Tohoku Journal of Experimental Medicine最新文献

Studies have found that miRNAs can participate in the progression of hypertension by affecting the function of endothelial cells and inflammatory response. This study was to investigate the clinical value of miR-320b in patients with hypertension and its potential effect on Angiotensin (Ang) II-induced endothelial cells. Real-time quantitative PCR (RT-qPCR) was used to detect the differential expression of miR-320b in all subjects, and the diagnostic value of miR-320b in hypertension was further evaluated by the receiver operating characteristic (ROC) curve. Ang II-induced human umbilical vein endothelial cells (HUVECs) were established as a model of hypertension injury. The possible downstream target gene AKT serine/threonine kinase 3 (AKT) of miR-320b was predicted through TargetScan, and the interaction between miR-320b and AKT3 was verified by luciferase reporter gene. The results showed that serum miR-320b was reduced in patients with hypertension compared with healthy people (P < 0.001). With the increase of hypertension grade, the serum miR-320b level of patients gradually decreased (P < 0.001). ROC analysis showed that miR-320b had the ability to distinguish patients from healthy people. Cell analysis proved that Ang II induced the decrease of HUVECs viability and the activation of apoptosis and inflammation, while overexpression of miR-320b inhibited Ang II-induced apoptosis and inflammation and promoted cell growth (P < 0.05). Luciferase reporter gene showed that AKT3 was the downstream target gene of miR-320b. In summary, this study suggests that miR-320b alleviates Ang II-induced apoptosis, inflammation and the inhibition of cell viability by targeting AKT3 expression, and may be involved in the pathogenesis of hypertension.

The effects of Gastrodin (GD) on cerebral ischemia stimulated researchers to investigate its possible role in the progression of arrhythmia associated with cardiac ischemia-reperfusion (IR) damage in rats. 40 Sprague-Dawley rats were divided into four groups: Sham, Model, GD 50 mg/kg, and GD 100 mg/kg. Myocardial ischemia (MI) was caused by the procedure of ligating the left coronary artery, followed by reperfusion. Heart rate (HR), mean arterial pressure (MAP), and rate pressure product (RPP) in rats were assessed before and after ischemia and reperfusion, as well as cardiac arrhythmia in experimental rats. The I/R damage was evaluated by measuring levels of Na ⁺-K⁺ATPase and Ca²⁺-Mg²⁺ATPase, Creatine Kinase-MB (CK-MB), Cardiac Troponin I (cTnI), Gap Junction α-1 (GJα-1), Phospho-GJα-1/total-GJα-1, Kir2.1, Bax, Bcl-2, and oxidative indicators. MGL's Autodock and Vina programs were used for in silico docking studies to identify possible interactions between GJα-1 and Gastrodin. The animals in the model group expressed a substantial decrease in HR, MAP, and RPP compared to the Sham group. GD-treated rats revealed slightly higher values compared to the model group. Expression of CK-MB and cTnI was reduced, and Na⁺-K⁺ATPase and Ca²⁺-Mg²⁺ATPase expression was increased on GD pre-conditioning. Phospho-Cx43/total-Cx43 ratio and Bax expression were increased, whereas GD reduced Bcl-2 expression. In silico molecular docking studies suggested the potential binding of GD with the GJα-1 protein, thus confirming the in vivo results. GD corrected the arrhythmia in rats subjected to I/R injury by increasing Na⁺-K⁺ATPase and Ca²⁺-Mg²⁺ATPase expression, targeting GJα-1, and modulating the expression of Kir2.1.

Arteriosclerosis obliterans (ASO) is characterized by arterial narrowing and blockage due to atherosclerosis, influenced by endothelial dysfunction and inflammation. This research focuses on exploring the role of MAGOH-DT, a long noncoding RNA, in mediating endothelial cell dysfunction through endothelial-mesenchymal transition (EndMT) under inflammatory and hyperglycemic stimuli, aiming to uncover potential therapeutic targets for ASO. Differential expression of lncRNAs, including MAGOH-DT, was initially identified in arterial tissues from ASO patients compared to healthy controls through lncRNA microarray analysis. Validation of MAGOH-DT expression in response to tumor necrosis factor-alpha (TNF-α) and high glucose (HG) was performed in human umbilical vein endothelial cells (HUVECs) using RT-qPCR. The effects of MAGOH-DT and HNRPC knockdown on EndMT were assessed by evaluating EndMT markers and TGF-β2 protein expression with Western blot analysis. RNA-immunoprecipitation assays were used to explore the interaction between MAGOH-DT and HNRPC, focusing on their role in regulating TGF-β2 translation. In the results, MAGOH-DT expression is found to be upregulated in ASO and further induced in HUVECs under TNF-α/HG conditions, contributing to the facilitation of EndMT. Silencing MAGOH-DT or HNRPC is shown to inhibit the TNF-α/HG-induced increase in TGF-β2 protein expression, effectively attenuating EndMT processes without altering TGF-β2 mRNA levels. In conclusion, MAGOH-DT is identified as a key mediator in the process of TNF-α/HG-induced EndMT in ASO, offering a promising therapeutic target. Inhibition of MAGOH-DT presents a novel therapeutic strategy for ASO management, especially in cases complicated by diabetes mellitus. Further exploration into the therapeutic implications of MAGOH-DT modulation in ASO treatment is warranted.

Helicobacter pylori (H. pylori) plays an important role in chronic atrophic gastritis (CAG). Interestingly, Shaoyao Gancao decoction (SGD), a traditional Chinese analgesic prescription, has the efficacy of relaxing spasms and relieving pain. Here, we aimed to identify whether SGD alleviates CAG and the underlying mechanism. A CAG mouse model was developed using H. pylori colonization and a high-salt diet. Histological staining was used to study the histopathological damage changes, and RT-qPCR assays the production of inflammatory responses in the gastric mucosa of mice. H. pylori and a high-salt diet induced gastric mucosal damage and apoptosis of gastric mucosal epithelial cells in mice, eliciting a significant inflammatory response. Treatment with SGD alleviated CAG-induced gastric mucosal damage, reduced apoptosis of gastric mucosal epithelial cells, and inhibited the inflammatory response. Bioinformatics was then used to construct the pharmacological network of SGD to explore its potential targets. SGD inhibited inflammatory response in mice with CAG by suppressing the expression of MAOB. Overexpression of MAOB impaired the therapeutic effect of SGD on inflammation in mice with CAG. Collectively, our findings indicated that SGD has the potential to alleviate CAG via downregulating MAOB.