DSCAM-AS1 promotes the development of prostate cancer.

PURPOSE: The purpose of this study was to investigate the role of lncRNA DSCAM-AS1 in prostate cancer to find new therapeutic targets and promote the research progress of prostate cancer. METHODS: RT-qPCR was used to detect DSCAM-AS1 expression in prostate cancer tissues, normal tissues, human normal prostate epithelial cells (RWPE), and four prostate cancer cell lines. The clinical and prognostic role of DSCAM-AS1 was evaluated by the Kaplan-Meier curve and chi-square test. Secondly, a dual luciferase reporter gene assay was used to study the regulatory mechanism between miR-338-3p and DSCAM-AS1. Finally, the roles of DSCAM-AS1 and miR-338-3p in prostate cancer cell proliferation and metastasis were explored by CCK-8 and Transwell assays. RESULTS: It was found that DSCAM-AS1 upregulation could serve as a warning of deterioration and poor prognosis in prostate cancer patients, and that knockdown of DSCAM-AS1 expression inhibited the progression of prostate cancer cells. In addition, miR-338-3p, a target of DSCAM-AS1, was found to be down-regulated in prostate cancer cells and miR-338-3p knockdown could reverse the inhibitory effect of DSCAM-AS1 silencing on prostate cancer. CONCLUSION: DSCAM-AS1 is up-regulated in prostate cancer and regulates the progression of prostate cancer cells by targeting miR-338-3p.

The effects of paroxetine therapy on depressive symptom and motor function in the treatment of depression with Parkinson's disease: A meta-analysis.

BACKGROUND: Paroxetine therapy has been used for treatment of patients with depression and Parkinson's disease (dPD) in many clinical studies, but, the effects of paroxetine in dPD patients are not completely understood. The aim of this study was to systematically evaluate the effects of paroxetine therapy on depressive symptom and motor function in the treatment of dPD, in order to confer a reference for clinical practice. METHODS: Randomized controlled trials (RCTs) of paroxetine for dPD published up to October, 2022 were retrieved. Standardised mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. The outcomes of interest were as follows: the efficacy, Hamilton depression rating scale score, unified Parkinson's disease rating scale score, Hamilton anxiety rating scale score or adverse events. RESULTS: Thirty-four RCTs with 2819 participants were included. Compared with control group, the pooled effects of paroxetine therapy on depression were (22 trials; OR 3.62, 95% CI 2.63 to 4.98, P < .00001) for antidepressant response (25 trials; SMD -2.14, 95% CI -2.73 to -1.56, P < .00001) for Hamilton depression rating scale score, the pooled effects of paroxetine therapy on motor function were (10 trials; OR 4.63, 95% CI 3.15 to 6.79, P < .00001) for anti-PD efficacy (18 trials; SMD -2.02, 95% CI -2.48 to -1.55, P < .00001) for total unified Parkinson's disease rating scale score. The Hamilton anxiety rating scale score showed significant decrease in the paroxetine treatment group compared to control group (10 trials; SMD -1.93, 95% CI -2.65 to -1.22, P < .00001). In addition, paroxetine therapy reduced the number of any adverse events obviously in dPD patients (twenty trials; OR 0.42, 95% CI 0.31 to 0.57, P < .00001). CONCLUSIONS: Paroxetine therapy has clinical benefits for improvement of depressive symptom and motor function in dPD patients, moreover, it is of high drug safety. Further well-designed, multi-center RCTs needed to identify these findings.

SIRT3 expression alleviates microglia activation­induced dopaminergic neuron injury through the mitochondrial pathway.

The mitochondrial protein sirtuin 3 (SIRT3) can counteract cell damage caused by oxidative stress and inflammation, and contribute to cell survival primarily by improving mitochondrial function. However, the effects of SIRT3 in dopaminergic neuronal cells (DACs) remain unclear. In our previous studies, microglia activation-associated cytotoxicity was observed to promote the apoptosis of DACs, along with the decrease of SIRT3 expression. The aim of the present study was to explore the potential neuroprotective effect of SIRT3 expression against dopaminergic neuron injury caused by microglia activation, and clarify its possible mechanisms. SIRT3 overexpression in DACs reduced the production of intracellular reactive oxygen species (ROS), cell apoptosis rate, mitochondrial membrane potential (ΔΨm) depolarization, opening of mitochondrial permeability transition pore (mPTP) and cyclophilin D (CypD) protein level, and promoted cell cycle progression. However, SIRT3 siRNA-mediated knockdown further aggravated microglia activation-mediated cytotoxicity, including ROS accumulation, increased cell apoptosis and mPTP opening, elevated the CypD level, enhanced mitochondrial ΔΨm depolarization, concomitant to cell cycle arrest at G0/G1 phase. The mechanisms of SIRT3 mitigated microglia activation-induced DAC dysfunction, which included decreased mPTP opening and Bax/Bcl-2 ratio, inhibition of mitochondrial cytochrome c release to the cytoplasm, reduced caspase-3/9 activity, increased LC3II/LC3I and beclin-1 protein expression levels, and decreased nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain-containing protein 3 (NLRP3), caspase-1, IL-1ß and IL-18 protein expression. In conclusion, these results indicated that SIRT3 expression attenuated cell damage caused by microglia activation through the mitochondrial apoptosis pathway in DACs. The mitophagy-NLRP3 inflammasome pathway may also be associated with this neuroprotection. These findings may provide new intervention targets for the survival of dopaminergic neurons and the prevention and treatment of Parkinson's disease.

