MicroRNAs (miRNAs) are involved in the regulation of a variety of biological processes, such as inflammation. Dysregulation of miRNAs have been implicated in many human disease, including cardiovascular diseases. Polymorphisms in miRNA genes may affect the miRNA biogenesis and function, and thus cause changes in the expression of thousands of genes. The aim of this study was to examine whether miRNA polymorphisms (miR-146a rs2910164, miR-149 rs71428439, miR-196a2 rs11614913, miR-218 rs11134527, and miR-499 rs3746444) contribute to the risk for the development of myocardial infarction (MI). Five miRNA polymorphisms were genotyped in a total of 1808 subjects composed of 919 MI patients and 889 control individuals. The GG genotype of rs3746444 was found to be associated with a significantly increased risk of MI (recessive model, adjusted OR = 1.710, 95% CI: 1.058-2.763, P = 0.029). Although the CC genotype of rs2910164 significantly increased the risk of MI under dominant and additive models (P < 0.05), this difference disappeared after adjustment for age, sex, blood pressure, triglycerides, total cholesterol, HDL, LDL and diabetes. In addition, when rs3746444 and rs2910164 were evaluated together by the number of putative high-risk alleles, we found an increased risk of MI for subjects carrying 3-4 risk alleles (3-4 risk alleles vs. 0-1 risk allele, adjusted OR = 1.580, 95% CI: 1.069-2336, P = 0.022; 3-4 risk alleles vs. 0-2 risk allele, adjusted OR = 1.513, 95% CI: 1.031-2.219, P = 0.034). These findings indicate that miR-499 rs3746444 and miR-146a rs2910164 may represent novel markers of MI susceptibility.

Abstract. The aim of the present study was to investigate the effect of curcumin on acute renal injury in a rat model of severe acute pancreatitis (SAP). A SAP model with acute kidney injury was established in rats by retrograde injection of 5% sodium taurocholate into the pancreatic duct. The serum amylase, creatinine (Cr) and blood urea nitrogen (BUN) levels in rats were measured. Hematoxylin and eosin staining was used to assess pancreatic and renal histological changes. Serum tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels were measured using ELISA kits. Renal protein levels of Janus kinase (JAK) 2/signal transducer and activator of transcription (STAT) 3 pathway components were determined by western blot assay. The results showed that curcumin significantly decreased serum amylase, Cr and BUN levels, and alleviated pancreatic and renal histological changes in SAP rats. Furthermore, curcumin markedly decreased serum TNF-α and IL-6 levels and downregulated renal protein levels of JAK2/STAT3 pathway components. These results proved that curcumin ameliorates acute renal injury in a rat model of SAP. The molecular mechanism of its effect may be associated with the suppression of the JAK2/STAT3 pathway to reduce TNF-α and IL-6 levels in SAP-induced acute renal injury. Therefore, the findings of the present study revealed the potential use of curcumin for the prevention and treatment of SAP and the associated renal injury. IntroductionSevere acute pancreatitis (SAP), an acute inflammatory condition of the pancreas, is considered to be a paradigm of sterile inflammation leading to systemic multiple organ dysfunction syndrome (MODS) and death. Acute renal injury (ARI) is one of the main complications of SAP and significantly increases the mortality rate of patients with AP (66.6 vs. 14.5%) (1). However, the underlying mechanisms of ARI occurring in patients with SAP have remained to be clarified. Increasing evidence has indicated that pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α) and interleukin (IL)-6, have an important role in the pathological mechanisms of SAP and SAP-associated organ failure (2-4). Therefore, inhibiting the transcription and translation of mediators to reduce the secretion of pro-inflammatory factors may ameliorate inflammation and renal failure in SAP.Signal transducers and activators of transcription (STATs), a protein family comprised of seven members (STAT1, -2, -3, -4, -5a, -5b and -6), generally transduce signals from activated receptors or intracellular kinases to the nucleus, thus activating and regulating gene transcription (5). The Janus kinase 2 (JAK2)/STAT3 pathway is well known to be involved in the immune response of numerous cytokines, including TNF-α and IL-6 (6). In addition, evidence derived from numerous clinical and experimental studies suggests the involvement of the JAK2/STAT3 pathway in pancreatitis (7-9) or renal diseases (10-12).Curcumin (diferuloylmethane), the active phytochemical component of turmeric (a spice used mostly in Asia) h...

The aim of the present study was to investigate the increase in serum and urine levels of high mobility group box protein 1 (HMGB1) during sepsis and the effect of blood purification treatments on HMGB1 levels and patient prognosis. A total of 40 intensive care patients with sepsis were randomly assigned to different groups (n=10 per group): A control group (sepsis group), a continuous renal replacement treatment (CRRT) group, a hemoperfusion (HP) group and an HP+CRRT group. The blood purification treatments using HP and/or CRRT were performed immediately after the diagnosis of sepsis. HMGB1 levels were measured using ELISA, and Acute Physiology and Chronic Health Evaluation (APACHE) II scores and 30-day survival rates were evaluated. Relative to a healthy control group (n=10), HMGB1 levels were observed to be significantly upregulated during sepsis (P<0.05). Following the initiation of sepsis, serum HMGB1 continued to increase in the sepsis group and was significantly elevated at 24 h (P<0.05), whereas urine HMGB1 levels decreased significantly at 12 and 24 h (P<0.05). Serum HMGB1 levels were significantly positively correlated with APACHE II scores (r=0.7284, P<0.01) and significantly negatively correlated with urine HMGB1 levels (r=−0.5103, P=0.026). Serum HMGB1 levels were significantly reduced in the HP and HP+CRRT groups by 12 and 24 h following the initiation of treatment (both P<0.05). Changes in the urine HMGB1 level differed in each group. Relative to the sepsis group, the APACHE II scores of all blood purification groups were significantly reduced (P<0.05) and the 30-day survival rate of the HP+CRRT group was significantly increased (P=0.0107). The results of the present study indicate that blood purification initiated at the point of diagnosis in patients with sepsis may attenuate serum HMGB1 upregulation, promote urinary excretion of HMGB1 and improve the prognosis of sepsis.

BackgroundTo study the effects of different positive end expiratory pressure (PEEP) on blood pressure and heart function in elderly patients with hypertension.MethodsForty elderly patients above 65 years of age treated with mechanical ventilation were divided into two groups: a control group of non-hypertensive subjects (n = 18) and a hypertension group (n = 22) patients with essential hypertension. Changes in blood pressure, central venous pressure (CVP), central venous oxygen saturation (ScvO2), heart rate, and airway pressure were determined in response to different selected PEEP levels of 0, 2, 4, 6, 8, 10 and 12 cm H2O under SIMV(PC) + PSV mode throughout the study.ResultsIn both groups, the increase in PEEP led to an increase in CVP and airway pressure. When PEEP was above 4 cm H2O in the hypertension group, a decrease in blood pressure and ScvO2, and an increase of heart rate were observed. These results indicated that cardiac output significantly decreased.ConclusionHigh levels of PEEP can significantly influence changes in blood pressure and heart function in elderly patients with hypertension.Trial registrationThis trial was retrospectively registered, The Chinese trial registration number is ChiCTR-ROC-17012873. The date of registration is 10-2-2017.