Online now: Jia et al. reveal that KRAS-mutant leukemic cells, which express low SLC25A51 protein, are selectively killed by 615 through reducing mitochondrial NAD+. 615 simultaneously binds to and inhibits both SLC25A51, a mitochondrial NAD+ importer, and SDHA, an ETC component. It further reduces SLC25A51 protein by decreasing K264 succinylation, thereby depleting mitochondrial NAD+.
Metastasis remains the leading cause of death in most cancers, particularly colon, breast and lung cancer. Currently, the first detectable sign of the metastatic process is the presence of circulating tumor cells in the blood or in the lymphatic system. By then, it is already too late to prevent their spread. Furthermore, while the mutations that lead to the formation of the original tumors are well understood, no single genetic alteration can explain why, in general, some cells migrate and others do not.
“The difficulty lies in being able to determine the complete molecular identity of a cell – an analysis that destroys it – while observing its function, which requires it to remain alive,” explains the senior author. “To this end, we isolated, cloned and cultured tumor cells,” adds a co-first author of the study. “These clones were then evaluated in vitro and in a mouse model to observe their ability to migrate through a real biological filter and generate metastases.”
The analysis of the expression of several hundred genes, carried out on about thirty clones from two primary colon tumors, identified gene expression gradients closely linked to their migratory potential. In this context, accurate assessment of metastatic potential does not depend on the profile of a single cell, but on the sum of interactions between related cancer cells that form a group.
The gene expression signatures obtained were integrated into an artificial intelligence model developed by the team. “The great novelty of our tool, called ‘Mangrove Gene Signatures (MangroveGS)’, is that it exploits dozens, even hundreds, of gene signatures. This makes it particularly resistant to individual variations,” explains another co-first author of the study. After training, the model achieved an accuracy of nearly 80% in predicting the occurrence of metastases and recurrence of colon cancer, a result far superior to existing tools. In addition, signatures derived from colon cancer can also predict the metastatic potential of other cancers, such as stomach, lung and breast cancer.
After training, the model achieved an accuracy of nearly 80% in predicting the occurrence of metastases and recurrence of colon cancer, a result far superior to existing tools. In addition, signatures derived from colon cancer can also predict the metastatic potential of other cancers, such as stomach, lung and breast cancer.
Thanks to MangroveGS, tumor samples are sufficient: cells can be analysed and their RNA sequenced at the hospital, then the metastatic risk score quickly transmitted to oncologists and patients via an encrypted Mangrove portal that has analysed the anonymised data.
“This information will prevent the overtreatment of low-risk patients, thereby limiting side effects and unnecessary costs, while intensifying the monitoring and treatment of those at high risk,” adds the senior author. “It also offers the possibility of optimising the selection of participants in clinical trials, reducing the number of volunteers required, increasing the statistical power of studies, and providing therapeutic benefits to the patients who need it most.” ScienceMission sciencenewshighlights.
Researchers at NYU Abu Dhabi have developed a new light-based nanotechnology that could improve how certain cancers are detected and treated, offering a more precise and potentially less harmful alternative to chemotherapy, radiation, and surgery. The study advances photothermal therapy, a treatment approach that uses light to generate heat inside tumors and destroy cancer cells.
The research is published in the journal Cell Reports Physical Science.
The NYU Abu Dhabi team designed tiny, biocompatible and biodegradable nanoparticles that carry a dye activated by near-infrared light. When exposed to this light, the particles heat up, damaging tumor tissue while minimizing harm to healthy cells. Near-infrared light was chosen specifically as it penetrates the body to greater depth than visible light, thereby enabling treatment of tumors that are not close to the surface.
In Ruijs-Aalfs progeria syndrome, patients experience accelerated aging and liver cancer.
Now, scientists showed that mutations in a certain gene prevent cells from repairing DNA damage during mitosis, triggering inflammatory immune responses that may fuel premature aging.
Read more.
Researchers have shown that harmful bonds between protein and DNA fuel immune attack in progeria. Pumping up a protein that cuts these bonds could prevent symptoms.
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Hello and welcome! My name is Anton and in this video, we will talk about a strange bacterial communication technique similar to radio waves.
Links:
https://www.cell.com/current-biology/fulltext/S0960-9822…all%3Dtrue.
Previous videos: https://www.youtube.com/watch?v=4M872c27bSc.
https://www.science.org/doi/10.1126/sciadv.adj1539
#science #radio #bacteria.
0:00 Bacterial communication and social lives.
1:20 Quorum sensing and multilingual bacteria?
4:20 Physical bridge communication.
5:20 New communication involves radio like processing.
8:00 What this is used for.
9:15 Why this is important for the medical fields.
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Studying mice and two clinical cohorts, researchers in Science TranslationalMedicine show that the protein meteorin-like worsens outcomes during invasive candidiasis by suppressing antifungal macrophages, suggesting the protein could offer a marker and potential target.
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METRNL is elevated in candidemia in mice and humans and provides a potential therapeutic target for life-threatening candidemia.
Scientists have identified a previously unknown molecular safeguard that protects the heart during pregnancy, shedding new light on the causes of peripartum cardiomyopathy (PPCM), a rare and life-threatening form of pregnancy-related heart failure.
In a study published in Nature Communications, the team reveal that the gene the peptidyl-tRNA hydrolase 2 (PTRH2) plays a critical role in helping the maternal heart adapt to pregnancy-induced stress.
In wild-type female mice hearts, Ptrh2 protein levels significantly increase during pregnancy and decrease postpartum, demonstrating a protective role in response to pregnancy-initiated cardiac stresses.
Using advanced mouse models, the researchers showed that loss of PTRH2 leads to severe postpartum heart failure. “During pregnancy, the heart increases in size to account for increased blood flow—but without PTRH2, the heart doesn’t return to normal,” explained a co-first author. “That kind of enlargement can be extremely dangerous and, in many cases, fatal.”
The authors also demonstrate that infusion of a caspase 3-specific inhibitor attenuated the PPCM phenotype. Thus, Ptrh2 act as a negative regulator of pregnancy-induced cardiac stresses by activating pro-survival signals and blocking apoptotic signals.
The findings point to new therapeutic possibilities and underscore the urgent need for better treatments. ScienceMission sciencenewshighlights.
Blood pressure is one of the most common health problems worldwide, yet it remains difficult to control for many patients even with daily medication. New research from the United Kingdom suggests a different approach could help. Scientists report that a treatment given just twice a year may offer sustained blood pressure reductions for people whose hypertension has proven hard to manage.
The findings come from a large international clinical trial published in JAMA and led by researchers at Queen Mary University of London. The study focused on a long-acting injectable therapy designed to work alongside existing blood pressure medications rather than replace them.