Efficacy and safety of combination therapy with pramipexole and levodopa vs levodopa monotherapy in patients with Parkinson disease: A systematic review and meta-analysis.

BACKGROUND: Pramipexole (P) or levodopa (L) treatment has been suggested as a therapeutic method for Parkinson disease (PD) in many clinical studies. Nonetheless, the combined effects of 2 drugs for PD patients are not completely understood.The aim of this research was to evaluate the clinical efficacy and safety of P plus L (P+L) combination therapy in the treatment of PD compared to that of L monotherapy, in order to confer a reference for clinical practice. METHODS: Randomized controlled trials (RCTs) of P+L for PD published up to April, 2020 were retrieved. Standardized mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. Sensitivity analysis was also carried out. The outcomes of interest were as follows: the efficacy, unified Parkinson disease rating scale (UPDRS) scores, Hamilton depression rating scale score or adverse events. RESULTS: Twenty-four RCTs with 2171 participants were included. Clinical efficacy of P+L combination therapy was significantly better than L monotherapy (9 trials; OR 4.29, 95% CI 2.78 to 6.64, P < .00001). Compared with L monotherapy, the pooled effects of P+L combination therapy on UPDRS score were (22 trials; SMD -1.31, 95% CI -1.57 to -1.04, P < .00001) for motor UPDRS score, (16 trials; SMD -1.26, 95% CI -1.49 to -1.03, P < .00001) for activities of daily living UPDRS score, (12 trials; SMD -1.02, 95% CI -1.27 to -0.77, P < .00001) for mental UPDRS score, (10 trials; SMD -1.54, 95% CI -1.93 to -1.15, P < .00001) for complication UPDRS score. The Hamilton depression rating scale score showed significant decrease in the P+L combination therapy compared to L monotherapy (12 trials; SMD -1.56, 95% CI -1.90 to -1.22, P < .00001). In contrast to L monotherapy, P+L combination therapy reduced the number of any adverse events obviously in PD patients (16 trials; OR 0.36, 95% CI 0.27 to 0.50, P < .00001). CONCLUSIONS: P+L combination therapy is superior to L monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+L combination therapy is better than that of L monotherapy. Further well-designed, multicenter RCTs needed to identify these findings.

Effects of valsartan combined with α-lipoic acid on renal function in patients with diabetic nephropathy: a systematic review and meta-analysis.

BACKGROUND: Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes, valsartan and α-lipoic acid alone or in combination has been used for the treatment of patients with DN. However, some results in these clinical reports were still controversial. The purpose of this study was to evaluate the efficacy of valsartan combined with α-lipoic acid on renal function in patients with DN. METHODS: We searched the electronic databases including PubMed, Sciencedirect, EMBASE, Cochrane library, Chinese national knowledge infrastructure (CNKI) and Wanfang databases, and the publication deadline was limited to January 2020. Randomized controlled trials (RCTs) evaluating the effects of valsartan combined with α-lipoic acid in DN patients were included. Pooled estimates were conducted using a fixed or random effect model. The outcomes included urinary albumin excretion rate (UAER), and the level of urinary albumin, ß2-microglobulin (ß2-MG), hypersensitive C-reactive protein (hs-CRP) and oxidative stress. RESULTS: 11 studies with 1294 participants were included in this study. The pooled analysis indicated that α-lipoic acid combined with valsartan could remarkably reduce UAER (P < 0.00001, SMD = -1.95, 95%CI = -2.55 to - 1.20; P = 0.03, SMD = -0.85, 95%CI = -1.59 to - 0.1) and the level of urinary albumin (P = 0.001, SMD = -1.48, 95%CI = - 2.38 to - 0.58; P = 0.01, SMD = -1.67, 95%CI = -3.00 to - 0.33), ß2-MG (P < 0.001,SMD = - 2.59, 95%CI = -3.78 to - 1.40; P = 0.03, SMD = -0.48, 95%CI = -0.93 to - 0.04) when compared with valsartan or lipoic acid monotherapy in patients with DN. However, there was no significant difference in the level of hs-CRP among the three therapies (P = 0.06, SMD = -2.80, 95%CI = -5.67 to 0.07; P = 0.10, SMD = -0.42, 95%CI = - 0.92 to 0.08). In addition, α-lipoic acid combined with valsartan markedly increased the level of SOD (P = 0.03, SMD = 1.24, 95%CI = 0.32 to 1.03; P = 0.0002, SMD = 0.68, 95%CI = 0.32 to 1.03) and T-AOC (P < 0.00001, SMD = 0.89, 95%CI = 0.62 to 1.16; P = 0.02, SMD = 0.58, 95%CI = 0.10 to1.07), and reduced the level of MDA(P = 0.0002, SMD = -1.99, 95%CI = -3.02 to - 0.96; P = 0.0001, SMD = -0.69, 95%CI = -1.04 to - 0.34). CONCLUSIONS: α-lipoic acid combined with valsartan could significantly reduce the level of urinary albumin and oxidative stress, increase antioxidant capacity and alleviate renal function damage in patients with DN, and this will provide a reference for the selection of treatment drugs for DN.

