“Atlas” of mouse microbiome strengthens reproducibility of animal testing

Prof. Dr. Bahtiyar Yilmaz, Research group leader at the Department for Biomedical Research (DBMR) of the University of Bern and Department of Visceral Surgery and Medicine, Inselspital, Bern University Hospital.
Photo Credit: © Courtesy of Bahtiyar Yilmaz

Laboratory mice are indispensable for biomedical discovery, yet even genetically identical mice can yield conflicting experimental results depending on their resident microbiota. The complex interplay between microbial communities and their associated metabolic functions in the intestine can profoundly influence experimental results, therapeutic interventions, and our understanding of various biological processes. Understanding the dynamics of the gut microbiome is therefore of paramount importance for biomedical research, as it plays a vital role in shaping health and disease outcomes. This groundbreaking study addresses a fundamental question in microbiome science: how does the composition of microbial communities affect their metabolic function? By exploring this relationship, the research aims to provide insights that could lead to more effective strategies for utilizing mouse models in biomedical studies. 

Led by researchers from the Department of Biomedical Research of the University of Bern and the Department of Visceral Surgery and Medicine from the Inselspital, Bern University Hospital, this collaborative effort involved a vast global consortium, that meticulously analyzed approximately 4,000 intestinal samples from mice. The study forms the geographically most comprehensive mouse microbiome dataset to date and revealed that, despite immense differences in bacterial species across facilities, metabolic outputs in the intestine are strikingly consistent. The findings represent a significant milestone in microbiome research and were recently published in the scientific journal Cell Host & Microbe.

Bioinformatics Uncovers Regenerative Therapy for Spinal Cord Injury

Human brain cells are notoriously difficult to culture in the lab, but UC San Diego researchers successfully grew human brain cells, shown here, in order to test a new treatment approach for spinal cord injury.
Photo Credit: Mark H. Tuszynski/UC San Diego Health Sciences

Spinal cord injury (SCI) remains a major unmet medical challenge, often resulting in permanent paralysis and disability with no effective treatments. Now, researchers at University of California San Diego School of Medicine have harnessed bioinformatics to fast-track the discovery of a promising new drug for SCI. The results will also make it easier for researchers around the world to translate their discoveries into treatments.

One of the reasons SCI results in permanent disability is that the neurons that form our brain and spinal cord cannot effectively regenerate. Encouraging neurons to regenerate with drugs offers a promising possibility for treating these severe injuries. 

The researchers found that under specific experimental conditions, some mouse neurons activate a specific pattern of genes related to neuronal growth and regeneration. To translate this fundamental discovery into a treatment, the researchers used data-driven bioinformatics approaches to compare their pattern to a vast database of compounds, looking for drugs that could activate these same genes and trigger neurons to regenerate.

New nanomedicine wipes out leukemia in animal study

The real-time cellular uptake of spherical nucleic acids (SNAs) and fusion with leukemia cells’ lysosomes, where the SNAs degrade and release potent chemotherapeutics. SNAs are shown in red; cells’ cytoskeletons are green; and cells’ nuclei are blue.
Video Credit: Chad A. Mirkin Research Group

In a promising advance for cancer treatment, Northwestern University scientists have re-engineered the molecular structure of a common chemotherapy drug, making it dramatically more soluble and effective and less toxic.

In the new study, the team designed a new drug from the ground up as a spherical nucleic acid (SNA) — a nanostructure that weaves the drug directly into DNA strands coating tiny spheres. This design converts a poorly soluble, weakly performing drug into a powerful, targeted cancer killer that leaves healthy cells unharmed.

Missing nutrient in breast milk may explain health challenges in children of women with HIV

UCLA study finds tryptophan is depleted in breast milk of mothers living with HIV
Photo Credit: Julia Koblitz

A new UCLA study reveals that breast milk from women living with HIV contains significantly lower levels of tryptophan, an essential amino acid likely important for infant immune function, growth, and brain development. This discovery may help explain why children born to women living with HIV experience higher rates of illness and developmental challenges, even when the children themselves are not infected with the virus. 

Approximately 1.3 million children are born to women living with HIV annually worldwide. Even with effective antiretroviral therapy that prevents HIV transmission, these children who are exposed to HIV but not infected continue to face a 50% increase in mortality in low-income settings along with increased risks of infections, growth problems, and cognitive challenges. Prior to antiretroviral therapy, these children had mortality rates that were two to three times higher than infants not exposed to HIV. Understanding why these children remain vulnerable despite not being infected has been a critical gap in maternal and child health research. This study provides the first metabolic explanation for these persistent health disparities and points toward potential nutritional interventions that could protect vulnerable infants.

