Multi-omics reveals the mechanism of Trimethylamine N-oxide derived from gut microbiota inducing liver fatty of dairy cows

BMC Genomics, Год журнала: 2025, Номер 26(1)

Опубликована: Янв. 6, 2025

Trimethylamine N-oxide (TMAO) is a metabolite produced by gut microbiota, and its potential impact on lipid metabolism in mammals has garnered widespread attention the scientific community. Bovine fatty liver disease, metabolic disorder that severely affects health productivity of dairy cows, poses significant economic burden global industry. However, specific role pathogenesis TMAO bovine disease remain unclear, limiting our understanding treatment condition. This study aims to construct cell model using an integrated approach combines transcriptomic, proteomic, metabolomic data. The objective investigate at molecular level explore regulatory mechanisms. We established vitro conducted comprehensive analysis cells treated with high-throughput omics sequencing technologies. Bioinformatics methods were employed delve into effects metabolism, several key genes validated through RT-qPCR. Treatment significantly affected 4790 genes, 397 proteins, 137 metabolites. KEGG enrichment revealed altered molecules primarily involved pathways related pathology such as pathways, insulin resistance, hepatitis B, AMPK signaling pathway. Moreover, joint analysis, we further uncovered interaction between TMAO-mediated oxidative phosphorylation might be mechanism promoting accumulation liver. Our provides new insights offers basis for developing more effective strategies.

Язык: Английский

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Investigating the Protective Effects of Luteolin and Gallic Acid from Luffa acutangula L. (Roxb.) amara (Roxb.) C. B. Clarke. Fruit Pericarp Against Alcohol-Induced Liver Toxicity: Extraction, Bioactivity-Guided Fractionation, Molecular Docking, and Dynamics Studies

Journal of Ethnopharmacology, Год журнала: 2025, Номер unknown, С. 119377 - 119377

Опубликована: Янв. 1, 2025

Язык: Английский

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The synergistic effects of citicoline and silymarin on liver injury and thyroid hormone disturbances in γ-irradiated rats

Molecular Biology Reports, Год журнала: 2025, Номер 52(1)

Опубликована: Янв. 30, 2025

Язык: Английский

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Humic Acid Derived from Vermicompost Improves Bone Mineral Content and Alters Oxidative Stress Markers in Ovariectomized Mice

Biomedicines, Год журнала: 2025, Номер 13(2), С. 495 - 495

Опубликована: Фев. 17, 2025

Background: Estrogen depletion alters bone mineralization and oxidative stress. Antioxidants like humic acids (HA) may help mitigate demineralization redox imbalances. Thus, this study evaluated the effects of HA on mineral composition stress markers in an experimental menopause model. Methods: Twenty-four female C57BL/6 mice were divided into four groups (n = 6/group): Sham; Sham + HA; Ovariectomized (OVX); OVX HA. The model was induced by bilateral ovariectomy at beginning experiment. derived from biomass vermicompost administered daily gavage for 28 days. After euthanasia, femurs fragments gastrocnemius muscle, liver, kidney collected. Bone elemental analyzed using scanning electron microscopy (SEM) coupled with energy dispersive spectroscopy (EDS). Superoxide dismutase (SOD), catalase (CAT), hydrogen peroxide (H2O2) activities assessed renal, hepatic tissues. Data two-way ANOVA Bonferroni's post hoc test. Results: Untreated exhibited a significant reduction femoral calcium content (p < 0.05). However, treatment increased levels improved Ca/P ratio H2O2 activity reduced liver compared to untreated animals CAT muscle group Conclusions: modulated

Язык: Английский

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Cellular Metabolomics Reveals Differences in the Scope of Liver Protection Between Ammonium-Based Glycyrrhizinate and Magnesium Isoglycyrrhizinate

Metabolites, Год журнала: 2025, Номер 15(4), С. 263 - 263

Опубликована: Апрель 10, 2025

Background: Despite the well-established liver-protective efficacy of monoammonium glycyrrhizinate (MONO), diammonium (DIAM), and magnesium isoglycyrrhizinate (MAGN), which has been translated into clinical practice, their differentiation remains elusive owing to structural similarities overlapping therapeutic effects. Methods: The present study delves pharmacokinetics, cellular-level potencies, underlying mechanisms action these three compounds through a comprehensive analysis. Results: findings reveal that both DIAM MAGN exhibit superior bioavailability hepatoprotective profiles compared MONO. Notably, an investigation metabolic pathways mediating liver protection in normal human cells (LO2), utilizing ultra-performance liquid chromatography-time flight tandem mass spectrometry (UPLC-TOF-MS/MSe) platform, demonstrated augments antioxidant components, thereby favoring its application drug-induced injury (DILI). Conversely, appears be more suitable candidate for addressing non-alcoholic fatty disease (NAFLD) viral hepatitis. Conclusion: This contributes novel perspectives on potential utilities prevention management.