Calculus-related functional protein expression in ureteral calculus-adhered polyp: A preliminary study.

ABSTRACT: To explore the expressions of calculus-related functional proteins in the ureteral calculus-adhered polyp tissues and investigate the role of these proteins in the formation of adhesions between the calculus and polyp.Patients with ureteral calculi and polyps who underwent ureteroscopic lithotripsy for the excision of polyps between January 2019 and June 2019 were enrolled. Polyps obtained from each patient were divided into 2 groups using a matched pairs design: observation group (polyps adhered to calculus) and control group (polyps not adhered to calculus). Histopathological examination of polyps was performed using hematoxylin and eosin staining. Polyp tissues were immunohistochemically stained to assess the expressions of calculus-related functional proteins, that is, annexin A1, calcium-binding protein S100A9 (S100A9), uromodulin, and osteopontin. Furthermore, quantitative analysis was performed using the H-score of tissue staining; Pearson correlation analysis was performed for proteins with high expression.Overall, 40 polyp specimens were collected from 20 patients with ureteral calculi combined with polyps (observation group, 20 specimens; control group, 20 specimens). Hematoxylin and eosin staining revealed obvious epithelial cell proliferation in polyps of both groups; crystals were observed in the epithelial cells of the polyp tissue in the observation group. The expression levels of annexin A1 and S100A9 in the observation group were significantly greater than those in the control group (P < .05). However, no obvious expression of osteopontin or uromodulin was observed in the polyp tissues of both groups. There was a strong correlation between the increased expressions of annexin A1 and S100A9 in the observation group (R = 0.741, P = .022).We documented increased expressions of annexin A1 and S100A9 in the ureteral calculus-adhered polyp tissues. Annexin A1 and S100A9 may play an essential role in the adhesion of calculus and polyp and the growth of calculi.

The role of pramipexole in the treatment of patients with depression and Parkinson's disease: A meta-analysis of randomized controlled trials.

OBJECTIVE: The aim of this report was to evaluate the clinical efficacy and safety of pramipexole therapy for patients with depression and Parkinson's disease (dPD), in order to confer a reference for clinical practice. METHODS: Randomized controlled trials (RCTs) of pramipexole for dPD published up to June 2020 were retrieved. Standardised mean difference (SMD), risk ratio (RR), and 95 % confidence interval (CI) were calculated. The outcomes included efficacy, Hamilton depression rating scale (HAMD) score, unified Parkinson's disease rating scale (UPDRS) scores, self-rating depression scale (SDS) score, self-rating anxiety scale (SAS) score or adverse events. RESULTS: Eighteen RCTs with 1789 participants were included. Clinical efficacy in pramipexole treatment group was significantly better than control group (RR 1.26, 95 % CI 1.20-1.33, P < 0.00001). Compared with control group, the pooled effects of pramipexole therapy on depression were (SMD -1.90, 95 % CI -2.58 to -1.23, P < 0.00001) for HAMD score, (SMD -3.94, 95 % CI -4.73 to -3.15, P < 0.00001) for SDS score, pramipexole therapy also decreased SAS score markedly (P < 0.0001). Compared with control group, the pooled effects of pramipexole on motor UPDRS score and activities of daily living UPDRS score were statistically significant (P < 0.01). Furthermore, pramipexole therapy didn't increase the number of any adverse events in dPD patients (RR 0.72, 95 % CI 0.37-1.41, P = 0.34). CONCLUSIONS: Pramipexole therapy can alleviate depressive symptoms and motor dysfunction in dPD patients, and there were no more side effects associated with drug intervention. These findings should be further validated by high-quality and well-designed RCTs.

Comparison of pramipexole and levodopa/benserazide combination therapy versus levodopa/benserazide monotherapy in the treatment of Parkinson's disease: a systematic review and meta-analysis.