Rebalancing the Gut: How AI Solved a 25-Year Crohn’s Disease Mystery

Electron micrographs show how macrophages expressing girdin neutralize pathogens by fusing phagosomes (P) with the cell’s lysosomes (L) to form phagolysosomes (PL), compartments where pathogens and cellular debris are broken down (left). This process is crucial for maintaining cellular homeostasis. In the absence of girdin, this fusion fails, allowing pathogens to evade degradation and escape neutralization (right).
Image Credit: UC San Diego Health Sciences

The human gut contains two types of macrophages, or specialized white blood cells, that have very different but equally important roles in maintaining balance in the digestive system. Inflammatory macrophages fight microbial infections, while non-inflammatory macrophages repair damaged tissue. In Crohn’s disease — a form of inflammatory bowel disease (IBD) — an imbalance between these two types of macrophages can result in chronic gut inflammation, damaging the intestinal wall and causing pain and other symptoms. 

Researchers at University of California San Diego School of Medicine have developed a new approach that integrates artificial intelligence (AI) with advanced molecular biology techniques to decode what determines whether a macrophage will become inflammatory or non-inflammatory. 

The study also resolves a longstanding mystery surrounding the role of a gene called NOD2 in this decision-making process. NOD2 was discovered in 2001 and is the first gene linked to a heightened risk for Crohn’s disease.

Researchers decipher a mechanism that determines the complexity of the glucocorticoid receptor

Above, from left to right, Pilar Montanyà-Vallugera, José Luis Torbado-Gardeazábal, Inés Montoya-Novoa and Montse Abella-Monleón. Below, from left to right, Alba Jiménez-Panizo, Pablo Fuentes-Prior, Eva Estébanez-Perpiñá and Andrea Alegre-Martí.
Photo Credit: Courtesy of University of Barcelona

Drugs to treat inflammatory and autoimmune diseases — such as asthma, psoriasis, rheumatoid arthritis or Chrousos syndrome — act mainly through the glucocorticoid receptor (GR). This essential protein regulates vital processes in various tissues, so understanding its structure and function at the molecular level is essential for designing more effective and safer drugs. Now, a study published in the journal Nucleic Acids Research (NAR) has revealed the mechanism of multimerization — the association of different molecules to form complex structures — of the glucocorticoid receptor, a process critical to its physiological function.

Deciphering how the GR forms oligomers — through the binding of several subunits — opens a crucial avenue for developing more selective drugs. These new drugs could modulate this association and thus minimize serious adverse effects, such as immunosuppression or bone loss.

Treating fibrosis with a chemical derived from Lawsonia inermis

Treatment with Lawsone converts a liver with fibrosis into a healthy liver.
Image Credit: Osaka Metropolitan University

Lawsonia inermis is best known for making henna, a versatile dye that is used to change the color of skin and clothes. Now, researchers from Osaka Metropolitan University have found another use for the pigments extracted from the dye: treating liver disease.

Specifically, they could treat liver fibrosis, a disease that causes excess fibrous scar tissue to build up in the liver as a result of chronic liver injury caused by lifestyle choices such as excessive drinking. Patients with liver fibrosis have increased risks of cirrhosis, liver failure, and cancer. Despite 3–4% of the population having the advanced form of the disease, treatment options remain limited.

New antivirals could help prevent cold sores by changing cell structures

Pin1 inhibitors suppress HSV-1 replication by inhibiting viral protein synthesis and preventing nucleocapsid egress from the nucleus.
Illustration Credit: Takemasa Sakaguchi/Hiroshima University

A class of antivirals called Pin1 inhibitors could reduce or stop outbreaks of herpes simplex virus 1 (HSV-1), the common infection behind oral herpes, according to new research published in Antiviral Research.

HSV-1 causes sores around the mouth, commonly called cold sores or fever blisters. Most people are infected with HSV-1 in childhood, and between 50% and 90% of people worldwide have HSV-1. After the initial infection, HSV-1 remains in the body and can reactivate throughout a person’s life. While HSV-1 infections are usually mild, they can be serious and even deadly for people with suppressed immune systems. Finding new, more effective antivirals for this common illness is essential. 

Researchers focused on an enzyme called peptidyl-prolyl cis-trans isomerase NIMA-interacting 1, or Pin1, that regulates protein stability, function, and cellular structure. When this enzyme is dysregulated, it can play a role in a variety of conditions, including obesity, cancer, heart failure, and more. Viruses, such as cytomegalovirus (CMV) and SARS-CoV-2, are known to affect Pin1, and Pin1 inhibitors have been developed to reduce the impact of these viruses. 

