UNC scientists discover how cells respond to common prescription drugs

Dissociation of G protein from drug-bound GPCR (orange) is captured in accelerated molecular dynamics simulations, starting from the bound (blue) to free state (red), with a trace of its C-terminal residue colored in a blue-white-red scale.
Photo Credit: Courtesy of Yinglong Miao, Anh T. N. Nguyen and Lauren May

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers at the UNC School of Medicine elucidated the precise molecular pathways by which G proteins dissociate from drug-activated G protein-coupled receptors (GPCRs) to initiate intracellular signaling.
• Methodology: The team utilized a computational technique known as "accelerated molecular dynamics" to simulate these protein interactions, with findings validated by experimental laboratory results in collaboration with Monash University.
• Specific Mechanism: The study, published in Proceedings of the National Academy of Sciences, demonstrated that specific small-molecule drug leads can bind to GPCRs with high selectivity and effectively slow down the G protein dissociation process.
• Key Statistic: This insight is highly relevant to pharmaceutical development, as GPCRs are the molecular targets for approximately one-third of all currently prescribed drugs.
• Significance/Future Application: Understanding this mechanism allows for the creation of precise medicines that fine-tune cell signaling—such as non-addictive treatments for neuropathic pain—by minimizing toxic side effects through selective receptor modulation.

Researcher contributes to study revealing hidden diversity of E. coli in diabetic foot infections

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Escherichia coli found in diabetic foot infections is not a uniform pathogen but constitutes a highly diverse array of genetic groups, with distinct lineages independently adapting to the diabetic wound environment.
• Methodology: Researchers conducted the first comprehensive whole-genome sequencing analysis of 42 E. coli strains isolated from diabetic foot ulcers across diverse global populations, including the UK, Nigeria, Brazil, and the USA.
• Key Statistic: Approximately 8% of the analyzed strains were classified as multidrug-resistant or extensively drug-resistant, possessing mechanisms to withstand multiple or nearly all available antibiotic classes.
• Specific Mechanism: The genomic data identified critical virulence factors—specifically genes enabling tissue attachment and immune evasion—that explain the rapid progression and severity of these infections.
• Significance: This genomic characterization provides a foundation for developing precision diagnostics and targeted therapies, directly addressing the urgent need to reduce treatment failure and lower-limb amputations in diabetic patients.

When a virus releases the immune brake: New evidence on the onset of multiple sclerosis

Fluorescence microscope image of a mouse brain. The protective myelin layer (red) surrounds the nerve cell extensions. Cells infected with a virus are visible in light blue. Such infections cause immune cells to invade the brain and attack the myelin layer.
Image Credit: Hyein Kim, University of Basel

Scientific Frontline: "At a Glance" Summary

• Discovery of Initiation Mechanism: Researchers have identified a specific biological sequence where the Epstein-Barr virus (EBV) triggers early multiple sclerosis (MS)-like damage by allowing self-reactive B cells to bypass immune checkpoints.
• Molecular Mimicry: The mechanism relies on a viral protein (Latent Membrane Protein 1) that mimics a crucial "approval" signal usually provided by other immune cells, preventing the programmed elimination of B cells that target the body's own proteins.
• Localized Pathogenesis: Experimental mouse models demonstrated that these "out-of-control" B cells capture myelin antigens and cause localized demyelinating lesions in the central nervous system, mirroring the earliest stages of MS.
• B Cell Direct Action: The study shifts the understanding of B cells from indirect influencers of inflammation to direct agents of lesion formation, suggesting they are the primary "spark" for chronic brain inflammation.
• Therapeutic Correlation: The findings explain the clinical efficacy of current B-cell depleting therapies and emphasize that MS risk is shaped by the timing and sequence of rare immune events rather than infection alone.
• Future Prevention: This discovery highlights the potential for preventive strategies, such as targeted vaccinations designed to inhibit severe EBV infections and prevent the subsequent invasion of the brain by pathogenic B cells.

