline for the management of cryptococcosis, a fungal infection that can have serious health consequences, published in the journal ‘The Lancet Infectious Diseases’

A group of international mycology experts led by Professor Dr Oliver A. Cornely at the University of Cologne has jointly drafted a guideline for the diagnosis and treatment of cryptococcosis, which aims at improving infection management and thus the survival rate of patients. Cryptococcosis is a fungal infection of mainly the lungs that might lead to meningitis. The article ‘Global guideline for the diagnosis and management of cryptococcosis’ was published in the journal The Lancet Infectious Diseases.

Cryptococcosis, especially cryptococcal meningitis (CM) as the most fatal form, is responsible for a high fatality rate among patients. It is one of the most widespread invasive fungal infections in the world and is a major threat particularly to people suffering from immunodeficiencies. For example, around one million cases of cryptococcal meningoencephalitis are diagnosed worldwide every year in people with HIV alone, and more than 600,000 people die from the disease each year. Patients who have undergone a bone marrow transplant or organ transplant are also at high risk of infection. It is transmitted through the inhalation of spores from soil. Other organs are then also infected via the bloodstream. The lungs, brain, skin and bones are most frequently affected.

A standard blood test can predict a heart attack

Researchers have proceeded from the hypothesis that several important biological processes are active during the months before a heart attack and that these could be detected using a simple blood test.
Photo Credit: Fernando Zhiminaicela

Using the results of a standard blood test and an online tool, you can find out if you are at increased risk of having a heart attack within six months. The tool has been developed by a research group at Uppsala University in the hope of increasing patients’ motivation to change their lifestyle.

Heart attacks are the most common cause of death in the world and are increasing globally. Many high-risk people are not identified or do not take their preventive treatment.

Now researchers led by Professor Johan Sundström at Uppsala University have found that heart attacks can be predicted with a standard blood test.

The problem, according to the researchers, is that risk factors have previously been verified in studies involving five to ten years of follow-up, where only factors that are stable over time can be identified.

“However, we know that the time just before a heart attack is very dynamic. For example, the risk of a heart attack doubles during the month after a divorce, and the risk of a fatal heart event is five times as high during the week after a cancer diagnosis,” says Sundström, who is a cardiologist and professor of epidemiology at Uppsala University.

Immunotherapy before surgery leads to promising long-term survival in sarcoma patients

From Left to Right Christina Roland, M.D. and Neeta Somaiah, M.D.
Image Credit: Courtesy of University of Texas MD Anderson Cancer Center

Patients with soft-tissue sarcoma treated with neoadjuvant, or pre-surgical, immunotherapy had very little residual tumor at the time of surgery and promising long-term survival, according to Phase II trial results published today in Nature Cancer by researchers at The University of Texas MD Anderson Cancer Center.

After treatment with a combination of immunotherapy and radiation followed by surgical removal of the residual mass, 90% of patients with undifferentiated pleomorphic sarcoma (UPS) had less than 15% viable tumor cells remaining, better than what has historically been seen with radiation alone. The overall survival (OS) rate at two years after first treatment was 82% in resectable retroperitoneal dedifferentiated liposarcoma (DDLPS) and 90% in UPS.

“These results demonstrate the role immunotherapy treatment can have on soft-tissue sarcomas and how the neoadjuvant treatment platform can help identify novel treatment options for patients,” said co-principal investigator Christina Roland, M.D., associate professor of Surgical Oncology. “Sarcoma patients have limited systemic therapy options to consider, and this trial offers data to support the use of immunotherapy in their treatment.”

Researchers identify a new mechanism that could improve the efficiency of diabetes treatments

The study led by the UB and CIBERDEM reveals new strategies to inhibit glucose synthesis in the liver and reduce levels in patients affected by metabolic pathologies.
Image Credit: Gemini Advance AI

A study led by the University of Barcelona and the Biomedical Research Networking Center in Diabetes and Associated Metabolic Disorders (CIBERDEM) reveals how a new mechanism could improve the efficiency of currently available treatments for diabetes. The study, carried out on mice and cell cultures, may open up new ways of approaching metabolic diseases that are a global health problem.

The study, published in the journal Metabolism, focuses on the GDF15 protein, a factor that is expressed at high levels in many diseases, such as heart failure, cancer and fatty liver disease. Obese patients also have elevated levels of this protein, but its function is altered and those affected may develop resistance to GDF15 — that is, a reduction in the effectiveness of its activity.

The study is led by Professor Manuel Vázquez-Carrera, from the Faculty of Pharmacy and Food Sciences of the UB, the Institute of Biomedicine of the UB (IBUB), the Sant Joan de Déu Research Institute (IRSJD) and CIBERDEM. The study also highlights the participation of researchers Patricia Rada and Ángela María Valverde, also collaborators at CIBERDEM, the Spanish National Research Council (CSIC) and the Autonomous University of Madrid (UAM). The work has the collaboration of Professor Walter Wahli of the University of Lausanne (Switzerland), among other experts.

Artificial cartilage with the help of 3D printing

The spheroids in which living cells are grown, can be assembled into almost any shape.
Image Credit: Technische Universität Wien

A new approach to producing artificial tissue has been developed at TU Wien: Cells are grown in microstructures created in a 3D printer.

Is it possible to grow tissue in the laboratory, for example to replace injured cartilage? At TU Wien (Vienna), an important step has now been taken towards creating replacement tissue in the lab - using a technique that differs significantly from other methods used around the world.

A special high-resolution 3D printing process is used to create tiny, porous spheres made of biocompatible and degradable plastic, which are then colonized with cells. These spheroids can then be arranged in any geometry, and the cells of the different units combine seamlessly to form a uniform, living tissue. Cartilage tissue, with which the concept has now been demonstrated at TU Wien, was previously considered particularly challenging in this respect.

Brain cell discovery sparks hope for fertility treatments

Photo Credit: Yoshihisa Uenoyama, Graduate School of Bioagricultural Sciences, Nagoya University

Researchers at Nagoya University’s Graduate School of Bioagricultural Sciences and the National Institute of Physiological Sciences in Japan have demonstrated how a specific type of neuron in the brain affects the release of hormones that control ovarian function, such as follicular development and ovulation in females. These findings, published in the journal Scientific Reports, could help researchers understand and treat reproductive disorders in both animals and humans.  

Kisspeptin neurons in the brain regulate the release of hypothalamic gonadotropin-releasing hormone (GnRH) and pituitary follicle-stimulating hormone/luteinizing hormone (LH). This process is important for reproduction, as pituitary hormones stimulate the ovaries to perform their reproductive functions. Examples include follicular development and ovulation in all mammals, including humans.   

There are two main areas of the brain involved in the process: the arcuate nucleus (ARC), in which kisspeptin neurons maintain the regular rhythmic (pulsatile) secretion of GnRH/LH that maintains normal follicular development and sex steroid production; and the anteroventral periventricular nucleus (AVPV), in which kisspeptin neurons trigger a surge of GnRH/LH that leads to ovulation.