The purpose of this research was to evaluate the clinical efficacy and safety of pramipexole plus levodopa/benserazide (P+LB) combination therapy in the treatment of Parkinson's disease (PD) compared to that of LB monotherapy, in order to confer a reference for clinical practice. Randomized controlled trials (RCTs) of P+LB for PD published up to April 2020 were retrieved. Heterogeneity and sensitivity analysis were executed. Twenty-nine RCTs with 3017 participants were included. Clinical efficacy of P+LB combination therapy was significantly better than LB monotherapy (RR 1.27, 95% CI 1.22 to 1.32, P<0.00001). Compared with LB monotherapy, the pooled effects of P+LB combination therapy on UPDRS score were (SMD -1.41, 95% CI -1.71 to -1.11, P<0.00001) for motor UPDRS score, (SMD -1.65, 95% CI -2.25 to -1.04, P<0.00001) for activities of daily living UPDRS score, (SMD -2.20, 95% CI -3.32 to -1.09, P=0.0001) for mental UPDRS score, and (SMD -1.60, 95% CI -2.06 to -1.15, P<0.00001) for complication UPDRS score. The HAMD score showed significant decrease in the P+LB combination therapy compared to LB monotherapy (SMD -1.32, 95% CI -1.80 to -0.84, P<0.00001). In contrast to LB monotherapy, P+LB combination therapy decreased the number of any adverse events obviously in PD patients (RR 0.53, 95% CI 0.45 to 0.63, P<0.00001). In conclusion, P+LB combination therapy is superior to LB monotherapy for improvement of clinical symptoms in PD patients. Moreover, the safety profile of P+LB combination therapy is better than that of LB monotherapy. Further well-designed, multi-center RCTs needed to identify these findings.

Correlation between CYP11B2 polymorphism and the risk of preeclampsia.

BACKGROUND: Many studies have evaluated the association between aldosterone synthase (CYP11B2) C-344T polymorphism and preeclampsia (PE) susceptibility, however, the results from different studies are inconsistent. OBJECTIVE: The study aimed to derive a more precise estimation of this association. METHODS: We searched PubMed, Embase, Chinese National Knowledge Infrastructure, China Biological Medicine, and Wanfang Database. The association was evaluated by calculating the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). RESULTS: Seven case-control studies with a total of 720 cases and 766 controls were eligible to be included in this meta-analysis. Overall, there was no significant association between CYP11B2 C-344T polymorphism and PE (for the allele model T vs.C: OR=0.78, 95%CI 0.60-1.01, p=0.06; for the codominant model CT vs. CC: OR=1.08, 95%CI 0.80-1.46, p=0.63; for the dominant model TT + CT vs. CC: OR=0.91, 95%CI 0.68-1.20, p=0.49). Similar results were obtained in sensitivity analysis. CONCLUSION: In summary, the present meta-analysis suggests that CYP11B2 C-344T polymorphism may not be associated with genetic susceptibility of PE, but the association remains indeterminate due to the insufficient evidence.

Association of transferrin G258A and transferrin receptor A82G polymorphisms with the risk of Parkinson disease in certain area.

BACKGROUND: It has been reported that polymorphisms of transferrin (TF) G258A and transferrin receptor (TFR) A82G might be associated with susceptibility to Parkinson disease (PD). OBJECTIVE: Owing to limitation of sample size and inconclusive results, we conducted a meta-analysis to clarify the association. METHODS: By searching PubMed, Embase, Chinese National Knowledge Infrastructure, China Biological Medicine Database, and Wanfang Databases, the published articles about studies of the association of the TF G258A, TFR A82G gene polymorphisms with the risk of PD were collected. Q-statistics and I statistics were calculated to examine heterogeneity and summary odds ratios (ORs) and 95% confidence intervals (95%CI) were evaluated the association. RESULTS: Five studies assessed the relationship between TF G258A and risk of PD. A significant increased protective of A allele and AA genotype was observed in allele model and recessive model (the allele model A vs G: OR = 0.54, 95%CI 0.40-0.72, P < .001; the recessive model AA vs GA + GG: OR = 0.32, 95%CI 0.20-0.52, P < .001). The remaining models of the TF G258A genotype showed no significant association with PD risk, while the protective tendency were increased (the heterozygote model GA vs GG: OR = 0.93, 95%CI 0.61-1.43, P = .75; the homozygous model AA vs GG: OR = 0.47, 95%CI 0.21-1.04, P = .06; the dominant model GA + AA vs GG: OR = 0.75, 95%CI 0.50-1.11, P = .15). There was also a lack of association between TFR A82G polymorphism and PD (the allele model G vs A: OR = 0.92, 95%CI 0.75-1.13, P = .43; the heterozygote model AG vs AA: OR = 1.17, 95%CI 0.79-1.71, P = .43; the homozygous model GG vs AA: OR = 0.91, 95%CI 0.60-139, P = .66; the dominant model AG + GG vs AA: OR = 1.05, 95%CI 0.73-1.49, P = .81; the recessive model GG vs AG +AA: OR = 0.80, 95%CI 0.59-1.09, P = .16). CONCLUSION: Our study suggests that TF G258A polymorphism may be associated with PD, while TFR A82G polymorphism may not contribute to PD based on the current evidence.

