Objective: This study aimed to use network pharmacology to predict the therapeutic mechanism of oroxyli semen (OS) on triple-negative breast cancer (TNBC) and validate it through in vitro experiments. Methods: The active ingredients and target proteins of OS were retrieved from the Traditional Chinese Medicine Systems Pharmacology database, and the TNBC-related target genes were obtained from the GeneCards database. The overlapping genes were used to construct a protein–protein interaction (PPI) network via the String database. Furthermore, we employed an online bioinformatics analysis platform (https://www.bioinformatics.com.cn/) to perform gene ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses to evaluate biological processes, molecular functions, and cellular components and generate simulated signal pathways. Additionally, molecular docking was used to evaluate the binding ability of small molecule drugs and signaling pathway targets. CCK8 assay was conducted to detect the effect of small molecule drugs on TNBC cell viability, and Western Blot was utilized to verify the expression of AKT, VEGF, and hypoxia-inducible factor 1-alpha (HIF-1α) proteins. Results: Fifteen active ingredients and 166 therapeutic targets of OS were obtained from the Traditional Chinese Medicine Systems Pharmacology database. The Venn diagram revealed that 163 targets were related to TNBC. The protein–protein interaction network analysis identified AKT1, IL-6, JUN, vascular endothelial growth factor A (VEGFA), CASP3, and HIF-1α as potential core targets through which OS may treat TNBC. Furthermore, the molecular docking results indicated that the active ingredient chryseriol in OS had good binding ability with VEGFA, and HIF-1α. CCK8 assay results indicated that chryseriol inhibited the viability of MDA-MB-231 and BT-20 cells. Western Blot demonstrated that chryseriol intervention led to a decrease in VEGFA, and HIF-1α protein expression compared with the control group (P < .05), increased the cleaved PARP. Conclusion: OS may exert its therapeutic effects on TNBC through multiple cellular signaling pathways. Chryseriol, the active component of OS, can enhance the apoptosis of TNBC cells by targeting VEGFA/HIF-1α pathway. This study provided new insights into the potential therapeutic mechanism of OS for TNBC and may aid in the development of novel therapeutic approaches for TNBC.

To investigate the causal relationship between sleep duration and heart failure (HF) in a European population. We focused on the continuous sleep duration of 460,099 European individuals as our primary exposure. Genome-wide significant single nucleotide polymorphisms (SNPs, n = 9851,867) linked to continuous sleep duration were adopted as instrumental variables. The outcome of interest was based on HF events in a European cohort (n = 977,323; with 930,014 controls and 47,309 cases). We employed a two-sample Mendelian randomization (MR) approach to infer causality between sleep duration and the incidence of HF. For validation purposes, an additional cohort of 336,965 European individuals diagnosed with insomnia was selected as a secondary exposure group. Using its SNPs, a subsequent two-sample MR analysis was conducted with the HF cohort to further corroborate our initial findings. Employing the MR methodology, we selected 57 SNPs that are associated with sleep duration, and 24 SNPs that are associated with insomnia as instrumental variables. We discerned a substantial association between genetically inferred sleep duration and HF risk (odds ratio: 0.61; 95% confidence interval: 0.47–0.78, P < .0001). Our subsequent analysis highlighted a pronounced increased HF risk associated with insomnia (odds ratio: 1.54; 95% confidence interval: 1.08–2.17, P < .02). These conclusions were further bolstered by consistent results from sensitivity analyses. Our study suggests a causal linkage between sleep duration and the onset risk of HF in the European population. Notably, shorter sleep durations were associated with a heightened risk of HF.

Background Prostate cancer (PC) is a common urinary system malignancy in men, and smoking is a clear risk factor. Among them, nicotine and tar in cigarettes play a key role in the development of PC, but the specific mechanism is not completely clear. Objective To explore the mechanism of PC immune inflammation caused by nicotine and tar, and to provide the theoretical basis and new targets for the prevention and treatment of PC. Methods Through network toxicology and immune infiltration analysis, to analyze the effects of nicotine and tar on PC related cells and tissues, and machine analysis of related cytokines, signaling pathway and gene expression changes. Key genes were validated by immunohistochemistry and in vitro cellular assays. Results This study screened multiple targets of nicotine and tar that may be related to the occurrence of PC. In addition, based on these targets and signaling pathways, they may be key molecular mechanisms leading to PC. In the formation and progression of PC, we found significant infiltration of M2 macrophages, with increased secretion of VEGF, MMPs, IL-10, etc., promoting tumor angiogenesis, extracellular matrix degradation, and leading to immune escape in the body. Inhibition of T cell activity, macrophages interact with tumor cells, smooth muscle cells, affect each other’s functions. Functional of CD8 + T cells, tumor cells promote immune escape by binding of PD-L1 and PD-1. Hub targets such as MAOA and MAOB are affected by nicotine and tar, interference with neurotransmitters, hormones, lipid metabolism, activation of the inflammatory signals, altering the immune microenvironment, to promote the development and development of PC. Conclusion Nicotine and tar may contribute to the development of PC through complex immuno-inflammatory mechanisms, and in-depth study of these mechanisms could help develop more effective prevention and treatment strategies for PC.

Renal fibrosis is a major pathological process in the progression of chronic kidney disease (CKD). It contributes to progressive loss of kidney function and may ultimately lead to end-stage renal disease. Mitochondrial homeostasis plays a central role in cellular energy metabolism and oxidative balance, while mitochondrial dysfunction is closely associated with various kidney diseases. Ferroptosis, an iron-dependent form of regulated cell death, has been increasingly implicated in kidney injury and fibrotic remodeling. This review summarizes molecular mechanisms linking mitochondrial homeostasis and ferroptosis in renal fibrosis. We discuss how disrupted iron metabolism can induce mitochondrial dysfunction and sensitize renal cells to ferroptosis, thereby promoting fibrogenesis. We integrate recent evidence on the interplay among iron homeostasis, mitochondrial dysfunction, oxidative stress, and regulated cell death pathways in renal fibrosis. We also highlight candidate therapeutic targets, including iron chelation and iron-export regulation (e.g., the FPN-hepcidin axis), restoration of the GPX4-System Xc^- antioxidant defense, activation of Nrf2 signaling, and modulation of mitochondrial quality control/mitophagy.