Angiotensin II mediates the high-glucose-induced endothelial-to-mesenchymal transition in human aortic endothelial cells

<p>Abstract</p> <p>Background</p> <p>Substantial evidence suggests that high glucose (HG) causes endothelial cell damage; however, the potential mechanism therein has yet to be clarified. The aim of this study was to investigate the influence of HG on the endothelial-to-mesenchymal transition (EndMT) and its relevance to the activation of the renin-angiotensin system.</p> <p>Methods</p> <p>Primary human aortic endothelial cells (HAECs) were divided into three groups: a normal glucose (NG) group, HG group, and irbesartan (1 μM)-treated (HG+irbesartan) group. The concentration of angiotensin II in the supernatant was detected by radioimmunoassay. Pathological changes were investigated using fluorescence microscopy and electron microscopy. Immunofluorescence staining was performed to detect the co-expression of CD31 and fibroblast markers, such as fibroblast-specific protein 1 (FSP1). The expressions of FSP1 and α-SMA were detected by RT-PCR and Western blot.</p> <p>Results</p> <p>The treatment of HAECs in the HG group resulted in significant increases in the expressions of FSP1 and angiotensin II in dose-and time-dependent manners. The incubation of HAECs exposure to HG resulted in a fibroblast-like phenotype, wherein increased microfilamentation and a roughened endoplasmic reticulum structure were observed in the cytoplasm. The expressions of FSP1 and α-SMA were significantly increased in the HG group, and these changes were inhibited by irbesartan treatment (<it>P </it>< 0.05). Double staining of the HAECs indicated a co-localization of CD31 and FSP1 and that some cells acquired spindle-shaped morphologies and a loss of CD31 staining; however, treatment with irbesartan attenuated the expression of EndMT (<it>P </it>< 0.05).</p> <p>Conclusions</p> <p>These findings suggest a novel mechanism in HG-induced endothelial damage via the mediation of the EndMT by angiotensin II, which was inhibited by Irbesartan.</p

Analyzing clinical characteristics of patients with different cumulative hemodialysis durations: a cross-sectional study

Background The objective of this study was to examine the clinical characteristics of patients with different cumulative hemodialysis (HD) durations, so as to improve their survival rate. Methods In this cross-sectional study, we extracted background information and relevant clinical data from 145 patients who were undergoing maintenance HD three times a week at the Affiliated Hospital of Nantong University between January 1998 and January 2019. The study subjects were divided into four groups according to the duration of their HD: 15 years of HD. We collected the medical history and relevant clinical parameters for each subject, and measured the urea reduction ratio (URR), hemoglobin (Hb), serum calcium, phosphorus, parathyroid hormone (iPTH), and serum albumin (ALB) levels for each group. Results The average patient age was 52.06 ±  11.93 years old. The average patient age in the 10–15 years and >15 years groups was significantly lower than in the <5 years and 5–10 years groups (P = 0.002, P < 0.001, P = 0.012, and P = 0.0025, respectively). The most common cause of end-stage renal disease (ESRD) was chronic glomerulonephritis. We found no significant differences in URR, Hb, serum calcium, serum phosphorus, iPTH, and ALB levels. Conclusion A prolonged HD duration was related to a younger mean age at the start of HD treatment. The leading cause of ESRD was chronic glomerulonephritis. We predominantly found diabetic nephropathy in the group with a duration of <5 years cumulative HD. Most of the indexes related to hemodialysis almost satisfied the recommended values in these patients

Geochemical characteristics and genesis of Paleozoic natural gas in the Ordos Basin

The geochemical characteristics and genesis of Paleozoic natural gas in the Ordos Basin are complex, with some disputes on the gas source of Lower Paleozoic. In order to better grasp the overall geochemical characteristics and variation laws of Paleozoic natural gas in the basin, the geochemical data of more than 700 natural gas samples from the whole basin are comprehensively analyzed based on the systematic collection, collation and analysis of previous data, and the genesis of natural gas is explored by combining the analysis of key elements such as natural gas formation, hydrocarbon formation and reservoir formation. The results show that the main body of Upper Paleozoic natural gas is coal-based gas controlled by maturity, with maturity increasing from northeast to southwest, and the southern part of the basin has a mixture of Upper and Lower Paleozoic gas. The Lower Paleozoic gas is dominated by oil-type gas from marine carbonate formations, of which the upper combination is characterized by a two-source composite reservoir of Upper Paleozoic coal-type gas and Lower Paleozoic oil-type gas; the middle-lower combination is a relatively independent oil-type gas reservoir, subject to different degrees of secondary transformation based on geological conditions and the degree of thermal evolution of organic matter, resulting in significant anomalies in its carbon isotope composition. The research has proved that marine hydrocarbon sources including carbonate rocks exist in the Lower Paleozoic of the basin, and the natural gas in the Upper and Lower Paleozoic has mixed to varying degrees in different locations of the basin

