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Category: biotech/medical – Page 31

‘Zombie’ cells spark inflammation in severe fatty liver disease, researchers find

Mayo Clinic researchers have uncovered how aging “zombie cells” trigger harmful inflammation that accelerates a severe and increasingly common form of fatty liver disease called metabolic dysfunction-associated steatohepatitis (MASH). As obesity rates rise worldwide, MASH is projected to increase and is already one of the leading causes of liver transplantation.

“Liver scarring and inflammation are hallmarks of MASH. If left untreated, it can progress to liver cancer. This is why it’s so important to understand the mechanisms driving the disease so that we can prevent it or develop more effective treatments,” says Stella Victorelli, Ph.D., who is the lead author of the study published in Nature Communications.

Dr. Victorelli and colleagues, who study aged or senescent “zombie” cells, identified a mechanism by which these cells drive liver scarring and inflammation. They found that small molecules called mitochondrial RNA, typically found within the cell’s energy-producing mitochondria, can leak into the main part of the cell, where they mistakenly activate antiviral sensors called RIG-I and MDA5—normally triggered when a virus infects a cell. In this case, the danger signal comes from the cell’s own mitochondria, prompting a wave of inflammation that can damage nearby healthy tissue.

Fertility gene helps glioblastoma tumors survive chemotherapy and return after treatment, researchers discover

Research by University of Sydney scientists has uncovered a mechanism that may explain why glioblastoma returns after treatment, offering new clues for future therapies which they will now investigate as part of an Australian industry collaboration.

Glioblastoma is one of the deadliest brain cancers, with a median survival rate of just 15 months. Despite surgery and chemotherapy, more than 1,250 clinical trials over the past 20 years have struggled to improve survival rates.

Published in Nature Communications, the study shows that a small population of drug-tolerant cells known as “persister cells” rewires its metabolism to survive chemotherapy, using an unexpected ally as an invisibility cloak: a fertility gene called PRDM9.

Abstract: From synaptogenic to synaptotoxic

This issue’s cover features work by Alberto Siddu & team on the promotion of synapse formation in human neurons by free amyloid-beta peptides, in contrast to aggregated forms that are synaptotoxic:

The image shows a human induced neuron exposed to a nontoxic concentration of amyloid-beta42 peptide, revealing enhanced synaptogenesis, visible as synaptic puncta along the dendritic arbor.

Address correspondence to: Alberto Siddu, Lorry Lokey Stem Cell Building, 265 Campus Dr., Room G1015, Stanford, California 94,305, USA. Phone: 650.721.1418; Email: [email protected]. Or to: Thomas C. Südhof, Lorry Lokey Stem Cell Building, 265 Campus Dr., Room G1021, Stanford, California 94,305, USA. Phone: 650.721.1418; Email: [email protected].

A power move in the study of sepsis-associated acute kidney injury

Using a new strategy for quantifying mitochondrial DNA, Mark L. Hepokoski & team show the release of mtDNA from the kidney directly contributes to interleukin-6 release during sepsis associated AKI.

1VA San Diego Healthcare System, San Diego, California, USA.

2Division of Pulmonary and Critical Care and Sleep Medicine, UCSD, La Jolla, California, USA.

3Department of Critical Care Medicine, Yantai Yuhuangding Hospital, Affiliated with Medical College of Qingdao University, Yantai, Shandong, China.

Exercise slows tumor growth in mice by shifting glucose uptake to muscles

It’s well known that exercise is good for health and helps to prevent serious diseases, like cancer and heart disease, along with simply making people feel better overall. However, the molecular mechanisms responsible for preventing cancer or slowing its progression are not well understood. But, a new study, published in the Proceedings of the National Academy of Sciences, reveals how exercise can increase glucose and oxygen uptake in the skeletal and cardiac muscles, instead of allowing it to “feed” tumors.

Reduced tumor growth in exercised mice To study how exercise-induced metabolic changes affect tumor growth, the research team injected mice with breast cancer cells and fed some of the mice a high-fat diet (HFD), consisting of 60% calories from fat, while others were fed a normal diet as a control. The HFD mice were given running wheels for exercise, although exercise was voluntary. The team used stable isotope tracer studies [U-13C6] glucose and [U-13C5] glutamine to track metabolic changes.

After 4 weeks of wheel running, the team found a significant difference in tumor sizes between mice that chose to exercise, compared to those that did not—even when they were fed the same diet.

Characterizing Fibroblast Heterogeneity in Diabetic Wounds Through Single-Cell RNA-Sequencing

DDX3X acts as a selective dual switch regulator of mRNA translation in acute ER stress.

Shawky et al. show that DDX3X selectively promotes or represses mRNA translation in a stress-dependent manner. This bidirectional regulation involves position-specific binding to the mRNA 5′ UTR and early coding region, reflecting distinct mechanisms, including initiation control during 48S scanning and translational repression associated with ac4C post-transcriptional modification.

Early Alpha-Fetoprotein Response Predicts Sustained Tumor Response Following Immune Checkpoint Inhibitors Combined with Targeted Therapy in Liver Cancer

Background: Although immune checkpoint inhibitors (ICI) have revolutionized liver cancer treatment, some patients experience early tumor progression after therapy, missing the window for other potential treatments, such as neoadjuvant therapy. Therefore, identifying the predictive factors for early progression is critical for timely therapeutic adjustment and the optimization of patient outcomes. Methods: This retrospective study enrolled patients with liver cancer who received their first ICI combined with targeted therapy at the Fifth Medical Center of the PLA General Hospital between June 2022 and December 2023. Early tumor progression was defined as tumor progression within 6 months of therapy initiation.

Reversing treatment resistance in prostate cancer

Scientists at the Herbert Irving Comprehensive Cancer Center (HICCC) have discovered a key mechanism that makes prostate cancer cells resistant to the latest drugs used to treat them. Their findings, reported in the current issue of Nature, solve a longstanding puzzle in tumor biology and present preclinical data on a drug compound that could soon enter the clinic.

The work grew out of decades of prostate cancer research by Michael Shen, Ph.D., co-leader of the Tumor Biology and Microenvironment research program at the HICCC. Shen’s research focuses on lineage plasticity, the ability of cancer cells to reprogram themselves to impersonate other types of cells.

“Plasticity is a hallmark of cancer in general and a very important feature of advanced prostate cancer, particularly when it comes to the emergence of treatment resistance,” says Shen. Treatment with androgen receptor inhibitors, which have become the standard of care in recent years, often stimulate prostate tumor cells to adopt neuroendocrine characteristics, rendering them resistant to the drugs.

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