Researchers uncover possible new treatment to target a devastating childhood brain cancer

Professor Peter Lewis
Photo Credit: Courtesy of University of Wisconsin–Madison

Using fruit flies, University of Wisconsin–Madison researchers have developed a new model for investigating the genetic drivers of a rare but aggressive brain tumor in children. The work has already identified potential treatment targets for the deadly cancer that has previously had few therapeutic options.

“Right now, these tumors are incurable, and the standard of care hasn’t changed for 30 years,” says Peter Lewis, a professor in the Department of Biomolecular Chemistry.

The cancer is called pediatric diffuse midline glioma. As its name suggests, the malignancy arises along the midline of the brain or spinal cord and infiltrates surrounding tissue in a way that makes it impossible to remove with surgery. Instead, typical treatment revolves around radiation therapy, and that extends a patient’s life by just months or at most a few years.

Professor Peter Lewis: “What we found might extend well beyond these very rare childhood tumors into more common ones.”

The limited treatment options have driven researchers to more closely examine the genetic mutations that cause the cancer to develop in the first place, with an eye on finding ways to disrupt that process. 

In the case of diffuse midline glioma, previous research identified mutations in certain DNA-packaging proteins as a likely culprit.

Cholesterol-lowering drugs could reduce the risk of dementia

Low cholesterol can reduce the risk of dementia, a new University of Bristol-led study with more than a million participants has shown.

The research, led by Dr Liv Tybjærg Nordestgaard while at the University of Bristol and the Department of Clinical Biochemistry at Copenhagen University Hospital – Herlev and Gentofte, found that people with certain genetic variants that naturally lower cholesterol have a lower risk of developing dementia.

The study, which is based on data from over a million people in Denmark, England, and Finland, has been published in the journal Alzheimer's & Dementia: The Journal of the Alzheimer's Association. 

Some people are born with genetic variants that naturally affect the same proteins targeted by cholesterol-lowering drugs, such as statins and ezetimibe. To test the effect of cholesterol-lowering medication on the risk of dementia, the researchers used a method called Mendelian Randomization — this genetic analysis technique allowed them to mimic the effects of these drugs to investigate how they influence the risk of dementia, while minimizing the influence of confounding factors like weight, diet, and other lifestyle habits.

Air Pollution Can Contribute to Obesity and Diabetes

The most significant sources of fine air pollutants include exhaust fumes from cars, industrial plants and heating systems, as well as emissions from construction sites and forest fires.
Photo Credit: Uvi D

Long-term exposure to fine air pollution can impair metabolic health by disrupting the normal function of brown fat in mice. A study co-led by the University of Zurich shows that this occurs through complex changes in gene regulation driven by epigenetic mechanisms. The results demonstrate how environmental pollutants contribute to the development of insulin resistance and metabolic diseases.

There is growing evidence that air pollution is not just harmful to our lungs and heart, but also plays a significant role in the development of metabolic disorders like insulin resistance and type 2 diabetes. A new study co-led by Francesco Paneni, professor at the Center for Translational and Experimental Cardiology of the University of Zurich (UZH) and the University Hospital Zurich (USZ), and Sanjay Rajagopalan, professor at the Case Western Reserve University, Cleveland, now sheds light on the topic.

Researchers discover of a new type of diabetes in babies

Photo Credit: Rene Terp

Advanced DNA sequencing technologies and a new model of stem cell research has enabled an international team to discover a new type of diabetes in babies.

The University of Exeter Medical School worked with Université Libre de Bruxelles (ULB) in Belgium and other partners to establish that mutations in the TMEM167A gene are responsible for a rare form of neonatal diabetes.

Some babies develop diabetes before the age of six months. In over 85 per cent of cases this is due to genetic mutation in their DNA. Research led by the University of Exeter found that in six children with additional neurological disorders such as epilepsy and microcephaly identified alterations in a single gene: TMEM167A.

To understand its role, ULB researcher Professor Miriam Cnop’s team used stem cells differentiated into pancreatic beta cells and gene-editing techniques (CRISPR). They found that when the TMEM167A gene is altered, insulin-producing cells can no longer fulfill their role. They then activate stress mechanisms that lead to their death.

