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Hyperglycemia is a typical pathogenic factor in a series of complications among patients with type II diabetes. Epigallocatechin-3-gallate (EGCG) is the major polyphenol extracted from green tea and is reported to be an antioxidant. The aim of the present study was to examine the effect of EGCG on insulin resistance in human HepG2 cells pretreated with high concentrations of glucose. The protein kinase B (AKT)/glycogen synthase kinase (GSK) pathways were analyzed using western blot analysis in HepG2 cells and primary mouse hepatocytes treated with high glucose and/or EGCG. Cellular glycogen content was determined using a glycogen assay kit. Reactive oxygen species (ROS) production was determined using dihydroethidium staining and flow cytometry. c‑JUN N‑terminal kinase (JNK)/insulin receptor substrate 1 (IRS1)/AKT/GSK signaling was explored using western blot analysis in HepG2 cells treated with high glucose and/or EGCG or N-acetyl-cysteine. High glucose significantly decreased the levels of phosphorylated AKT and GSK in HepG2 cells and mouse primary hepatocytes. Pretreatment with EGCG significantly restored the activation of AKT and GSK in HepG2 cells and primary hepatocytes exposed to high glucose. In HepG2 cells and primary hepatocytes, glycogen synthesis was improved by EGCG treatment in a dose‑dependent manner. High glucose significantly stimulated the production of ROS while EGCG protected high glucose‑induced ROS production. ROS is known to serve a major role in high glucose induced‑insulin resistance by increasing JNK and IRS1 serine phosphorylation. In the present study, EGCG was observed to enhance the insulin‑signaling pathway. EGCG ameliorated high glucose‑induced insulin resistance in the hepatocytes by potentially decreasing ROS‑induced JNK/IRS1/AKT/GSK signaling.

To evaluate the prognostic significance of the altered expression of capicua transcriptional repressor (CIC) in isocitrate dehydrogenase (IDH)-mutant oligodendroglial tumors, a cohort of 54 IDH-mutant oligodendroglial tumors (designated as the Xijing cohort) were examined by immunohistochemistry (IHC), and two public expression data sets from The Cancer Genome Atlas (TCGA; n=265) and the Gene Expression Omnibus (GEO; n=45) were analyzed in the present study. The prognostic value was evaluated by survival analysis and Cox hazards models. Overall survival (OS) was investigated with Kaplan-Meier curves and log-rank tests. Gene set enrichment analysis (GSEA) was also performed to characterize the functional profiles of each subgroup. It was revealed that in IDH-mutant, 1p/19q co-deleted oligodendroglial tumors, higher CIC expression (at mRNA and protein levels) was associated with a more favorable OS time (log-rank P-values: TCGA, P=0.034; GEO, P=0.012; Xijing cohort, P=0.029). By contrast, among IDH-mutant, 1p/19q intact tumors, higher CIC expression was associated with poorer OS time (log-rank P-values: TCGA, P=0.007; GEO, P=0.017; Xijing cohort, P=0.012). To the best of our knowledge, this is the first study demonstrating the distinct prognostic value of altered CIC expression with regard to the 1p/19q status among IDH-mutant oligodendroglial tumors. The dual roles of CIC may be influenced by its transcriptional regulatory activity and the consequent functional profiles. Additionally, a simple risk classification scheme based on CIC expression alone is proposed for the optimal prediction of prognosis in patients with oligodendroglial tumors.

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Context Salvia miltiorrhizae Bunge (Lamiaceae) is a traditional Chinese medicine (TCM) for the treatment of ‘thoracic obstruction’. Transient receptor potential canonical channel 1 (TRPC1) is a important target for myocardial injury treatment. Objective This work screens the active component acting on TRPC1 from Salvia miltiorrhizae . Materials and methods TCM Systems Pharmacology Database and Analysis Platform (TCMSP) was used to retrieve Salvia miltiorrhiza compounds for preliminary screening by referring to Lipinski’s rule of five. Then, the compound group was comprehensively scored by AutoDock Vina based on TRPC1 protein. Surface plasmon resonance (SPR) was used to determine the affinity of the optimal compound to TRPC1 protein. Western blot assay was carried out to observe the effect of the optimal compound on TRPC1 protein expression in HL-1 cells, and Fura-2/AM detection was carried out to observe the effect of the optimal compound on calcium influx in HEK293 cells. Results Twenty compounds with relatively good characteristic parameters were determined from 202 compounds of Salvia miltiorrhiza . Rosmarinic acid (RosA) was obtained based on the molecular docking scoring function. RosA had a high binding affinity to TRPC1 protein (KD value = 1.27 µM). RosA (50 μM) could reduce the protein levels (417.1%) of TRPC1 after oxygen-glucose deprivation/reperfusion (OGD/R) in HL-1 cells and it could inhibit TRPC1-mediated Ca 2+ influx injury (0.07 ΔRatio340/380) in HEK293 cells. Discussion and conclusions We obtained the potential active component RosA acting on TRPC1 from Salvia miltiorrhizae , and we speculate that RosA may be a promising clinical candidate for myocardial injury therapy.

