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Category: biotech/medical

A poorly “cleaned” brain increases the risk of psychosis

A new study from the University of Geneva points to the brain’s waste-clearance system — the glymphatic system — as a possible piece of the psychosis puzzle. In people with 22q11.2 deletion syndrome, a high-risk genetic condition, researchers found developmental differences in an MRI-derived marker linked to glymphatic function, along with associations to hippocampal excitation/inhibition balance and psychosis vulnerability.

A team from UNIGE shows that early alterations in the brain’s clearance system could contribute to vulnerability to psychosis.

How can we explain the onset of psychotic symptoms characteristic of schizophrenia? Despite their major and often irreversible impact on intellectual abilities and autonomy, the biological mechanisms that precede their emergence remain poorly understood. A team from the Department of Psychiatry at the Faculty of Medicine and the Synapsy Center for Neuroscience Research in Mental Health at the University of Geneva (UNIGE) provides new insight into this question. Early dysfunction of the glymphatic system, the network responsible for removing waste from the brain, could be a key vulnerability factor. This research has been published in Biological Psychiatry: Global Open Science.

Hallucinations and delusions are among the characteristic psychotic symptoms of schizophrenia spectrum disorders, which may also be accompanied by social withdrawal and cognitive decline. These disorders, considered neurodevelopmental conditions, most often emerge during adolescence or early adulthood and have an estimated prevalence of 0.5–3% in the general population.

Understanding protein motion could greatly aid new drug design

For many people, “protein” is the key element of a food order. However, beyond the preferred choice of meats or plant-based alternatives, proteins encompass a large class of complex biomolecules whose chemical structure is encoded in our genes. Proteins have critical functions in living cells; they help repair and build body tissues, drive metabolic reactions, maintain pH and fluid balance, and keep our immune systems strong.

To perform their important functions, many proteins have a dynamic molecular structure capable of adopting multiple conformations. For a long time, scientists have suspected that proteins don’t change shape at random. Instead, they seem to move according to deep, slow rhythms—like a building that sways gently in the wind rather than shaking violently.

Those slow rhythms guide how a protein bends, twists, and shifts between its different forms. If one could understand those rhythms, one might be able to predict—and even hurry along—the protein’s movements.

Energy crisis drives T cells to exhaustion in tumors

The immune system’s killer T cells do a commendable job of detecting and destroying cancer cells. But the harsh environment at the heart of tumors often saps them of their vitality, pushing them into a state of permanent lassitude called “terminal exhaustion.” The phenomenon accounts for why so many tumors resist routine immune clearance and even cancer immunotherapies devised to stimulate their lethal capabilities.

Terminal exhaustion is characterized by an accumulation of dysfunctional mitochondria—the bean-shaped energy generators in cells—and extensive genetic reprogramming that stalls proliferation and hobbles the cell-killing weaponry of T cells. Yet how mitochondrial dysfunction is linked to genetic reprogramming in the cells was unclear. No longer. Researchers in the journal Nature show that how the accumulation of useless mitochondria is linked to T cell exhaustion through a complex series of subcellular processes.

The researchers report in their paper that the glut of dysfunctional mitochondria enhances the activity of a cellular protein digesting machine, known as the proteasome, in T cells. The activated proteasome, they show, preferentially degrades mitochondrial heme-containing proteins.

As might be expected, this bias leads to quite the buildup of heme in the cells, resulting in the generation of a functionally distinct form of the molecule referred to as “regulatory heme,” which zips into the nucleus through a transporter named PGRMC2. There it binds to a transcription factor, a protein that regulates gene expression, causing its degradation. This kicks off a series of events that culminates in the activation of genetic programs known to induce terminal exhaustion.

The researchers show that genetic disruption of PGRMC2 abrogates this effect, keeping anti-tumor T cells in a functionally vibrant state, suggesting it is a potential drug target for the enhancement of T cell-activating cancer immunotherapies.