Intraoperative Tumor Histology May Enable More-Effective Cancer Surgeries

From left to right: Images of kidney tissue as detected with UV-PAM, as imaged by AI to mimic traditional H&E staining, and as they appear when directly treated with H&E staining.
Image Credit: Courtesy of California Institute of Technology

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers developed ultraviolet photoacoustic microscopy (UV-PAM) integrated with deep learning to perform rapid, label-free, subcellular-resolution histology on excised tumor tissue directly in the operating room.
• Mechanism: A low-energy laser excites the absorption peaks of DNA and RNA nucleic acids to generate ultrasonic vibrations; AI algorithms then process these signals to create virtual images that mimic traditional hematoxylin and eosin (H&E) staining without chemical processing.
• Key Data: The system achieves a spatial resolution of 200 to 300 nanometers and delivers diagnostic results in under 10 minutes (potentially under 5 minutes), effectively identifying the dense, enlarged nuclei characteristic of cancer cells.
• Context: Unlike standard pathology, which requires time-consuming freezing, fixation, and slicing that can damage fatty tissues like breast tissue, this method preserves sample integrity and eliminates preparation artifacts.
• Significance: This technology aims to drastically reduce re-operation rates—currently up to one-third for breast cancer lumpectomies—by allowing surgeons to confirm clean tumor margins intraoperatively across various tissue types (breast, bone, skin, organ).

X-raying auditory ossicles – a new technique reveals structures in record time

Scientists at PSI were able to observe the local collagen structures in an ossicle by scanning it with an X-ray beam. The different colours of the cylinders indicate how strongly the collagen bundles are spatially aligned in a section measuring 20 by 20 by 20 micrometres.
Image Credit: © Paul Scherrer Institute PSI/Christian Appel

Scientific Frontline: "At a Glance" Summary

• Main Discovery: Researchers refined a "tensor tomography" X-ray diffraction technique that simultaneously detects biological structures ranging from nanometers to millimeters, significantly accelerating the imaging process.
• Methodology: The team used a precisely rotated X-ray beam (approx. 20 micrometers wide) to generate millions of interference patterns around two axes, which software then reconstructed into a 3D tomogram.
• Key Statistic: The optimized process reduced the measurement time for a complete tomogram from roughly 24 hours to just over one hour.
• Context: To validate the method, the team imaged the auditory ossicle (anvil) of the ear, successfully mapping the spatial orientation of nanometer-sized collagen fibers crucial for sound transmission.
• Significance: This drastic reduction in scan time makes statistical studies involving hundreds of samples feasible, aiding biomedical research in areas like bone tissue analysis and implant development.

What Is: Organoid

Organoids: The Science and Ethics of Mini-Organs
Image Credit: Scientific Frontline / AI generated

The "At a Glance" Summary

• Defining the Architecture: Unlike traditional cell cultures, organoids are 3D structures grown from pluripotent stem cells (iPSCs) or adult stem cells. They rely on the cells' intrinsic ability to self-organize, creating complex structures that mimic the lineage and spatial arrangement of an in vivo organ.
• The "Avatar" in the Lab: Organoids allow for Personalized Medicine. By growing an organoid from a specific patient's cells, researchers can test drug responses on a "digital twin" of that patient’s tumor or tissue, eliminating the guesswork of trial-and-error prescriptions.
• Bridge to Clinical Trials: Organoids serve as a critical bridge between the Petri dish and human clinical trials, potentially reducing the failure rate of new drugs and decreasing the reliance on animal testing models which often fail to predict human reactions.
• The Ethical Frontier: As cerebral organoids (mini-brains) become more complex, exhibiting brain waves similar to preterm infants, science faces a profound question: At what point does biological complexity become sentience?

New test shows which antibiotics actually work

Some bacterial pathogens play dead to dodge antibiotics. A new test watches them closely—and helps choose drugs that finish the job
Image Credit: Scientific Frontline / AI generated

Scientific Frontline: "At a Glance" Summary

• Researchers at the University of Basel and University Hospital Basel developed "antimicrobial single-cell testing," a novel method that precisely measures the lethality of antibiotics against bacteria rather than merely their ability to inhibit growth.
• The technique utilizes high-throughput microscopic imaging to film millions of individual bacteria under thousands of conditions over several days, tracking the survival and death kinetics of each cell in real-time.
• Validation involved testing 65 combination therapies on Mycobacterium tuberculosis and analyzing bacterial samples from 400 patients infected with Mycobacterium abscessus.
• Unlike traditional susceptibility tests that often fail to detect dormant bacteria capable of reviving post-treatment, this approach identifies "antibiotic tolerance," where pathogens survive exposure without reproducing.
• This technology enables personalized medicine by tailoring antibiotic regimens to a patient's specific bacterial strain and offers a more accurate predictor of therapeutic success than current clinical or animal model data.