Background: Zanthoxyli Bungeanum (ZB) has been reported have an effect on lung carcinoma (LC).However,the defined pharmacological mechanism of ZB on LC has not been expounded completely because of the complicated ingredients Objective: The aim of this work was to explore the active ingredients and mechanisms of ZB against LC by network pharmacology. Method: In this study, a systemic network pharmacology were used to explore the underlying mechanism of ZB, including pivotal components collection, target prediction, networks construction, Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. At last, molecular docking was carried out to elucidate the involved pharmacological mechanisms. Results: Twenty-eight potential active compounds with 317 related targets and 598 LC-related targets were collected. Finally, 79 intersection targets were obtained used to GO and KEGG pathway enrichment analysis. Based on component-target-pathway network, quercetin, β-sitosterol, and β-amyrin and 6 targets were selected, including RAC-alpha serine/thre-onine-protein kinase(AKT1),mitogen-active protein kinase1(MAPK1),Transcription factor p65(RELA), Caspase-9(CASP9), G1/S-specifi cyclin-D1 (CCND1) and PI3-kinase subunit gamma (PIK3CG),these six predicted targets were highly involved in the PI3K-AKT signaling pathway Conclusion: The active ingredients and mechanisms of ZB against LC were firstly investigated using network pharmacology. This work provides scientific evidence to support the clinical effect of ZB on LC, provides new signs of the anti-LC mechanism of ZB, and supply a guidance for further study.

Background Cuproptosis is a novel method of modulating cell death that regulates tumorigenesis and progression processes. Cuproptosis-associated lncRNAs (CALs) are not clearly understood in colon cancer (CC). Furthermore, it is currently unknown how CALs affect prognosis and how they relate to the immune microenvironment of CC. Our study investigated the potential prognostic value of CALs and their association with immune microenvironments in CC patients.Methods The RNA of CC patients was sequenced, and medical data were retrieved from The Cancer Genome Atlas (TCGA) portal. A total of 446 participants were randomly assigned to the training and testing cohorts. The Pearson correlation analysis was used to recognize CALs. To choose significant markers in the training cohort, we used univariate regression with the LASSO method, followed by multivariate Cox regression analysis to develop the final prediction model. Therefore, we developed a predictive model based on the cuproptosis signature. The performance of the proposed model was assessed using the receiving operating characteristic (ROC) analysis. We also investigated the relationship between this signature and medication susceptibility, somatic mutations, and immunological infiltration.Results CC patients were divided into two risk cohorts using a 5-CAL signature; the patients in the elevated-risk cohort exhibited a poorer prognosis. The ROC analysis revealed the predictive accuracy of the developed risk model. We also detected variations in immune cell infiltration between the two cohorts, such as CD8 + T cells, regulatory T cells, and M0 and M1 macrophages. The high-risk cohort also exhibited lower IC50 values for several chemotherapy drugs.Conclusion We recognized a novel CAL signature that accurately predicts the prognosis of CC patients. CALs may be therapeutic targets for CC and may have a function in the antitumor immune system.

As one of the most challenging inflammatory diseases, the incidence of ulcerative colitis (UC) is increasing year by year, but the existing therapeutic drugs are not effective and lack of targeting. Nanomaterials are expected to become promising delivery system due to their good targeting effects. Here, we designed a nanomaterial sensitive to reactive oxygen species, which can be used to treat IBD, especially UC. It is a self-assembled polyether micelle that can be oxidized at the inflammation site where the concentration of reactive oxygen increases, and effectively release the encapsulated budesonide (Bud). Experiments have proved that for DSS-induced colitis, the synthetic drug-loaded nanoparticles have excellent therapeutic effects, can effectively repair intestinal barrier, and significantly improve the damaged colon tissue. At the same time, it has a beneficial regulatory effect on inflammatory factors. Molecular mechanism studies have shown that it achieves its therapeutic effects by activating the peroxisome proliferators-activated receptors-γ (PPAR-γ) pathway and inhibiting the nuclear factor (NF)-κB pathway. This study proves that oral nano-micelles have an important impact on improving the efficacy of UC treatment drugs and have far-reaching significance for the targeted treatment of gastrointestinal diseases.