Lowering expression of Epsin-3 inhibits migration and invasion of lung adenocarcinoma cells by inhibiting the epithelial-mesenchymal transition.

The epithelial-mesenchymal transition (EMT) is a genetic reprogramming that tumor cells utilize for metastasis. Epsin-3 (EPN3) is an endocytic adapter protein involved in clathrin-mediated endocytosis and had been previously linked to EMT in breast cancer and glioma metastasis. In this study, identified the role of epsin-3 in lung adenocarcinoma and metastasis and epsin-3 levels identified using an expression profile analysis of patient data indicated the protein was abnormally overexpressed in lung adenocarcinoma patients and this was directly linked to disease severity. Gene knockdowns of EPN3 in human adenocarcinoma cell line A549 and the non-small cell lung carcinoma cell line H1299 decreased the levels of mesenchymal markers, including vimentin (VIM), N-cadherin (NCAD) and embryonic transcription factors like zinc finger E-box binding homeobox 1(ZEB1), snail, and the key molecules of Wnt pathway such as ß-catenin and resulted in increased expression of the epithelial marker E-cadherin (ECAD). Our data links EPN3 to the EMT process in lung cancer and inhibition of its expression reduced the metastatic and invasive ability of lung adenocarcinoma cells by inhibiting the EMT process.

Cellular mechanism underlying leptin-induced anion secretion of rat epididymal epithelial cells.

BACKGROUND: A large number of studies have shown that leptin plays an important role in the regulation of fertility via the hypothalamus-pituitary-gonad axis. However, its peripheral function in epididymis was still elusive. OBJECTIVE: The purpose of this study was to determine the pro-secretion effect of leptin on the rat epididymal epithelium. MATERIALS AND METHODS: In the present study, real-time quantitative polymerase chain reaction, western blot, and immunohistochemical analysis were employed to detect the expression pattern of leptin receptors in rat epididymis. The pro-secretion effect of leptin on epididymal epithelial cells was measured by short-circuit current, and the prostaglandin E2 and cyclic adenosine monophosphate level was evaluated by enzyme-linked immunosorbent assay. RESULTS: We verified that the leptin receptor was located on the epididymal epithelium, with a relatively high expression level in corpus and cauda epididymis. Ussing chamber experiments showed that leptin stimulated a significant rise of the short-circuit current in rat epididymal epithelial cells, which could be abolished by the specific leptin receptor antagonist peptide Allo-aca, or by removing the ambient Cl- and HCO3 -. Furthermore, the leptin-stimulated short-circuit current response could be abrogated by blocking the apical cystic fibrosis transmembrane regulator or the basolateral Na+-K+-2Cl- cotransporter. Our pharmacological experiments manifested that interfering with the prostaglandin H synthase-2-prostaglandin E2-EP2/EP4-adenylate cyclase pathways could significantly blunt the cystic fibrosis transmembrane regulator-mediated anion secretion induced by leptin. The enzyme-linked immunosorbent assay demonstrated that leptin could induce a substantial increase in prostaglandin E2 release and cyclic adenosine monophosphate synthesis of primary cultured rat cauda epididymal epithelial cells. Our data also suggested that JAK2, ERK, and PI3K-dependent phosphorylation may be involved in the activation of prostaglandin H synthase-2 and the subsequent prostaglandin E2 production. CONCLUSIONS: The present study demonstrated the pro-secretion function of leptin in rat epididymal epithelium via the activation of cystic fibrosis transmembrane regulator and Na+-K+-2Cl- cotransporter, which was dependent on the paracrine/autocrine prostaglandin E2 stimulated EP2/EP4-adenylate cyclase pathways, and thus contributed to the formation of an appropriate microenvironment essential for sperm maturation.

Efficacy and safety of different traditional Chinese health exercises in patients with coronary heart disease combined with chronic heart failure: A network meta-analysis.

BACKGROUND: Non-pharmacological treatments, particularly TCM health exercises, have garnered attention for their affordability, ease of access, and potential health advantages. Despite this interest, systematic and direct comparative studies assessing the effectiveness and safety of these therapies in patients with CHD-CHF remain scarce. METHODS: This study aimed to compare the efficacy and safety of conventional treatment, conventional treatment integrated with aerobic endurance training, and various TCM health exercises in treating patients with CHD-CHF using NMA. The analysis was designed to provide a reference for developing treatment plans. To achieve this, literature databases were searched for RCTs on different TCM health exercises for CHD-CHF patients up to December 6, 2022. Major outcomes analyzed included NT-proBNP, LVEF, 6-minute walk test, MLHFQ, clinical effectiveness, and adverse event occurrence. The Cochrane risk of bias tool was employed to assess the risk of bias in the included RCT studies. Systematic review with NMA was conducted using RevMan 5.4 and Stata for cumulative ranking, and comparative adjustment funnel plot analysis. RESULTS: Traditional Chinese medicine gong methods included BaDuanJin (A) and TaiChiQuan (B). The NMA and SUCRA results revealed that: A + D and A + C + D were most likely to be the best interventions to improve NT-proBNP; B + D and A + C + D were most likely to be the best interventions to improve LVEF; A + D and A + C + D were the best interventions to improve 6WMT in CHD-CHF patients; B + C + D had the best effect on shrinking LVESD;A + D and B + C + D was likely the best interventions for contracting LVEDD;B + D and A + D were consistent in their capacity to improve MLHFQ in patients with CHD-CHF, but B + D had better efficacy. Unlike A + C + D, B + C + D was the best intervention to improve MLHFQ. In contrast with interventions, including Dand C + D, B + D was the most clinically effective intervention. Unlike interventions including B + C + D, C + D, and D, A + C + D was the most clinically efficient intervention. CONCLUSION: The findings of this NMA showed that traditional Chinese health exercises integrated with conventional treatment are more effective than conventional treatment (D) alone in patients with CHD-CHF, with A + D, B + D, B + C + D, and A + C + D considered potentially optimal treatment interventions.