Harnessing evolution: Evolved synthetic disordered proteins could address disease, antibiotic resistance

Yifan Dai and his team designed a method based on directed evolution to create synthetic intrinsically disordered proteins that can facilitate diverse phase behaviors in living cells. Intrinsically disordered proteins have different phase behaviors that take place at increasing or decreasing temperatures, as shown in the image above. The intrinsically disordered proteins on the left are cold responsive, and those on the right are hot responsive. The tree image in the center depicts the directed evolution process with the reversible intrinsically disordered proteins near the top. Feeding into the process from the bottom are soluble intrinsically disordered proteins.
Illustration Credit: Dai lab

The increased prevalence of antibiotic resistance could make common infections deadly again, which presents a threat to worldwide public health. Researchers in the McKelvey School of Engineering at Washington University in St. Louis have developed the first directed evolution-based method capable of evolving synthetic condensates and soluble disordered proteins that could eventually reverse antibiotic resistance.

Yifan Dai, assistant professor of biomedical engineering, and his team designed a method that is directed evolution-based to create synthetic intrinsically disordered proteins that can facilitate diverse phase behaviors in living cells. This allows them to build a toolbox of synthetic intrinsically disordered proteins with distinct phase behaviors and features that are responsive to temperatures in living cells, which helps them to create synthetic biomolecular condensates. In addition to reversing antibiotic resistance, the cells can regulate protein activity among cells. 

Stem cell engineering breakthrough paves way for next-generation living drugs

UBC research associate Dr. Ross Jones in the lab where they are working to develop cell-based therapies from stem cells.
Photo Credit: Phillip Chin.

For the first time, researchers at the University of British Columbia have demonstrated how to reliably produce an important type of human immune cell—known as helper T cells—from stem cells in a controlled laboratory setting.  

The findings, published today in Cell Stem Cell, overcome a major hurdle that has limited the development, affordability and large-scale manufacturing of cell therapies. The discovery could pave the way for more accessible and effective off-the-shelf treatments for a wide range of conditions like cancer, infectious diseases, autoimmune disorders and more.   

“Engineered cell therapies are transforming modern medicine,” said co-senior author Dr. Peter Zandstra, professor and director of the UBC School of Biomedical Engineering. “This study addresses one of the biggest challenges in making these lifesaving treatments accessible to more people, showing for the first time a reliable and scalable way to grow multiple immune cell types.”  

AI model predicts disease risk while you sleep

SleepFM utilizes diverse physiological data streams, highlighting the potential to improve disease forecasting and better understand health risks.
Image Credit: Scientific Frontline / AI generated (Gemini)

The first artificial intelligence model of its kind can predict more than 100 health conditions from one night’s sleep.

A poor night’s sleep portends a bleary-eyed next day, but it could also hint at diseases that will strike years down the road. A new artificial intelligence model developed by Stanford Medicine researchers and their colleagues can use physiological recordings from one night’s sleep to predict a person’s risk of developing more than 100 health conditions.

Known as SleepFM, the model was trained on nearly 600,000 hours of sleep data collected from 65,000 participants. The sleep data comes from polysomnography, a comprehensive sleep assessment that uses various sensors to record brain activity, heart activity, respiratory signals, leg movements, eye movements, and more.

International research breakthrough for remote Alzheimer’s testing

Photo Credit: Courtesy of University of Exeter

A groundbreaking international study has demonstrated that Alzheimer’s disease biomarkers can be accurately detected using simple finger-prick blood samples that can be collected at home and mailed to laboratories without refrigeration or prior processing. 

The research, led by US institute Banner Health working with the University of Exeter Medical School and supported by the National Institute for Health and Care Research (NIHR), published today in Nature Medicine. It represents the first large-scale validation of this accessible testing approach that removes geographic barriers and opens brain disease research to global populations without requiring specialized healthcare infrastructure. 

