Salidroside alleviates ulcerative colitis via inhibiting macrophage pyroptosis and repairing the dysbacteriosis‐associated Th17/Treg imbalance

Phytotherapy Research, Год журнала: 2022, Номер 37(2), С. 367 - 382

Опубликована: Ноя. 4, 2022

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by flora disequilibrium and mucosal immunity disorder. Here, we report that salidroside effectively restricts experimental from two aspects of intestinal macrophage pyroptosis dysbacteriosis-derived colonic Th17/Treg imbalance. In innate immunity, the upregulated TREM1 pyroptosis-related proteins in inflamed colons were inhibited administration further experiments vitro showed suppressed LPS/ATP-induced bone marrow-derived macrophages (BMDMs) evident decline LDH IL-1β release as well protein level NLRP3, caspase-1, GSDMD p30. Moreover, inhibitor weakened effect on BMDMs pyroptosis, whereas still could downregulate when NLRP3 was inhibited. adaptive improved gut microflora diversity ratio DSS-induced mice, especially promoting abundance Firmicutes. Clearance blocked benefit inflammation but transplanting salidroside-treated foecal bacterium into flora-depleted wild mice reproduced resistance to inflammation. Taken together, our data demonstrated protected via skewing balance, indicating its potential UC other immune disorders.

Язык: Английский

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Short-chain fatty acid-butyric acid ameliorates granulosa cells inflammation through regulating METTL3-mediated N6-methyladenosine modification of FOSL2 in polycystic ovarian syndrome

Clinical Epigenetics, Год журнала: 2023, Номер 15(1)

Опубликована: Май 13, 2023

Abstract Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by chronic low-grade inflammation. Previous studies have demonstrated that the gut microbiome can affect host tissue cells’ mRNA N6-methyladenosine (m6A) modifications. This study aimed to understand role of intestinal flora in ovarian cells inflammation regulating m6A modification particularly inflammatory state PCOS. The composition PCOS Control groups was analyzed 16S rRNA sequencing, short chain fatty acids were detected patients’ serum mass spectrometry methods. level butyric acid found be decreased obese group (FAT) compared other groups, this correlated with increased Streptococcaceae Rikenellaceae based on Spearman’s rank test. Additionally, we identified FOSL2 as a potential METTL3 target using RNA-seq MeRIP-seq methodologies. Cellular experiments addition led decrease methylation levels expression suppressing METTL3, methyltransferase. NLRP3 protein cytokines (IL-6 TNF-α) downregulated KGN cells. Butyric supplementation mice improved function local factors ovary. Taken together, correlation between may unveil crucial mechanisms for specific microbiota pathogenesis Furthermore, present new prospects future treatments.

Язык: Английский

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The influence of seminal microbiota on human testicular steroidogenesis: a prospective study

Journal of Assisted Reproduction and Genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 7, 2025

Язык: Английский

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Metformin inhibits ovarian granular cell pyroptosis through the miR-670-3p/NOX2/ROS pathway

Aging, Год журнала: 2023, Номер 15(10), С. 4429 - 4443

Опубликована: Май 25, 2023

Recent studies have demonstrated that ovarian granular cells (OGCs) pyroptosis is present in the ovaries of polycystic ovary syndrome (PCOS) mice and NLRP3 activation destroys follicular functions. Metformin has been shown to protect against PCOS by reducing insulin resistance women, whereas its role OGC unknown. This study aimed investigate impact metformin on underlying mechanisms. The results showed treating a human granulosa-like tumor cell line (KGN) with significantly decreased LPS-induced expression miR-670-3p, NOX2, NLRP3, ASC, cleaved caspase-1, GSDMD-N. Cellular caspase-1 activity; ROS production; oxidative stress; secretion IL-1β, IL-6, IL-18, TNF-α were also diminished. These effects amplified adding N-acetyl-L-cysteine (NAC), pharmacological inhibitor ROS. In contrast, metformin's anti-pyroptosis anti-inflammatory robustly ameliorated NOX2 overexpression KGN cells. Moreover, bioinformatic analyses, RT-PCR, Western blotting miR-670-3p could directly bind (encoded CYBB gene humans) 3'UTR decrease expression. Metformin-induced suppression expression, production, stress, was alleviated transfection inhibitor. findings suggest inhibits via miR-670-3p/NOX2/ROS pathway.

Язык: Английский

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The role of macrophages in polycystic ovarian syndrome and its typical pathological features: A narrative review

Biomedicine & Pharmacotherapy, Год журнала: 2023, Номер 167, С. 115470 - 115470

Опубликована: Сен. 15, 2023

Polycystic ovarian syndrome (PCOS) is the most common endocrine and metabolic disorder in women of childbearing age, with ovulatory dysfunction, hyperandrogenism, polycystic morphology (PCOM) as clinical features. Androgen excess, insulin resistance, obesity, adipose tissue gut microbiota dysbiosis are main pathological features pathogenesis PCOS related to systemic chronic low-grade inflammation PCOS. With advances immune-endocrine interaction studies, research on role immune cells occurrence development gradually increasing. As core innate immunity, macrophages play an indispensable inflammatory response. Meanwhile, they involved maintaining stability function ovary abundant tissue. Studies humans mice have found that polarization into M1 type plays multiple roles This review describes distribution characteristics macrophage subpopulations patients animal models PCOS, discusses macrophage-related summarizes relationship between PCOS-related its possible mechanisms, further understand reveal it. In addition, interactions can also provide direction for finding new therapeutic targets

