Adipokines regulate the development and progression of MASLD through organellar oxidative stress

Hepatology Communications, Journal Year: 2025, Volume and Issue: 9(2)

Published: Jan. 29, 2025

The prevalence of metabolic dysfunction–associated steatotic liver disease (MASLD), which is increasingly being recognized as a leading cause chronic pathology globally, increasing. pathophysiological underpinnings its progression, currently under active investigation, involve oxidative stress. Human adipose tissue, an integral endocrine organ, secretes array adipokines that are modulated by dietary patterns and lifestyle choices. These intricately orchestrate regulatory pathways impact glucose lipid metabolism, stress, mitochondrial function, thereby influencing the evolution hepatic steatosis progression to steatohepatitis (MASH). This review examines recent data, underscoring critical interplay reactive oxygen species, redox signaling in adipokine-mediated mechanisms. role various regulating onset MASLD/MASH through dysfunction endoplasmic reticulum stress underlying mechanisms discussed. Due emerging correlation between development MASLD positions, these potential targets for innovative therapeutic interventions management. A comprehensive understanding pathogenesis instrumental identifying therapies MASH.

Language: Английский

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Identification and Validation of miR-222-3p and miR-409-3p as Plasma Biomarkers in Gestational Diabetes Mellitus Sharing Validated Target Genes Involved in Metabolic Homeostasis

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(8), P. 4276 - 4276

Published: April 12, 2022

Gestational diabetes mellitus (GDM) causes both maternal and fetal adverse outcomes. The deregulation of microRNAs (miRNAs) in GDM suggests their involvement pathogenesis complications. Exosomes are extracellular vesicles (EVs) endosomal origin, released via exocytosis into the compartment. Through EVs, miRNAs delivered distant target cells able to affect gene expression. In this study, miRNA expression was analyzed find new that could improve classification molecular characterization. MiRNA were profiled total plasma EVs patients normal glucose tolerance (NGT) women. Samples collected at third trimester gestation from two centers. a discovery cohort using multiplexed NanoString nCounter Human v3 miRNA. Validation analysis performed second independent RT-qPCR. A set resulted be differentially expressed (DE) GDM. Among them, miR-222-3p miR-409-3p validated cohort. MiR-222-3p levels correlated with fasting (FPG) (p < 0.001) birth weight = 0.012), whereas FPG inversely gestational age 0.001). major genes deregulated consistently linked type 2 pathophysiology. circulating biomarkers power act context events leading metabolic alterations observed

Language: Английский

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MicroRNA-204-5p reduction in rat hippocampus contributes to stress-induced pathology via targeting RGS12 signaling pathway

Journal of Neuroinflammation, Journal Year: 2021, Volume and Issue: 18(1)

Published: Oct. 21, 2021

Neuroinflammation occupies a pivotal position in the pathogenesis of most nervous system diseases, including depression. However, underlying molecular mechanisms neuroinflammation associated with neuronal injury depression remain largely uncharacterized. Therefore, identifying potential and therapeutic targets would serve to better understand progression this condition.Chronic unpredictable stress (CUS) was used induce depression-like behaviors rats. RNA-sequencing detect differentially expressed microRNAs. Stereotactic injection AAV virus overexpress or knockdown miR-204-5p. The oxidative markers inflammatory related proteins were verified by immunoblotting immunofluorescence assay. enzyme products using enzyme-linked assay kit. Electron microscopy analysis observe synapse ultrastructural pathology. Finally, electrophysiological recording analyze synaptic transmission.Here, we found that expression miR-204-5p within hippocampal dentate gyrus (DG) region rats significantly down-regulated after chronic unpredicted (CUS), accompanied stress-induced damage DG these In contrast, overexpression CUS alleviated directly targeting regulator G protein signaling 12 (RGS12), effects which amelioration depressive-like addition, down-regulation induced deterioration regions rats.Taken together, results suggest plays key role regulating CUS-induced pathological processes Such findings provide evidence involvement depressive phenotype.

Language: Английский

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Epigenetic regulation of inflammation in insulin resistance

Seminars in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 154, P. 185 - 192

Published: Sept. 13, 2022

Epigenetics focuses on the study of changes in gene expression based modifications that do not interfere with DNA sequence, such as methylation, post-translational histone modification, and non-coding RNA. Epigenetic regulate many genes, including inflammatory ones. Chronic inflammation is often accompanied by insulin resistance (IR), which characteristic inter alia type 2 diabetes. Recently, it has been reported altered epigenetic signature promoter regions genes may contribute to development IR. Therefore, aim this review present current state knowledge regarding regulation It includes original papers published from 2014 2022. appears hypomethylation SOCS3 increases risk IR, while alteration H3K4me NF-kB promotes phenotype. Finally, hyperglycemic states associated levels H3K4/K9m3 H3K9/K14ac result increased cytokine IL-6. In addition, numerous miRNAs have identified become a target fight against diseases related Future studies should examine IR markers environmental factors.

