Microvessels-on-chip: Exploring endothelial cells and COVID-19 plasma interaction with nitric oxide metabolites.

COVID-19, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), primarily manifests as a flu-like illness with lung injury, often necessitating supplemental oxygen. Elderly individuals and those with pre-existing cardiovascular diseases are at increased risk of mortality. The endothelial barrier disruption observed in patients indicates systemic viral invasion and widespread endotheliitis.

In situ architecture of a nucleoid-associated biomolecular co-condensate that regulates bacterial cell division.

In most bacteria, cell division depends on the tubulin-homolog FtsZ that polymerizes in a GTP-dependent manner to form the cytokinetic Z-ring at the future division site. Subsequently, the Z-ring recruits, directly or indirectly, all other proteins of the divisome complex that executes cytokinesis. A critical step in this process is the precise positioning of the Z-ring at the future division site.

Advancements in Immunity and Dementia Research: Highlights from the 2023 AAIC Advancements: Immunity Conference.

The immune system is a key player in the onset and progression of neurodegenerative disorders. While brain resident immune cell-mediated neuroinflammation and peripheral immune cell (eg, T cell) infiltration into the brain have been shown to significantly contribute to Alzheimer's disease (AD) pathology, the nature and extent of immune responses in the brain in the context of AD and related dementias (ADRD) remain unclear. Furthermore, the roles of the peripheral immune system in driving ADRD pathology remain incompletely elucidated.

Exploring the Fecal Metabolome in Infants With Cow's Milk Allergy: The Distinct Impacts of Cow's Milk Protein Tolerance Acquisition and of Synbiotic Supplementation.

Scope: Cow's milk allergy (CMA) is one of the most prevalent food allergies in early childhood, often treated via elimination diets including standard amino acid-based formula or amino acid-based formula supplemented with synbiotics (AAF or AAF-S). This work aimed to assess the effect of cow's milk (CM) tolerance acquisition and synbiotic (inulin, oligofructose, Bifidobacterium breve M-16 V) supplementation on the fecal metabolome in infants with IgE-mediated CMA.

Methods And Results: The CMA-allergic infants received AAF or AAF-S for a year during which fecal samples were collected.

Structure and mechanism of the Zorya anti-phage defense system.

Zorya is a recently identified and widely distributed bacterial immune system that protects bacteria from viral (phage) infections. Three Zorya subtypes have been discovered, each containing predicted membrane-embedded ZorAB complexes paired with soluble subunits that differ among Zorya subtypes, notably ZorC and ZorD in type I Zorya systems. Here, we investigate the molecular basis of Zorya defense using cryo-electron microscopy, mutagenesis, fluorescence microscopy, proteomics, and functional studies.

Metabolic alterations of endothelial cells under transient and persistent hypoxia: study using a 3D microvessels-on-chip model.

Numerous signaling pathways are activated during hypoxia to facilitate angiogenesis, promoting interactions among endothelial cells and initiating downstream signaling cascades. Although the pivotal role of the nitric oxide (NO) response pathway is well-established, the involvement of arginine-specific metabolism and bioactive lipid mechanisms in 3D flow-activated in vitro models remains less understood. In this study, we explored the levels of arginine-specific metabolites and bioactive lipids in human coronary artery endothelial cells (HCAECs) under both transient and persistent hypoxia.

A Unique Case of Bilateral Testicular Tumours: Nonseminomatous Germ Cell Tumour and Contralateral Spermatocytic Tumour 27 Years Apart.

Introduction: Bilateral testicular tumours occur in 3-5% of all cases with testicular neoplasms. In the majority of cases, histology of the two new growths is identical. The time interval between the two neoplastic events rarely exceeds 10 years.

The emerging role of disease-associated microglia in Parkinson's disease.