Polybrominated diphenyl ethers in urban Jinan, eastern China: Characterization, source identification, and respiratory exposure assessment

In order to assess the characteristics of polybrominated diphenyl ether (PBDEs) in the atmosphere of urban Jinan, eastern China, gas phase and PM2.5 were hereby sampled in July 2020. The concentration and composition characteristics of 11 PBDEs were obtained. The Human exposure was evaluated by the daily exposure calculation method. During the observation period, the average concentration of ∑11PBDEs in PM2.5 and gas phase was 214.8±31.3 pg/m3, that of low-PBDEs was 119.1±2.1 pg/m3, and that of BDE209 was 95.8±15.4 pg/m3. Among the 10 low-PBDEs, the highest single content was BDE99, followed by BDE47, accounting for 43%. PCA showed the main sources of PBDEs in the atmosphere of urban Jinan were Penta-BDEs and Deca-BDEs. The daily respiratory exposure of children were higher than that of adults, and the potential risk should be taken seriously

TAK-242, a Toll-Like Receptor 4 Antagonist, Protects against Aldosterone-Induced Cardiac and Renal Injury.

Cardiovascular and renal inflammation induced by Aldosterone (Aldo) plays an important role in the pathogenesis of hypertension and renal fibrosis. Toll-like receptor 4 (TLR4) signaling contributes to inflammatory cardiovascular and renal diseases, but its role in Aldo-induced hypertension and renal damage is not clear. In the current study, rats were treated with Aldo-salt combined with TAK-242 (a TLR4 signaling antagonist) for 4 weeks. Hemodynamic, cardiac and renal parameters were assayed at the indicated time. We found that Aldo-salt-treated rats present cardiac and renal hypertrophy and dysfunction. Cardiac and renal expression levels of TLR4 as well as levels of molecular markers attesting inflammation and fibrosis are increased by Aldo infusion, whereas the treatment of TAK-242 reverses these alterations. TAK-242 suppresses cardiac and renal inflammatory cytokines levels (TNF-a, IL-1β and MCP-1). Furthermore, TAK-242 inhibits hypertension, cardiac and renal fibrosis, and also attenuates the Aldo-induced Epithelial-Mesenchymal Transition (EMT). In experimental hyperaldosteronism, upregulation of TLR4 is correlated with cardiac and renal fibrosis and dysfunction, and a TLR4 signaling antagonist, TAK-242, can reverse these alterations. TAK-242 may be a therapeutic option for salt-sensitive hypertension and renal fibrosis

ADAR1-regulated miR-142-3p/RIG-I axis suppresses antitumor immunity in nasopharyngeal carcinoma

Following the initial treatment of nasopharyngeal carcinoma (NPC), tumor progression often portends an adverse prognosis for these patients. MicroRNAs (miRNAs) have emerged as critical regulators of tumor immunity, yet their intricate mechanisms in NPC remain elusive. Through comprehensive miRNA sequencing, tumor tissue microarrays and tissue samples analysis, we identified miR-142-3p as a significantly upregulated miRNA that is strongly associated with poor prognosis in recurrent NPC patients. To elucidate the underlying molecular mechanism, we employed RNA sequencing, coupled with cellular and tissue assays, to identify the downstream targets and associated signaling pathways of miR-142-3p. Our findings revealed two potential targets, CFL2 and WASL, which are directly targeted by miR-142-3p. Functionally, overexpressing CFL2 or WASL significantly reversed the malignant phenotypes induced by miR-142-3p both in vitro and in vivo. Furthermore, signaling pathway analysis revealed that miR-142-3p repressed the RIG-I-mediated immune defense response in NPC by inhibiting the nuclear translocation of IRF3, IRF7 and p65. Moreover, we discovered that ADAR1 physically interacted with Dicer and promoted the formation of mature miR-142-3p in a dose-dependent manner. Collectively, ADAR1-mediated miR-142-3p processing promotes tumor progression and suppresses antitumor immunity, indicating that miR-142-3p may serve as a promising prognostic biomarker and therapeutic target for NPC patients