Hepatocyte‐Derived FGF1 Alleviates Isoniazid and Rifampicin‐Induced Liver Injury by Regulating HNF4α‐Mediated Bile Acids Synthesis DOI Creative Commons

Qian Lin,

Jiaren Zhang, Jie Qi

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Isoniazid and rifampicin co-therapy are the main causes of anti-tuberculosis drug-induced liver injury (ATB-DILI) acute failure, seriously threatening human health. However, its pathophysiology is not fully elucidated. Growing evidences have shown that fibroblast growth factors (FGFs) play a critical role in diverse aspects pathophysiology. The aim this study to investigate FGFs pathogenesis isoniazid (INH) (RIF)-induced injury. Through systematic screening, finds hepatic FGF1 expression significantly downregulated both mouse model patients challenged with INH RIF. Hepatocyte-specific Fgf1 deficiency exacerbates RIF-induced resulted from elevated bile acids (BAs) synthases aberrant BAs accumulation. Conversely, pharmacological administration non-mitogenic analog - FGF1ΔHBS alleviated via restoring homeostasis. Mechanically, repressed hepatocyte nuclear factor 4α (Hnf4α) transcription activating FGF receptor 4 (FGFR4)-ERK1/2 signaling pathway, thus reducing synthase. findings demonstrate functions as negative regulator biosynthesis protect against normalizing homeostasis, providing novel mechanistic insights into ATB-DILI potential therapeutic strategies for treatment ATB-DILI.

Language: Английский

Screening of bile salt hydrolase-producing lactic acid bacteria and evaluation of cholesterol-lowering activity in vitro DOI

Chenglong Lv,

Xinyi Pang, Jun Sun

et al.

Food Bioscience, Journal Year: 2024, Volume and Issue: 62, P. 105338 - 105338

Published: Nov. 7, 2024

Language: Английский

Citations

2
Yellow Teas Protect against DSS-Induced Ulcerative Colitis by Inhibiting TLR4/NF-κB/NLRP3 Inflammasome in Mice DOI Creative Commons
Dawei Xing, Tao Zheng, Xiaoju Chen

et al.

Foods, Journal Year: 2024, Volume and Issue: 13(17), P. 2843 - 2843

Published: Sept. 7, 2024

Yellow tea (YT), a slightly fermented with unique yellowing process and mellow taste, is becoming widely popular. Currently, the YT includes bud yellow (BYT), small-leaf (SYT), large-leaf (LYT) based on maturity of raw materials. Previous studies have shown that has outstanding potential in preventing metabolic syndrome. However, distinct effects mechanisms different types ulcerative colitis (UC) are still unclear. This study investigated continuous or intermittent intervention three water extracts (YTEs) dextran sulfate sodium (DSS)-induced CD-1 mice. The results showed YTE significantly improves syndrome DSS-induced UC Mechanistic reveal YTEs increase expression levels tight junction (TJ) proteins reduce pro-inflammatory cytokines colon by inactivating TLR4/NF-κB/NLRP3. treatment protected intestinal barrier integrity reduced serum lipopolysaccharide (LPS) levels. Interestingly, our indicate better alleviating effect than BYT SYT. before DSS administration certain degree preventive colitis, while after induction significant reversing damage caused DSS. Our indicated drinking may therapeutic UC, especially LYT.

Language: Английский

Citations

1
Bile Acids in Inflammatory Bowel Disease: From Pathophysiology to Treatment DOI Creative Commons
Samantha Hsieh,

Arun Chandnani,

Siyan Cao

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2910 - 2910

Published: Dec. 20, 2024

Inflammatory bowel disease (IBD) is a chronic condition that affects about 7 million people worldwide, and new therapies are needed. Understanding the complex roles bile acids (BAs) play in IBD may lead to development of novel treatments independent direct immunosuppression. This review discusses latest discoveries BAs pathogenesis explores how these offer promising therapeutic targets treat improve patient outcomes. Several discussed include specific BA receptor (BAR) agonists, dietary therapies, supplements, probiotics, mesenchymal stem cell have all been shown decrease activity.

Language: Английский

Citations

1
Ca2+-Dependent Processes of Innate Immunity in IBD DOI Creative Commons
Francesco Palestra,

Gina Memoli,

Annagioia Ventrici

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(13), P. 1079 - 1079

Published: June 21, 2024

IBD is an uncontrolled inflammatory condition of the gastrointestinal tract, which mainly manifests in two forms: ulcerative colitis (UC) and Crohn's disease (CD). The pathogenesis appears to be associated with abnormal response innate adaptive immune cells. Innate immunity cells, such as macrophages, mast granulocytes, can produce proinflammatory (e.g., TNF-α) oxidative stress (ROS) mediators promoting intestinal damage, their responses induce imbalance immunity, leading production cytokines that increase abate barrier functions, aggravate inflammation. Considering Ca