Disease-associated microglia (DAM) are a subset of microglia that appear at various stages of central nervous system neurodegenerative diseases. DAM were identified using single-cell RNA sequencing within Alzheimer's Disease (AD) where they were characterized by their unique localization near amyloid-β plaques and their phagocytic and lipid-metabolizing features. Unfortunately, activation and etiology of DAM are only understood within the context of AD where Triggering Receptor Expressed On Myeloid Cells 2 (TREM2), a receptor for amyloid-β, appears to be the key regulator in microglial transition to a DAM state.

Strategies for Using Postcolumn Infusion of Standards to Correct for Matrix Effect in LC-MS-Based Quantitative Metabolomics.

The matrix effect limits the accuracy of quantitation of the otherwise popular metabolomics technique liquid chromatography coupled to mass spectrometry (LC-MS). The gold standard to correct for this phenomenon, whereby compounds coeluting with the analyte of interest cause ionization enhancement or suppression, is to quantify an analyte based on the peak area ratio with an isotopologue added to the sample as an internal standard. However, these stable isotopes are expensive and sometimes unavailable.

A Micro-Flow Liquid Chromatography-Mass Spectrometry Method for the Quantification of Oxylipins in Volume-Limited Human Plasma.

Oxylipins are well-known lipid mediators in various inflammatory conditions. Their endogenous concentrations range from low picomolar to nanomolar, and there are growing demands to determine their concentrations in low-volume matrices for pathological studies, including blood, cerebrospinal fluids from animal disease models, infants, and microsampling devices. Most of the published quantification methods for comprehensive profiling of oxylipins still require more than 50 µL plasma as a starting volume to detect these low levels.

Recent developments in the analytical approaches of acyl-CoAs to assess their role in mitochondrial fatty acid oxidation disorders.

Fatty acid oxidation disorders (FAOD) are inborn errors of metabolism that occur due to deficiency of specific enzyme activities and transporter proteins involved in the mitochondrial metabolism of fatty acids, causing a deficiency in ATP production. The identification of suitable biomarkers plays a crucial role in predicting the future risk of disease and monitoring responses to therapies. Acyl-CoAs are directly involved in the steps of fatty acid oxidation and are the primary biomarkers associated with FAOD.

Sonic Hedgehog reduces inflammatory response, decreases blood-spinal cord barrier permeability, and improves locomotor function recovery in an acute spinal cord injury rat model.

Background: Sonic Hedgehog (Shh), extensively researched for its role in early neurogenesis and brain development, has recently been recognized for its neuroprotective potential following neuronal injuries. This study examines the immediate impact of early administered Shh on the local inflammatory response post-acute spinal cord injury in rats.

Methods: Thirty-four female Wistar rats underwent either sham surgery (laminectomy; n = 10) or clip compression/contusion spinal cord injury (SCI) at the T9 level.

Enabling high-sensitivity live single-cell mass spectrometry using an integrated electrical lysis and nano electrospray ionization interface.

Background: Live single-cell metabolomic studies encounter inherent difficulties attributed to the limited sample volume, minimal compound quantity, and insufficient sensitivity in the Mass Spectrometry (MS) method used to obtain single-cell data. However, understanding cellular heterogeneity, functional diversity, and metabolic processes within individual cells is essential. Exploring how individual cells respond to stimuli, including drugs, environmental changes, or signaling molecules, offers insights into biology, oncology, and drug discovery.

Tracer-based metabolomics for profiling nitric oxide metabolites in a 3D microvessels-on-chip model.

Endothelial dysfunction, prevalent in cardiovascular diseases (CVDs) and linked to conditions like diabetes, hypertension, obesity, renal failure, or hypercholesterolemia, is characterized by diminished nitric oxide (NO) bioavailability-a key signaling molecule for vascular homeostasis. Current two-dimensional (2D) in vitro studies on NO synthesis by endothelial cells (ECs) lack the crucial laminar shear stress, a vital factor in modulating the NO-generating enzyme, endothelial nitric oxide synthase (eNOS), under physiological conditions. Here we developed a tracer-based metabolomics approach to measure NO-specific metabolites with mass spectrometry (MS) and show the impact of fluid flow on metabolic parameters associated with NO synthesis using 2D and 3D platforms.

