[Protective effect of edaravone on balance of mitochondrial fusion and fission in MPP+-treated PC12 cells].

The aim of this study was to investigate the effect of edaravone (Eda) on the balance of mitochondrial fusion and fission in Parkinson's disease (PD) cell model. A cell model of PD was established by treating PC12 cells with 500 µmol/L 1-methyl-4-phenylpyridinium (MPP+). Thiazole blue colorimetry (MTT) was used to detect the effect of different concentrations of Eda on the survival rate of PC12 cells exposed to MPP+. The mitochondrial morphology was determined by laser confocal microscope. Western blot was used to measure the protein expression levels of mitochondrial fusion- and fission-related proteins, including OPA1, MFN2, DRP1 and Fis1. The results showed that pretreatment with different concentrations of Eda antagonized MPP+-induced PC12 cell damage in a dose-dependent manner. The PC12 cells treated with MPP+ showed mitochondrial fragmentation, up-regulated DRP1 and Fis1 protein expression levels, and down-regulated MFN2 and OPA1 protein expression levels. Eda could reverse the above changes in the MPP+-treated PC12 cells, but did not affect Fis1 protein expression. These results suggest that Eda has a protective effect on the mitochondrial fusion disruption induced by MPP+ in PC12 cells. The mechanism may be related to the up-regulation of OPA1/MFN2 and down-regulation of DRP1.

Comparisons of periodontal regenerative therapies: A meta-analysis on the long-term efficacy.

AIM: We conducted a meta-analysis for the long-term differences in treatment outcomes between periodontal regeneration therapies and flap operation. METHODS: A systematic literature search was conducted using the EMBASE, PubMed and Cochrane databases up to June 2016. Treatment outcomes were changes in probing pocket depth and clinical attachment level. We extracted data reported at different time points after periodontal surgery and incorporated all data into the same model. The restricted cubic spline regression was used to estimate the non-linear trend in treatment outcomes. As some studies reported outcomes at multiple time points, we considered several correlation structures for data reported by the same study. RESULTS: A total of 52 randomized controlled trials were included in our longitudinal meta-analysis. The follow-up length ranged from 0.5 year to 10 years. The trends in the treatment outcomes were similar under different correlation structures. Enamel matrix derivatives (EMD) and guided tissue regeneration (GTR) achieved greater probing pocket depth (PPD) reduction and clinical attachment level (CAL) gain than flap operation (FO) in the long-term follow up, but no differences were found between EMD and GTR. CONCLUSION: Compared with FO, periodontal regeneration surgeries achieved greater PPD reduction and gain in CAL after 1 year, and its effects may last for 5-10 years.

Bias propagation in network meta-analysis models.

Network meta-analysis combines direct and indirect evidence to compare multiple treatments. As direct evidence for one treatment contrast may be indirect evidence for other treatment contrasts, biases in the direct evidence for one treatment contrast may affect not only the estimate for this particular treatment contrast but also estimates of other treatment contrasts. Because network structure determines how direct and indirect evidence are combined and weighted, the impact of biased evidence will be determined by the network geometry. Thus, this study's aim was to investigate how the impact of biased evidence spreads across the whole network and how the propagation of bias is influenced by the network structure. In addition to the popular Lu & Ades model, we also investigate bias propagation in the baseline model and arm-based model to compare the effects of bias in the different models. We undertook extensive simulations under different scenarios to explore how the impact of bias may be affected by the location of the bias, network geometry and the statistical model. Our results showed that the structure of a network has an important impact on how the bias spreads across the network, and this is especially true for the Lu & Ades model. The impact of bias is more likely to be diluted by other unbiased evidence in a well-connected network. We also used a real network meta-analysis to demonstrate how to use the new knowledge about bias propagation to explain questionable results from the original analysis.

[Exogenous hydrogen sulfide delays the senescence of human umbilical vein endothelial cells by lessening oxidative stress].