Язык: Английский

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Gut microbiota in health and disease: advances and future prospects

MedComm, Год журнала: 2024, Номер 5(12)

Опубликована: Ноя. 20, 2024

Abstract The gut microbiota plays a critical role in maintaining human health, influencing wide range of physiological processes, including immune regulation, metabolism, and neurological function. Recent studies have shown that imbalances composition can contribute to the onset progression various diseases, such as metabolic disorders (e.g., obesity diabetes) neurodegenerative conditions Alzheimer's Parkinson's). These are often accompanied by chronic inflammation dysregulated responses, which closely linked specific forms cell death, pyroptosis ferroptosis. Pathogenic bacteria trigger these death pathways through toxin release, while probiotics been found mitigate effects modulating responses. Despite insights, precise mechanisms influences diseases remain insufficiently understood. This review consolidates recent findings on impact immune‐mediated inflammation‐associated conditions. It also identifies gaps current research explores potential advanced technologies, organ‐on‐chip models microbiome–gut–organ axis, for deepening our understanding. Emerging tools, single‐bacterium omics spatial metabolomics, discussed their promise elucidating microbiota's disease development.

Язык: Английский

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Nanocomposites based on nanoceria regulate the immune microenvironment for the treatment of polycystic ovary syndrome

Journal of Nanobiotechnology, Год журнала: 2023, Номер 21(1)

Опубликована: Ноя. 7, 2023

The immune system is closely associated with the pathogenesis of polycystic ovary syndrome (PCOS). Macrophages are one important cell types in ovarian proinflammatory microenvironment, and ameliorate inflammatory status mainly through M2 phenotype polarization during PCOS. Current therapeutic approaches lack efficacy immunomodulatory capacity, a new method needed to prevent inflammation alleviate Here, octahedral nanoceria nanoparticles powerful antioxidative ability were bonded anti-inflammatory drug resveratrol (CeO2@RSV), which demonstrates crucial strategy that involves efficacy, thereby facilitating proliferation granulosa cells Notably, our demonstrated possess potent via activities effectively alleviated endocrine dysfunction, injury dehydroepiandrosterone (DHEA)-induced PCOS mouse model. Collectively, this study revealed tremendous potential newly developed ameliorating microenvironment promoting function cells, representing first attempt treat by using CeO2@RSV providing insights combating clinical

Язык: Английский

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Mechanisms of probiotic modulation of ovarian sex hormone production and metabolism: a review

Food & Function, Год журнала: 2024, Номер 15(6), С. 2860 - 2878

Опубликована: Янв. 1, 2024

Effects of the brain, liver, pancreas, and fat on ovarian sex hormone production through gut.

Язык: Английский

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Spotlight on iron overload and ferroptosis: Research progress in female infertility

Life Sciences, Год журнала: 2023, Номер 340, С. 122370 - 122370

Опубликована: Дек. 22, 2023

Язык: Английский

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Exploration of key genes associated with oxidative stress in polycystic ovary syndrome and experimental validation

Frontiers in Medicine, Год журнала: 2025, Номер 12

Опубликована: Фев. 27, 2025

The current study demonstrated that oxidative stress (OS) is closely related to the pathogenesis of polycystic ovary syndrome (PCOS). However, there are numerous factors lead OS, therefore, identifying key genes associated with PCOS contribute OS crucial for elucidating and selecting appropriate treatment strategies. Four datasets (GSE95728, GSE106724, GSE138572, GSE145296) were downloaded from gene expression omnibus (GEO) database. GSE95728 GSE106724 combined identify differentially expressed (DEGs) in PCOS. weighted correlation network analysis (WGCNA) was used screen module Differentially (DE-OSRGs) obtained by overlapping DEGs, genes, OSRGs. Subsequently, optimal machine model comparing performance random forest (RF), support vector (SVM), generalized linear (GLM). molecular networks constructed reveal non-coding regulatory mechanisms based on GSE138572 GSE145296. Drug-Gene Interaction Database (DGIdb) predict potential therapeutic agents Finally, OSRGs validated RT-PCR. In this study, 8 DE-OSRGs identified. Based residuals root mean square error three models, best RF derived 7 (TNFSF10, CBL, IFNG, CP, CASP8, APOA1, DDIT3) GSEA enrichment revealed TNFSF10, DDIT3, INFG all enriched NOD-like receptor signaling pathway natural killer cell-mediated cytotoxicity pathways. uncovered both TNFSF10 CBL regulated RNAs. Additionally, 70 drugs predicted, ibuprofen DDIT3 IFNG. RT-qPCR validation confirmed trends APOA1 consistent dataset, observed differences statistically significant (P < 0.05). identification seven through bioinformatics great significance exploring strategies

Язык: Английский

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