MicroRNA-126 enhances the biological function of endothelial progenitor cells under oxidative stress via PI3K/Akt/GSK3ß and ERK1/2 signaling pathways.

Endothelial progenitor cell (EPC) transplantation is a safe and effective method to treat acute myocardial infarction (AMI). However, oxidative stress leads to the death of a large number of EPCs in the early stage of transplantation, severely weakening the therapeutic effect. Previous studies demonstrated that microRNAs regulate the biological function of EPCs. The aim of the current study was to investigate the effect of microRNA on the biological function of EPCs under oxidative stress. Quantitative reverse transcription PCR was performed to detect the expression of miR-126, miR-508-5p, miR-150, and miR-16 in EPCs from rats, among which miR-126 showed a relatively higher expression. Treatment with H2O2 decreased miR-126 expression in EPCs in a dose-dependent manner. EPCs were further transfected with miR-126 mimics or inhibitors, followed by H2O2 treatment. Overexpression of miR-126 enhanced the proliferation, migration, and tube formation of H2O2-treated EPCs. MiR-126 overexpression also inhibited reactive oxygen species and malondialdehyde levels and enhanced superoxide dismutase levels, as well as increased angiopoietin (Ang)1 expression and decreased Ang2 expression in H2O2-treated EPCs. Moreover, miR-126 participated in the regulation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase 3ß (GSK3ß) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling in EPCs, where both pathways were activated after miR-126 overexpression in H2O2-treated EPCs. Overall, we showed that miR-126 promoted the biological function of EPCs under H2O2-induced oxidative stress by activating the PI3K/Akt/GSK3ß and ERK1/2 signaling pathway, which may serve as a new therapeutic approach to treat AMI.

ERK1/2-PPARγ pathway is involved in Chlamydia pneumonia-induced human umbilical vein endothelial cell apoptosis through increased LOX-1 expression.

Chlamydia pneumonia (C.pn) is a common respiratory pathogen that is involved in human cardiovascular diseases and promotes the development of atherosclerosis in hyperlipidemic animal models. C.pn reportedly up-regulated lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) in endothelial cells. Recently, the anti-atherosclerotic activity of peroxisome proliferator-activated receptor γ (PPARγ) has been documented. In the present study, we investigated the effect of C.pn on LOX-1 expression in human umbilical vein endothelial cells (HUVECs) and identified the involvement of the PPARγ signaling pathway therein. The results showed that C.pn increased the expression of LOX-1 in HUVECs in a dose- and time-dependent manner. C.pn-induced up-regulation of LOX-1 was mediated by ERK1/2, whereas p38 MAPK and JNK had no effect on this process. C.pn induced apoptosis, inhibited cell proliferation, and decreased the expression PPARγ in HUVECs. Additionally, LOX-1 activity and cell injury caused by C.pn through activation of ERK1/2 was completely inhibited by rosiglitazone, a PPARγ agonist. In conclusion, we inferred that activation of PPARγ in HUVECs suppressed C.pn-induced LOX-1 expression and cell damage by inhibiting ERK1/2 signaling.

Predictive value of long non-coding RNA intersectin 1-2 for occurrence and in-hospital mortality of severe acute pancreatitis.

BACKGROUND: This study aimed to investigate the predictive value of long non-coding RNA intersectin 1-2 (lnc-ITSN1-2) for severe acute pancreatitis (SAP) risk, and its correlation with disease severity and in-hospital mortality in SAP patients. METHODS: Plasma samples from 60 SAP, 60 moderate-severe acute pancreatitis (MSAP) and 60 mild acute pancreatitis (MAP) patients were collected within 24 hours, and plasma samples from 60 age and gender-matched healthy controls (HCs) were collected when enrollment. Lnc-ITSN1-2 was detected by reverse transcription-quantitative polymerase chain reaction. In AP patients, disease severity was evaluated and in-hospital deaths were recorded. RESULTS: Lnc-ITSN1-2 was increased in SAP patients compared with MSAP, MAP patients, and HCs, and it is well-discriminated SAP patients from MSAP patients (area under curve (AUC): 0.699, 95% confidence interval (CI): 0.605-0.792), MAP patients (AUC: 0.862, 95% CI: 0.798-0.926), and HCs (AUC: 0.958, 95% CI: 0.925-0.990). For disease severity, lnc-ITSN1-2 was positively correlated with Ranson's score, acute pathologic and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, and C-reactive protein (CRP) in SAP patients, MSAP patients, and MAP patients; meanwhile, the correlation coefficients were highest in SAP patients. Furthermore, lnc-ITSN1-2 displayed a good predictive value for increased in-hospital mortality in SAP (AUC: 0.803, 95% CI: 0.673-0.933) and MSAP (AUC: 0.854, 95% CI: 0.752-0.956) patients, which was similar with several common prognostic factors (including Ranson's score, APACHE II score, SOFA score, and CRP). CONCLUSION: Lnc-ITSN1-2 might be a potential biomarker for discrimination of SAP to improve the prognosis of SAP patients.

