New insights into the interplay between autophagy, gut microbiota and inflammatory responses in IBD

Autophagy, Год журнала: 2019, Номер 16(1), С. 38 - 51

Опубликована: Июль 9, 2019

One of the most significant challenges inflammatory bowel disease (IBD) research is to understand how alterations in symbiotic relationship between genetic composition host and intestinal microbiota, under impact specific environmental factors, lead chronic inflammation. Genome-wide association studies, followed by functional have identified a role for numerous autophagy genes IBD, especially Crohn disease. Studies using vitro vivo models, addition human clinical studies revealed that pivotal homeostasis maintenance, gut ecology regulation, appropriate immune responses anti-microbial protection. This review describes latest researches on mechanisms which dysfunctional leads disrupted epithelial function, dysbiosis, defect peptide secretion Paneth cells, endoplasmic reticulum stress response aberrant pathogenic bacteria. A better understanding IBD pathogenesis may provide sub-classification phenotypes novel approaches management.Abbreviations: AIEC: adherent-invasive Escherichia coli; AMPK: AMP-activated protein kinase; ATF6: activating transcription factor 6; ATG: related; Atg16l1[ΔIEC] mice: mice with Atg16l1 depletion specifically cells; Atg16l1[HM] hypomorphic expression; BCL2: B cell leukemia/lymphoma 2; BECN1: beclin 1, CALCOCO2: calcium binding coiled-coil domain CASP: caspase; CD: disease; CGAS: cyclic GMP-AMP synthase; CHUK/IKKA: conserved helix-loop-helix ubiquitous CLDN2: claudin DAPK1: death associated kinase 1; DCs: dendritic DSS: dextran sulfate sodium; EIF2A: eukaryotic translation initiation 2A; EIF2AK: 2 alpha ER: reticulum; ERBIN: Erbb2 interacting protein; ERN1/IRE1A: ER nucleus signaling FNBP1L: formin 1-like; FOXP3: forkhead box P3; GPR65: G-protein coupled receptor 65; GSK3B: glycogen synthase 3 beta; IBD: IECs: IFN: interferon; IL: interleukin; IL10R: interleukin 10 receptor; IRGM: immunity related GTPase M; ISC: stem cell; LAMP1: lysosomal-associated membrane LAP: LC3-associated phagocytosis; MAP1LC3B: microtubule-associated 1 light chain LPS: lipopolysaccharide; LRRK2: leucine-rich repeat MAPK: mitogen-activated MHC: major histocompatibility complex; MIF: macrophage migration inhibitory factor; MIR/miRNA: microRNA; MTMR3: myotubularin 3; MTOR: mechanistic target rapamycin MYD88: myeloid differentiation primary gene 88; NLRP3: NLR family, pyrin containing NOD2: nucleotide-binding oligomerization NPC: Niemann-Pick type C; NPC1: NPC intracellular cholesterol transporter OMVs: outer vesicles; OPTN: optineurin; PI3K: phosphoinositide 3-kinase; PRR: pattern-recognition PTPN2: tyrosine phosphatase, non-receptor PTPN22: 22 (lymphoid); PYCARD/ASC: PYD CARD containing; RAB2A: RAB2A, member RAS oncogene family; RELA: v-rel reticuloendotheliosis viral homolog (avian); RIPK2: (TNFRSF)-interacting serine-threonine ROS: reactive oxygen species; SNPs: single nucleotide polymorphisms; SQSTM1: sequestosome TAX1BP1: Tax1 Th: T helper TIRAP/TRIF: toll-interleukin (TIR) domain-containing adaptor TLR: toll-like TMEM173/STING: transmembrane 173; TMEM59: 59; TNF/TNFA: tumor necrosis Treg: regulatory T; TREM1: triggering expressed cells UC: ulcerative colitis; ULK1: unc-51 like WT: wild-type; XBP1: X-box XIAP: X-linked inhibitor apoptosis.

Язык: Английский

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Ginsenoside Rd: A promising natural neuroprotective agent

Phytomedicine, Год журнала: 2021, Номер 95, С. 153883 - 153883

Опубликована: Дек. 8, 2021

Язык: Английский

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Ginsenoside F2 from the leaves of Panax ginseng alleviates DSS-induced ulcerative colitis: An in silico analysis and in vivo investigation

Industrial Crops and Products, Год журнала: 2025, Номер 225, С. 120458 - 120458

Опубликована: Янв. 8, 2025

Язык: Английский

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Macrophage-based nanotherapeutic strategies in ulcerative colitis

Journal of Controlled Release, Год журнала: 2020, Номер 320, С. 363 - 380

Опубликована: Янв. 27, 2020

Язык: Английский

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Regulatory Mechanisms of the NLRP3 Inflammasome, a Novel Immune-Inflammatory Marker in Cardiovascular Diseases

Frontiers in Immunology, Год журнала: 2019, Номер 10

Опубликована: Июль 10, 2019

The nod-like receptor family pyrin domain containing 3 (NLRP3) is currently the most widely studied inflammasome and has become a hot topic of recent research. As macromolecular complex, NLRP3 activated to produce downstream factors, including caspase-1, IL-1β, IL-18, which then promote local inflammatory responses induce pyroptosis, leading unfavorable effects. A growing number studies have examined relationship between cardiovascular diseases (CVDs). However, some shown that not involved in occurrence certain diseases. Therefore, identifying mechanism action its potential involvement pathological process disease progression utmost importance. This review discusses mechanisms activation CVDs, coronary atherosclerosis, myocardial ischemia/reperfusion, cardiomyopathies arrhythmia, as well CVD-related treatments.

