[Effects of Huangqin Tang on NLRP3/Caspase-1 pathway in mice model of ulcerative colitis].

The aim of this study was to explore the effects of Huangqin Tang(HQT) on the NLRP3/Caspase-1 signaling pathway in mice with DSS-induced ulcerative colitis(UC). C57BL/6J mice were randomly divided into a blank group, a model group(DSS group), and low-, medium-and high-dose HQT groups(HQT-L, HQT-M, and HQT-H), and western medicine mesalazine group(western medicine group). The UC model was induced in mice. Subsequently, the mice in the HQT-L, HQT-M, HQT-H groups, and the western medicine group were given low-, medium-, high-dose HQT, and mesalazine suspension by gavage, respectively, while those in the blank and DSS groups were given an equal volume of distilled water by gavage. After 10 days of administration, the body weight, DAI scores, and colonic histopathological score of mice in each group were determined. The levels of IL-6, IL-10, IL-1ß, and TNF-α in serum were determined by ELISA. The mRNA expression of NLRP3 and Caspase-1 in colon tissues was determined by RT-qPCR. The protein expression of NLRP3 and Caspase-1 in colon tissues was detected by immunohistochemistry. The results showed that compared with the blank group, the DSS group showed decreased body weight of mice and increased DAI scores and intestinal histopathological score. Compared with the DSS group, the HQT groups and the western medicine group showed improved DAI scores, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). The intestinal histopathological scores of the HQT groups and the western medicine group significantly decreased, especially in the HQT-M, HQT-H, and the western medicine groups(P<0.05). In addition, compared with the blank group, the DSS group showed elevated expression of NLRP3 and Caspase-1 in colon tissues, increased serum levels of IL-6, IL-1ß, and TNF-α, and decreased IL-10 level. Compared with the DSS group, the HQT groups and the western medicine group displayed decreased expression of NLRP3 and Caspase-1 in colon tissues, reduced serum levels of IL-6, IL-1ß, and TNF-α, and increased IL-10 level. The improvement was the most significant in the HQT-H group and the western medicine group(P<0.01). In conclusion, HQT may reduce the expression of NLRP3 and Caspase-1 in colon tissues, reduce the se-rum levels of IL-6, IL-1ß, and TNF-α, and increase the expression of IL-10 by regulating the classic pyroptosis pathway of NLRP3/Caspase-1, thereby improving the symptoms of intestinal injury and inflammatory infiltration of intestinal mucosa in DSS mice to achieve its therapeutic effect.

CCDC68 predicts poor prognosis in patients with colorectal cancer: a study based on TCGA data.

Background: The prognostic value of coiled-coil domain containing 68 (CCDC68) in colorectal cancer (CRC) is unclear. We evaluated the role of CCDC68 in CRC based on The Cancer Genome Atlas (TCGA) database. Methods: Patients with CRC were collected from TCGA. We determined CCDC68 expression using the Wilcoxon rank sum test. Logistic analysis was applied to study the relationship between CCDC68 expression and clinicopathologic features. Cox regression and the Kaplan-Meier method were used to determine the predictive value of CCDC68 on clinical outcomes in CRC patients. Gene Set Enrichment Analysis (GSEA) and the single-sample Gene Set Enrichment Analysis (ssGSEA) were also conducted to annotate the biological function of CCDC68. Results: Reduced CCDC68 expression in CRC was significantly correlated with N stage [odds ratio (OR) =0.95 for N1/N2 vs. N0], M stage (OR =0.91 for M1 vs. M0), pathologic stage (OR =0.95 for stage III/stage IV vs. stage I/stage II), neoplasm type (OR =0.92 for rectum adenocarcinoma vs. colon adenocarcinoma), tumor protein 53 (TP53) status [OR =0.93 for Mut (mutant) vs. WT (wild type)], and kirsten rat sarcoma viral oncogene (KRAS) status (OR =0.97 for Mut vs. WT) (all P values <0.05). Kaplan-Meier survival analysis showed that low CCDC68 expression had a poorer overall survival (OS) (P=0.008), progression-free interval (PFI) (P=0.006), and disease-specific survival (DSS) (P=0.023). Cox regression analysis revealed that CCDC68 was a risk factor for OS (P=0.047), PFI (P=0.048), and DSS (P=0.038). GSEA demonstrated that the chemokine signaling pathway, the Janus kinase-signal transducers and activators of transcription (JAK-STAT) signaling pathway, high-affinity IgE receptor (FcεRI)-mediated nuclear factor-κB (NF-κB) activation, cell adhesion molecules (CAMs), complement cascade, FcεRI-mediated mitogen-activated protein kinase (MAPK) activation, intestinal immune network for immunoglobulin A (IgA) production, and Toll-like receptor signaling pathway were differentially enriched in the high CCDC68 expression phenotype, while the Wnt signaling pathway was significantly enriched in the low CCDC68 expression phenotype. SsGSEA found that CCDC68 expression was positively correlated with T helper 2 (Th2) and T helper cells. Conclusions: CCDC68 expression may be a potential prognostic molecular marker for poor survival in CRC. Moreover, CCDC68 may participate in the development of CRC via multiple signaling pathways.

Danggui Sini decoction protects against oxaliplatin-induced peripheral neuropathy in rats.

The effects of Danggui Sini decoction on peripheral neuropathy in oxaliplatin-induced peripheral is established. The results indicated that Danggui Sini decoction treatment significantly reduced the current amplitude of dorsal root ganglia cells undergoing agonists stimuli compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly inhibited the inflammatory response of dorsal root ganglia cells compared to the model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment significantly enhanced the amounts of Nissl bodies in dorsal root ganglia cells compared to the Model-dorsal root ganglia group (P < 0.05). Danggui Sini decoction treatment improved ultra-microstructures of dorsal root ganglia cells. In conclusion, Danggui Sini decoction protected against neurotoxicity of oxaliplatin-induced peripheral neuropathy in rats by suppressing inflammatory lesions, improving ultra-microstructures, and enhancing amounts of Nissl bodies.

[Injury of human gastric epithelial GES-1 cells by MNNG and its effects on Wnt/ß-catenin signaling pathway].

The aim of this study was to investigate the mechanisms of mono-functional alkylating agent MNNG to damage human gastric epithelial GES-1 cells and roles of Wnt/ß-catenin signaling pathway in the process. The GES-1 cells were treated with MNNG (2 × 10-5 mol/L) for 24 h. The morphological changes of the GES-1 cells were observed under inverted microscope 2 d after treatment. The cell viability was measured by MTT assay. The apoptosis and cell cycle distribution of the GES-1 cells were analyzed by flow cytometry. The mRNA expressions of ß-catenin, GSK-3ß, c-Met and MMP7 in the GES-1 cells were detected by qPCR. The protein expressions of ß-catenin, GSK-3ß, p-GSK-3ß and c-Met were determined by Western blot. The results showed that MNNG induced the injury of GES-1 cells and changed the normal cell morphology to irregular long spindle shape. MNNG induced the apoptosis of GES-1 cells and blocked the cell cycle progression obviously. MNNG up-regulated the mRNA expressions of ß-catenin, GSK-3ß, c-Met and MMP7, and increased the protein expressions of ß-catenin, GSK-3ß and p-GSK-3ß. These results suggest that the damage of GES-1 cells induced by MNNG may be related to the activation of Wnt/ß-catenin signaling pathway, which will provide the basis for the study of cell model of gastric mucosal cell injury.