Mechanism of Action of NvZhen ErXian HeJi in Ovariectomized Rats with Myocardial Infarction based on Network Pharmacology.

OBJECTIVE: NvZhen ErXian HeJi (NZEXHJ) is used to treat perimenopausal syndrome (PS), but its effect on perimenopausal coronary heart disease is unclear. Furthermore, the aim of this research is to study the effect of NZEXHJ on perimenopausal coronary heart disease (PMCHD) in a rat model based on a network pharmacology approach. MATERIALS AND METHODS: Based on network pharmacological analysis combined with molecular docking, we predicted the potential therapeutic target and pharmacological mechanism of NZEXHJ in the treatment of PMCHD. We used an ovariectomized rat (OVR) model to understand the effect of NZEXHJ on myocardial injury and further verified the target of NZEXHJ in the intervention of PMCHD. RESULTS: We selected 52 active components of NZEXHJ against PMCHD and an intersection of their targets on network pharmacology, to which SCN5A, SER1, AR, and PGR were significantly correlated. The protein- protein interaction network revealed CASP3, CXCL8, IL6, MAPK1, TNF, TP53, and VEGFA in the treatment of PMCHD with NZEXHJ. Kaempferol, luteolin, and mistletoe presented good affinity towards the aforementioned targets by Molecular docking NZEXHJ exerted protecting cardiomyocytes for OVR. The mechanism was related to a reduction in the expression levels of the CXCL8, TNF, and regulating PI3K-Akt signaling pathways. CONCLUSION: This study reveals the potential multi-component, multi-target, and multi-pathway pharmacological effects of NZEXHJ and predicts its protection against myocardial infarction in ovariectomized rats through the PI3K Akt pathway, providing a theoretical basis for the treatment of PMCHD.

Long non-coding RNAs: Modulators of phenotypic transformation in vascular smooth muscle cells.

Long non-coding RNA (lncRNAs) are longer than 200 nucleotides and cannot encode proteins but can regulate the expression of genes through epigenetic, transcriptional, and post-transcriptional modifications. The pathophysiology of smooth muscle cells can lead to many vascular diseases, and studies have shown that lncRNAs can regulate the phenotypic conversion of smooth muscle cells so that smooth muscle cells proliferate, migrate, and undergo apoptosis, thereby affecting the development and prognosis of vascular diseases. This review discusses the molecular mechanisms of lncRNA as a signal, bait, stent, guide, and other functions to regulate the phenotypic conversion of vascular smooth muscle cells, and summarizes the role of lncRNAs in regulating vascular smooth muscle cells in atherosclerosis, hypertension, aortic dissection, vascular restenosis, and aneurysms, providing new ideas for the diagnosis and treatment of vascular diseases.

Effects of glycemic traits on left ventricular structure and function: a mendelian randomization study.

BACKGROUND: Adverse ventricular structure and function is a key pathogenic mechanism of heart failure. Observational studies have shown that both insulin resistance (IR) and glycemic level are associated with adverse ventricular structure and function. However, whether IR and glycemic level are causally associated with cardiac structure and function remains unclear. METHODS: Genetic variants for IR, fasting insulin, HbA1c, and fasting glucose were selected based on published genome-wide association studies, which included 188,577, 108,557, 123,665, and 133,010 individuals of European ancestry, respectively. Outcome datasets for left ventricular (LV) parameters were obtained from UK Biobank Cardiovascular Magnetic Resonance sub-study (n = 16,923). Mendelian randomization (MR) analyses with the inverse-variance weighted (IVW) method were used for the primary analyses, while weighted median, MR-Egger, and MR-PRESSO were used for sensitivity analyses. Multivariable MR analyses were also conducted to examine the independent effects of glycemic traits on LV parameters. RESULTS: In the primary IVW MR analyses, per 1-standard deviation (SD) higher IR was significantly associated with lower LV end-diastolic volume (ß = - 0.31 ml, 95% confidence interval [CI] - 0.48 to - 0.14 ml; P = 4.20 × 10-4), lower LV end-systolic volume (ß = - 0.34 ml, 95% CI - 0.51 to - 0.16 ml; P = 1.43 × 10-4), and higher LV mass to end-diastolic volume ratio (ß = 0.50 g/ml, 95% CI 0.32 to 0.67 g/ml; P = 6.24 × 10-8) after Bonferroni adjustment. However, no associations of HbA1c and fasting glucose were observed with any LV parameters. Results from sensitivity analyses were consistent with the main findings, but with a slightly attenuated estimate. Multivariable MR analyses provided further evidence for an independent effect of IR on the adverse changes in LV parameters after controlling for HbA1c. CONCLUSIONS: Our study suggests that genetic liability to IR rather than those of glycemic levels are associated with adverse changes in LV structure and function, which may strengthen our understanding of IR as a risk factor for heart failure by providing evidence of direct impact on cardiac morphology.

Comparative physiological and transcriptomics analysis revealed crucial mechanisms of silicon-mediated tolerance to iron deficiency in tomato.

Iron (Fe) deficiency is a common abiotic stress in plants grown in alkaline soil that causes leaf chlorosis and affects root development due to low plant-available Fe concentration. Silicon (Si) is a beneficial element for plant growth and can also improve plant tolerance to abiotic stress. However, the effect of Si and regulatory mechanisms on tomato plant growth under Fe deficiency remain largely unclear. Here, we examined the effect of Si application on the photosynthetic capacity, antioxidant defense, sugar metabolism, and organic acid contents under Fe deficiency in tomato plants. The results showed that Si application promoted plant growth by increasing photosynthetic capacity, strengthening antioxidant defense, and reprogramming sugar metabolism. Transcriptomics analysis (RNA-seq) showed that Si application under Fe deficiency up-regulated the expression of genes related to antioxidant defense, carbohydrate metabolism and organic acid synthesis. In addition, Si application under Fe deficiency increased Fe distribution to leaves and roots. Combined with physiological assessment and molecular analysis, these findings suggest that Si application can effectively increase plant tolerance to low Fe stress and thus can be implicated in agronomic management of Fe deficiency for sustainable crop production. Moreover, these findings provide important information for further exploring the genes and underlying regulatory mechanisms of Si-mediated low Fe stress tolerance in crop plants.