Downregulation of ATP13A2 in midbrain dopaminergic neurons is related to defective autophagy in a mouse model of Parkinson's disease.

Parkinson's disease (PD) is one of the most common diseases of the nervous system characterized by movement disorders arising from loss of midbrain dopaminergic neurons. The relationship between PD and autophagy has received considerable attention. This study aimed to investigate the involvement of the ATP13A2 gene in damage of dopaminergic neurons induced by abnormal autophagy in a MPTP-induced PD mouse model. MPTP was intraperitoneally injected into C57BL mice at 40 mg/kg for 7 days in experimental group. Saline was injected into mice in the control group. After the injection, the mice were tested at different time points for abnormal limb movement by a swimming test. The brain tissue was collected on day 1, 5, and 7 to measure concentration of intracellular calcium. The expression of ATP13A2 was evaluated by real-time PCR. The expression of α-synclein, LC3, LAMP-2, and CaMKK protein was detected by western blot. We found significant motor dysfunction on day 7 in the experimental group, and the expression of α-synclein in the substantia nigra of the midbrain was significantly increased while the expression of ATP13A2 gene was reduced significantly compared with the control group. The concentration of intracellular calcium in the experimental group was significantly higher than in the control group. Autophagy associated proteins LC3-II and LAMP-2 were downregulated and CaMKK protein was upregulated in midbrain tissues of the experimental group compared to control group. In conclusion, our findings suggest that decreased expression of ATP13A2 may lead to defective autophagy and damage to midbrain dopaminergic neurons.

Adjuvant rhubarb alleviates organs dysfunction and inhibits inflammation in heat stroke.

The aim of the present study was to investigate the effects of adjuvant rhubarb on the recovery of patients with heat stroke. A total of 85 patients with heat stroke were randomly assigned to two treatment groups: One group receiving conventional treatment for heat stroke (conventional group) and one group receiving rhubarb supplement in addition to conventional treatment (rhubarb group). Liver and kidney function parameters, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, plasma interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP) levels and venous white blood cell count (WBC) were analyzed. The length of stay in the intensive care units (ICUs) and hospital were recorded. Kaplan-Meier curves were drawn to determine the 30-day survival of the patients. The results indicated that rhubarb supplementation significantly reduced the WBC, as well as CRP, PCT and IL-6 levels at treatment days 3-5. Furthermore, rhubarb intake was observed to limit heat stroke-induced damage to liver and kidney function by decreasing the abnormally high levels of plasma aspartate aminotransferase, alanine aminotransferase and creatinine. Finally, patients in the rhubarb group had shorter ICU and hospital stays as well as a lower APACHE II score than those in the conventional group. However, no significant difference in the 30-day mortality rate was observed between the two groups. In conclusion, rhubarb intake provided a significant benefit for patients with heat stroke by inhibiting systemic inflammation and mitigating liver and kidney injury.

Plasma long noncoding RNA IL-7R as a prognostic biomarker for clinical outcomes in patients with acute respiratory distress syndrome.

BACKGROUND: Long non-coding RNAs (lncRNAs) regulate a variety of genes and biological processes. Lnc-IL7R plays a considerable role in the regulation of inflammation, but its prognostic potential in acute respiratory distress syndrome (ARDS) has not been fully explained. In this study, the role of lnc-IL7R as a potential biomarker in ARDS was examined. OBJECTIVE: Role of lnc-IL7R as potential biomarker in ARDS. METHODS: LncRNA-IL7R was isolated from the plasma of patients with ARDS and healthy controls and clinical indexes were obtained within 24 h after admission. The relative expression of lnc-IL7R was obtained by quantitative real-time PCR. The correlations between lnc-IL7R and continuous variables in ARDS were tested using Spearman's coefficients. RESULTS: A total of 85 ARDS patients and 49 healthy controls were included. Plasma lnc-IL7R was significantly down-regulated in ARDS compared with the levels in healthy control individuals, especially in severe ARDS (P < .01). The area under the curve (AUC) of lnc-IL7R for ARDS diagnosis was 0.87 (sensitivity 75.3%, specificity 93.9%). The lnc-IL7R levels were correlated with the severity of ARDS (ρ = -0.31, P = .0215), oxygenation index (ρ = 0.61, P < .001), APACHE II score (ρ = -0.04, P = .0230), CRP (ρ = -0.26, P = .0148) and WBC (ρ = -0.29, P = .0064). Lnc-IL7R relative value ≥ 0.33 showed the lower 28-day mortality in the patients with ARDS(P < .05).The survivors showed higher lnc-IL7R level and lower APACHE II score, SOFA score and length of mechanical ventilation than in the non-survivors (P = .0109, P < .001, P < .001 and P = .017, respectively). CONCLUSIONS: Lnc-IL7R is a novel biomarker for the diagnosis of ARDS and predicts the severity of ARDS and 28-day mortality in this patients cohort. TRIAL REGISTRATION: The study was registered with the Chinese Clinical Trial Registry (ChiCTR-DOD-16008657).

Emodin alleviates jejunum injury in rats with sepsis by inhibiting inflammation response.

Emodin is an anthraquinone derived from Chinese herb that exerts anti-inflammation effects. This study aimed to investigate whether emodin provides the protection for jejunum injury by inhibiting inflammation. We established a model of sepsis caused by cecal ligation and puncture. Forty-eight male Wistar rats were divided into four groups (n=12). Jejunum injury was assessed by pathological examination. The activity of pJAK1/pSTAT3 and protein levels of Bcl-2 and Bax were detected by Western blot analysis. Inflammatory factors IL-6, TNF-α and procalcitonin were detected by ELISA. Apoptosis was detected by TUNEL. We found that emodin alleviated jejunum damage and apoptosis induced by sepsis and decreased the levels of IL-6, TNF-α and procalcitonin in septic rats. Furthermore, we observed that emodin increased the levels of pJAK1 and of pSTAT3, which were decreased in rats with sepsis. In addition, emodin enhanced the expression of Bcl-2 which was downregulated by sepsis and decreased the expression of Bax which was upregulated by sepsis. In conclusion, these results indicate that emodin suppresses inflammatory response induced by sepsis. Emodin activates JAK1/STAT3 signaling pathway and regulates Bcl-2 and Bax expression to protect the jejunum in rats with sepsis.