Comparison of selegiline and levodopa combination therapy versus levodopa monotherapy in the treatment of Parkinson's disease: a meta-analysis.

BACKGROUND: Selegiline or levodopa treatment has been suggested as a therapeutic method for Parkinson's disease (PD) in many clinical trial reports. However, the combined effects of two drugs still remain controversial. The aim of this report was to evaluate the clinical efficacy and safety of selegiline plus levodopa (S + L) combination therapy in the treatment of PD compared to that of L monotherapy, to provide a reference resource for rational drug use. METHODS: Randomized controlled trials (RCTs) of S + L for PD published up to September, 2018 were searched. Mean difference (MD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I2 test. Sensitivity analysis was also performed. The outcomes measured were as follows: the unified Parkinson's disease rating scale (UPDRS) scores, modified Webster score, adverse events and mortality. RESULTS: Fourteen RCTs with 2008 participants were included. Compared with L monotherapy, the pooled effects of S + L combination therapy on UPDRS score were (eleven trials; MD - 7.00, 95% CI - 8.35 to - 5.65, P < 0.00001) for total UPDRS score (nine trials; MD - 5.74, 95% CI - 7.71 to - 3.77, P < 0.00001) for motor UPDRS score (seven trials; MD - 1.61, 95% CI - 2.18 to - 1.04, P < 0.00001) for activities of daily living UPDRS score (three trials; MD - 0.38, 95% CI - 0.61 to - 0.14, P = 0.002) for mental UPDRS score. The Webster score showed significant decrease in the S + L combination therapy compared to L monotherapy (four trials; MD - 5.71, 95% CI - 7.11 to - 4.32, P < 0.00001). Compared with L monotherapy, S + L combination therapy did not increase the number of any adverse events significantly in PD patients (ten trials; OR 1.58, 95% CI 0.83-3.00, P = 0.16). CONCLUSIONS: S + L combination therapy is superior to L monotherapy for the improvement of clinical symptoms in PD patients. Moreover, the safety profile of S + L combination therapy is comparable with that of L monotherapy.

Rasagiline combined with levodopa therapy versus levodopa monotherapy for patients with Parkinson's disease: a systematic review.

OBJECTIVE: The aim of this report was to systematically evaluate the efficacy and safety of rasagiline (R) plus levodopa (L) (R + L) for the treatment of Parkinson's disease (PD) compared with that of L monotherapy, in order to provide a reference resource for rational drug use. METHODS: Randomized controlled trials (RCTs) of R + L for PD published up to September 2018 were searched. Sensitivity analyses were also performed. RESULTS: Fourteen RCTs with 2531 participants were included. Compared with L monotherapy, the pooled effects of R + L combination therapy on unified Parkinson's disease rating scale (UPDRS) score were (SMD - 0.50, 95% CI - 0.70 to - 0.30, P < 0.00001) for UPDRS motor score, (SMD - 0.59, 95% CI - 0.79 to - 0.39, P < 0.00001) for UPDRS activities of daily living (ADL) score, (SMD - 0.65, 95% CI - 0.81 to - 0.49, P < 0.00001) for UPDRS total score. R + L combination therapy was better than L monotherapy in reducing daily off-time (SMD - 1.15, 95% CI - 2.13 to - 0.17, P = 0.02), but there was a statistically nonsignificant result in daily on-time increase (SMD 1.39, 95% CI - 0.69 to 3.48, P = 0.19). There were no statistical differences in number of adverse events (OR 1.33, 95% CI 0.97 to 1.82, P = 0.07) and number of dropout (OR 0.88, 95% CI 0.65 to 1.19, P = 0.39) between R + L combination therapy and L monotherapy. CONCLUSIONS: R + L combination therapy was superior to L monotherapy for improvement of UPDRS scores and off-time in PD patients. Moreover, R + L combination therapy and L monotherapy were similar in terms of safety and tolerability.

Association of polymorphisms in the MCP-1 and CCR2 genes with the risk of Parkinson's disease.