Engineered “natural killer” cells could help fight cancer

Caption:A new study identifies genetic modifications that make “natural killer” cells more effective at destroying cancer cells.
Image Credit: NIAID
(CC BY-NC-ND 4.0)

One of the newest weapons that scientists have developed against cancer is a type of engineered immune cell known as CAR-NK (natural killer) cells. Similar to CAR-T cells, these cells can be programmed to attack cancer cells.

MIT and Harvard Medical School researchers have now come up with a new way to engineer CAR-NK cells that makes them much less likely to be rejected by the patient’s immune system, which is a common drawback of this type of treatment.

The new advance may also make it easier to develop “off-the-shelf” CAR-NK cells that could be given to patients as soon as they are diagnosed. Traditional approaches to engineering CAR-NK or CAR-T cells usually take several weeks.

“This enables us to do one-step engineering of CAR-NK cells that can avoid rejection by host T cells and other immune cells. And, they kill cancer cells better and they’re safer,” says Jianzhu Chen, an MIT professor of biology, a member of the Koch Institute for Integrative Cancer Research,and one of the senior authors of the study.

Antibody discovered that blocks almost all known HIV variants in neutralization assays

Image Credit; Scientific Frontline / AI Generated

 A Cologne-led research team has discovered the antibody 04_A06, which neutralizes the human immunodeficiency virus (HIV) in almost all tested variants in vitro and even overcomes typical resistance mechanisms. The discovery potentially opens up new perspectives for the prevention and treatment of HIV infections.

An international research team led by the University of Cologne has discovered an antibody that could advance the fight against HIV. The newly identified antibody 04_A06 proved to be particularly effective in laboratory tests. It was able to neutralize 98.5 percent of more than 300 different HIV strains, making it one of the broadest antibodies against HIV identified. In experiments with humanized mice – animals whose immune system has been modified to resemble that of humans – 04_A06 permanently reduced the HIV viral load to undetectable levels. Most other HIV antibodies, in contrast, only achieve short-term effects in this animal model, as resistance develops quickly. The study ‘Profiling of HIV-1 elite neutralizer cohort reveals a CD4bs bNAb for HIV-1 prevention and therapy’ was published in Nature Immunology.

Chemists create red fluorescent dyes that may enable clearer biomedical imaging

Caption:MIT chemists have created a fluorescent, boron-containing molecule that is stable when exposed to air and can emit light in the red and near-infrared range. The dye can be made into crystals (shown in these images), films, or powders. The images at top were taken in ambient light and the images at bottom in UV light.
Image Credit: Courtesy of the researchers
(CC BY-NC-ND 4.0)

MIT chemists have designed a new type of fluorescent molecule that they hope could be used for applications such as generating clearer images of tumors.

The new dye is based on a borenium ion — a positively charged form of boron that can emit light in the red to near-infrared range. Until recently, these ions have been too unstable to be used for imaging or other biomedical applications.

In a study appearing today in Nature Chemistry, the researchers showed that they could stabilize borenium ions by attaching them to a ligand. This approach allowed them to create borenium-containing films, powders, and crystals, all of which emit and absorb light in the red and near-infrared range.

That is important because near-IR light is easier to see when imaging structures deep within tissues, which could allow for clearer images of tumors and other structures in the body.

“One of the reasons why we focus on red to near-IR is because those types of dyes penetrate the body and tissue much better than light in the UV and visible range. Stability and brightness of those red dyes are the challenges that we tried to overcome in this study,” says Robert Gilliard, the Novartis Professor of Chemistry at MIT and the senior author of the study.

New mechanism revealed: How leukemia cells trick the immune system

Thoas Fioretos, Niklas Landberg, and Carl Sandén are the research team behind the study now being published in Nature Cancer.
Photo Credit: Tove Smeds

A research team at Lund University in Sweden has discovered a mechanism that helps acute myeloid leukemia cells to evade the body’s immune system. By developing an antibody that blocks the mechanism, the researchers could restore the immune system’s ability to kill the cancer cells in laboratory trials and in mice. The discovery is published in Nature Cancer.

Immunotherapy has improved the treatment for many cancers, but progress has been limited in leukemia. Acute myeloid leukemia (AML) is particularly intractable, with a five-year survival rate of just over 30 per cent. The existing treatments are often aggressive and may include both strong chemotherapy and stem cell transplantations.

“We wanted to see if we could find surface proteins unique to leukemia stem cells, and which would therefore act as interesting targets for a targeted treatment. If such proteins were not present on healthy blood stem cells it might be possible to attack the tumor – without harming the healthy blood system,” says Thoas Fioretos, research group leader and professor of clinical genetics at Lund University, and senior consultant at Skåne University Hospital.

