Network Pharmacology Analysis, Molecular Docking Integrated Experimental Verification Reveal the Mechanism of Gynostemma pentaphyllum in the Treatment of Type II Diabetes by Regulating the IRS1/PI3K/Akt Signaling Pathway.

Gynostemma pentaphyllum (Thunb.) Makino (GP), a plant with homology of medicine and food, as a traditional Chinese medicine, possesses promising biological activities in the prevention and treatment of type 2 diabetes mellitus (T2DM). However, the material basis and the mechanism of action of GP in the treatment of T2DM have not been fully elucidated. This study aimed to clarify the active components, potential targets and signaling pathways of GP in treating T2DM. The chemical ingredients of GP were collected by combining UPLC-HRMS analysis and literature research. Network pharmacology revealed that GP had 32 components and 326 potential targets in treating T2DM. The results showed that GP affected T2DM by mediating the insulin resistance signaling pathway, PI3K/Akt signaling pathway and FoxO1 signaling pathway, which had a close relationship with T2DM. Molecular docking results showed that STAT3, PIK3CA, AKT1, EGFR, VEGFA and INSR had high affinity with the active compounds of GP. In vitro, GP extracts obviously increased the glucose uptake and glucose consumption in IR-HepG2 cells. GP extracts increased the levels of PI3K, p-AKT, p-GSK3ß and p-FoxO1 and decreased the expression of p-IRS1, p-GS, PEPCK and G6Pase, which indicated that GP could promote glycogen synthesis and inhibit gluconeogenesis by regulating the IRS1/PI3K/Akt signaling pathway. The results demonstrated that GP could improve insulin resistance by promoting glucose uptake and glycogen synthesis and inhibiting gluconeogenesis through regulating the IRS1/PI3K/Akt signaling pathway, which might be a potential alternative therapy for T2DM.

Metabolites of traditional Chinese medicine targeting PI3K/AKT signaling pathway for hypoglycemic effect in type 2 diabetes.

Type 2 diabetes mellitus is a chronic metabolic disease characterized by insulin resistance, with high morbidity and mortality worldwide. Due to the tightly intertwined connection between the insulin resistance pathway and the PI3K/AKT signaling pathway, regulating the PI3K/AKT pathway and its associated targets is essential for hypoglycemia and the prevention of type 2 diabetes mellitus. In recent years, metabolites isolated from traditional Chinese medicine has received more attention and acceptance for its superior bioactivity, high safety, and fewer side effects. Meanwhile, numerous in vivo and in vitro studies have revealed that the metabolites present in traditional Chinese medicine possess better bioactivities in regulating the balance of glucose metabolism, ameliorating insulin resistance, and preventing type 2 diabetes mellitus via the PI3K/AKT signaling pathway. In this article, we reviewed the literature related to the metabolites of traditional Chinese medicine improving IR and possessing therapeutic potential for type 2 diabetes mellitus by targeting the PI3K/AKT signaling pathway, focusing on the hypoglycemic mechanism of the metabolites of traditional Chinese medicine in type 2 diabetes mellitus and elaborating on the significant role of the PI3K/AKT signaling pathway in type 2 diabetes mellitus. In order to provide reference for clinical prevention and treatment of type 2 diabetes mellitus.

Lysine demethylase 1B (Kdm1b) enhances somatic reprogramming through inducing pluripotent gene expression and promoting cell proliferation.

Lysine demethylase 1B (Kdm1b) is known as an epigenetic modifier with demethylase activity against H3K4 and H3K9 histones and plays an important role in tumor progression and tumor stem cell enrichment. In this study, we attempted to elucidate the role of Kdm1b in somatic cell reprogramming. We found that exogenous expression of Kdm1b in human dermal fibroblasts (HDFs) can influence the epigenetic modifications of histones. Subsequent analysis further suggests that the overexpression of Kdm1b can promote cell proliferation, reprogram metabolism and inhibit cell apoptosis. In addition, a series of multipotent factors including Sox2 and Nanog, and several epigenetic factors that may reduce epigenetic barriers were upregulated to varying degrees. More importantly, HDFs transfected with the combination of Oct4 (POU5F1), Sox2, Klf4 and c-Myc and Kdm1b (OSKMK) achieved higher reprogramming efficiency. Therefore, we suggest that Kdm1b is an important epigenetic factor associated with pluripotency.