Emodin alleviates lung injury in rats with sepsis.

BACKGROUND: Sepsis has high morbidity and mortality. The aim of this study was to investigate whether emodin, an anthraquinone derived from Chinese herb, exerts protective effects on lung injury in rat model of sepsis. MATERIALS AND METHODS: Forty-eight male Wistar rats were randomly divided into four groups (n = 12): normal group, sham-operated group, cecal ligation and puncture (CLP) model group, and emodin-treated group. Saline or emodin (25 mg/kg) was injected intraperitoneally 0.5 h before CLP. The rats were sacrificed 48 h after CLP. Lung wet-to-dry weight ratio and pathologic changes in the lung were examined, the contents of malondialdehyde and myeloperoxidase in lung tissue were detected, serum tumor necrosis factor alpha and interleukin 6 levels were measured by enzyme-linked immunosorbent assay, and the phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was detected by Western blot analysis. RESULTS: Compared with control group, CLP group exhibited higher wet-to-dry weight ratio and water content in the lung (P < 0.01), but these indexes were reduced and pathologic changes in the lung were relieved in the emodin-treated group. In addition, lung malondialdehyde and myeloperoxidase contents, serum levels of tumor necrosis factor alpha and interleukin 6, and phosphorylation of p38 MAPK increased in the CLP group but decreased in the emodin-treated group (P < 0.05). CONCLUSIONS: Emodin exerts protective effects on lung injury in septic rats, which is related to the inhibition of p38 MAPK pathway and the reduction of oxidative stress and inflammation response during sepsis.

Low-molecular-weight heparin and intermittent pneumatic compression for thromboprophylaxis in critical patients.

The efficacy and safety of physiotherapeutic prophylaxis for venous thromboembolism in critically ill patients with heparin contraindication remains unclear. In the present study it was hypothesized that physiotherapy prophylaxis with intermittent pneumatic compression (IPC) would be safe and effective for patients unable to receive low-molecular-weight heparin (LMWH). In addition, this study investigated whether a combined therapy of IPC with LMWH would be more effective for the prophylaxis of deep vein thrombosis (DVT) in critical patients. A total of 500 patients were divided into four groups according to the prophylaxis of DVT. The IPC group consisted of 95 patients with heparin contraindication that received IPC treatment; the LMWH group consisted of 185 patients that received an LMWH injection; the LMWH + IPC group consisted of 75 patients that received IPC treatment and LMWH injection; and the control group consisted of 145 patients that received no IPC treatment or injection of LMWH. Each patient was evaluated clinically for development of DVT and the diagnosis was confirmed by Doppler study. Venous thromboembolism was a common complication among the trauma patients with severe injuries. Patients responded positively to the treatment used in the intervention groups. Patients exhibited an improved response to LMWH + ICP compared with IPC or LMWH alone, while no significant difference was detected between the IPC and LMWH groups. These results were applicable to patients that had a Wells score of ≥3; however, no significant differences in DVT incidence were observed among the patients who had a Wells score of <3. In this observational study, LMWH + ICP appeared to be more effective than either treatment alone in treating critically ill trauma patients with severe injuries that are at high risk for VTE and bleeding simultaneously.

Dynamic Changes of Soluble Fas and IL-2/IL-10 in serum and Fas Expression in Lung in the Rats of Acute Necrotizing Pancreatitis.

BACKGROUND: To investigate the dynamic changes of serum IL-2, IL-10, sFas and IL-2/IL-10 in a rat model with acute necrotizing pancreatitis (ANP). To explore the role of Th1/Th2 polarization and the Fas expression in the lung of rats with ANP. METHODS: A total of 64 Sprague-Dawley rats were randomly divided into normal control group and ANP model group. ANP models were induced by injection of 50 g/L sodium taurocholate (4 mL/kg) under the pancreatic membrane. In the normal control group, the rats received isovolumetric injection of 9 g/L normal saline solution. The blood samples in each group were obtained via superior mesenteric vein for measuring IL-2, IL-10 and soluble Fas. The levels of IL-2, IL-10 and soluble Fas were determined by ELISA. The severity of lung injury was evaluated by pathologic score. The expression of Fas in lung was measured by immunohistochemistry. RESULTS: In the ANP model group, levels of serum IL-2 were significantly higher than those of control group (P < 0.01), and peaked at 6 hours; levels of serum IL-10 were significantly higher than those of control group at 6 and 12 hours (P < 0.01); the ratios of IL-2/IL-10 were significantly higher than those of control group at 0.5 hours and 2 hours, however, they were significantly lower than those of control group at 6 hours, (P < 0.01), and returned to the normal level (P > 0.05). In Fas/APO-1 assay, there was no significant difference between the two groups. The pathological changes were aggravated significantly in model group compared with the control group. Immunohistochemistry stain showed Fas expression was absent in normal pulmonary tissue, whereas in pulmonary tissue Fas expression gradually increased 0.5 hours after induction of pancreatitis, and reached their peaks at 12 hours. CONCLUSIONS: Fas are involved in the pathogenesis of pancreatitis associated lung injury, the mechanism might be related to the Fas mediated T helper cell apoptosis.