Effects of Sleep Deprivation (SD) on Rats via ERK1/2 Signaling Pathway.

BACKGROUND Sleep deprivation (SD) is common in humans, and sleep loss has a significant influence on health and produces related diseases. Orexin-A has been demonstrated to play a role in physiological processes, including feeding, sleep/wake cycle, and energy metabolism. The aim of this study was to investigate the effect of SD on rats and to define the underlying mechanism. MATERIAL AND METHODS We constructed an SD rat model. The Morris water maze test was used to assess rat learning and memory. Imaging of hippocampus and hippocampal tissue in rats were captured by magnetic resonance imaging or electron microscopy. We used the CCK-8 kit to assess cell viability. The level of protein was measured using Western blot analysis, and qRT-PCR was used to evaluate mRNA level. RESULTS SD rats had poorer learning and memory and had damage to the hippocampus. SD resulted in shrinkage of hippocampal volume and encephalocele size. SD increased the expression of Orexin-A, OX1R, OX2R, and PARP-1, and decreased the expression of ERK1/2 and p-ERK1/2. Orexin-A (0-10 µM) improved neuron viability, whereas orexin-A (10-100 µM) attenuated neuron viability. SB334867 treatment reduced the viability of neurons treated with orexin-A. NU1025 treatment increased cell viability, especially in neurons treated with orexin-A. SB334867 treatment decreased the p-ERK1/2 levels in neurons treated with orexin-A. NU1025 increased the expression of p-ERK1/2 in neurons treated with orexin-A. CONCLUSIONS SD decreases learning and memory through damage to the hippocampus. Higher concentrations of orexin-A had a major negative effect on hippocampal neurons via OX1R and PARP-1 through inhibition of the ERK1/2 signaling pathway.

The Efficacy and Safety of Mainstream Medications for Patients With cDMARD-Naïve Rheumatoid Arthritis: A Network Meta-Analysis.

Background: The mainstream medications for rheumatoid arthritis (RA) include conventional disease-modifying antirheumatic drugs (cDMARDs), which mostly are methotrexate (MTX), and biologic agents such as adalimumab (ADA), certolizumab (CZP), etanercept (ETN), golimumab (GOL), infliximab (IFX), and tocilizumab (TCZ). This network meta-analysis was aimed at evaluating the efficacy and safety of the medications above and interventions combining cDMARDs and biologic agents for patients with RA. Methods: PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov were searched systematically for eligible randomized controlled trials (RCTs). Outcomes concerning efficacy and safety were evaluated utilizing odds ratios (ORs) and 95% credible intervals (CrI). The outcomes of efficacy would be evaluated through remission and American College of Rheumatology (ACR) scores. The surface under the cumulative ranking curve (SUCRA) was calculated to rank each treatment on each index. Results: A total of 20 RCTs with 9,047 patients were included, and the efficacy and safety of the concerning interventions for RA were evaluated. Compared with cDMARDs alone, TCZ+MTX, ETN+MTX, IFX+MTX, TCZ, and ADA+MTX showed significant statistical advantage on ACR20, ACR50, and ACR70. Apart from that, as for remission, TCZ+MTX, IFX+MTX, TCZ, and CZP+MTX performed better compared to cDMARDs alone. The SUCRA ranking also indicated that TCZ+MTX was the intervention with best ranking in the entire four efficacy indexes followed by ETX+MTX and IFX+MTX. However, there was no obvious difference among these medications compared with cDMARDs when it comes to safety, which need more specific studies on that. Conclusion: TCZ+MTX was potentially the most recommended combination of medications for RA due to its good performance in all outcomes of efficacy. ETX+MTX and IFX+MTX, which also performed well, could be introduced as alternative treatments. However, considering the adverse events, the treatments concerning should be introduced with caution.

Human recombinant-B-type natriuretic peptide protect ventricular function and structure in ST-elevation myocardial infarction.

