Effects of iguratimod on inflammatory factors and apoptosis of submandibular gland epithelial cells in NOD mice.

Non-obese diabetic (NOD) mice were taken as primary Sjögren's syndrome (pSS) model mice to examine the therapeutic impact of iguratimod (IGU) on inflammatory factors levels and apoptosis of submandibular epithelial cells, and provide experimental basis for the treatment of pSS by iguratimod. Twenty-four NOD murine models were divided into the model, high-dose (IGU 30 mg/kg) and low-dose (IGU 10 mg/kg) groups, eight mice per group. The normal control group comprised eight C57B/L mice. From 8 weeks of age, the NOD mice were administered IGU by intragastric gavage administration every day for 8 weeks; their water consumption, saliva secretion, submandibular gland, and spleen indices were measured. The levels of serum inflammatory factor (IL-1ß, TNF-α, IL-6, and IL-17) were evaluated, and Bax, caspase-3, and Bcl-2 levels were detected. The histological alterations in the submandibular glands were discovered. IGU can reduce the water intake of NOD mice (p < 0.01), increase the saliva secretion and the submandibular gland index (p < 0.01); reduce the spleen index and the serum inflammatory factors (p < 0.01); improve the pathological tissue damage and cell apoptosis of the submandibular gland (p < 0.05). IGU can reduce the expression levels of inflammatory mediators in the serum and the extent of lymphocyte infiltration and apoptosis in submandibular gland epithelial cells. It can also regulate apoptosis-related protein expression, thereby improving the secretory function of exocrine glands.

Exploring the mechanisms of action of Zengye decoction (ZYD) against Sjogren's syndrome (SS) using network pharmacology and animal experiment.

CONTEXT: Zengye decoction (ZYD) has been considered to have a curative effect on Sjogren's syndrome (SS). However, its therapeutic mechanisms remain obscure. OBJECTIVES: This research explores the mechanisms of ZYD against SS. MATERIALS AND METHODS: The active compounds and targets of ZYD were searched in the TCMSP and BATMAN-TCM databases. SS-related targets were obtained from the GeneCards database. The GO and KEGG enrichment analyses elucidated the molecular mechanisms. Animal experiments were performed using 8 C57BL/6 mice that served as the control group (physiological saline treatment) and 16 NOD mice randomly divided into the model group (physiological saline treatment) and the ZYD group (ZYD treatment) for 8 weeks to verify the therapeutic effects of ZYD on SS. RESULTS: Twenty-nine active compounds with 313 targets of ZYD and 1038 SS-related targets were screened. Thirty-two common targets were identified. ß-Sitosterol and stigmasterol might be important components. GO analysis suggested that the action of ZYD against SS mainly involved oxidative stress, apoptotic processes, and tumor necrosis factor receptor superfamily binding, etc. KEGG analysis indicated the most significant signaling pathway was apoptosis-multiple species. Animal experiments showed that ZYD improved lymphocytic infiltration of the submandibular glands (SMGs), reduced the serum levels of TNF-α, IL-1ß, IL-6, and IL-17, upregulated the expression of Bcl-2, and downregulated the expression of Bax and Caspase-3 in the model mice. DISCUSSION AND CONCLUSION: ZYD has anti-inflammatory and anti-apoptotic effects on SS, which provides a theoretical basis for the treatment of SS with ZYD.

Disease-Associated Gut Microbiota Reduces the Profile of Secondary Bile Acids in Pediatric Nonalcoholic Fatty Liver Disease.

