Tingli Dazao Xiefei Decoction ameliorates asthma in vivo and in vitro from lung to intestine by modifying NO–CO metabolic disorder mediated inflammation, immune imbalance, cellular barrier damage, oxidative stress and intestinal bacterial disorders

Journal of Ethnopharmacology, Journal Year: 2023, Volume and Issue: 313, P. 116503 - 116503

Published: April 26, 2023

Language: Английский

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Babao Dan alleviates gut immune and microbiota disorders while impacting the TLR4/MyD88/NF-кB pathway to attenuate 5-Fluorouracil-induced intestinal injury

Biomedicine & Pharmacotherapy, Journal Year: 2023, Volume and Issue: 166, P. 115387 - 115387

Published: Aug. 27, 2023

Adjuvant chemotherapy based on 5-fluorouracil (5-FU), such as FOLFOX, is suggested a treatment for gastrointestinal cancer. Yet, intestinal damage continues to be prevalent side effect which there are no practical prevention measures. We investigated whether Babao Dan (BBD), Traditional Chinese Medicine, protects against induced by 5-FU controlling immune response and gut microbiota. was injected intraperitoneally establish the mice model, then 250 mg/kg BBD gavaged five days straight. led marked weight loss, diarrhea, fecal blood, histopathologic damage. Administration of reduced these symptoms, inhibited proinflammatory cytokine (IL-6, IL-1β, IFN-γ, TNF-α) secretion, upregulated ratio CD3(+) T cells CD4(+)/CD8(+) ratio. According 16S rRNA sequencing, dramatically repaired disruption microbiota caused in time-dependent way, increased Firmicutes/Bacteroidetes (F/B) Transcriptomic results showed that mechanism mainly concentrated NF-κB pathway, we found concentration LPS suspension serum, TLR4/MyD88/NF-κB pathway activation. Furthermore, at genus level fifth day, abundance unidentified_Corynebacteriaceae, Aerococcus, Blautia, Jeotgalicoccus, Odoribacter, Roseburia, Rikenella, Intestinimonas, unidentified_Lachnospiraceae, Enterorhabdus, Ruminiclostridium, downregulated Bacteroides, Parabacteroides, Parasutterella, Erysipelatoclostridium, were highly correlated with injury or pathway. In conclusion, established network involving 5-FU, BBD, response, microbiota, key pathways explain pharmacology oral preventing 5-FU-induced injury.

Language: Английский

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The Molecular Pharmacology of Phloretin: Anti-Inflammatory Mechanisms of Action

Biomedicines, Journal Year: 2023, Volume and Issue: 11(1), P. 143 - 143

Published: Jan. 6, 2023

The isolation of phlorizin from the bark an apple tree in 1835 led to a flurry research on its inhibitory effect glucose transporters intestine and kidney. Using as prototype drug, antidiabetic agents with more selective activity towards transport at kidney have subsequently been developed. In contrast, hydrolysis product body, phloretin, which is also found plant, has weak properties. Phloretin, however, displays range pharmacological effects including antibacterial, anticancer, cellular organ protective properties both vitro vivo. this communication, molecular basis anti-inflammatory mechanisms that attribute scrutinised. These include inhibiting signalling pathways inflammatory mediators' expression support suppressive immune cells overactivation, obesity-induced inflammation, arthritis, endothelial, myocardial, hepatic, renal lung injury, inflammation gut, skin, nervous system, among others.

