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Category: biotech/medical

Mitochondrial DNA Acts as a “First Hit” for Antibody-Mediated TRALI

Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortality, but its pathogenesis is complex and not well understood. TRALI is thought to develop under a “2-hit” model. In 80% of cases, the second hit is caused by antibodies (specifically anti-HLA class I or II or anti-human neutrophil antigen antibodies); bioactive lipids, extracellular vesicles and other storage-related transfusion products have been linked to the remainder of the TRALI cases. The first-hit, which is related to the patient’s underlying clinical condition, is less well defined. Since patients receiving intensive care are more prone to TRALI and often have elevated levels of extracellular mitochondrial DNA (mtDNA), researchers used a murine model to examine whether mitochondria, mtDNA or other damage-associated molecular patterns (DAMPs) can act as a first-hit in an antibody-dependent murine model of TRALI. Injection of purified mitochondria or mtDNA followed by a monoclonal antibody (as a second-hit) caused significantly greater lung injury with increased pulmonary edema, elevated plasma macrophage inflammatory protein-2 (MIP-2; the mouse ortholog of human IL-8), enhanced neutrophil lung infiltration, hypothermia, and respiratory distress compared to an isotype control. Researchers found that an antagonist to toll-like receptor-9 (TLR-9) attenuated many of the TRALI-like symptoms in mice suggesting that mtDNA and TLR-9 may be involved in the first-hit in some TRALI cases. Targeting mtDNA or the TLR-9 receptor may prove to be a novel therapeutic strategy to prevent the first-hit and TRALI, but further research is needed.

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Nanowire platform reveals elusive astrocytes in their natural state

Scientists have engineered a nanowire platform that mimics brain tissue to study astrocytes, the star-shaped cells critical for brain health, for the first time in their natural state.

Astrocytes are the brain’s most abundant and mysterious cells, responsible for regulating communication between neurons and helping to maintain the blood-brain barrier. They are also highly dynamic shape-shifters, something they do not do on typical petri dishes, leaving major gaps in our understanding of how they operate.

“Frustratingly, little is known about the stunning diversity of astrocyte morphology and we also don’t know much about the molecular machinery behind these shape shifts,” said co-senior author Ishan Barman, a Johns Hopkins University bioengineer. “They won’t take on these shapes on glass, so the question for us was how do we replicate the in vivo shape but in vitro?”

Quantifying cerebrospinal fluid dynamics: A review of human neuroimaging contributions to CSF physiology and neurodegenerative disease

The accompanying diagram presents a comprehensive anatomical overview of the human brain, integrating both lateral surface morphology and a midsagittal section to illustrate the spatial organization of cortical and subcortical structures. Major gyri, sulci, and lobar divisions are delineated alongside deep nuclei, commissural pathways, and the ventricular system. The transparent rendering of the ventricles highlights their relationship to surrounding neural tissue and emphasizes the topology of cerebrospinal fluid pathways. This visualization serves as a structural reference point for understanding functional domains such as sensorimotor processing, higher-order cognition, limbic integration, and autonomic regulation. Collectively, the diagram provides a detailed framework for interpreting neuroanatomical connectivity and its relevance to neural function.

#study:

Cerebrospinal Fluid Mechanics and Its Coupling to Cerebrovascular Dynamics: https://www.annualreviews.org/content/journals/10.1146/annur…#45;034321

CSF dynamics throughout the ventricular system using 4D flow MRI: associations to arterial pulsatility, ventricular volumes, and age: https://link.springer.com/article/10.1186/s12987-024-00570-4

Fundamental functional differences between gyri and sulci: implications for brain function, cognition, and behavior: https://pubmed.ncbi.nlm.nih.gov/38665307/?utm_source=chatgpt.com.

Brain ventricles as windows into brain development and disease: https://www.sciencedirect.com/science/article/pii/S089662732…hatgpt.com

Continue reading “Quantifying cerebrospinal fluid dynamics: A review of human neuroimaging contributions to CSF physiology and neurodegenerative disease” | >

Validation of a Risk Score for Cancer-Associated Thrombosis Using Nationwide EHR Data

This study externally validated the EHR-CAT risk score for cancer-associated thrombosis (CAT) using the Epic Cosmos database, with similar performance as the original derivation, showing promise EHR integration across diverse health systems.