Язык: Английский

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Saponins regulate intestinal inflammation in colon cancer and IBD

Pharmacological Research, Год журнала: 2019, Номер 144, С. 66 - 72

Опубликована: Апрель 5, 2019

Язык: Английский

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Mst1 inhibition attenuates non-alcoholic fatty liver disease via reversing Parkin-related mitophagy

Redox Biology, Год журнала: 2019, Номер 21, С. 101120 - 101120

Опубликована: Янв. 27, 2019

Obesity-related non-alcoholic fatty liver disease (NAFLD) is connected with mitochondrial stress and hepatocyte apoptosis. Parkin-related mitophagy sustains homeostasis viability. However, the contribution regulatory mechanisms of in NAFLD are incompletely understood. Macrophage stimulating 1 (Mst1) a novel upstream regulator which excerbates heart cancer apoptosisn via repressing activity. The aim our study to explore whether Mst1 contributes disrupting mitophagy. A model was generated wild-type (WT) mice knockout (Mst1-KO) using high-fat diet (HFD). Cell experiments were conducted palmitic acid (PA) treatment primary hepatocytes. results demonstrated that significantly upregulated HFD-treated livers. Genetic ablation attenuated HFD-mediated hepatic injury sustained Functional studies illustrated knockdown reversed latter protected mitochondria hepatocytes against HFD challenge. Besides, we further figured out modulated Parkin expression AMPK pathway; blockade repressed recalled Altogether, data identified closely associated defective due upregulation. This finding may pave road new therapeutic modalities for disease.

Язык: Английский

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URB597 protects against NLRP3 inflammasome activation by inhibiting autophagy dysfunction in a rat model of chronic cerebral hypoperfusion

Journal of Neuroinflammation, Год журнала: 2019, Номер 16(1)

Опубликована: Дек. 1, 2019

Previous studies reported that URB597 (URB) had therapeutic potential for treating chronic cerebral hypoperfusion (CCH)-induced neuroinflammation and autophagy dysfunction. However, the interaction mechanisms underlying CCH-induced abnormal excessive remain unknown. In this study, we investigated roles of impaired in nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing (NLRP) 3 inflammasome activation rat hippocampus under condition induced CCH as well effect URB treatment.The model was established by bilateral common carotid artery occlusion (BCCAo), rats were randomly divided into 11 groups follows: (1) sham-operated, (2) BCCAo; (3) BCCAo+autophagy inhibitor 3-methyladenine (3-MA), (4) BCCAo+lysosome chloroquine (CQ), (5) BCCAo+microglial minocycline, (6) BCCAo+ROS scavenger N-acetylcysteine (NAC), (7) BCCAo+URB, (8) BCCAo+URB+3-MA, (9) BCCAo+URB+CQ, (10) BCCAo+URB+minocycline, (11) BCCAo+URB+NAC. The cell localizations LC3, p62, LAMP1, TOM20 NLRP3 assessed immunofluorescence staining. levels autophagy-related proteins (LC3, BNIP3 parkin), inflammasome-related (NLRP3, CASP1 IL-1β), microglial marker (OX-42) proinflammatory cytokines (iNOS COX-2) evaluated western blotting, (IL-1β TNF-a) determined ELISA. Reactive oxygen species (ROS) dihydroethidium mitochondrial ultrastructural changes examined electron microscopy.CCH overactivation ROS accumulation, promoting release IL-1β. Blocked mitophagy flux enhanced NLRP3-CASP1 pathway. alleviated decreasing restoring lysosomal function, which would further inhibit pathway.These findings extended previous indicating function mitigation ischemic injury brain.

Язык: Английский

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Targeting NLRP3 Inflammasome in Inflammatory Bowel Disease: Putting out the Fire of Inflammation

Inflammation, Год журнала: 2019, Номер 42(4), С. 1147 - 1159

Опубликована: Апрель 1, 2019

Язык: Английский

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Natural Anti-Inflammatory Compounds as Drug Candidates for Inflammatory Bowel Disease

Frontiers in Pharmacology, Год журнала: 2021, Номер 12

Опубликована: Июль 14, 2021

Inflammatory bowel disease (IBD) represents chronic recurrent intestinal inflammation resulting from various factors. Crohn’s (CD) and ulcerative colitis (UC) have been identified as the two major types of IBD. Currently, most drugs for IBD used commonly in clinic adverse reactions, only a few present long-lasting treatment effects. Moreover, issues drug resistance recurrence are frequent difficult to resolve. Together, these cause difficulties treating patients with Therefore, development novel therapeutic agents prevention is significance. In this context, research on natural compounds exhibiting anti-inflammatory activity could be approach developing effective strategies Phytochemicals such astragalus polysaccharide (APS), quercetin, limonin, ginsenoside Rd, luteolin, kaempferol, icariin reported treatment. brief, activities considered important candidate The review discusses potential certain their synthetic derivatives

Язык: Английский

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