Longitudinal analysis of rhesus macaque metabolome during acute SIV infection reveals disruption in broad metabolite classes

Journal of Virology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 6, 2025

ABSTRACT Persons living with HIV experience significant metabolic dysregulation, frequently resulting in immune and other cellular dysfunction. However, our understanding of metabolism its relationship to immunity the context remains incompletely understood, especially as it relates acute early chronic phases infection. Herein, we employed mass spectrometry a simian immunodeficiency virus (SIV)-infected rhesus macaque model characterize changes over 500 plasma metabolites throughout SIV This broad metabolomic approach recapitulated known pathogenic signatures HIV, such perturbed tryptophan/kynurenine ratio, but also identified novel changes. We observed general decrease amino acid concentrations, notable exceptions elevated aspartate glutamate. Acute infection was marked by transient increase lactate dehydrogenase activity, indicating shift toward anaerobic metabolism. Indoleamine 2,3-dioxygenase defined kynurenine/tryptophan significantly increased both strongly correlated viral load. These results provide comprehensive characterization fluctuations during lentiviral infection, furthering crucial interplay between response. Our findings highlight systemic consequences potential targets for therapeutic intervention or biomarkers disease progression. IMPORTANCE Despite advances antiretroviral therapy pre-exposure prophylaxis, global challenge. Understanding underlying mechanisms is critical improving control development. Cellular represents yet underappreciated area system function. Metabolite availability pathway preferences directly influence functional response capacity cells are highly dysregulated To further impacts utilized cutting-edge spectrometry-based metabolome interrogation measure using an macaques. analysis provides insights into dynamic landscape revealing signatures. enhance complex infections, potentially informing new strategies detection, prevention, treatment HIV.

Language: Английский

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Myocardial dysfunction caused by MyBPC3 P459fs mutation in hypertrophic cardiomyopathy: evidence from multi-omics approaches and super-resolution imaging

Frontiers in Cardiovascular Medicine, Journal Year: 2025, Volume and Issue: 12

Published: Feb. 27, 2025

Mutations in the sarcomere protein, particularly cardiac myosin binding protein C gene (MyBPC3), were most frequent genetic cause of hypertrophic cardiomyopathy (HCM). The pathogenic MyBPC3 P459fs mutation has been reported HCM patients. However, there was limited knowledge structure-function relationships and potential pathways clinical with mutation. We used multi-omics approaches super-resolution imaging to explore effects on humans cells. patients carrying (MyBPC3-P459fs HCMs) healthy controls (HCs) evaluated for myocardial function using both conventional advanced echocardiography. In parallel, H9C2 cells infected either (P459fs cells) or its wild type (WT investigated fiber formation behind this metabolomics proteomics. First, echocardiography showed that MyBPC3-P459fs HCMs exhibited left ventricular diastolic systolic dysfunction. Subsequently, indicated formed fewer shorter fibers cytoplasm compared WT Moreover, our metabolomic proteomic data suggested several key components mitochondrial membrane integrity, remodeling, energy metabolism, oxidative stress, inflammation, actin capacity significantly altered response This investigation dysfunction disarray added underlying this. These findings provided a link between observed structural functional disorders onset pathogenesis might have significant translational contribution effective treatment

Language: Английский

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Lipid-based peptide and gene delivery to lungs

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown, P. 491 - 510

Published: Jan. 1, 2025

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Fatty acid content and DNA concentration of the Mediterranean green crab Carcinus aestuarii’s hepatopancreas in relation to dimethoate acute toxicity

Toxicology and Environmental Health Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Language: Английский

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Interrogating mediators of single-cell transcriptional changes in the acute damaged cerebral cortex: Insights into endothelial-astrocyte interactions

Molecular and Cellular Neuroscience, Journal Year: 2025, Volume and Issue: unknown, P. 104003 - 104003

Published: March 1, 2025

Language: Английский

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Alterations in phosphatidylethanolamine metabolism impacts hepatocellular lipid storage, energy homeostasis, and proliferation

Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids, Journal Year: 2025, Volume and Issue: unknown, P. 159608 - 159608

Published: March 1, 2025

Language: Английский

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The Emerging Role of Water Loss in Dog Aging