BACKGROUND: ST-elevation myocardial infarction (STEMI) is the most serious clinical type of coronary artery disease (CAD), which will lead to a loss of contractile function asa result of adverse left ventricular (LV) remodeling. Post-myocardial infarction remodeling is detrimental to the left ventricular function, which is strongly related to clinical outcome,including heart failure and cardiac death. And our study was designed to assess the efficacy of 72-hour IV infusion of rh-BNP therapy in STEMI patients with or without successful primary PCI, in preventing adverse LV remodeling and preserving LV function. METHODS: 100 patients diagnosed as STEMI combined with acute heart failure (Killip classification ≥ 2) were recorded. And they were divided into "rh-BNP treatment group" (n=50) and "control group" (n=50). In addition to conventional heart failure therapy, patients in the rh-BNP group received rh-BNP infusion for 72 hours. All patients were followed up at 3 month after discharge. Their medical history was taken, as well as the presence or absence of relevant symptoms. 6-minute walking test, as well as echocardiographic indexes were recorded to evaluate the improvement of cardiac function. RESULTS: The data analysis about demographic comparison, including those related complicated diseases among groups showed no significant difference. After the follow-up, the indicators were all better than baseline among four subgroups (all P<0.001). Results showed that rh-BNP was able to significantly reduce the NT-pro BNP levels (P<0.001), decrease LVESD (P<0.01), and increase LVEF (P<0.05). The difference of 6WMT between two groups was significant (P<0.001). According to the classification of 6WMT, the multivariate Cox regression showed that the usage of rh-BNP was an independent predictor for 6WMT (OR 0.478, 95% CI, 0.290-0.787), while it may not for MACE (OR 1.762, 95% CI, 0.793-3.913). CONCLUSIONS: Although the use of rh-BNP was not an independent risk factor in prediction of MACE in our study, the current data still showed that rh-BNP is a useful prognosis factor of 6WMT in the STEMI patients. The protection of ventricular function and structure in STEMI patients is affirmative.

Effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rats.

OBJECTIVE: To observe effect of alprostadil combined with Diammonium glycyrrhizinate on renal interstitial fibrosis in SD rats. METHODS: A total of 75 SD rats were randomly divided into A, B, C, D, E groups with 15 in each group. Rats in group A served as the control group received just only but tissue separation without modeling operation, while model of unilateral ureteral obstruction (UUO) was established in B, C, D, E groups. Rats in A, B group were given saline lavage placebo treatment, while rats in C, D, E groups were given diammonium glycyrrhizinate and alprostadil injection. Five rats were sacrificed 1, 2, 3 weeks after modeling, serum creatinine level of femoral venous blood was determined. Transforming growth factor - ß1 (TGF - ß1) and concentration of connective tissue growth factor (CTGF) were also detected by using ELISA. Line renal interstitial tissue was taken after HE staining, renal interstitial TGF - ß1 and CTGF expression were detected by using immunohistochemical method. RESULTS: Serum creatinine levels of B, C, D, E group at different time points in were significantly higher than that of group A (P<0.05); serum creatinine levels in group B were significantly higher than that of C, D, E group at each time point (P<0.05). Serum creatinine level of Group E was significantly lower than C, D group after 2, 3 weeks (P<0.05). Rats in A group at each time point showed no significant changes in TGF - ß1 and CREA concentration in serum and kidney tissues (P>0.05); while serum and kidney tissue TGF - ß1, concentration of CREA, expression of rats in B, C, D, E groups showed a gradual increasing trend over time. TGF - ß1 and CREF of Group B in serum and kidney tissues at each time point were significantly higher than that of the other groups (P<0.05). TGF - ß1 and CREF of Group E in serum and kidney tissues at each time point were significantly lower than that of B, C, D group at all time points in serum and kidney tissues (P<0.05). CONCLUSIONS: Alprostadil combined with diammonium glycyrrhizinate can significantly lower the expression of TGF - ß1 and CTGF in serum and tissues of SD rat with renal interstitial fibrosis, thus inhibit rat renal interstitial fibrosis process. It has synergy protective effect.