Neuroinflammation in post-acute sequelae of COVID-19 (PASC) as assessed by [11C]PBR28 PET correlates with vascular disease measures

Brain Behavior and Immunity, Journal Year: 2024, Volume and Issue: 119, P. 713 - 723

Published: April 18, 2024

The COVID-19 pandemic caused by SARS-CoV-2 has triggered a consequential public health crisis of post-acute sequelae (PASC), sometimes referred to as long COVID. mechanisms the heterogeneous persistent symptoms and signs that comprise PASC are under investigation, several studies have pointed central nervous vascular systems being potential sites dysfunction. In current study, we recruited individuals with diverse symptoms, examined relationship between neuroinflammation circulating markers We used [

Language: Английский

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Chronic Kidney Disease with Mineral Bone Disorder and Vascular Calcification: An Overview

Life, Journal Year: 2024, Volume and Issue: 14(3), P. 418 - 418

Published: March 21, 2024

Chronic kidney disease (CKD) is a global health issue with rising prevalence, affecting 697.5 million people worldwide. It imposes substantial burden, contributing to 35.8 disability-adjusted life years (DALYs) and 1.2 deaths in 2017. The mortality rate for CKD has increased by 41.5% between 1990 2017, positioning it as significant cause of mortality. associated diverse complications, impacting cardiovascular, neurological, nutritional, endocrine aspects. One prominent complication CKD–mineral bone disorder (MBD), complex condition involving dysregulation turnover, mineralization, strength, accompanied soft tissue vascular calcification. Alterations mineral metabolism, including calcium, phosphate, parathyroid hormone (PTH), vitamin D, fibroblast growth factor-23 (FGF-23), Klotho, play pivotal roles CKD-MBD. These disturbances, observed early CKD, contribute the progression disorders renal osteodystrophy (ROD). Vascular calcification (VC) key component CKD-MBD, accelerated CKD. pathophysiology involves processes smooth muscle cells formation calciprotein particles (CPP). VC closely linked cardiovascular events mortality, emphasizing its prognostic significance. Various serum markers imaging techniques, lateral plain X-ray, Kauppila Score, Adragao pulse wave velocity, aid detection. Additionally, pQCT provides valuable information on arterial calcifications, offering an advantage over traditional scoring systems. poses CKD-MBD VC, significantly morbidity Understanding intricate relationships disorders, crucial effective diagnosis therapeutic interventions.

Language: Английский

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AI-Based Prediction of Protein Corona Composition on DNA Nanostructures

ACS Nano, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

DNA nanotechnology has emerged as a powerful approach to engineering biophysical tools, therapeutics, and diagnostics because it enables the construction of designer nanoscale structures with high programmability. Based on base pairing rules, nanostructure size, shape, surface functionality, structural reconfiguration can be programmed degree spatial, temporal, energetic precision that is difficult achieve other methods. However, properties structure constructs are greatly altered in vivo due spontaneous protein adsorption from biofluids. These adsorbed proteins, referred corona, remain challenging control or predict, subsequently, their functionality fate engineer. To address these challenges, we prepared library diverse nanostructures investigated relationship between design features composition corona. We identified characteristics important for developed machine-learning model predicts which proteins will enriched based structures' properties. Our work help understand program function biomedical applications.

Language: Английский

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The Interconnection between Hepatic Insulin Resistance and Metabolic Dysfunction-Associated Steatotic Liver Disease—The Transition from an Adipocentric to Liver-Centric Approach

Current Issues in Molecular Biology, Journal Year: 2023, Volume and Issue: 45(11), P. 9084 - 9102

Published: Nov. 14, 2023

The central mechanism involved in the pathogenesis of MAFLD is insulin resistance with hyperinsulinemia, which stimulates triglyceride synthesis and accumulation liver. On other side, free fatty acid hepatocytes promotes via oxidative stress, endoplasmic reticulum lipotoxicity, increased secretion hepatokines. Cytokines adipokines cause resistance, thus promoting lipolysis adipose tissue ectopic fat deposition muscles Free acids along cytokines contribute to liver activation numerous signaling pathways. hepatokines, hormone-like proteins, primarily by disturbed impairs pathways, causing metabolic dysregulation ER stress unfolded protein response play significant roles aggravation through apoptosis, inflammatory response, impairment mediated IRE1/PERK/ATF6 pathways upregulation SREBP 1c. Circadian rhythm derangement biological clock desynchronization are related disorders, NAFLD, suggesting genes as a potential target for new therapeutic strategies. This review aims summarize mechanisms hepatic NAFLD development progression.

Language: Английский

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A simple and robust serum-free media for the proliferation of muscle cells

Food Research International, Journal Year: 2023, Volume and Issue: 172, P. 113194 - 113194

Published: June 29, 2023

Cultivated meat production requires an efficient, robust and highly optimized serum-free cell culture media for the needed upscaling of muscle expansion. Existing formulations are complex, expensive have not been cells. Thus, we undertook this work to develop a simple proliferation bovine satellite cells (SCs) through Design Experiment (DOE) Response Surface Methodology (RSM) using precise high-throughput image-based cytometry. Proliferative attributes were investigated with transcriptomics long-term performance was validated multiple live assays. Here formulated based on three components; FGF2 (2 ng/mL), fetuin (600 µg/mL) BSA (75 which together insulin-transferrin-selenium (1x) supplement, sustained SCs, porcine SCs murine C2C12 Remarkably, cultured in our named Tri-basal 2.0+ performed better than 10% FBS, respect proliferation. Hence, enhanced attachment proliferation, providing alternative solution use FBS cultivated meat.