The DROP-AD project, conducted across seven European medical centers including the University of Gothenburg and University of Exeter, successfully tested 337 participants and proved that finger-prick blood collection can accurately measure key markers of Alzheimer’s pathology and brain damage. This breakthrough enables worldwide research participation by eliminating the logistical constraints that have historically limited biomarker studies to well-resourced medical facilities. 

Researchers find breast cancer drug boosts leukemia treatment

Jeffrey Tyner, Ph.D., and Melissa Stewart, Ph.D., led a team at OHSU that discovered a new drug combination that may help people with acute myeloid leukemia.
Photo Credit: OHSU/Christine Torres Hicks

A research team at Oregon Health & Science University has discovered a promising new drug combination that may help people with acute myeloid leukemia overcome resistance to one of the most common frontline therapies.

In a study published in Cell Reports Medicine, researchers analyzed more than 300 acute myeloid leukemia, or AML, patient samples and found that pairing venetoclax, a standard AML drug, with palbociclib, a cell-cycle inhibitor currently approved for breast cancer, produced significantly stronger and more durable anti-leukemia activity than venetoclax alone. The findings were confirmed in human tissue samples as well as in mouse models carrying human leukemia cells.

“Of the 25 drug combinations tested, venetoclax plus palbociclib was the most effective. That really motivated us to dig deeper into why it works so well, and why it appears to overcome resistance seen with current therapy,” said Melissa Stewart, Ph.D., research assistant professor in the OHSU School of Medicine and Knight Cancer Institute and lead author of the study.

More than 20,000 Americans are diagnosed with AML each year, making it one of the most common types of leukemia — and one of the most aggressive.

Chew on this: Losing teeth weakens key memory hub in mouse brains

Mice that lost their molars showed significant memory decline despite receiving the same diet as controls, hinting at the impact of reduced chewing on brain health.
Illustration Credit: Rie Hatakeyama

Tooth loss doesn’t just make eating harder, it may also make thinking more challenging. A new study from Hiroshima University shows that aging mice missing their molars experience measurable cognitive decline, even when their nutrition remains perfectly intact.

“Tooth loss is common in aging populations, yet its direct neurological impact has remained unclear,” said Rie Hatakeyama, postdoctoral researcher at Hiroshima University’s (HU) Graduate School of Biomedical and Health Sciences and first author of the study. 

Menopause hormone therapy does not appear to impact dementia risk

Photo Credit: Vitaly Gariev

A major review of prior research has found no evidence that menopause hormone therapy either increases or decreases dementia risk in post-menopausal women, in a new study led by University College London researchers and supported by the University of Exeter. 

The findings, commissioned by the World Health Organization (WHO) and published in The Lancet Healthy Longevity, add much-needed clarity to a hotly debated topic, and reinforce current clinical guidance that menopause hormone therapy, also called hormone replacement therapy or HRT, should be guided by perceived benefits and risks and not for dementia prevention. 

Professor Chris Fox from the University of Exeter Medical School said: “The role of menopause hormone treatment and relationship to dementia is a worry for many women. But our state-of-the-art review indicates there is no evidence that menopause hormone treatment reduces or increases the risk of dementia. When deciding whether to take menopause hormone treatment, reducing one’s risk of dementia should not be part of that decision “ 

Restoring the healthy form of a protein could revive blood vessel growth in premature infants’ lungs

A blood vessel organoid.
Video Credit: Yunpei Zhang and Enbo Zhu, Mingxia Gu Lab

A UCLA-led research team has discovered a molecular switch that determines whether tiny blood vessels in premature infants’ lungs can regenerate after injury. A failure of this repair process is a hallmark of bronchopulmonary dysplasia, or BPD, a serious lung disease that affects babies born very early. It arises from a combination of premature birth, inflammation or infection, and exposure to the high levels of oxygen and breathing support that are necessary to keep these infants alive during a critical period of lung development.

The researchers found that in BPD, the blood vessel cells in the lungs begin producing a shortened, nonfunctional isoform — a version of a protein — called NTRK2, which has been extensively studied in the nervous system but not in the pulmonary vasculature. When this shortened isoform dominates, the lung cannot rebuild the delicate network of tiny blood vessels needed for healthy breathing.