Studies investigating the impact of polymorphisms on monocyte chemotactic protein-1 (MCP-1) and CC chemokine receptor (CCR2) on the susceptibility of Parkinson's disease (PD) have reported inconsistent results. Owing to mixed and inconclusive results, we conducted a meta-analysis to systematically summarize and clarify the association between the two gene polymorphisms and PD risk. We performed a meta-analysis of five eligible studies to summarize the data describing the association between PD risk and polymorphisms in MCP-1 A2518G and CCR2 V64I. The association was evaluated by calculating the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). A significant increased risk of PD was observed in the MCP-1 A2518G polymorphism in allele model (G vs. A: OR 1.12, 95% CI 1.01-1.25, p = 0.03). The dominant model of MCP-1 A2518G genotype showed no significant association with PD risk, while the risk tendency was increased (AG + GG vs. AA: OR 1.20, 95% CI 1.00-1.42, p = 0.05). In addition, CCR2 V64I polymorphism showed no significant association with PD risk (I vs. V: OR 0.33, 95% CI 0.06-1.92, p = 0.22; VI + II vs. VV: OR 1.00, 95% CI 0.83-1.21, p = 0.99). In subgroup analysis by ethnicity, no significant difference was found in both Caucasians and Asians between CCR2 V64I polymorphism and PD risk, while a significant statistical association was identified in Asians between MCP-1 A2518G polymorphism and PD risk. When the data were stratified by study area, the increased risk of PD was observed only in studies conducted in China. In summary, the present meta-analysis suggests that genetic polymorphisms of MCP-1 A2518G may influence the susceptibility of PD in Asian countries, especially in China. However, CCR2 V64I polymorphism is not correlated with PD risk. The results should be interpreted with caution due to limited sample and heterogeneity. Large scale and well-designed studies are needed to validate our findings.

Microglia activation induces oxidative injury and decreases SIRT3 expression in dopaminergic neuronal cells.

Microglia activation-mediated neuroinflammation plays an important role in the progression of Parkinson's disease (PD). However, effects of microglia activation on dopaminergic neuronal cell (DAC) fate are still poorly understood. The objective of this study was to explore the neurotoxic effects of microglia activation-mediated oxidative injury in DACs and its possible mechanisms. In the present study, microglia-DACs co-culture systems (murine BV-2 and MN9D cells, or primary microglia and mesencephalic neurons) were used to display the crosstalk between both cell types. The cytotoxicity of lipopolysaccharide-induced microglia activation led to the accumulation of intracellular reactive oxygen species, increased cell apoptosis rate, reduced number of DACs, concomitant to cell cycle arrest at G1 phase. Molecular mechanisms of apoptosis caused by microglia activation-induced oxidative injury included the increased opening of mitochondrial permeability transition pore and enhanced membrane potential depolarization in MN9D cells, down-regulation of Bcl-2 and up-regulation of Bax, caspase-3 expression in DACs. In addition, microglia activation made a significant reduction of SIRT3 and superoxide dismutase 2 gene expression in DACs. Taken together, these data imply that microglia activation promotes cell apoptosis through mitochondrial pathway and decreases SIRT3 expression in DACs, which may provide some support for PD progression promoted by neuroinflammation.

Prostaglandin E1 plus methylcobalamin combination therapy versus prostaglandin E1 monotherapy for patients with diabetic peripheral neuropathy: A meta-analysis of randomized controlled trials.

BACKGROUND: Prostaglandin E1 (P) or methylcobalamin (M) treatment has been suggested as a therapeutic approach for diabetic peripheral neuropathy (DPN) in many clinical trial reports. However, the combined effects of 2 drugs still remain dubious. OBJECTIVE: The aim of this report was to evaluate the efficacy of M plus P (M + P) for the treatment of DPN compared with that of P monotherapy, in order to provide a reference resource for rational drug use. METHODS: Randomized controlled trials (RCTs) of M + P for DPN published up to September 2017 were searched. Risk ratio (RR), mean difference (MD), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I test. Subgroup and sensitivity analyses were also performed. The outcomes measured were as follows: the clinical efficacy, median motor nerve conduction velocities (MNCV), median sensory nerve conduction velocity (SNCV), peroneal MNCV, peroneal SNCV, and adverse effects. RESULTS: Sixteen RCTs with 1136 participants were included. Clinical efficacy of M + P combination therapy was significantly better than P monotherapy (fifteen trials; RR 1.25, 95% CI 1.18-1.32, P < .00001, I = 27%). Compared with P monotherapy, the pooled effects of M + P combination therapy on nerve conduction velocity were (MD 6.29, 95% CI 4.63-7.94, P < .00001, I = 90%) for median MNCV, (MD 5.68, 95% CI 3.53-7.83, P < .00001, I = 94%) for median SNCV, (MD 5.36, 95% CI 3.86-6.87, P < .00001, I = 92%) for peroneal MNCV, (MD 4.62, 95% CI 3.48-5.75, P < .00001, I = 86%) for peroneal SNCV. There were no serious adverse events associated with drug intervention. CONCLUSIONS: M + P combination therapy was superior to P monotherapy for improvement of neuropathic symptoms and NCVs in DPN patients. Moreover, no serious adverse events occur in combination therapy.

Correlation between MCP-1-2518A/G polymorphism and the risk of Alzheimer's disease.