The present study was aimed to investigate the effect of pretreatment with hydrogen sulfide (H2S) on human umbilical vein endothelial cells (HUVECs) senescence and the underlying mechanism. Cultured HUVECs at twelfth and fourth passages were taken as old and young groups, respectively. Sodium hydrosulfide (NaHS, donor of H2S) group was treated with NaHS from fourth to twelfth passage. The cell senescence was determined by senescence-associated ß-galactosidase (SA ß-gal) staining. DAPI fluorescent dye was used to detect cellular apoptosis. Western blot was used to analyze the expression levels of xanthine oxidase (XOD), manganese-superoxide dismutase (Mn-SOD) and the subunits p67(phox) of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase in the HUVECs. Colorimetric method was used to detect SOD activity and cellular hydrogen peroxide (H2O2) level. The results showed that, compared with young group, the old group exhibited higher SA ß-gal positive rate and cellular apoptosis, while NaHS pretreatment decreased SA ß-gal positive rate and cellular apoptosis. Compared with the young group, the old group showed increased expression levels of XOD and p67(phox), as well as lower Mn-SOD expression level. With the pretreatment of NaHS, the up-regulations of XOD and p67(phox) levels and down-regulation of Mn-SOD level were inhibited. Compared with the young group, the old group showed lower SOD activity and higher H2O2 level, whereas NaHS pretreatment reversed the changes of SOD activity and H2O2 level. These results suggest that H2S delays senescence of HUVECs through lessening oxidative stress.

Smarcd1 antagonizes the apoptosis of injured MES23.5 DA cells by enhancing the effect of Six2 on GDNF expression.

Glial cell line-derived neurotrophic factor (GDNF) played critical roles in the survival and repair of dopaminergic (DA) neurons. Transcription factor Six2 could repair injured DA cells by promoting the expression of GDNF, however, the underlying molecular mechanisms remain largely unknown. In this study, we screened forty-three proteins that interacted with Six2 in MES23.5 DA cells treated with 6-OHDA by liquid chromatography - electrospray - ionization tandem mass spectrometry (LC-ESI-ITMS/MS). Among these proteins, Smarcd1 is a member of SWI/SNF chromatin-remodeling complex family. Our results confirmed that Smarcd1 formed a transcription complex with Six2, and Smarcd1 mainly binded to the 2840 bp-2933 bp region of the GDNF promoter. Furthermore, knockdown of Smarcd1 inhibited the effect of Six2 on GDNF expression, and resulted in decreased cell viability and increased the apoptosis of injured DA neurons, and the result of overexpression of Smarcd1 is opposite to knockdown. Taken together, our results indicate that smarcd1 can be recruited to the promoter region of GDNF by transcription factor Six2 to promote the effect of Six2 on GDNF expression and protect injured MES23.5 DA cells, which could be useful in identifying potential drug targets for promoting endogenous GDNF expression.

Apelin-13 as a novel target for intervention in secondary injury after traumatic brain injury.

The adipocytokine, apelin-13, is an abundantly expressed peptide in the nervous system. Apelin-13 protects the brain against ischemia/reperfusion injury and attenuates traumatic brain injury by suppressing autophagy. However, secondary apelin-13 effects on traumatic brain injury-induced neural cell death and blood-brain barrier integrity are still not clear. Here, we found that apelin-13 significantly decreases cerebral water content, mitigates blood-brain barrier destruction, reduces aquaporin-4 expression, diminishes caspase-3 and Bax expression in the cerebral cortex and hippocampus, and reduces apoptosis. These results show that apelin-13 attenuates secondary injury after traumatic brain injury and exerts a neuroprotective effect.

H(2)S-releasing aspirin protects against aspirin-induced gastric injury via reducing oxidative stress.

The aim of this study was to examine the effect of ACS14, a hydrogen sulfide (H(2)S)-releasing derivative of aspirin (Asp), on Asp-induced gastric injury. Gastric hemorrhagic lesions were induced by intragastric administration of Asp (200 mg/kg, suspended in 0.5% carboxymethyl cellulose solutions) in a volume of 1 ml/100 g body weight. ACS14 (1, 5 or 10 mg/kg) was given 30 min before the Asp administration. The total area of gastric erosions, H(2)S concentration and oxidative stress in gastric tissues were measured three hours after administration of Asp. Treatment with Asp (200 mg/kg), but not ACS14 (430 mg/kg, at equimolar doses to 200 mg/kg Asp), for 3 h significantly increased gastric mucosal injury. The damage caused by Asp was reversed by ACS14 at 1-10 mg/kg in a concentration-dependent manner. ACS14 abrogated Asp-induced upregulation of COX-2 expression, but had no effect on the reduced PGE(2) level. ACS14 reversed the decreased H(2)S concentrations and blood flow in the gastric tissue in Asp-treated rats. Moreover, ACS14 attenuated Asp-suppressed superoxide dismutase-1 (SOD-1) expression and GSH activity, suggesting that ACS14 may stimulate antioxidants in the gastric tissue. ACS14 also obviously inhibited Asp-induced upregulation of protein expression of oxidases including XOD, p47(phox) and p67(phox). In conclusion, ACS14 protects Asp induced gastric mucosal injury by inhibiting oxidative stress in the gastric tissue.