Question Can routinely collected electronic health record (EHR) data from diverse health systems be used to model cancer-associated thrombosis (CAT) risk?

Findings In this prognostic study using a retrospective cohort of 732 594 patients with cancer receiving systemic therapy between 2018 and 2023 from 184 health systems, the EHR-CAT score significantly outperformed the benchmark Khorana score and had 20% improved accuracy. The model had consistent calibration by demographic subgroups, health system sites, and cohorts stratified by bleeding risk.

Meaning These results suggest that standardized structured EHR data from different health systems can support scalable validation and implementation of CAT risk assessment.

An AI-Based System Has Found a Potential Longevity Drug

In a preprint published in bioRxiv, Prof. Vadim Gladyshev and a team of researchers have used an artificial intelligence-based system to discover a wide variety of potential interventions, including a drug that significantly improves biomarkers of frailty in mice.

Repurposing previous data

Previous research efforts have created a massive dataset in the form of the Gene Expression Omnibus (GEO), which contains the results of a great many experiments related to potentially disease-modifying drugs, many of which are tissue-specific [1]. These researchers refer to this dataset as a “massive missed opportunity” in aging research, because the vast majority of the experiments in the GEO were unrelated to aging and their data was never investigated in that context.

Super-Rare ‘Hybrid’ Blood Type Discovered in Just 3 People

An investigation into why blood doesn’t always behave as doctors expect has revealed a super-rare mutation in an extremely uncommon variation of blood.

Testing more than 544,000 blood samples in a hospital in Thailand revealed three people carrying a never-before-seen version of the B(A) phenotype – a genetic quirk estimated to occur in about 0.00055 percent of people, or roughly one in 180,000.

This discovery, says a team led by hematologist Janejira Kittivorapart of Mahidol University in Thailand, suggests that there may be more rare blood variants out there, too subtle for standard testing to detect.

Scientists discover compounds that help cells fight a wide range of viruses

Researchers at MIT and other institutions have identified compounds that can fight off viral infection by activating a defense pathway inside host cells. These compounds, they believe, could be used as antiviral drugs that work against not just one but any kind of virus.

The researchers identified these compounds, which activate a host cell defense system known as the integrated stress response pathway, in a screen of nearly 400,000 molecules. In tests in human cells, the researchers showed that the compounds help cells fend off infection from RSV, herpes virus, and Zika virus. They also proved effective in combating herpes infection in a mouse model.

The research team now plans to test the compounds against additional viruses, in hopes of developing them for eventual clinical trials.

Scientists Discover Speech Trait That Foreshadows Cognitive Decline

Early signs of Alzheimer’s disease may be hidden in the way a person speaks, but it’s not yet clear which details of our diction are most critical for diagnosis.

A study from 2023 suggests that as we age, how we say something may matter more than what we say. Researchers at the University of Toronto think the pace of everyday speech may be a better indicator of cognitive decline than difficulty finding a word.

“Our results indicate that changes in general talking speed may reflect changes in the brain,” said cognitive neuroscientist Jed Meltzer when the research was published.

Metabolites produced in intestine play central role in controlling obesity and diabetes, study shows

A study conducted at Harvard University identified a group of metabolites that travel from the intestine to the liver and then to the heart, where they are pumped throughout the body. These metabolites play an important role in controlling metabolic pathways in the liver and insulin sensitivity. This discovery may contribute to future treatments for obesity and type 2 diabetes. The results were published in the journal Cell Metabolism.

“The hepatic portal vein drains much of the blood from the intestine to the liver. Therefore, it’s the first place to receive products from the gut microbiome. In the liver, they can be conjugated, transformed, or eliminated, and then enter the systemic circulation,” explains Vitor Rosetto Muñoz, first author of the study and postdoctoral researcher at the Ribeirão Preto School of Physical Education and Sports at the University of São Paulo (EEFERP-USP) in Brazil.

“By analyzing the blood leaving the intestine and the peripheral blood circulating throughout the body, we were able to more accurately observe the enrichment of these metabolites derived from the gut microbiome in each location and, consequently, how they can modify hepatic metabolism and metabolic health,” adds Muñoz. He conducted this research during an internship at the Joslin Diabetes Center at Harvard Medical School under the supervision of researcher Carl Ronald Kahn.

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