Intestinal melatonin levels and gut microbiota homeostasis are independent of the pineal gland in pigs.

Introduction: Melatonin (MEL) is a crucial neuroendocrine hormone primarily produced by the pineal gland. Pinealectomy (PINX) has been performed on an endogenous MEL deficiency model to investigate the functions of pineal MEL and its relationship with various diseases. However, the effect of PINX on the gastrointestinal tract (GIT) MEL levels and gut microbiome in pigs has not been previously reported. Methods: By using a newly established pig PINX model, we detected the levels of MEL in the GIT by liquid chromatography-tandem mass spectrometry. In addition, we examined the effects of PINX on the expression of MEL synthesis enzymes, intestinal histomorphology, and the intestinal barrier. Furthermore, 16S rRNA sequencing was performed to analyze the colonic microbiome. Results: PINX reduced serum MEL levels but did not affect GIT MEL levels. Conversely, MEL supplementation increased MEL levels in the GIT and intestinal contents. Neither PINX nor MEL supplementation had any effect on weight gain, organ coefficient, serum biochemical indexes, or MEL synthetase arylalkylamine N-acetyltransferase (AANAT) expression in the duodenum, ileum, and colon. Furthermore, no significant differences were observed in the intestinal morphology or intestinal mucosal barrier function due to the treatments. Additionally, 16S rRNA sequencing revealed that PINX had no significant impact on the composition of the intestinal microbiota. Nevertheless, MEL supplementation decreased the abundance of Fibrobacterota and increased the abundance of Actinobacteriota, Desulfobacterota, and Chloroflexi. Conclusion: We demonstrated that synthesis of MEL in the GIT is independent of the pineal gland. PINX had no influence on intestinal MEL level and microbiota composition in pigs, while exogenous MEL alters the structure of the gut microbiota.

CCl4 inhibits the expressions of hepatic taurine biosynthetic enzymes and taurine synthesis in the progression of mouse liver fibrosis.

Carbon tetrachloride (CCl4) is a widely used hepatotoxin for the studies of liver fibrosis and cirrhosis, and taurine has function to abate liver fibrosis induced by CCl4. But the interacting mechanisms between taurine and CCl4 in liver are still largely unknown. These made us to hypothesize that CCl4 may induce liver fibrosis by affecting the expressions of taurine biosynthetic enzymes and taurine synthesis. We thus assayed the expressions of hepatic cysteine dioxygenase (CDO), cysteine sulfonate acid decarboxylase (CSAD) and taurine transporter (TauT) in the progression of mouse liver fibrosis induced by CCl4. The results demonstrated that CCl4 treatment markedly decreased hepatic CSAD, CDO expressions, and taurine levels in hepatic tissue, although TauT expression did not exhibit significant decline. It was contrasting that hepatic α-SMA, serum AST, ALT, ALP kept increasing, which were accompanied by the pathological characters of liver, whereas taurine supplement attenuated the progression of liver fibrosis induced by CCl4. These results demonstrate that CCl4 may induce liver fibrosis by inhibiting hepatic CSAD and CDO expressions and taurine synthesis, which are crucial for our understanding the mechanisms of liver fibrosis induced by CCl4, and also potential for establishing therapeutic strategies of liver fibrosis and related diseases.

Efficacy and safety of Xijiao Dihuang decoction in treating Henoch-Schönlein purpura: Study protocol for systematic review.

BACKGROUND: Henoch-Schönlein purpura is one of the most common systemic vascular inflflammatory disease in childhood with purpuric rash, arthritis, renal involvement, and abdominal pain. As a treatment for it, Xijiao Dihuang decoction, a traditional herbal formula, has been used. The object of this systematic review and meta-analysis is to assess the effificacy and safety on Xijiao Dihuang decoction in treating allergic purpura. METHODS: The following electronic databases will be systematically searched up to November 7, 2019 for eligible studies: The Cochrane Library, Embase, PubMed, Web of Science, the Chinese National Knowledge Infrastructure (CNKI), the Chinese Biomedical LiteratureDatabase (CBM), the Chinese Scientifific Journal Database (VIP), andtheWanfang Database. Thetreatment group in the included studies will receive both routine western medicines and Xijiao Dihuang decoction, while the control group will receive routine western medicines. Data extraction and risk of bias assessments will be conducted by 2 independent reviewers. Heterogeneity will be assessed by I2 statistics, while reporting bias will be evaluated by funnel plots and Begg and Egger test. Sensitivity analysis and Subgroup analysis will be performed when necessary. Review Manager software (RevManV.5.3.0) and Stata will be used for all statistical analyses. Ethics approval is not required as no privacy data were involved. This systematic review and meta analysis will be published in a peer-reviewed journal. RESULTS: This study could provide a systematically evaluated therapeutic efficacy and safety of XJDHD on patients with HSP via including RCTs that matches the needs. And we also expect to find predictors of treatment through subgroup analysis, helping patients with HSP detect as well as cope with the disease as early as possible. CONCLUSION: The conclusion of our study will provide the systematical review of the efficacy and safety of XJDHD on patients with HSP, and provide predictors of treatment. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42018111293.