Язык: Английский

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Combining nutraceuticals and a mediterranean diet for managing metabolic dysfunction associated with steatotic liver disease

World Journal of Hepatology, Год журнала: 2025, Номер 17(4)

Опубликована: Апрель 25, 2025

This study was performed by Cano Contreras et al, who explored the effects of alpha-lipoic acid (ALA) and Silybum marianum (SM) supplementation combined with a mediterranean diet (MD) on metabolic dysfunction-associated steatotic liver disease (MASLD). The randomized controlled design use transient elastography provide methodological strengths, whereas focus Mexican cohort addresses critical gap in regional MASLD research. Although improvements visceral fat attenuation parameters (CAP) were observed, key markers, including transaminases lipid profiles, showed no significant changes, raising concerns about intervention's comprehensive impact. reliance CAP absence mechanistic biomarker analysis limit insights into antioxidant anti-inflammatory pathways ALA SM. Future research should explore synergistic other nutraceuticals, such as vitamin E polyphenols, include extended follow-up patient stratification to assess long-term benefits personalized therapeutic outcomes. Addressing these limitations could solidify role nutraceuticals management enable development more effective sustainable interventions.

Язык: Английский

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Anti-Viral Activity of Bioactive Molecules of Silymarin against COVID-19 via In Silico Studies

Pharmaceuticals, Год журнала: 2023, Номер 16(10), С. 1479 - 1479

Опубликована: Окт. 17, 2023

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) infection drove the global coronavirus disease 2019 (COVID-19) pandemic, causing a huge loss of human life and negative impact on economic development. It is an urgent necessity to explore potential drugs against viruses, such as SARS-CoV-2. Silymarin, mixture herb-derived polyphenolic flavonoids extracted from milk thistle, possesses potent antioxidative, anti-apoptotic, anti-inflammatory properties. Accumulating research studies have demonstrated killing activity silymarin dengue virus, chikungunya hepatitis C virus. However, anti-COVID-19 mechanisms remain unclear. In this study, multiple disciplinary approaches methodologies were applied evaluate anti-viral agent SARS-CoV-2 infection. silico molecular docking, network pharmacology, bioinformatic methods incorporated assess ligand–protein binding properties analyze protein–protein interaction network. DAVID database was used gene functions, Kyoto Encyclopedia Genes Genomes (KEGG) pathway Gene Ontology (GO) enrichment. TCMSP GeneCards identify drug target genes COVID-19-related genes. Our results revealed that compounds, silybin A/B silymonin, displayed triplicate functions infection, including directly with angiotensin-converting enzyme 2 (ACE2) inhibit entry into host cells, viral proteins RdRp helicase replication proliferation, regulating immune response indirectly Specifically, targets molecules in regulation screened out, proinflammatory cytokines TNF IL-6 cell growth factors VEGFA EGF. addition, mechanism drug-target protein investigated, pockets ACE2 proteins, formation hydrogen bonds, hydrophobic interactions, other drug–protein ligand interactions. Finally, drug-likeness candidate passed criteria for screening. Overall, study demonstrates

Язык: Английский

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Role of Mitochondria in the Chronification of Inflammation: Focus on Dysfunctional Mitophagy and Mitochondrial DNA Mutations

Gene Expression, Год журнала: 2023, Номер 22(4), С. 329 - 344

Опубликована: Ноя. 30, 2023

Inflammation is a natural reaction of the innate immune system that evolved primarily to protect human body from invading pathogens and heal injuries. There are two different types inflammation, acute chronic differing in duration, underlying causes, characteristics. The acute-to-chronic transition can be determined by several pathomechanisms, including dysregulation response failure eliminate cause. Moreover, epigenetic changes refer modifications gene expression heritable but do not involve DNA sequence also contribute prolonged inflammation. Emerging evidence suggests dysfunctional mitochondria promote development In this respect, mechanisms triggering defective mitophagy, selective form autophagy exterminates maintain cellular homeostasis, attracted special attention. hypothesis on pivotal role mutations mitochondrial causing mitophagy stimulated area research applies editing genome. mitoCAS9 vector single guide RNAs G15059A mutation were used macrophage-like cells. normal activity initially was restored intact cells, confirming causal disruption process. unraveling inflammation will help develop targeted therapeutic approaches aimed at restoring health alleviating for treatment wide range inflammatory diseases.

Язык: Английский

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Preventive and Therapeutic Effects of Silybum marianum Seed Extract Rich in Silydianin and Silychristin in a Rat Model of Metabolic Syndrome

ACS Pharmacology & Translational Science, Год журнала: 2023, Номер 6(11), С. 1715 - 1723

Опубликована: Окт. 27, 2023

Metabolic syndrome (MetS) has become an increasing global health problem, which leads to cardiovascular diseases and type 2 diabetes.

Язык: Английский

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Redox Biology and Liver Fibrosis

International Journal of Molecular Sciences, Год журнала: 2023, Номер 25(1), С. 410 - 410

Опубликована: Дек. 28, 2023

Hepatic fibrosis is a complex process that develops in chronic liver diseases. Even though the initiation and progression of rely on underlying etiology, mutual mechanisms can be recognized targeted for therapeutic purposes. Irrespective primary cause disease, persistent damage to parenchymal cells triggers overproduction reactive species, with consequent disruption redox balance. Reactive species are important mediators homeostasis both hepatocytes non-parenchymal cells. Indeed, other than acting as cytotoxic agents, able modulate specific signaling pathways may relevant hepatic fibrogenesis. After brief introduction biology fibrogenesis, this review aims summarize current evidence involvement redox-dependent focuses possible targets.

Язык: Английский

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