Scientists Have Created New Lanthanum Complex Promising for Anti-cancer Therapy

Lanthanum complexes demonstrate antioxidant activity, anti-inflammatory effect, acceleration of tissue regeneration and anesthesia.
Photo Credit: Louis Reed

As a result of the joint work of an international group of scientists from Russia (Ural Federal University), Bulgaria (Medical University, Sofia), and Spain (Complutense University of Madrid, Rey Juan Carlos University), a new lanthanum (III) complex with a luminescent triazole ligand has been obtained that is able to selectively regulate the level of reactive oxygen species (ROS) in cells. The result opens up prospects for the development of new anti-cancer and anti-infective drugs. The interim results of the study were published in the journal Molecules.

“New lanthanum complexes demonstrate a wide range of biological effects such as antioxidant activity, anti-inflammatory effect, acceleration of tissue regeneration and anesthesia. In a study that we conducted together with biologists from the Medical University of Sofia, we found out that both lanthanum complexes of La(III) and free organic ligands can affect the level of reactive oxygen species. At the same time, we found that they have a dual effect: in some tests, they act as antioxidants, protecting healthy cells, in others, as pro-oxidants, contributing to the death of tumor cells. This specific focus of action makes them promising candidates for the development of new drugs for cancer,” said Natalia Belskaya, Professor at UrFU Department of Technology pf Organic Synthesis.

Fat particles could be key to treating metabolic brain disorders

For decades, it was widely accepted that neurons relied exclusively on glucose to fuel their functions in the brain. This is not the case.
Photo Credit: The University of Queensland

Evidence challenging the long-held assumption that neuronal function in the brain is solely powered by sugars has given researchers new hope of treating debilitating brain disorders.

A University of Queensland study led by Dr Merja Joensuu showed that neurons also use fats for fuel as they fire off the signals for human thought and movement.

“For decades, it was widely accepted that neurons relied exclusively on glucose to fuel their functions in the brain,” Dr Joensuu said.

“But our research shows fats are undoubtedly a crucial part of the neuron’s energy metabolism in the brain and could be a key to repairing and restoring function when it breaks down.”

Dr Joensuu from the Australian Institute for Bioengineering and Nanotechnology along with lab members PhD candidate Nyakuoy Yak and Dr Saber Abd Elkader from UQ’s Queensland Brain Institute set out to examine the relationship of a particular gene (DDHD2) to hereditary spastic paraplegia 54 (HSP54).

Researchers use nanotubes to improve blood flow in bioengineered tissues

Assistant Professors Ying Wang (Department of Biomedical Engineering) and Yingge Zhou (School of Systems Science and Industrial Engineering) collaborated on research about engineered tissues.
Photo Credit: Jonathan Cohen.

When biomedical researchers need to test their latest ideas, they often turn to engineered human tissue that mimics the responses in our own bodies. It’s become an important intermediary step before human clinical trials.

One limiting factor: The cells need blood circulation to survive, and achieving that can be difficult in three-dimensional cell structures. Without proper vascular systems — even primitive ones — engineered tissue faces restricted size and functionality, even developing necrotic regions of dead cells.

New research from Binghamton University’s Thomas J. Watson College of Engineering and Applied Science offers a possible solution to the problem. In a paper recently published in the journal Biomedical Materials, Assistant Professors Ying Wang and Yingge Zhou show how the latest nanomanufacturing techniques can create a better artificial vascular system.

Simple test can predict risk of severe liver disease

The researchers' new method can contribute to earlier detection of cirrhosis and liver cancer.
Image Credit: Scientific Frontline / AI Generated

A new study from Karolinska Institutet, published in the scientific journal The BMJ, shows how a simple blood analysis can predict the risk of developing severe liver disease. The method may already start to be applied in primary care to enable the earlier detection of cirrhosis and cancer of the liver.

“These are diseases that are growing increasingly common and that have a poor prognosis if detected late,” says Rickard Strandberg, affiliated researcher at Karolinska Institutet’s Department of Medicine, Huddinge, who has developed the test with his departmental colleague Hannes Hagström. “Our method can predict the risk of severe liver disease within 10 years and is based on three simple routine blood tests.” 

For the study, the researchers at Karolinska Institutet and their colleagues in Finland evaluated how well the method can estimate the risk of severe liver disease. The model, which is called CORE, was produced with advanced statistical methods and is based on five factors: age, sex and levels of three common liver enzymes (AST, ALT and GGT), which are commonly measured during regular health checks.