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It is well known that vitamin C could protect against influenza infection, but little is known about the mechanisms. This study aimed to investigate the influence and possible mechanisms of vitamin C on pneumonia induced by influenza virus in stressed mice. Results showed that restraint stress significantly increased the mortality and the severity of pneumonia in mice caused by A/FM/1/47(H1N1) virus infection, which was attenuated by oral administration of vitamin C (125 and 250 mg/kg). Moreover, vitamin C administration significantly decreased expression of susceptibility genes, including mitochondrial antiviral signaling (MAVS) and interferon regulatory factor 3 (IRF3), and increased expression of NF-κB. These work in conjunction to induce type I interferons (IFNs) and elicit innate antiviral response as key factors in RIG-I-mediated signal transduction pathway. The above effects of vitamin C were further found to relate with inhibition of excess CORT synthesis by regulating steroid hydroxylating enzymes in adrenal gland. In conclusion, the protective effects of vitamin C on influenza virus-caused pneumonia might be related to its inhibition of CORT synthesis, which reduces the susceptibility to influenza viral infection in restraint-stressed mice. These findings provide a new mechanism for the effects of vitamin C on influenza virus-induced pneumonia in restraint-stressed mice.

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Phosphodiesterase-4D (PDE4D) has been proved to be a potential therapeutic target against strokes. In the present study, a procedure of integrating pharmacophore, molecular docking, molecular dynamics (MD) simulations, binding free energy calculations, and finally validation with bioassay was developed and described to search for novel PDE4D inhibitors from the SPECS database. Among the 29 compounds selected by our MD-augmented strategy, 15 hits were found with IC50 between 1.9 and 50 μM (a hit rate of 52%) and 6 potent hits showed IC50 less than 10 μM, which suggested that MD simulations can explore the intermolecular interactions of PDE4D-inhibitor complexes more precisely and thus significantly enhanced the hit rate of this screening. The effective and efficient integrated procedures described in this study could be readily applied to screening studies toward other drug targets.

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Background and Aim Inflammatory bowel disease results from a dysregulated immune response to intestinal microbial flora in individuals with genetic predisposition(s). This study aimed to determine the effects of compound polysaccharides (CP) containing yam polysaccharide and inulin on the rat model of colitis induced by 2,4,6‐trinitrobenzenesulfonic acid (TNBS) and to explain the mechanism in terms of gut microbiota composition and function. Methods Male SD rats were divided into three groups: the control group, the model group, and the CP group. Disease activity index, serum myeloperoxidase level, and the composition and function of gut microbiota were analyzed. Results The data in the study showed CP reduced inflammation in the rat model of colitis induced by TNBS and ameliorated the experimental colitis. The results also indicated that CP not only reversed TNBS‐induced gut dysbiosis‐indexed by increased short‐chain fatty acids (SCFAs)‐producing bacteria, lactic acid‐producing bacteria, and decreased Bacteroides, Proteobacteria as well as sulfate‐reducing bacteria, but also restored the dysregulated microbiota function of colitic rats into a normal condition, including an improvement on basic metabolism and a reduction on oxidative stress, cell motility, signal transduction, xenobiotics biodegradation, and metabolism as well as pathogenesis processes. Conclusions Compound polysaccharides ameliorated the experimental colitis of rats induced by TNBS by modulating the gut microbiota composition and function profiles, which makes it possible to be used as prebiotic agents to treat gut dysbiosis in colitis individuals.

Currently, cerebral infarction (CI) is the leading cause of disability and the second leading cause of mortality in China, seriously affecting patient quality of life. Ischemia (IS) is considered to be the early stage of CI. The present study aims to investigate the variation of intestinal microbial communities in patients with CI and IS using high throughput sequencing technology, and then analyze the results to identify a novel potential pathogenic mechanism of CI and IS. In total, 8 patients with CI, 2 patients with IS and 10 healthy volunteers as a control were selected. Throughput sequencing technology was used to analyze the character and microbial population of the gut. The abundance of Escherichia, Bacteroides, Megamonas, Parabacteroides, Akkermansia, Prevotella, Faecalibacterium, Dialister, Bifidobacterium and Ruminococcus was the significant difference in the intestinal microbial communities of the CI and IS patients compared with the healthy group. It was also observed that CI and IS were closely associated with internal glucose metabolism. The intestinal gut disturbance of CI patients may be one of the causes inducing CI by glucose metabolism and maybe considered as a potential method to predict the disease.

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