Language: Английский

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Bacterial targets of fecal host miRNAs in high-fat diet-fed mice

PLoS ONE, Journal Year: 2025, Volume and Issue: 20(2), P. e0315871 - e0315871

Published: Feb. 11, 2025

The gut microbiome composition is intricately linked to the host’s health status, yet mechanisms underlying its interaction with host are not fully understood. MicroRNAs (miRNAs), facilitating intercellular communication, found in bodily fluids, including intestinal content, where they may affect microbiome. However, their role type 2 diabetes (T2D)-associated and treatment implications explored. Our study investigated how miRNAs influence changes related metformin a T2D mouse model. Analyzing fecal mucosal samples via small RNA sequencing, we correlated results sequencing data, identifying miRNA-microbiome correlations, bacterial targets, proteins targeted these bacteria. Significant differences miRNA expression based on diet location were noted, minor effects from proximal intestine of non-diabetic male mice. Key targeting bacteria included mmu-miR-5119, mmu-miR-5126, mmu-miR-6538, mmu-miR-2137, primarily affecting Oscillospiraceae_NOV, Lachnospiraceae_NOV, Bacteroides. analysis revealed diverse biological molecular effects. Further research into miRNA-bacteria interactions could lead new strategies for manipulating beyond.

Language: Английский

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Berberine combined with stachyose improves glycometabolism and gut microbiota through regulating colonic microRNA and gene expression in diabetic rats

Life Sciences, Journal Year: 2021, Volume and Issue: 284, P. 119928 - 119928

Published: Sept. 1, 2021

Berberine is effective for type 2 diabetes mellitus (T2DM), but has limited use in clinic. This study aims to evaluate the effect of berberine combined with stachyose on glycolipid metabolism and gut microbiota explore underlying mechanisms diabetic rats.

Language: Английский

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Circ_0000064 promotes high glucose-induced renal tubular epithelial cells injury to facilitate diabetic nephropathy progression through miR-532-3p/ROCK1 axis

BMC Endocrine Disorders, Journal Year: 2022, Volume and Issue: 22(1)

Published: March 15, 2022

Circular RNA (circRNA) has been shown to mediate diabetic nephropathy (DN) development by regulating renal tubular epithelial cells (RTECs) injury. However, the role and mechanism of circ_0000064 in high glucose (HG)-induced RTECs injury have not fully elucidated.Human (HK-2) were exposed HG induce cell Cell oxidative stress was assessed detecting levels stress-markers. Moreover, proliferation apoptosis determined CCK8 assay, EDU assay flow cytometry. The protein markers, markers Rho-associated coiled-coil-containing kinase 1 (ROCK1) measured using western blot analysis. Furthermore, quantitative real-time PCR performed assess expression circ_0000064, microRNA (miR)-532-3p ROCK1. interaction between miR-532-3p or ROCK1 confirmed dual-luciferase reporter pull-down assay.Our results revealed that treatment could promote HK-2 stress, apoptosis, fibrosis, inhibit proliferation. Circ_0000064 increased serum DN patients HG-induced cells, silenced relieve MiR-532-3p be sponged its overexpression also alleviated Besides, regulation knockdown on reversed inhibitor. Additionally, a target miR-532-3p, inhibited knockdown. inhibition effect overexpressing ROCK1.In summary, might alleviate via miR-532-3p/ROCK1 axis, which provided new perspective for treatment.

Language: Английский

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The Preliminary Exploration of What Role miRNAs Derived From Urinary Exosomes Play in Kidney Stone Formation

Urology, Journal Year: 2022, Volume and Issue: 166, P. 104 - 110

Published: May 28, 2022

Language: Английский

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miR‑146b‑5p promotes colorectal cancer progression by targeting TRAF6

Experimental and Therapeutic Medicine, Journal Year: 2022, Volume and Issue: 23(3)

Published: Jan. 20, 2022

Increasing evidence highlights the multiple roles of microRNAs (miRs) in tumorigenesis colorectal cancer (CRC); however, molecular mechanism, particularly target miR-146b-5p CRC has not been fully elucidated. The present study aimed to elucidate influence via regulating tumor necrosis factor receptor-associated 6 (TRAF6) CRC. expression levels and TRAF6 tissue cells were determined by reverse transcription quantitative PCR western blotting. Binding between was examined using a dual luciferase reporter gene assay. impact on proliferation migration Cell Counting Kit-8 Transwell assays, respectively. An animal model established determine carcinogenic effect miR-146b-5p-TRAF6 axis. results demonstrated that highly expressed samples compared with normal adjacent NCM460 cell line, whereas at low levels. Overexpression decreased HT29 SW620 cells. targeted inhibited Furthermore, transfection mimic promoted proliferation, invasion growth; these effects abolished overexpression. Transfection inhibitor suppressed Taken together, from could enhance initiation targeting TRAF6. These will help mechanisms underlying development facilitate therapy for

Language: Английский

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MicroRNA Regulation of Bone Marrow Mesenchymal Stem Cells in the Development of Osteoporosis in Obesity

Frontiers in Bioscience-Scholar, Journal Year: 2022, Volume and Issue: 14(3)

Published: June 23, 2022

Obesity and osteoporosis are global health problems characterized by high rates of prevalence mortality due to complications. As people with visceral obesity age, the adipogenic differentiation bone marrow mesenchymal stem cells (BMSCs) increases, adipocytes become predominant stromal in microenvironment, which hinders physiological regeneration mineralization tissue. Primary secondary remain severe progressive diseases. Both associated microRNAs (miRNAs) that induce adipogenesis osteoresorption. This review presents analyses roles clinical potential miRNAs epigenetic control BMSC formation function osteoclasts without obesity. Understanding fine-tuned regulation expression genes critical for balance osteogenesis/osteolysis processes may provide hope development effective safe therapies future.

Language: Английский

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