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 545 - 545

Published: April 4, 2025

Aging involves progressive physiological changes, including the dysregulation of water homeostasis, essential for cellular function, neuronal signaling, and musculoskeletal integrity. This review explores emerging role loss as a central underestimated driver functional decline in aging, with focus on dog, both clinically relevant target species model human aging. Age-related alterations metabolism—driven by changes body composition, aquaporin (AQP) expression, electrolyte imbalances, reduced thirst perception, impaired urine concentration—lead to intracellular extracellular dehydration, exacerbating decline. We examine molecular mechanisms regulation involving AQPs osmolytes, describe how dehydration contributes structural metabolic dysfunction across key biological compartments, kidney, brain, bone, skeletal muscle. Physiological hallmark intensifies inflammaging, accelerating tissue degeneration. In particular, we highlight impairs solvent capacity, solute transport, protein conformation, communication. Despite known macronutrients geriatric nutrition, hydration remains an often-overlooked factor aging management. argue its inclusion fourth pillar nutritional approach veterinary geriatrics, alongside protein, fat, fiber. By investigating aging-associated dogs—species that share environments lifestyle patterns humans—we propose hydration-centered strategies promote healthy comparative medicine.

Language: Английский

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Comprehensive metabolomics analysis reveals novel biomarkers and pathways in falsely suspected glutaric aciduria Type-1 newborns

Clinica Chimica Acta, Journal Year: 2024, Volume and Issue: 557, P. 117861 - 117861

Published: March 13, 2024

Language: Английский

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Unveiling the “hidden quality” of the walnut pellicle: a precious source of bioactive lipids

Frontiers in Plant Science, Journal Year: 2024, Volume and Issue: 15

Published: June 18, 2024

Tree nut consumption has been widely associated with various health benefits, walnuts, in particular, being linked improved cardiovascular and neurological health. These benefits have attributed to walnuts’ vast array of phenolic antioxidants abundant polyunsaturated fatty acids. However, recent studies revealed unexpected clinical outcomes related walnut consumption, which cannot be explained simply the aforementioned molecular hallmarks. With goal discovering potential sources these unexplained outcomes, an exploratory untargeted metabolomics analysis isolated pellicle was conducted. This a myriad unusual lipids, including oxylipins endocannabinoids. lipid classes, are likely present enhance seeds’ defenses due their antimicrobial properties, also known potent bioactivities as mammalian signaling molecules homeostatic regulators. Given value this tissue for human health, respect its “bioactive” fraction, we sought quantify amounts compounds pellicle-enriched waste by-products mechanized processing California. An impressive repertoire matrices, notably significant concentrations. discovery establishes low-value agriculture wastes promising candidates valorization translation into high-value, health-promoting products; represent explanation consumption. “hidden quality” may encourage further industries benefit from revaluation streams, leading increased sustainability profitability through upcycling.

Language: Английский

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Golgi protein ACBD3 downregulation sensitizes cells to ferroptosis

Cell Biology International, Journal Year: 2024, Volume and Issue: 48(10), P. 1559 - 1572

Published: July 2, 2024

Abstract Ferroptosis, a form of cell death driven by iron‐dependent lipid peroxidation, is emerging as promising target in cancer therapy. It regulated network molecules and pathways that modulate metabolism, iron homeostasis redox balance, related processes. However, there are still numerous regulatory intricately involved ferroptosis remain to be identified. Here, we indicated suppression Golgi protein acyl‐coenzyme A binding domain containing 3 (ACBD3) increased the sensitivity Henrieta Lacks PANC1 cells ferroptosis. ACBD3 knockdown increases labile levels promoting ferritinophagy. This increase free iron, coupled with reduced glutathione peroxidase 4 due knockdown, leads accumulation reactive oxygen species peroxides. Moreover, also results elevated polyunsaturated fatty acid‐containing glycerophospholipids through mechanisms elucidated. Furthermore, inhibition ferrtinophagy downregulated knocking down nuclear receptor co‐activator or Bafilomycin A1 treatment impeded Collectively, our findings highlight pivotal role governing cellular resistance suggest pharmacological manipulation strategy for

Language: Английский

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