A new study examining real-world hospital data reveals early indicators of who is most likely to benefit from Cobenfy, the first new schizophrenia drug mechanism approved in 50 years.
Category: biotech/medical – Page 500
Acetate from tumor-associated macrophages fuels liver cancer metastasis
@The researchers have revealed a mechanism that triggers metastasis of hepatocellular carcinoma (HCC)—the most common type of primary liver cancer—through the production of acetate by tumor-associated macrophages.
Acetate is important to cancer metastasis because it promotes the synthesis of acetyl-coenzyme A (acetyl-CoA), which is a pivotal metabolic intermediate in the catabolism of glucose, lipids, and amino acids, as well as the biosynthesis of lipids and the TCA cycle. Acetyl-CoA also functions as a signaling molecule due to its role in lysine acetylation. Increased acetyl-CoA production is characteristic of metastatic cancers.
Researchers have known that acetate levels in the blood are significantly lower than in cancer tissues, suggesting the presence of acetate-producing cells within the cancer microenvironment. However, the exact source of acetate in the cancer microenvironment was previously unclear.
The researchers have now identified a key acetate source by revealing how HCC cells trigger acetate secretion by tumor-associated macrophages (TAMs) through a metabolic interaction involving lactate and the lipid peroxidation–aldehyde dehydrogenase 2 (ALDH2) pathway.
A toast to BRD4: How acidity changes the immune response
It started with wine. Or more precisely, a conversation about it. “My colleagues and I were talking about how some people think drinking wine may be anti-inflammatory,” recalls Xu Zhou, Ph.D., from the Division of Gastroenterology, Hepatology, and Nutrition at Boston Children’s Hospital. “There’s no scientific ground for that, but we know wine is acidic.”
Around the same time, Zhou and his team were exploring a broader blind spot in immunology: the role of the tissue microenvironment (such as pH, oxygen, and salt concentration) in shaping immune function. While most research had focused on cellular messengers like cytokines, Zhou was curious about how the physical and chemical makeup of tissues might influence immune cells, especially in disease.
Inspired by their wine conversation and intrigued by these overlooked components, Zhou’s team launched a study to investigate how acidity affects immune cells. Their findings, published in Cell, show that a drop in pH can suppress immune responses by disrupting a protein called BRD4—an important regulator of gene activity in immune cells. That small chemical shift could have big implications for treating inflammation-related diseases.
Overcoming resistance to immune checkpoint inhibitors remains a major objective in cancer
Here, Richard Bucala & team show combined anti-MIF and anti–PD-1 reduces tumor growth and improves survival in melanoma and colorectal cancer mouse models:
The figure shows tumor regions of necrosis, immune infiltration, and reduced tumor volume in mice treated with MIF and PD-1.
1Yale Cancer Center, Department of Internal Medicine, and.
2Section of Rheumatology, Allergy & Immunology, Department of Internal Medicine, Yale School of Medicine, New Haven, Connecticut, USA.
3Department of Medicine, Trinity College Dublin, Dublin, Ireland.
As brain organoids grow increasingly complex, leading scientists and bioethicists call for global oversight
In an effort to address these ethical grey areas, 17 leading scientists and bioethicists from five countries are urging the establishment of an international oversight body to monitor advances in the rapidly expanding field of human neural organoids and to provide ethical and policy guidance as the science continues to evolve. The call to action, published Thursday in Science, comes as U.S. government agencies are making new investments in organoid science aimed at accelerating drug discovery and reducing reliance on animal models of disease.
In September, the National Institutes of Health announced $87 million in initial contracts to establish a new center dedicated to standardizing organoid research. The move followed an earlier pledge by both the NIH and the Food and Drug Administration to reduce, and possibly replace, testing on mice, primates, and other animals with other methods — including organoids and organ-on-a-chip technologies — for developing certain medicines.
Government promotion of human stem cell models more broadly will only increase the recruitment of new researchers into the field of neural organoids, which has seen an explosion from a few dozen labs a decade ago to hundreds around the world now, said Sergiu Pasca, a pioneering neuroscientist and stem cell biologist at Stanford University who co-authored the Science commentary.
Why Alzheimer’s patients forget loved ones
Few moments are more heartbreaking for families of Alzheimer’s disease patients than when a loved one no longer recognizes them. New research from the University of Virginia School of Medicine published in Alzheimer’s & Dementia may reveal why that happens and offer hope for prevention.
UVA’s Harald Sontheimer, graduate student Lata Chaunsali and their colleagues found that when protective structures around brain cells break down, people may lose the ability to recognize loved ones. In lab studies, keeping these structures intact helped mice remember one another.
“Finding a structural change that explains a specific memory loss in Alzheimer’s is very exciting,” said Sontheimer, chair of UVA’s Department of Neuroscience and member of the UVA Brain Institute. “It is a completely new target, and we already have suitable drug candidates in hand.”
Goodbye, Cavities? Scientists Just Found a Way to Regrow Tooth Enamel
A newly developed material has been used to create a gel capable of repairing and rebuilding tooth enamel, offering a potential breakthrough in both preventive and restorative dental care.
Scientists from the University of Nottingham’s School of Pharmacy and Department of Chemical and Environmental Engineering designed this bioinspired substance to restore damaged or eroded enamel, reinforce existing enamel, and help guard against future decay. Their findings were published in Nature Communications.
This protein-based gel, which contains no fluoride, can be quickly applied to teeth using the same method dentists use for traditional fluoride treatments. It imitates the natural proteins responsible for guiding enamel formation early in life. Once in place, the gel forms a thin, durable coating that seeps into the tooth surface, filling small cracks and imperfections.