Prediction of Prognosis, Immunotherapy and Chemotherapy with an Immune-Related Risk Score Model for Endometrial Cancer.

Endometrial cancer (EC) is the most common gynecologic cancer. The overall survival remains unsatisfying due to the lack of effective treatment screening approaches. Immunotherapy as a promising therapy has been applied for EC treatment, but still fails in many cases. Therefore, there is a strong need to optimize the screening approach for clinical treatment. In this study, we employed co-expression network (GCN) analysis to mine immune-related GCN modules and key genes and further constructed an immune-related risk score model (IRSM). The IRSM was proved effective as an independent predictor of poor prognosis. The roles of IRSM-related genes in EC were confirmed by IHC. The molecular basis, tumor immune microenvironment and clinical characteristics of the IRSM were revealed. Moreover, the IRSM effectiveness was associated with immunotherapy and chemotherapy. Patients in the low-risk group were more sensitive to immunotherapy and chemotherapy than those in the high-risk group. Interestingly, the patients responding to immunotherapy were also more sensitive to chemotherapy. Overall, we developed an IRSM which could be used to predict the prognosis, immunotherapy response and chemotherapy sensitivity of EC patients. Our analysis not only improves the treatment of EC but also offers targets for personalized therapeutic interventions.

Poria cocos polysaccharide improves intestinal barrier function and maintains intestinal homeostasis in mice.

The function of the intestinal tract is critical to human health. Poria cocos is a widely used functional edible fungus in Asia and has been reported to modulate gastrointestinal function. However, the effects of polysaccharides, the main active constituents of Poria cocos, on the intestinal tract remains unclear and is the focus of the study. Poria cocos polysaccharides (PCP) were extracted, characterized, and administered to mice by gavage. The results show that PCP used in this study has a typical polysaccharide peak with a molecular weight of 11.583 kDa and is composed primarily of mannose, D-glucosamine hydrochloride, glucose, galactose, and fucose with a molar ratio of 15.308: 0.967: 28.723: 31.631: 23.371. The methylation results suggest that the PCP backbone may be t-Gal(p), 6-Gal(p) and 2,6-Gal(p). The effects of PCP on the mucosal barrier function of the mouse intestine (duodenum, jejunum, and ileum) were examined in terms of intestinal physiological status, physical barrier, biochemical barrier, immune barrier, and microbial barrier. The results showed that PCP significantly improved the physiological state of mouse intestine. Moreover, PCP strengthened the intestinal physical barrier by upregulating the expression of intestinal Occludin and ZO-1 and downregulating the levels of serum endotoxin, DAO, D-lactate, and intestinal MPO. Regarding biochemical barrier, PCP could upregulate the expression of MUC2, ß-defensin, and SIgA in intestinal tissues. In addition, PCP modulated the immune barrier by increasing IL-2, IL-4, IL-6, IL-10, TGF-ß, and IFN-γ expression. Besides, PCP increased the level of SCFAs in small intestinal contents. PCP modulates intestinal barrier function by altering the microbial composition of the gut. We also found that PCP could maintain intestinal barrier function by increasing the expression of Wnt/ß-Catenin and Lrp5 proteins. Generally, our findings suggested that PCP may be used as a functional food to regulate intestinal mucosal function, thereby enhancing the health of the intestinal and host.

Poria cocos polysaccharide prevents alcohol-induced hepatic injury and inflammation by repressing oxidative stress and gut leakiness.

Alcoholic liver disease (ALD) is a major worldwide chronic liver disease accompanied by hepatic inflammation, gut leakiness, and abnormal oxidative stress. Our previous study demonstrated substantial hepatoprotective activity of the active Poria cocos polysaccharide (PCP-1C). The present study explored whether PCP-1C protects against ALD among hepatic inflammation, gut leakiness, and abnormal oxidative stress. The results showed that PCP-1C significantly improved alcohol-induced liver injury by decreasing serum biochemical parameters, alleviating hepatic steatosis, and reducing lipid accumulation caused by ALD. Moreover, PCP-1C treatment reduced hepatic inflammation by inhibiting the toll-like receptor 4 (TLR4)/nuclear factor-kappa B (NF-κB) signaling pathway and also improved hepatocyte apoptosis by inhibiting the cytochrome P450 2E1 (CYP2E1)/reactive oxygen species (ROS)/mitogen-activated protein kinases (MAPKs) signaling pathway. Regarding intestinal protection, PCP-1C could repair the intestinal barrier and reduce lipopolysaccharide (LPS) leakage. Generally, PCP-1C exerts a positive therapeutic effect on ALD, which may play a pivotal of decreasing inflammatory factor release, inhibiting oxidative stress and apoptosis, and improving intestinal barrier injury.

