Serum platelet distribution width predicts cardiovascular and all-cause mortality in patients undergoing peritoneal dialysis.

BACKGROUND: Platelet distribution width (PDW) is a predictor for all-cause mortality in patients with cardiovascular diseases (CVD). This study aimed to evaluate the prognostic implication of PDW in predicting cardiovascular and all-cause mortality in patients undergoing peritoneal dialysis (PD). METHODS: In total, 762 PD patients from a single center were recruited retrospectively from 2005 to 2017 and followed up until 2021. The primary and secondary outcomes were cardiovascular and all-cause mortality, respectively. Survival analysis was conducted using Kaplan-Meier estimates and Cox regression analysis. RESULTS: During a median of 52.2 months of follow-up, 135 (17.7%) cases of CVD and 253 (33.2%) cases of all-cause mortality were reported. After multivariate adjustment, high levels of PDW were associated with an increased risk of death from CVD (HR: 1.583; 95% CI: 1.109-2.258; P = 0.011) and all-cause mortality (HR: 1.313; 95% CI: 1.006-1.758; P = 0.045). Subgroup analysis indicated a stronger association between PDW and all-cause mortality among female participants (P-value for interaction = 0.033). Higher levels of PDW predicted an increased risk of all-cause mortality in female patients (HR: 1.986; 95% CI,1.261-3.127). CONCLUSION: High levels of PDW are independently associated with cardiovascular and all-cause mortality in the PD population, and differences by sex exist in the association of PDW with all-cause mortality.

Mollugin induced oxidative DNA damage via up-regulating ROS that caused cell cycle arrest in hepatoma cells.

Mollugin has been proven to have anti-tumor activity. However, its potential anti-tumor mechanism remains to be fully elaborated. Herein, we investigated the growth inhibition of HepG2 cells, as well as the anti-tumor effect of mollugin and its molecular mechanism on H22-tumor bearing mice. In vitro, mollugin was shown to have a strong inhibitory effect on HepG2 cells in a concentration-dependent manner. Mollugin induced S-phase arrest of HepG2 cells, and increased intracellular reactive oxygen species (ROS) levels. Comet assay demonstrated that mollugin induced DNA damage in HepG2 cells, as well as an increase in the expression of p-H2AX. In addition, mollugin induced changes in cyclin A2 and CDK2. However, the addition of antioxidant glutathione (GSH) was able to reverse the effect of mollugin. In vivo, mollugin significantly inhibited tumor growth and reduced the tendency of tumor volume growth in mice. The tumor cell density was found to be decreased in the administration group, and the content of ROS in the tumor tissue significantly increased. The expression of p-H2AX, cyclin A2 and CDK2 were consistent with in vitro results. Mollugin demonstrated anti-hepatocellular carcinoma activity in vitro and in vivo, and its anti-hepatocellular carcinoma activity was found to be related to DNA damage and cell cycle arrest induced by excessive ROS production in cells.

Active Ingredients and Mechanism of Action of Rhizoma Coptidis against Type 2 Diabetes Based on Network-Pharmacology and Bioinformatics.

A pharmacological network of "component/target/pathway" for Rhizoma coptidis against type 2 diabetes (T2D) was established by network-pharmacology, and the active components of Rhizoma coptidis and its mechanism were explored. A literature-based and database study of the components of Rhizoma coptidis was carried out and screened by ADME parameters. The targets of Rhizoma coptidis were predicted by the ligand similarity method. Related pathways were analyzed with databases, and software was used to construct a "component/target/path" network. The mechanism was further confirmed by GEO database with R software. A total of 12 active components were screened from Rhizoma coptidis, involving 57 targets including MAPK1, STAT3, INSR, and 38 signaling pathways were associated with T2D. Related signaling pathways included essential pathways for T2D such as insulin resistance, and pathways that had indirect effect on T2D. It was suggested that Rhizoma coptidis may exert its effects against T2D through multi-component, multi-target, and multi-pathway forms.

Network Pharmacology-based Research of Active Components of Albiziae Flos and Mechanisms of Its Antidepressant Effect.

Albiziae Flos (AF) has been experimentally proven to have an antidepressant effect. However, due to the complexity of botanical ingredients, the exact pharmacological mechanism of action of AF in depression has not been completely deciphered. This study used the network pharmacology method to construct a component-target-pathway network to explore the active components and potential mechanisms of action of AF. The methods included collection and screening of chemical components, prediction of depression-associated targets of the active components, gene enrichment, and network construction and analysis. Quercetin and 4 other active components were found to exert antidepressant effects mainly via monoaminergic neurotransmitters and cAMP signaling and neuroactive ligand-receptor interaction pathways. DRD2, HTR1A, and SLC6A4 were identified as important targets of the studied bioactive components of AF. This network pharmacology analysis provides guidance for further study of the antidepressant mechanism of AF.