The -2518A/G polymorphism in monocyte chemotactic protein-1 (MCP-1) has been extensively investigated for association with Alzheimer's disease (AD); however, the results from different studies are inconsistent. The aim of this study was to draw an accurate conclusion of the association. All eligible case-control studies were searched in PubMed, Embase, Chinese National Knowledge Infrastructure, China Biological Medicine Databases, and Wanfang Databases. Eight case-control studies with a total of 2370 cases and 2413 controls were eligible to be included in this meta-analysis. The association was evaluated by calculating the odds ratios (ORs) with the corresponding 95% confidence intervals (CIs). Overall, there was no significant association between MCP-1-2518A/G polymorphism and AD risk in all genetic models (the allele model G vs. A: OR = 1.15, 95% CI 0.92-1.45, p = 0.22; the co-dominant model GG vs. AA: OR = 1.38, 95% CI 0.80-2.36, p = 0.25; the dominant model AG + GG vs. AA: OR = 1.14, 95% CI 0.89-1.46, p = 0.31; the recessive model GG vs. AG + AA: OR = 1.35, 95% CI 0.87-2.09, p = 0.18). In subgroup analysis by ethnicity, a significant difference was not detected in both Caucasians and Asians. In allele model (G vs. A), the required sample size of 31858 was calculated by applying trial sequential analysis. Cumulative z curve is always below the trial sequential monitoring boundary and is nominally statistically significant (Z = 1.96). A consistent result was obtained in other genetic models. In summary, the present meta-analysis suggests that MCP-1-2518A/G polymorphism may not be associated with genetic susceptibility of AD in general population, but the association remains indeterminate due to the insufficient evidence.

Fasudil combined with methylcobalamin or lipoic acid can improve the nerve conduction velocity in patients with diabetic peripheral neuropathy: A meta-analysis.

BACKGROUND: Fasudil (F) plus methylcobalamin (M) or lipoic acid (L) treatment has been suggested as a therapeutic approach for diabetic peripheral neuropathy (DPN) in numerous studies. However, the effect of the combined use still remains dubious. OBJECTIVE: The aim of this report was to evaluate the efficacy of F plus M or L (F + M or F + L) for the treatment of DPN compared with that of M or L monotherapy, respectively, in order to provide the basis and reference for clinical rational drug use. METHODS: Randomized controlled trials (RCTs) of F for DPN published up to September 2017 were searched. Relative risk (RR), mean difference (MD), and 95% confidence interval (CI) were calculated and heterogeneity was assessed with the I test. Sensitivity analyses were also performed. The outcomes measured were as follows: the clinical efficacy, median motor nerve conduction velocities (NCVs) (MNCVs), median sensory NCV (SNCV), peroneal MNCV, peroneal SNCV, and adverse effects. RESULTS: Thirteen RCTs with 1148 participants were included. Clinical efficacy of F + M combination therapy was significantly better than M monotherapy (8 trials; RR 1.26, 95% CI 1.17-1.35, P < .00001, I = 0%), the efficacy of F + L combination therapy was also obviously better than L monotherapy (4 trials; RR 1.27, 95% CI 1.16-1.39, P < .00001, I = 0%). Compared with monotherapy, the pooled effects of combination therapy on NCV were (MD 6.69, 95% CI 4.74-8.64, P < .00001, I = 92%) for median MNCV, (MD 6.71, 95% CI 1.77-11.65, P = .008, I = 99%) for median SNCV, (MD 4.18, 95% CI 2.37-5.99, P < .00001, I = 94%) for peroneal MNCV, (MD 5.89, 95% CI 3.57-8.20, P < .00001, I = 95%) for peroneal SNCV. Furthermore, there were no serious adverse events associated with drug intervention. CONCLUSION: Combination therapy with F plus M or L was superior to M or L monotherapy for improvement of neuropathic symptoms and NCVs in DPN patients, respectively. Moreover, no serious adverse events occur in combination therapy.

Lifestyle interventions to alleviate side effects on prostate cancer patients receiving androgen deprivation therapy: a meta-analysis.