MXene Enhanced the Electromechanical Performance of a Nafion-Based Actuator.

Ionic electroactive polymer-based actuators have attracted much attention due to their low potential stimuli. In this work, MXene-Nafion composite actuators were fabricated, and the actuation performances were tested. The morphology of the as-made MXene-Nafion composite showed that the composite membrane was homogeneous, with an MXene doping level up to 5 wt%. In addition, the results of blocked force, response speed, and durability demonstrated that the actuation behavior of the composite-based actuator was enhanced due to the efficient dispersion of the two-dimensional nanofiller MXene. In addition, the blocking force of the composite actuator with a doping level of 0.5 wt% was about 6 times that of the pure Nafion without back-relaxation and durability degradation during the testing period.

[Extracts of Poria cocos polysaccharides improves alcoholic liver disease in mice via CYP2E1 and NF-κB inflammatory pathways].

The present study investigated the effect of extract of Poria cocos polysaccharides(PCP) on cytochrome P450 2 E1(CYP2 E1) and nuclear factor κB(NF-κB) inflammatory signaling pathways in alcoholic liver disease(ALD) mice and explored its protective effect and mechanism. Sixty male C57 BL/6 N mice of SPF grade were randomly divided into a control group, a model group, a positive drug group(bifendate, 200 mg·kg~(-1)), and high-(200 mg·kg~(-1)) and low-dose(50 mg·kg~(-1)) PCP groups. Gao-binge mo-del was induced and the mice in each group were treated correspondingly. Liver morphological and pathological changes were observed and organ index was calculated. Serum levels of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were detected. Malondialdehyde(MDA) and superoxide dismutase(SOD) in liver tissues were detected by assay kits. The levels of interleukin-6(IL-6) and tumor necrosis factor-α(TNF-α) were detected by ELISA. The activation of macrophages was observed by immunofluorescence staining and protein expression of CYP2 E1, Toll-like receptor 4(TLR4), NF-κB p65, and phosphorylated NF-κB p65(p-NF-κB p65) were analyzed by Western blot. The ALD model was properly induced. Compared with the model group, the PCP groups significantly improved the pathological injury of liver tissues. Immunofluorescence staining revealed that compared with the model group, the groups with drug intervention showed decreased macrophages in liver tissues. Additionally, the PCP groups showed reduced ALT, AST, MDA, IL-6, and TNF-α(P<0.05), and potentiated activity of SOD(P<0.01). PCP extract has the protective effect against alcoholic liver injury in mice, and the underlying mechanism may be related to the regulation of the expression of CYP2 E1 and inhibition of TLR4/NF-κB inflammatory signaling pathway to reduce oxidative stress and inflammatory injury, thereby inhibiting the development of ALD.

Structural characterization and hepatoprotective activity of a galactoglucan from Poria cocos.

To find the polysaccharide with hepatoprotective activity from Poria cocos and clarify its structure, a galactoglucan (PCP-1C) with a molecular weight of 17 kDa was purified from the Poria cocos sclerotium by column chromatography and activity evaluation in the present work. It was composed of galactose, glucose, mannose, and fucose in a molar percentage of 43.5: 24.4: 17.4: 14.6. Structural characterization showed that PCP-1C has a backbone consisted of 1,6-α-D-Galp, which branches composed of 1,3-ß-D-Glcp, 1,4-ß-D-Glcp, 1,6-ß-D-Glcp, T-ß-D-Glcp, T-α-D-Manp, T-α-L-Fucp and 1,3-α-L-Fucp. In vivo experiments found that PCP-1C can apparently improve the damage of liver tissue in CCl4-treated mice and relieve oxidative stress and inflammation. PCP-1C also reduced the expression of CAR and CYP2E1 in the liver. These findings indicated strong hepatoprotective effect of PCP-1C, which was attributed to the reduction of CCl4 metabolism via inhibiting the CAR/CYP2E1 signal pathway.