Language: Английский

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NOX4 as a critical effector mediating neuroinflammatory cytokines, myeloperoxidase and osteopontin, specifically in astrocytes in the hippocampus in Parkinson's disease

Redox Biology, Journal Year: 2023, Volume and Issue: 62, P. 102698 - 102698

Published: April 10, 2023

Oxidative stress and mitochondrial dysfunction have been believed to play an important role in the pathogenesis of aging neurodegenerative diseases, including Parkinson's disease (PD). The excess reactive oxygen species (ROS) increases with age causes a redox imbalance, which contributes neurotoxicity PD. Accumulating evidence suggests that NADPH oxidase (NOX)-derived ROS, especially NOX4, belong NOX family is one major isoforms expressed central nervous system (CNS), associated progression We previously shown NOX4 activation regulates ferroptosis via astrocytic dysfunction. through astrocytes. However, it remains unclear why increase diseases leads astrocyte cell death by certain mediators. Therefore, this study was designed evaluate how hippocampus involved PD comparing MPTP-induced mouse model compared human patients. could detect dominantly elevated levels α-synuclein during neuroinflammatory cytokines, myeloperoxidase (MPO) osteopontin (OPN), were upregulated particularly Intriguingly, suggested direct intercorrelation MPO OPN hippocampus. Upregulation induces suppressing five protein complexes electron transport (ETC) level 4-HNE leading Overall, our findings indicate elevation cooperated inflammatory cytokines aberration hippocampal astrocytes

Language: Английский

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A magnetic separation method for isolating and characterizing the biomolecular corona of lipid nanoparticles

Proceedings of the National Academy of Sciences, Journal Year: 2024, Volume and Issue: 121(11)

Published: March 4, 2024

Lipid nanoparticle (LNP) formulations are a proven method for the delivery of nucleic acids gene therapy as exemplified by worldwide rollout LNP-based RNAi therapeutics and mRNA vaccines. However, targeting specific tissues or cells is still major challenge. After LNP administration, LNPs interact with biological fluids (i.e., blood), components which adsorb onto surface forming layer biomolecules termed “biomolecular corona (BMC)” affects stability, biodistribution, tissue tropism. The mechanisms BMC influences tissue- cell-specific remains largely unknown, due to technical challenges in isolating their from complex media. In this study, we present new technique that utilizes magnetic isolate LNP–corona complexes unbound proteins human serum. First, developed formulation, containing >40 superparamagnetic iron oxide nanoparticles (IONPs)/LNP, resulting (IOLNPs) displayed similar particle size morphology loaded acids. We further demonstrated isolation IOLNPs corresponding using separation (MS) system. profile MS system was compared exclusion column chromatography analyzed via mass spectrometry, revealing differences protein abundances. This approach enabled mild versatile its corona, while maintaining structural integrity. identification associated an intact provides insight into interactions fluids.

Language: Английский

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Characterization of the plasma proteomic profile of Fabry disease: Potential sex- and clinical phenotype-specific biomarkers

Translational research, Journal Year: 2024, Volume and Issue: 269, P. 47 - 63

Published: Feb. 21, 2024

Fabry disease (FD) is a X-linked rare lysosomal storage disorder caused by deficient α-galactosidase A (α-GalA) activity. Early diagnosis and the prediction of course are complicated clinical heterogeneity FD, as well frequently inconclusive biochemical genetic test results that do not correlate with course. We sought to identify potential biomarkers FD better understand underlying pathophysiology phenotypes. compared plasma proteomes 50 patients matched healthy controls using DDA SWATH-MS. The >30 proteins were differentially expressed between 2 groups included implicated in processes such inflammation, heme haemoglobin metabolism, oxidative stress, coagulation, complement cascade, glucose lipid glycocalyx formation. Stratification sex revealed certain sex-dependent manner. Apolipoprotein A-IV was upregulated complications, especially those chronic kidney disease, apolipoprotein C-III fetuin-A identified possible markers left ventricular hypertrophy. All these had greater capacity presence complications than lyso-GB3, standing out being more sensitive effective differentiating absence renal creatinine, glomerular filtration rate microalbuminuria. Identification can help further our understanding pathophysiological underlie heterogeneous manifestations associated FD.

Language: Английский

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Hepatokines and Their Role in Cardiohepatic Interactions in Heart Failure

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177356 - 177356

Published: Feb. 1, 2025

Language: Английский

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Gut microbiome responds to alteration in female sex hormone status and exacerbates metabolic dysfunction

Gut Microbes, Journal Year: 2023, Volume and Issue: 16(1)

Published: Dec. 28, 2023

Women are at significantly greater risk of metabolic dysfunction after menopause, which subsequently leads to numerous chronic illnesses. The gut microbiome is associated with obesity and dysfunction, but its interaction female sex hormone status the resulting impact on host metabolism remains unclear. Herein, we characterized inflammatory phenotypes as well ovariectomy high-fat diet feeding, compared gonadal intact low-fat controls. We then performed fecal microbiota transplantation (FMT) using gnotobiotic mice identify ovariectomy-associated outcomes. demonstrated that led gastrointestinal permeability inflammation organs, a exacerbated these phenotypes. Ovariectomy also alteration microbiome, including β-glucuronidase activity. However, differential changes in only occurred when fed diet, not diet. Gnotobiotic received from ovariectomized had weight gain hepatic gene expression related than those sham control-associated microbiome. These results indicate responds alterations contributes dysfunction. Identifying developing microbiome-targeted modulators regulate hormones may be useful therapeutically remediating menopause-related diseases.

Language: Английский

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