BACKGROUND: Prostate cancer (PCa) patients receiving androgen deprivation therapy (ADT) are prone to suffer a series of potential side effects, including metabolic change, declining physical strength and worsening fatigue. Recent studies found that the change of lifestyle interventions can help to alleviate some adverse reactions, but the results were controversial. Therefore, the aim of this review was to comprehensively evaluate the effects of these lifestyle interventions on the side effects on PCa patients who received ADT. METHODS: We searched several electronic databases, including ScienceDirect, PubMed, Cochrane library, CNKI and Wanfang database, without language restrictions. Among the literature, such lifestyle interventions as dietary advice, exercise and physical activities were carried out in the way of randomized controlled trials (RCTs) on PCa patients taking ADT. Pooled estimates were performed using fixed-effects or random-effects model. RESULTS: Eleven RCTs involving 905 participants were included in this review. Compared with usual care group, exercise intervention could significantly improve the quality of life (QoL) of PCa patients undergoing ADT (P = 0.05, SMD = 0.17, 95% CI -0.00 to 0.34), but exercise plus dietary advice could not significantly improve the QoL (P = 0.15, SMD = 0.45, 95% CI -0.17 to 1.08). Moreover, lifestyle intervention could significantly change body composition (P = 0.03, SMD = -0.1, 95% CI -0.19 to -0.01). However, there showed no obvious difference in mitigating fatigue and depression (P = 0.46, SMD = 0.11, 95% CI -0.18 to 0.39; P = 0.31, SMD = -0.18, 95% CI -0.54 to 0.17). CONCLUSIONS: The results of this meta-analysis from present study indicated that exercise interventions can better improve the QoL and alleviate treatment-related side effects on prostate cancer patients taking ADT, and better therapeutic regimens for PCa patients are likely to emerge in the process.

Efficacy and safety of liraglutide versus sitagliptin both in combination with metformin in patients with type 2 diabetes: A systematic review and meta-analysis.

BACKGROUND: The aim of this systematic review was to evaluate the efficacy and safety of liraglutide versus sitagliptin both in combination with metformin in patients with type 2 diabetes and provide reference basis for rational use of clinical drugs. METHODS: Several databases were searched, including Web of science, PubMed, Cochrane library, CNKI, and Wanfang database. Only randomized controlled trials (RCTs) of liraglutide versus sitagliptin both in combination with metformin up to 31 August 2016 were included. Data were extracted independently by 2 reviewers, and a fixed or random effects model were used to analyze outcomes that were expressed as odds ratio (OR) or mean difference (MD) and 95% confidence intervals (95% CIs) for different situations. RESULTS: Five RCTs involving 1440 participants were included. Compared with sitagliptin combination with metformin group, participants' treatment with 1.2 mg and 1.8 mg liraglutide with metformin could significantly lower the level of glycosylated hemoglobin (HbA1c) (P < .00001, MD = -0.35, 95% CI -0.51 to -0.20). Moreover, patients with 1.8 mg liraglutide group had significant body weight loss (P < .00001, MD = -1.12, 95% CI -1.54 to -0.70). However, there were no obvious differences in cutting down the systolic blood pressure and diastolic blood pressure between liraglutide-metformin and sitagliptin-metformin groups. The incidence of gastrointestinal problems was significantly higher than sitagliptin with metformin groups. CONCLUSION: The results of this meta-analysis indicated that Liraglutide added on to metformin therapy could significantly lower the level of HbA1c and increase body weight loss. Meanwhile, the adverse reactions such as gastrointestinal problems were common in the liraglutide treatment group. Thus, this will provide an important reference for the treatment of patients with type 2 diabetes.

SIRT3 in Neural Stem Cells Attenuates Microglia Activation-Induced Oxidative Stress Injury Through Mitochondrial Pathway.

Sirtuin 3 (SIRT3), a mitochondrial protein, is involved in energy metabolism, cell apoptosis and mitochondrial function. However, the role of SIRT3 in neural stem cells (NSCs) remains unknown. In previous studies, we found that microglia activation-induced cytotoxicity negatively regulated survival of NSCs, along with mitochondrial dysfunction. The aim of this study was to investigate the potential neuroprotective effects of SIRT3 on the microglia activation-induced oxidative stress injury in NSCs and its possible mechanisms. In the present study, microglia-NSCs co-culture system was used to demonstrate the crosstalk between both cell types. The cytotoxicity of microglia activation by Amyloid-ß (Aß) resulted in the accumulation of reactive oxygen species (ROS) and down-regulation of SIRT3, manganese superoxide dismutase (MnSOD) gene expression in NSCs, concomitant to cell cycle arrest at G0/G1 phase, increased cell apoptosis rate and opening of the mitochondrial permeability transition pore (mPTP) and enhanced mitochondrial membrane potential (ΔΨm) depolarization. Furthermore, SIRT3 knockdown in NSCs via small interfering RNA (siRNA) accelerated cell injury, whereas SIRT3 overexpression provided resistance to microglia activation-induced oxidative stress cellular damage. The mechanisms of SIRT3 attenuated activated microglia-induced NSC dysfunction included the decreased mPTP opening and cyclophilin D (CypD) protein expression, inhibition of mitochondrial cytochrome C (Cyt C) release to cytoplasm, declined Bax/B-cell lymphoma 2 (Bcl-2) ratio and reduced caspase-3/9 activity. Taken together, these data imply that SIRT3 ameliorates microglia activation-induced oxidative stress injury through mitochondrial apoptosis pathway in NSCs, these results may provide a novel intervention target for NSC survival.