Children with nonalcoholic fatty liver disease (NAFLD) display an altered gut microbiota compared with healthy children. However, little is known about the fecal bile acid profiles and their association with gut microbiota dysbiosis in pediatric NAFLD. A total of 68 children were enrolled in this study, including 32 NAFLD patients and 36 healthy children. Fecal samples were collected and analyzed by metagenomic sequencing to determine the changes in the gut microbiota of children with NAFLD, and an ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) system was used to quantify the concentrations of primary and secondary bile acids. The associations between the gut microbiota and concentrations of primary and secondary bile acids in the fecal samples were then analyzed. We found that children with NAFLD exhibited reduced levels of secondary bile acids and alterations in bile acid biotransforming-related bacteria in the feces. Notably, the decrease in Eubacterium and Ruminococcaceae bacteria, which express bile salt hydrolase and 7α-dehydroxylase, was significantly positively correlated with the level of fecal lithocholic acid (LCA). However, the level of fecal LCA was negatively associated with the abundance of the potential pathogen Escherichia coli that was enriched in children with NAFLD. Pediatric NAFLD is characterized by an altered profile of gut microbiota and fecal bile acids. This study demonstrates that the disease-associated gut microbiota is linked with decreased concentrations of secondary bile acids in the feces. The disease-associated gut microbiota likely inhibits the conversion of primary to secondary bile acids.

Uptrend prevalence of varicella parallel with low serum antibodies and low second-dose rate among children 10-14 years old in Wenzhou, China.

In recent years, the incidence of varicella cases is rising, and outbreaks of varicella are frequently being reported worldwide. Our study aims to analyze the association between the varicella incidence and serum antibody level in the post-vaccine era. We retrieved and analyzed the incidence and prevalence data for children age 1-14 years in Wenzhou, China during 2010-2018. A cross-sectional seroepidemiology analysis was carried out in a series of 168 general healthy children age 1-14 years as well as children at a varicella outbreak in Wenzhou. Our data showed a significant surge in the incidence and prevalence of varicella in children aged 10-14 years in 2017 and 2018 while they were kept relatively stable in 2010-2016. The seroepidemiological analysis revealed a 7.3-fold significantly higher level of serum varicella IgG in healthy control students who exposed at the outbreak than that in general healthy children (median 523.5 vs. 71.7 mIU/mL, p < .01). The children 10-14 years old had the lowest rate of second-dose vaccination among the three age classes (7%, 41%, and 65% in 10-14, 5-9, and 2-4 age class, respectively), and children 5-9 years old who received the second dose had a higher level of serum protective IgG than those who did not (254.7 vs 98 mIU/mL, p = .06). The findings from the present study warn a two-dose vaccine schedule to reduce the climbing incidence and prevalence observed in the older children and suggest a higher serum IgG threshold for effective protection of children from the varicella outbreak.

Mangiferin alleviates endoplasmic reticulum stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.

This study aimed to investigate the mechanism of mangiferin on regulating endoplasmic reticulum (ER) stress in acute liver injury. The mouse model of acute liver injury was established by injection of LPS/D-GalN. The primary mouse hepatocytes were stimulated with LPS to induce the in vitro model. The effect of miR-20a/101a on the luciferase activity of Nrf2 3'-UTR was assessed by luciferase reporter assay. Mangiferin improved the liver function, inhibited the oxidative stress and ER stress and down-regulated the expressions of miR-20a and miR-101a in LPS/D-GalN-induced mice and LPS-induced hepatocytes. The knockdown of miR-20a and miR-101a co-operatively alleviated ER stress of LPS-induced hepatocytes. miR-20a and miR-101a both targeted Nrf2 and the over-expression of miR-20a or miR-101a decreased Nrf2 protein level, while their silences increased Nrf2 protein level. The silence of miR-20a and miR-101a promoted Nrf2 expression and inhibited the ER stress in LPS-induced hepatocytes, while the knockdown of Nrf2 reversed these effects. The over-expression of miR-20a and miR-101a eliminated the effects of mangiferin on Nrf2 protein level and ER stress in LPS-induced hepatocytes and Nrf2 over-expression altered these trends. Our findings suggest that mangiferin alleviates ER stress in acute liver injury by regulating the miR-20a/miR-101a-Nrf2 axis.