Language: Английский

Citations

0
Intranasal Immunization of Pneumococcal pep27 Mutant Attenuates Allergic and Inflammatory Diseases by Upregulating Skin and Mucosal Tregs DOI Creative Commons
Hamid Iqbal, Dong‐Kwon Rhee

Vaccines, Journal Year: 2024, Volume and Issue: 12(7), P. 737 - 737

Published: July 3, 2024

Conventional immunization methods such as intramuscular injections lack effective mucosal protection against pathogens that enter through the surfaces. Moreover, conventional therapy often leads to adverse events and compromised immunity, followed by complicated outcomes, leading need switch other options. Thus, a develop safe treatment with long-term beneficial outcomes reduce risk of relapse is mandatory. Mucosal vaccines administered across surfaces, respiratory or intestinal mucosa, prompt robust localized systemic immune responses prevent public from acquiring pathogenic diseases. immunity contains unique cell milieu selectively identify limits transmission progression diseases, allergic dermatitis inflammatory bowel disease (IBD). It also offers infection at site entry, enables clearance on induction ability shape regulatory responses. Regulatory T (Treg) cells have been promising strategy suppress To find advances in treatment, we investigated therapeutic effects intranasal pep27 mutant immunization. Nasal protects but nasal antigen presentation appears entail for an adjuvant stimulate immunogenicity. Here, novel method developed induce Tregs via without potentially overcome diseases gut lung inflammation using lung–gut axis communication animal models. The implementation these therapies should be preceded studies Treg resilience clinical translational dietary changes.

Language: Английский

Citations

0
Balance between bile acid conjugation and hydrolysis activity can alter outcomes of gut inflammation DOI
Robert A. Quinn, Yousi Fu, Douglas V. Guzior

et al.

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Abstract Conjugated bile acids (BAs) are multi-functional detergents produced in the gastrointestinal (GI) tract by liver enzyme acid:amino acid N-acyltransferase (BAAT) and microbiome from acyltransferase activity of ubiquitous salt hydrolase (BSH). Humans with inflammatory bowel disease (IBD) have an enrichment both host microbially conjugated BAs (MCBAs), but their impacts on GI inflammation not well understood. We investigated role host-conjugated dextran sodium sulfate (DSS) model colitis using a BAAT knockout background. Baat-/- KO mice severe phenotypes DSS that were rescued supplementation taurocholate (TCA). Gene expression histological analysis showed this rescue was likely due to improved epithelial barrier goblet cell function. TCA also increased diversity, particularly BA metabolizing Lachnospiraceae. Metabolomics all known forms including microbial sources, hydrolysis metabolism secondary BAs. The ability improve pathology under despite its ready led us investigate BSH diverse gut bacteria panel in vitro vivo. Exposure 17 bacterial isolates 10 amino broad hydrolytic capacity depending bacterium. Host-produced MCBAs SerCA AlaCA readily hydrolyzed, whereas GluCA, AspCA ThrCA more resistant. This variability translated vivo where fed recalcitrant GluCA had less production compared TCA. complexity dysbiosis inflamed murine exploration BSHs genes metagenomic data human IBD patients. Certain bsh sequences enriched diseased states Ruminococcus gnavus Enterocloster clostridioformis people Crohn’s disease. Collectively, study shows may provide benefits those IBD, is dictated delicate balance between conjugation/deconjugation based present.

Language: Английский

Citations

0
Hepatocyte‐Derived FGF1 Alleviates Isoniazid and Rifampicin‐Induced Liver Injury by Regulating HNF4α‐Mediated Bile Acids Synthesis DOI Creative Commons

Qian Lin,

Jiaren Zhang, Jie Qi

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 27, 2024

Isoniazid and rifampicin co-therapy are the main causes of anti-tuberculosis drug-induced liver injury (ATB-DILI) acute failure, seriously threatening human health. However, its pathophysiology is not fully elucidated. Growing evidences have shown that fibroblast growth factors (FGFs) play a critical role in diverse aspects pathophysiology. The aim this study to investigate FGFs pathogenesis isoniazid (INH) (RIF)-induced injury. Through systematic screening, finds hepatic FGF1 expression significantly downregulated both mouse model patients challenged with INH RIF. Hepatocyte-specific Fgf1 deficiency exacerbates RIF-induced resulted from elevated bile acids (BAs) synthases aberrant BAs accumulation. Conversely, pharmacological administration non-mitogenic analog - FGF1ΔHBS alleviated via restoring homeostasis. Mechanically, repressed hepatocyte nuclear factor 4α (Hnf4α) transcription activating FGF receptor 4 (FGFR4)-ERK1/2 signaling pathway, thus reducing synthase. findings demonstrate functions as negative regulator biosynthesis protect against normalizing homeostasis, providing novel mechanistic insights into ATB-DILI potential therapeutic strategies for treatment ATB-DILI.

Language: Английский

Citations

0