Effects of pretreatment with terazosin and valsartan on intraoperative haemodynamics in patients with phaeochromocytoma.

OBJECTIVE: Surgery is the primary strategy for treating phaeochromocytoma (PCC), but it can lead to severe hypertension and heart failure. Although valsartan is effective in reducing high blood pressure, clinical data on the potential role of valsartan in PCC are currently limited. Therefore, the aim of this study was to investigate the effects of pretreatment with terazosin and valsartan on patients with PCC. METHODS: In this retrospective cohort study, 50 patients who underwent laparoscopic resection of PCC were enrolled. During preoperative preparation, the patients (n=25) in the control group were treated with terazosin, while those (n=25) in the combination treatment group were treated with terazosin and valsartan. The levels of catecholamine hormones before and after surgery were determined, and the intraoperative blood pressure and the incidence of complications were compared between the two groups. RESULTS: The results showed no significant differences in baseline patient characteristics or surgical conditions between the two groups (p>0.05). However, on the third day after surgery, the levels of catecholamine hormones in the two groups were significantly lower than those before surgery (p<0.05), while the levels in the combination treatment group were notably lower than those in the control group (p<0.05). The patients in the combination treatment group showed lower intraoperative blood pressure fluctuations and incidence of perioperative complications compared with the control group (p<0.05). CONCLUSIONS: Terazosin combined with valsartan can effectively improve perioperative haemodynamic instability and reduce postoperative complications in the preoperative management of PCC.

Silencing of ATP2B1-AS1 contributes to protection against myocardial infarction in mouse via blocking NFKBIA-mediated NF-κB signalling pathway.

Myocardial infarction (MI) is an acute coronary syndrome that refers to tissue infarction of the myocardium. This study aimed to investigate the effect of long intergenic non-protein-coding RNA (lincRNA) ATPase plasma membrane Ca2+ transporting 1 antisense RNA 1 (ATP2B1-AS1) against MI by targeting nuclear factor-kappa-B inhibitor alpha (NFKBIA) and mediating the nuclear factor-kappa-B (NF-κB) signalling pathway. An MI mouse model was established and idenepsied by cardiac function evaluation. It was determined that ATP2B1-AS1 was highly expressed, while NFKBIA was poorly expressed and NF-κB signalling pathway was activated in MI mice. Cardiomyocytes were extracted from mice and introduced with a series of mouse ATP2B1-AS1 vector, NFKBIA vector, siRNA-mouse ATP2B1-AS1 and siRNA-NFKBIA. The expression of NF-κBp50, NF-κBp65 and IKKß was determined to idenepsy whether ATP2B1-AS1 and NFKBIA affect the NF-κB signalling pathway, the results of which suggested that ATP2B1-AS1 down-regulated the expression of NFKBIA and activated the NF-κB signalling pathway in MI mice. Based on the data from assessment of cell viability, cell cycle, apoptosis and levels of inflammatory cytokines, either silencing of mouse ATP2B1-AS1 or overexpression of NFKBIA was suggested to result in reduced cardiomyocyte apoptosis and expression of inflammatory cytokines, as well as enhanced cardiomyocyte viability. Our study provided evidence that mouse ATP2B1-AS1 silencing may have the potency to protect against MI in mice through inhibiting cardiomyocyte apoptosis and inflammation, highlighting a great promise as a novel therapeutic target for MI.

MiR-128-3p accelerates cardiovascular calcification and insulin resistance through ISL1-dependent Wnt pathway in type 2 diabetes mellitus rats.

Vascular calcification is highly prevalent in patients with type 2 diabetes mellitus (T2DM), one of the most common chronic diseases with high morbidity and mortality. In recent years, microRNAs have been widely reported as potential biomarkers for the diagnosis and treatment of T2DM. We hypothesized that miR-128-3p is associated with cardiovascular calcification and insulin resistance (IR) in rats with T2DM by targeting ISL1 via the Wnt pathway. Microarray analysis was adopted to identify differentially expressed genes related to T2DM. T2DM models were induced in rats. Blood samples from normal and T2DM rats were used to detect islet ß-cell function, islet sensitivity, and calcium content. Next, islet tissues were obtained to identify the expression of miR-128-3p, ISL1, and the Wnt signaling pathway- and apoptosis-related genes. Finally, apoptosis of islet ß-cells was determined by flow cytometry. Through microarray analysis of GSE27382 and GSE23343, ISL1 was found to be downregulated in T2DM. In blood samples from T2DM rats, basic biochemical indicators, IR, and calcium content were increased, and islet sensitivity and islet ß-cell function were decreased. Furthermore, upregulation of miR-128-3p and ISL1 gene silencing promoted the expression of Wnt-1, ß-catenin, GSK-3ß, and Bax and the phosphorylation of ß-catenin and GSK-3ß, inhibited c-fos, PDX-1, and Bcl-2 expression, and enhanced cell apoptosis. The key findings of our study demonstrate that miR-128-3p aggravates cardiovascular calcification and IR in T2DM rats by downregulating ISL1 through the activation of the Wnt pathway. Thus, miR-128-3p may serve as a potential target for the treatment of T2DM.

Sevoflurane pretreatment inhibits the myocardial apoptosis caused by hypoxia reoxygenation through AMPK pathway: An experimental study.

OBJECTIVE: To study whether sevoflurane pretreatment inhibits the myocardial apoptosis caused by hypoxia reoxygenation through AMPK pathway. METHODS: H9c2 myocardial cell lines were cultured and divided into control group (C group), hypoxia reoxygenation group (H/R group), sevoflurane pretreatment + hypoxia reoxygenation group (SP group) and sevoflurane combined with Compound C pretreatment + hypoxia reoxygenation group (ComC group), and the cell proliferation activity and apoptosis rate, myocardial enzyme levels in culture medium as well as the expression of apoptosis genes and p-AMPK in cells were determined. RESULTS: p-AMPK expression in cells of H/R group was significantly lower than that of C group, SP group was significantly higher than that of H/R group; cell proliferation activity value and Bcl-2 expression in cells of H/R group were significantly lower than those of C group, SP group were significantly higher than those of H/R group, ComC group were significantly lower than those of SP group; apoptosis rate, LDH, CK and AST levels as well as the Bax and Caspase-3 expression in cells of H/R group were significantly higher than those of C group, SP group were significantly lower than those of H/R group, ComC group were significantly higher than those of SP group. CONCLUSIONS: Sevoflurane pretreatment can activate AMPK signaling pathway to inhibit the myocardial apoptosis caused by hypoxia reoxygenation.