Language: Английский

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Identification of Key Biomarkers Associated with Immunogenic Cell Death and Their Regulatory Mechanisms in Severe Acute Pancreatitis Based on WGCNA and Machine Learning

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(3), P. 3033 - 3033

Published: Feb. 3, 2023

Immunogenic cell death (ICD) is a form of programmed with strong sense inflammatory detection, whose powerful situational awareness can cause the reactivation aberrant immunity. However, role ICD in pathogenesis severe acute pancreatitis (SAP) has yet to be investigated. This study aims explore pivotal genes associated SAP and how they relate immune infiltration short-chain fatty acids (SCFAs), order provide theoretical foundation for further, in-depth mechanistic studies. We downloaded GSE194331 datasets from Gene Expression Omnibus (GEO). The use differentially expressed gene (DEG) analysis; weighted co-expression network analysis (WGCNA) least absolute shrinkage selection operator (LASSO) regression allowed us identify total three ICD-related hub (LY96, BCL2, IFNGR1) SAP. Furthermore, single sample set enrichment (ssGSEA) demonstrated that are closely specific cells, activation pathways metabolism SCFAs (especially butyrate). These findings were validated through expression patterns both clinical patients rat animal models In conclusion, first concept was proposed our study. important implications future investigations into pro-inflammatory mechanisms mediated by damage-associated molecular (DAMPs) late stages

Language: Английский

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Akkermansia muciniphila attenuated lipopolysaccharide-induced acute lung injury by modulating the gut microbiota and SCFAs in mice

Food & Function, Journal Year: 2023, Volume and Issue: 14(23), P. 10401 - 10417

Published: Jan. 1, 2023

Gut microbiota are closely related to lipopolysaccharide (LPS)-induced acute lung injury (ALI). Akkermansia muciniphila (A. muciniphila) maintains the intestinal barrier function and regulates balance of reduced glutathione/oxidized glutathione. However, it may be useful as a treatment strategy for LPS-induced injury. Our study aimed explore whether A. could improve by affecting gut microbiota. The administration effectively attenuated tissue damage significantly decreased oxidative stress inflammatory reaction induced LPS, with lower levels myeloperoxidase (MDA), enhanced superoxide dismutase (SOD) activity, pro-inflammatory cytokine levels, macrophage neutrophil infiltration. Moreover, maintained function, reshaped disordered microbial community, promoted secretion short-chain fatty acids (SCFAs). downregulated expression TLR2, MyD88 NF-kappa B (P < 0.05). Butyrate supplementation demonstrated significant improvement in response 0.05) mitigation histopathological mice ALI, thereby restoring butyric acid concentration. In conclusion, our findings indicate that inhibits accumulation cytokines attenuates activation TLR2/Myd88/NF-κB pathway due exerting anti-inflammatory effects through butyrate. This provides an experimental foundation potential application butyrate prevention ALI.

Language: Английский

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Mechanisms of Qingyi Decoction in Severe Acute Pancreatitis-Associated Acute Lung Injury via Gut Microbiota: Targeting the Short-Chain Fatty Acids-Mediated AMPK/NF-κB/NLRP3 Pathway

Microbiology Spectrum, Journal Year: 2023, Volume and Issue: 11(4)

Published: June 20, 2023

The pivotal roles of gut microbiota in severe acute pancreatitis-associated lung injury (SAP-ALI) are increasingly revealed, and recent discoveries the gut-lung axis have provided potential approaches for treating SAP-ALI. Qingyi decoction (QYD), a traditional Chinese medicine (TCM), is commonly used clinical to treat However, underlying mechanisms remain be fully elucidated. Herein, by using caerulein plus lipopolysaccharide (LPS)-induced SAP-ALI mice model antibiotics (Abx) cocktail-induced pseudogermfree model, we tried uncover administration QYD explored its possible mechanisms. Immunohistochemical results showed that severity intestinal barrier functions could affected relative depletion bacteria. composition was partially recovered after treatment with decreased Firmicutes/Bacteroidetes ratio increased abundance short-chain fatty acids (SCFAs)-producing Correspondingly levels SCFAs (especially propionate butyrate) feces, gut, serum, lungs were observed, generally consistent changes microbes. Western-blot analysis RT-qPCR indicated AMPK/NF-κB/NLRP3 signaling pathway activated oral QYD, which found possibly related regulatory effects on intestine lungs. In conclusion, our study provides new insights into through modulating has prospective practical value use future. IMPORTANCE Gut affects function. During SAP, significant increase pathogens (Escherichia, Enterococcus, Enterobacter, Peptostreptococcus, Helicobacter) observed. At same time, pathogenic bacteria SCFAs-producing (Bacteroides, Roseburia, Parabacteroides, Prevotella, Akkermansia). addition, mediated along may play an essential role preventing pathogenesis SAP-ALI, allows reduced systemic inflammation restoration barrier.

