Caspase-1 inhibitor exerts brain-protective effects against sepsis-associated encephalopathy and cognitive impairments in a mouse model of sepsis.

Sepsis-associated encephalopathy (SAE) manifested clinically in acute and long-term cognitive impairments and associated with increased morbidity and mortality worldwide. The potential pathological changes of SAE are complex and remain to be elucidated. Pyroptosis, a novel programmed cell death, is executed by caspase-1-cleaved GSDMD N-terminal (GSDMD-NT) and we investigated it in peripheral blood immunocytes of septic patients previously. Here, a caspase-1 inhibitor VX765 was treated with CLP-induced septic mice. Novel object recognition test indicated that VX765 treatment reversed cognitive dysfunction in septic mice. Elevated plus maze, tail suspension test and open field test revealed that depressive-like behaviors of septic mice were relieved. Inhibited caspase-1 suppressed the expressions of GSDMD and its cleavage form GSDMD-NT, and reduced pyroptosis in brain at day 1 and day 7 after sepsis. Meantime, inhibited caspase-1 mitigated the expressions of IL-1ß, MCP-1 and TNF-α in serum and brain, diminished microglia activation in septic mice, and reduced sepsis-induced brain-blood barrier disruption and ultrastructure damages in brain as well. Inhibited caspase-1 protected the synapse plasticity and preserved long-term potential, which may be the possible mechanism of cognitive functions protective effects of septic mice. In conclusion, caspase-1 inhibition exerts brain-protective effects against SAE and cognitive impairments in a mouse model of sepsis.

[Chloroplast DNA trnQ-rps16 variation and genetic structure of nine wild Chinese cherry (Cerasus pseudocerasus Lindl.) populations].

Chinese cherry (Cerasus pseudocerasus Lindl.) is one of the most economically domestic fruit trees in China. The rich variation of wild Chinese cherry is the most important breeding resource for existing cultivars. In order to reveal the levels and distribution of genetic variation within wild Chinese cherry of Sichuan Province, China, where is rich in wild Chinese cherry, the sequence variation of chloroplast DNA trnQ-rps16 intergenic spacer was analyzed in 145 individuals of all nine existing populations (seven from Sichuan, two from Shanxi and Guizhou provinces) of China. The results showed that trnQ-rps16 sequence were aligned with 13 polymorphic sites (1.87%), including 3 substitutions and 10 indels in 145 individuals, which revealed a low level of genetic diversity (h= 0.562, π= 0.00184). Compared to other regions (h= 0.733, π= 0.00243), a rather lower genetic diversity (h= 0.544, π= 0.00203) was found in the populations from Sichuan, and a large scale of genetic diversity among the seven populations was detected (h= 0-0.708; π= 0-0.00298), ranging from EM (h=0.000, π=0.000) to TL (h=0.708, π=0.00298). The low genetic diversity of populations may be strongly affected by founder effect and bottleneck effect because of the marginal nature, recent reduction, and consequent genetic drift of these populations. In addition, a fairly low genetic differentiation (FST= 0.21573) was found among the studied populations. This suggest that gene flow seems to originate from pronounced seed dispersal abilities of the species and it may play a significant role in shaping such a genetic structure. The long generation cycle of the species may also contribute to this structure. Based on these findings, a conservational plan for sampling or preserving fewer populations but more individuals from each population for the species was proposed.

Genome-wide methylation and expression profiling identify a novel epigenetic signature in gastrointestinal pan-adenocarcinomas.

Aim: To identify methylation-driven genes and establish a novel epigenetic signature for gastrointestinal (GI) pan-adenocarcinomas. Materials & methods: Methylation and RNA-seq data for GI adenocarcinomas were downloaded from the Cancer Genome Atlas database. A methylation-driven gene signature was established by multivariate Cox regression analysis. We developed a prognostic nomogram using a combination of methylation-driven gene risk score and clinicopathological variables. A joint survival analysis based on gene expression and methylation was conducted to further investigate the prognostic role of methylation-driven genes. Results: An epigenetic signature was established based on five methylation-driven genes. We also established a prognostic nomogram based on methylation-driven gene risk score and clinicopathologic factors, with a favorable predictive ability. Joint survival analysis revealed that 28 methylation-driven genes could be independent prognostic factors for overall survival for GI adenocarcinomas. Conclusion: An epigenetic signature was established that effectively predicts the overall survival for GI adenocarcinomas across anatomic boundaries.

[Studies on HPLC fingerprint of co-hirudo injection].

OBJECTIVE: Using HPLC To determine hypoxanthine in co-hirudo injection for establishing its HPLC fingerprint, and evaluating its internal quality. METHOD: The chromatographic separation was performed on a Kromasil C18 column (4.6 mm x 250 mm,5 microm). A linear gradient elution with A (0.01 mol x L(-1) x KH2PO4) and B (50% methanol) was used, the flow rate was 0.8 mL x min(-1), the detection wavelength was set at 254 nm, and the column temperature was at normal. RESULT: Hypoxanthine was used as the reference substance in the fingerprint of co-hirudo injection, it showed 15 common peaks and theirs similarity threshod was 0.97. CONCLUSION: This method was accurate, repeatable and useful for the quality control of co-hirudo injection.

Role of ROCK expression in gallbladder smooth muscle contraction.

Cholelithiasis is a common medical condition whose incidence rate is increasing yearly, while its pathogenesis has yet to be elucidated. The present study assessed the expression of Rho-kinase (ROCK) in gallbladder smooth muscles and its effect on the contractile function of gallbladder smooth muscles during gallstone formation. Thirty male guinea pigs were randomly divided into three groups: The control group, the gallstone model group and the fasudil interference group. The fasting volume (FV) and bile capacity of the gallbladder (FB) as well as the total cholesterol (TC) and triglyceride (TG) contents of the gallbladder bile were determined. In addition, the gallbladder was dissected to identify whether any gallstones had formed. Part of the gallbladder tissue specimens were used for immunohistochemical analysis of ROCK expression in gallbladder smooth muscles. The results showed that four guinea pigs in the model group and eight in the fasudil group displayed gallstone formation, while there was no gallstone formation in the control group. The FV and FB were significantly increased in the model and fasudil groups. Similarly, the TC and TG contents of gallbladder bile were increased in these groups. The positive expression rate of ROCK in gallbladder smooth muscles in the model and fasudil groups was significantly reduced compared with that in the control group (P<0.05). The results of the present study indicated that the reduction of ROCK expression in guinea pig gallbladder smooth muscles weakened gallbladder contraction and thereby promoted gallstone formation.