A natural cordycepin/chitosan complex hydrogel with outstanding self-healable and wound healing properties.

The chitosan-based hydrogel dressings have been intensively engaged in wound healing. In respect to the relatively unsatisfied anti-bacterial performance of chitosan, we developed a self-healable cordycepin (abbreviated to CY)/chitosan (abbreviated to CS) hydrogel dressing cross linking by non-covalent bonds (hydrogen bond and electrostatic interaction) for wound healing through one-step 'freeze-thaw' method without adding any cross-linking agent. The as-prepared hybrid hydrogel exhibited excellent biocompatibility, suitable swelling ratio and desired mechanical strength, providing remarkable antimicrobial effect with no side effects in vitro. The self-healable property enables this hydrogel to adapt irregularly shaped wound defects without premolding. Moreover, our in vivo experiments confirmed that CY/CS hydrogel served as a quicker re-epithelization of skin wounds and an apparent increasing collagen deposition compared with chitosan hydrogels. Additionally, the CY/CS hydrogel significantly increased the expressions of epithelial regeneration markers including laminin and involucrin. The present study highlights a facile hydrogel strategy to balance and optimize the biocompatibility, swelling ratio and self-adapting ability for treating wound healing.

[Establishment of the predictive model of source eutrophication using artificial neural network].

OBJECTIVE: To establish the predictive model of eutrophication in the main water source in Zhengzhou City. METHODS: Water temperature (WT), secchi-depth (SD), total phosphorus (TP), total nitrogen (TN), light illuminance (LI), chemical oxygen demand (CODMn), chlorophyll-a (Chla) were monitored in Xiliu lake and Huayuankou pool. Grading points method and comprehensive trophic state index method were used to evaluate the trophic state. Backpropagation artificial neural network with Levenberg-Marquardt algorithm was used to establish the forcasting model of eutrophication after the raw data normalized treated using standardization function. RESULTS: The results of evaluation of grade method revealed that the two waters source were in nutritional state and the tendencies of year grade indexes were from the lower critical value to eutrophic state to higher critical value of eutrophication of xiliu lake. The scope of hidden nodes was determined from 2 to 15 according to the calculated results using function of J = (mean square root of n + M) + a and the hidden nodes was 10 according to the training result. All of the physical chemistry factors were brought into the model. The training error was 1e-11 and the coefficient correlation of the network fitness result was 0.871. The fitting result was close to the aim and the predictive model of eutrophication in the main resource water in Zhengzhou City was established successfully. CONCLUSION: Eutrophication forcasting model could be established using artificial neural network, and the method of artificial neural network should be better to meet the actual demand.

[Characteristic analysis on the toxin of microcystis in life water source of Zhengzhou City].

OBJECTIVE: To analyze the toxic characteristic of microcystis in a life water source. METHODS: Microcystis in Huayuankou conservation pool and Xiliu lake were isolated by 96-microbiological assay and supreme dilution methods. Phycocyanin intergenic spacer region (PC-IGS) and microcystin synthetase gene B (McyB) were detected by whole-cell PCR method, And toxicities of microcystis were identified by solid pole of extraction (SPE) and high performance liquid chromatography (HPLC) method. RESULTS: The microcystis of the water source were cyanobacteria which could contain PC-IGS and McyB expressing positively, Comparition with reported meyB of Microcystis aeruginosa in Genbank, the homology of gene sequence was 99%. The main toxic isomers of the three microcystis were MC-LR, whose proportions of the whole toxin were 97.9%, 98.6% and 99.3%, respectively. CONCLUSION: The microcystis of the main life water source maybe poisonous and the main isomer maybe MC-LR.