Language: Английский

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Mitochondrial (mt)DNA–cyclic GMP–AMP synthase (cGAS)–stimulator of interferon genes (STING) signaling promotes pyroptosis of macrophages via interferon regulatory factor (IRF)7/IRF3 activation to aggravate lung injury during severe acute pancreatitis

Cellular & Molecular Biology Letters, Journal Year: 2024, Volume and Issue: 29(1)

Published: April 27, 2024

Abstract Background Macrophage proinflammatory activation contributes to the pathology of severe acute pancreatitis (SAP) and, simultaneously, macrophage functional changes, and increased pyroptosis/necrosis can further exacerbate cellular immune suppression during process SAP, where cyclic GMP–AMP synthase (cGAS)–stimulator interferon genes (STING) plays an important role. However, function mechanism cGAS–STING in SAP-induced lung injury (LI) remains unknown. Methods Lipopolysaccharide (LPS) was combined with caerulein-induced SAP wild type, cGAS −/− sting mice . Primary macrophages were extracted via bronchoalveolar lavage peritoneal lavage. Ana-1 cells pretreated LPS stimulated nigericin sodium salt induce pyroptosis vitro. Results triggered NOD-, LRR-, pyrin domain-containing protein 3 (NLRP3) inflammasome activation-mediated alveolar mouse model. Knockout / STING could ameliorate NLRP3 pyroptosis. In addition, mitochondrial (mt)DNA released from damaged mitochondria induced a cGAS- dose-dependent manner. Upregulated signal promote inflammasome-mediated increase serum interleukin (IL)-6, IL-1β, tumor necrosis factor (TNF)-α levels thus, SAP-associated LI (SAP-ALI). Downstream molecules STING, IRF7, IRF3 connect mtDNA–cGAS–STING axis NLRP3–pyroptosis axis. Conclusions Negative regulation any molecule mtDNA–cGAS–STING–IRF7/IRF3 pathway affect inflammasomes, thereby reducing improving SAP-ALI

Language: Английский

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Gut microbial metabolites in lung cancer development and immunotherapy: Novel insights into gut-lung axis

Cancer Letters, Journal Year: 2024, Volume and Issue: 598, P. 217096 - 217096

Published: July 4, 2024

Language: Английский

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Exploring immune-related pathogenesis in lung injury: Providing new insights Into ALI/ARDS

Biomedicine & Pharmacotherapy, Journal Year: 2024, Volume and Issue: 175, P. 116773 - 116773

Published: May 21, 2024

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) represent a significant global burden of morbidity mortality, with being the primary cause death in affected patients. The pathogenesis injury, however, remains complex issue. In recent years, role immune system has attracted extensive attention worldwide. Despite advancements our understanding various subtypes, limitations persist both prevention treatment. This review investigates immunopathogenesis ALI/ARDS, aiming to elucidate pathological processes mediated by dendritic cells (DCs), natural killer (NK) cells, phagocytes, neutrophils. Furthermore, article expounds on critical contributions gut microbiota, inflammatory pathways, cytokine storms development ALI/ARDS.

Language: Английский

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Short-Chain Fatty Acids: Promising Therapeutic Targets for Respiratory Syncytial Virus Infection

Clinical Reviews in Allergy & Immunology, Journal Year: 2025, Volume and Issue: 68(1)

Published: Jan. 28, 2025

Language: Английский

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