Qiliqiangxin Protects against Renal Injury in Rat with Cardiorenal Syndrome Type I through Regulating the Inflammatory and Oxidative Stress Signaling.

Cardiorenal syndrome (CRS) is a frequently encountered clinical condition when the dysfunction of either the heart or kidneys amplifies the failure progression of the other organ. CRS remains a major global health problem. Qiliqiangxin (QLQX) is a traditional Chinese herbs medication, which can improve cardiac function, urine volume, and subjective symptoms in patients with chronic heart failure. In the present study, we aim to investigate the role of QLQX in the treatment of CRS type I and the possible mechanism through establishment of a rat model of myocardial infarction. Rats in CRS-Q group were orally treated with QLQX daily for 2 weeks or 4 weeks, while in sham group and CRS-C group were treated with saline at the same time. Enzyme-linked immunosorbent assay (ELISA) analysis showed that QLQX significantly reduced the levels of angiotensin II (AngII), brain natriuretic peptides (BNP), creatinine (CRE), cystatin C (CysC), tumor necrosis factor (TNF)-α, interleukin (IL)-6, microalbuminuria (MAU), and neutrophil gelatinase-associated lipocalin (NGAL) in plasma induced by myocardial infarction. Western blot analysis showed that QLQX significantly reduced the expressions of AngII, non-phagocytic cell oxidase (NOX)2, and B-cell lymphoma (Bcl)2 associated X protein (Bax), and increased the expressions of Bcl2 and Angiotensin II Type 1 receptor (ATR) in the kidney as compared with the CRS-C group. Fluorescence microscopy showed that the content of reactive oxygen species (ROS) was significantly reduced in the kidney as compared with the CRS-C group. We also examined the apoptosis level in kidney by using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining, and the result showed that QLQX significantly reduced the apoptosis level in kidney induced by myocardial infarction. Taken together, we suggest that QLQX may be a potentially effective drug for the treatment of CRS by regulating inflammatory/oxidative stress signaling.

[Species distribution of pathogens and prognostic factors for catheter-related bloodstream infections in intensive care unit].

OBJECTIVE: To explore the incidence and species distribution of catheter-related bloodstream infection (CRBSI) in intensive care unit (ICU) at our hospital and analyze the risk factors for CRBSI. METHODS: Hospitalized patients microbiologically diagnosed as CRBSI were recruited from January 2012 to June 2013. And the clinical data were collected retrospectively and analyzed by software IBM SPSS 19.0. RESULTS: Among 67 patients diagnosed as nosocomial CRBSI, 24 cases (35.8%) died while 43 survived. And a total of 81 strains were detected, including 42 Gram-positive (G⁺) bacteria (51.9%), 36 Gram-negative (G⁻) bacteria (44.4%) and 3 fungi (3.7%).The predominant pathogenic G⁺ and G⁻ bacteria were Staphylococcus epidermidis and Acinetobacter baumannii respectively. With multiple Logistic regressions, age ≥ 65 years, higher acute physiology & chronic health evaluation II (APACHE II) score and polymicrobial CRBSI were independent predictors of worse outcomes. CONCLUSION: The recent prevalent pathogens of CRBSI in ICU are S.epidermidis and A.baumannii. Advanced age, disease severity and polymicrobial CRBSI are significant independent risk factor of mortality for CRBSI patients in ICU.