Exposure to PFAS and PCBs linked to higher odds of MS

Aina Vaivade and Kim Kultima have measured the levels of common environmental pollutants in the blood of people with MS using a mass spectrometer (pictured).
Photo Credit: Tobias Sterner/Uppsala University

People who have been exposed to both PFAS and PCBs are more likely to be diagnosed with multiple sclerosis (MS). These new research findings are based on analyses of blood samples from more than 1,800 individuals in Sweden, one of the most comprehensive studies to date on the influence of chemical environmental exposure on the development of MS. 

Multiple sclerosis (MS) is an autoimmune disease in which both genetic and environmental factors can contribute to the risk of the disease. In the current study, researchers analyzed blood from individuals who had recently been diagnosed with MS to investigate concentrations of the common environmental contaminants PFAS and PCBs. 

Capturing the moment a cell shuts the door on free radicals

The moment a cell shuts the door on free radicals.
Illustration Credit: Catrin Jakobsson, Lund University

For the first time, researchers have been able to show how a cell closes the door to free radicals – small oxygen molecules that are sometimes needed, but that can also damage our cells. The study is published in Nature Communications and was led by Lund University. 

For our cells to function, they need to maintain a careful balance between beneficial and harmful oxygen molecules known as free radicals. One of the most important is hydrogen peroxide – the same substance found in disinfectants, but which our cells use in very small amounts to send important signals. However, in excessive concentrations, hydrogen peroxide can cause damage and even cell death.  

A platform to test new cancer treatments

Differentiated hepatic cells growing in a flask re-gain the appearance of cells present in liver.
Image Credit: © FAMOL, UNIGE

Overcoming acquired treatment resistance is one of the major challenges in the fight against cancer. While combination therapies hold promise, their toxicity to healthy tissue remains a major hurdle. To anticipate these risks, researchers at the University of Geneva (UNIGE) have developed in vitro models of the kidneys, liver, and heart – three organs particularly sensitive to such therapies. This fast, animal-free approach paves the way for safer evaluation of new treatments. The findings are published in Biomedicine & Pharmacotherapy. 

Recent advances in immunotherapy, targeted therapies, and gene therapies have significantly improved survival rates for patients with cancer. However, over time, many tumors develop resistance to these treatments, undermining their effectiveness. This phenomenon, known as ‘acquired resistance’, has become one of the major challenges in oncology. 

Scientists identify small RNA molecule that regulates cholesterol and heart disease

Xiuchun Li is the first author of the research paper.
Photo Credit: UCR/Zhou lab

A team of researchers led by University of California, Riverside biomedical scientists has identified a small, previously overlooked small RNA molecule that plays a major role in controlling the body’s cholesterol production and the development of heart disease. The molecule, named tsRNA-Glu-CTC, could be a potential new target for future therapies aimed at lowering high cholesterol.

Using PANDORA-seq, a sequencing technology developed at UC Riverside, the scientists were able to detect hidden types of small RNAs in the liver, the organ central to cholesterol metabolism. They found that tsRNA-Glu-CTC is highly abundant in the liver (more than 65% of all detectable tsRNAs or tRNA-derived small RNAs) and responds directly to changes in cholesterol levels. The study was done in mice.

The research established a direct link between tsRNA-Glu-CTC and SREBP2 (Sterol Regulatory Element-Binding Protein 2), a key protein known as the “master regulator” of cholesterol production.

A delicate balance between growth hormone and stem cells

Andrei Chagin, Institute of Medicine, Sahlgrenska Academy at the University of Gothenburg.
Photo Credit: Magnus Gotander

Researchers at the University of Gothenburg can now demonstrate previously unexplained processes behind growth therapy. It involves hormonal mechanisms at the cellular level, with focus on a sensitive balance between stem cells and growth hormone. 

When children grow in length, it occurs from growth plates, a cartilage structure at both ends of the long bones found in the arms and legs. The growth plates contain special stem cells that continuously produce new cartilage cells, which are converted into bone tissue. 

In the case of growth disorders in children, with a height significantly below the average for their age and sex, injections of growth hormone are the most common treatment. In the development of growth hormone therapy, the University of Gothenburg has played a historically important role  

Previous research has shown that growth hormones act directly on the growth plate. However, it has been unclear which cells are targeted by growth hormones and how.