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BackgroundDai-Huang-Fu-Zi-Tang (DHFZT) is a famous traditional Chinese prescription with intestinal obstruction, acute pancreatitis and cholecystalgia for thousands of years. Our previous work found that DHFZT could act against pulmonary and intestinal pathological injury in rats with severe acute pancreatitis (SAP). But the underlying mechanism has not been fully elucidated. The aim of present study was to investigate whether DHFZT could relieve pulmonary and intestinal injury by regulating aquaporins after SAP induced by sodium taurocholate in rats.MethodsForty of SD rats were used for dose dependant experiments of DHFZT.Accurate-mass Time-of-flight liquid chromatography-mass spectrometry was used for qualitative screening of chemical compositions of DHFZT. Twenty-four rats were randomly divided into 3 groups: sham group (n = 8), model group (SAP, n = 8), DHFZT group (SAP with DHFZT treatment, n = 8). SAP models were established by retrograde injections of 5% sodium taurocholate solutions into rat pancreaticobiliary ducts. Blood samples were taken at 0, 12, 24, 48 h post-operation for detecting serum amylase, lipase, endotoxin, TNF-α, IL-6 and IL-10. Protein expression and location of aquaporin (AQP)1, 5, 8 and 9 were assessed by immunohistochemistry, western blot and immunofluorescence respectively.ResultsThe study showed that 27 kinds of chemical composition were identified, including 10 kinds in positive ion mode and 17 kinds in negative ion mode. The results showed that AQP1, AQP5 of lung, and AQP1, AQP5, AQP8 of intestine in model group were significantly lower than that of sham group (P < 0.05), and which were obviously reversed by treatment with DHFZT. In addition, protein levels of pro-inflammatory cytokines such as TNF-α, IL-6 and endotoxin in peripheral blood were significantly suppressed by DHFZT, and that anti-inflammatory cytokine like IL-10 was just opposite. Finally, we also noted that DHFZT reduced serum levels of amylase, lipase and endotoxin, and also improved edema and pathological scores of lung and intestine after SAP.ConclusionsDHFZT ameliorated the pulmonary and intestinal edema and injury induced by SAP via the upregulation of different AQPs in lung and intestine, and suppressed TNF-α, IL-6 expression and enhanced IL-10 expression.

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The protective roles of lipoic acid (LA)/vitamin C (VC) and mesna on preventing cyclophosphamide (CYP)-induced haemorrhagic cystitis (HC) were investigated. Swiss mice were divided into five groups randomly. HC was induced by a single dose of CYP injection (150-mg kg(-1) bodyweight). Group I was injected with saline (four times in total) throughout as control group. Group II received CYP and three equal doses of saline. Group III received CYP and three doses of mesna, whereas Group IV (or Group V) received CYP, mesna + two doses of VC (or LA). All injections were performed intraperitoneally. After 24 h of cystitis induction, the bladders were collected for all the experiments. Histological characterization showed that CYP injection resulted in severe HC. Reactive oxygen species (ROS) and thiobarbituric acid reactive substances' levels were increased in CYP group. The activities of antioxidant enzymes, e.g. superoxide dismutase, catalase, glutathione S-transferase and glutathione peroxidase, were inhibited significantly in CYP groups, respectively. In addition, activation of c-jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in the mechanism of CYP-induced HC but not extracellular signal regulated kinases (ERK). Significant suppression of p38 phosphorylation on Group V suggests that LA and mesna may have synergistic beneficial effect. In Groups III-V, all the parameters of HC and oxidative stress were inhibited significantly. Taking together, we found that these results illustrated that ROS play an important role on CYP-induced HC and the administration of LA/VC with mesna may have therapeutic potential against CYP-induced bladder HC.

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Background: The Goto-Kakizaki (GK) rat, developed from repeated inbreeding of glucoseintolerant Wistar rats, has been widely used to explore the development of spontaneous type-2 diabetes mellitus (T2DM). However, the gastric microbiota of GK and Wistar rats are still unclear. This study aimed to understand the gastric microbiota characteristics of GK rats by comparing it with non-diabetic Wistar rats. Materials and Methods: Male Wistar rats and GK rats were housed in specific pathogenfree (SPF) environment for 12 weeks with free access to sterilized food and water. Body weight and random blood glucose (BG) levels were determined. At the end of the experiment, the gastric contents of the rats were collected for the identification of gastric microbiota using 16S rRNA gene sequencing. Results: The richness of gastric microbiota in GK rats was similar to that of Wistar rats (P > 0.05). The results of Shannon, Simpson, beta diversity indices, and ANOSIM analysis showed that alpha and beta diversity of gastric microbiota in GK rats were significantly lower than that of Wistar rats (P < 0.01). Firmicutes (96.0%), Proteobacteria (1.9%) and Cyanobacteria (0.8%) were the dominant gastric microbiota in GK rats accounting for 72.9%, 14.7% and 10.9%, respectively. Linear discriminant analysis effect size (LEfSe) revealed that phylum Firmicutes and four genera (Anaerovibrio, Collinsella, Prevotellaceae_UCG_001, and Lactobacillus) were significantly abundant in the stomachs of GK rats. In contrast, seven genera (unidentified_Chloroplast, Porphyromonas, Neisseria, Rubrobacter, Veillonella, Lachnospiraceae_UCG_005, and unidentified_Erysipelotrichaceae) were significantly abundant in the stomachs of Wistar rats. Blood glucose was positively correlated with Anaerobibrio and Lactobacillus, and negatively correlated with four genera (Porphyromonas, Rubrobacter, Lachnospiraceae_UCG_005, and unidentified_Erysipelotrichaceae). In addition, chemoheterotrophy and fermentation were the most important functions of gastric microbiota. Conclusion:The gastric microbiota of GK rats with spontaneous T2DM showed the typical characteristics of low diversity and significant enrichment of Firmicutes phylum and four genera (Anaerovibrio, Collinsella, Prevotellaceae_UCG_001, and Lactobacillus) compared with gastric microbiota of Wistar rats.

Objective Lupus nephritis (LN) is one of the serious complications of systemic lupus erythematosus. The aim of this study was to identify core genes and pathways involved in the pathogenesis of LN. Methods We screened differentially expressed genes (DEGs) in LN patients using mRNA expression profile data from the Gene Expression Omnibus. The functional and pathway enrichment analysis of DEGs was performed utilizing the Database for annotation, Visualization and Integrated Discovery. Target genes with differentially expressed miRNAs (DEMIs) were predicted using the miRTarBase database, and the intersection between these target genes and DEGs was selected to be studied further. Results In total, 107 common DEGs (CDEGs) were identified from the Tub_LN group and Glom_LN group, and 66 DEMIs were identified. Fifty-three hub genes and two significant modules were identified from the protein–protein interaction (PPI) network, and a miRNA–mRNA network was constructed. The CDEGs, module genes in the PPI network and genes intersecting with the CDEGs and target genes of DEMIs were all associated with the PI3K-Akt signalling pathway. Conclusion In summary, this study reveals some crucial genes and pathways potentially involving in the pathogenesis of LN. These findings provide a new insight for the research and treatment of LN.