Prefabricated contoured foot orthoses to reduce pain and increase physical activity in people with hip osteoarthritis: A randomised feasibility trial.

Background: Hip osteoarthritis (OA) is a prevalent and burdensome condition that leads to impaired quality of life and a substantial economic burden. Encouraging physical activity, particularly walking, is crucial for OA management, but many individuals with hip OA fail to meet recommended activity levels. Prefabricated contoured foot orthoses have shown promise in improving hip muscle efficiency during walking in laboratory settings, but their real-world feasibility and efficacy remain uncertain.

Association of oxidative stress and inflammatory metabolites with Alzheimer's disease cerebrospinal fluid biomarkers in mild cognitive impairment.

Background: Isoprostanes and prostaglandins are biomarkers for oxidative stress and inflammation. Their role in Alzheimer's disease (AD) pathophysiology is yet unknown. In the current study, we aim to identify the association of isoprostanes and prostaglandins with the Amyloid, Tau, Neurodegeneration (ATN) biomarkers (Aβ-42, p-tau, and t-tau) of AD pathophysiology in mild cognitive impairment (MCI) subjects.

A deterministic, c-di-GMP-dependent program ensures the generation of phenotypically similar, symmetric daughter cells during cytokinesis.

Phenotypic heterogeneity in bacteria can result from stochastic processes or deterministic programs. The deterministic programs often involve the versatile second messenger c-di-GMP, and give rise to daughter cells with different c-di-GMP levels by deploying c-di-GMP metabolizing enzymes asymmetrically during cell division. By contrast, less is known about how phenotypic heterogeneity is kept to a minimum.

Oxygen-Dependent Interactions between the Ruthenium Cage and the Photoreleased Inhibitor in NAMPT-Targeted Photoactivated Chemotherapy.

Photoactivated chemotherapy agents form a new branch of physically targeted anticancer agents with potentially lower systemic side effects for patients. On the other hand, limited information exists on the intracellular interactions between the photoreleased metal cage and the photoreleased anticancer inhibitor. In this work, we report a new biological study of the known photoactivated compound in the glioblastoma cancer cell line, U87MG.

Unraveling interindividual variation of trimethylamine -oxide and its precursors at the population level.

Trimethylamine -oxide (TMAO) is a circulating microbiome-derived metabolite implicated in the development of atherosclerosis and cardiovascular disease (CVD). We investigated whether plasma levels of TMAO, its precursors (betaine, carnitine, deoxycarnitine, choline), and TMAO-to-precursor ratios are associated with clinical outcomes, including CVD and mortality. This was followed by an in-depth analysis of their genetic, gut microbial, and dietary determinants.

A Targeted LC-MRM Proteomic Approach for the Diagnosis of SARS-CoV-2 Infection in Nasopharyngeal Swabs.

Since its first appearance, severe acute respiratory syndrome coronavirus 2 quickly spread around the world and the lack of adequate PCR testing capacities, especially during the early pandemic, led the scientific community to explore new approaches such as mass spectrometry (MS). We developed a proteomics workflow to target several tryptic peptides of the nucleocapsid protein. A highly selective multiple reaction monitoring-cubed (MRM) strategy provided a sensitivity increase in comparison to conventional MRM acquisition.

Mechanism of phage sensing and restriction by toxin-antitoxin-chaperone systems.

Toxin-antitoxins (TAs) are prokaryotic two-gene systems composed of a toxin neutralized by an antitoxin. Toxin-antitoxin-chaperone (TAC) systems additionally include a SecB-like chaperone that stabilizes the antitoxin by recognizing its chaperone addiction (ChAD) element. TACs mediate antiphage defense, but the mechanisms of viral sensing and restriction are unexplored.