The researchers also examined how the pharmacological inhibition of the proteasome with an existing leukemia therapy, bortezomib, might affect CAR-T cells. Like bortezomib, CAR-T therapy is currently used to treat B cell acute lymphoblastic leukemia (B-ALL).

“We found that the transient and low-dose addition of bortezomib to CAR-T cell cultures during manufacturing reduces exhaustion-associated programs in the cells and induces durable reprogramming of their gene expression patterns to maintain them in a proliferative and functionally vibrant state,” said the author. ScienceMission sciencenewshighlights.

Continue reading “Energy crisis drives T cells to exhaustion in tumors” | >

Mitochondria Delivery Method Rescues Parkinson’s in Mice

Scientists used red blood cells as membrane donors to encapsulate healthy mitochondria and send them into diseased cells, achieving improvements across multiple models and conditions [1].

The delivery problem

Mitochondrial diseases are a diverse group of disorders that arise when mitochondria malfunction. They are often caused by mutations in mitochondrial DNA (mtDNA) itself or in nuclear genes encoding mitochondria-related proteins.

Heat shock proteins as a promising breast cancer therapeutic

Heat shock proteins are emerging as potential targets in breast cancer research.

In Molecular & Cellular Proteomics, Tyelor Reynolds and colleagues determined that both NDNB1 and NDNB1182 display moderate selectivity for TNBC cells, and inhibition of Hsp90β using these inhibitors led to alterations in proteins associated with cell cycle functions, cell signaling pathways and DNA repair mechanisms.

➡️ Explore the findings:. ➡️ Read the paper: https://www.mcponline.org/article/S1535-9476(25)00142-2/fulltext MolCellProt BreastCancerResearch proteomics.

Researchers used a range of mass spectrometry-based techniques to identify how inhibition of select heat shock proteins impacts triple-negative breast cancer prognosis. This work unveiled isoform-specific targets on heat shock protein 90 which may be beneficial in therapeutic development.

Weight Changes With Tirzepatide and Concomitant Weight-Inducing Medications: Post Hoc Analysis of Randomized Clinical Trials

In three RCTs, Tirzepatide was associated with clinically meaningful weight loss among adults with overweight or obesity, even when concomitant weight-inducing medications were initiated during treatment.

Question What is the association between tirzepatide and weight reduction among patients with overweight or obesity who initiated concomitant weight-inducing medications?

Findings In this post hoc analysis of participants in the SURMOUNT-1,-3, and-4 trials receiving at least 1 concomitant weight-inducing medication (17.3%-20.0%), tirzepatide treatment was associated with comparable weight loss to the primary study results.

Triple pre-surgery therapy may boost immunity against soft tissue sarcoma

Early results from preclinical studies and a clinical trial led by researchers at the UCLA Health Jonsson Comprehensive Cancer Center and Stanford Medicine suggest that combining targeted radiation therapy with an experimental immune-boosting drug called BO-112 and anti-PD-1 therapy before surgery may help the immune system fight aggressive soft tissue sarcomas.

The findings, published in Cancer Discovery, show that the approach can reshape the tumor microenvironment to activate the body’s immune cells against cancer.

Soft tissue sarcomas are a rare and often hard-to-treat group of cancers that typically require a combination of surgery, radiation therapy and other systemic treatments. However, these tumors may still be resistant to standard therapies, highlighting the need for new treatment strategies.

Unraveling the secrets of telomerase, an enzyme linked to aging and cancer

A central question in molecular biology is how cells protect their chromosomes from damage during repeated cell division. At the heart of this protective process is an enzyme called telomerase. Now an international research team has mapped the three-dimensional structure of telomerase in the yeast Saccharomyces cerevisiae, a widely used model organism in genetics.

Using cutting-edge technology, the scientists were able to visualize the architecture of this complex enzyme in unprecedented detail, uncovering unexpected features that may explain how it functions.

This major discovery was the result of an international collaboration between Pascal Chartrand, a professor in the Department of Biochemistry and Molecular Medicine at Université de Montréal, and researchers from Université de Sherbrooke and the MRC Laboratory of Molecular Biology in the U.K. Their findings were recently published in Science.

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