Effects and safety of Ophiocordyceps sinensis preparation in the adjuvant treatment for dialysis patients: A protocol for systematic review and meta-analysis.

INTRODUCTION: Ophiocordyceps sinensis(O. sinensis), a genus of ascomycete fungi, has been intensively studied in various disease models, which is a rich source of various bioactive compounds and used in the treatment for end-stage renal disease patients. This systematic review highlights the therapeutic roles of O. sinensis as adjuvant treatment for dialysis patients with clinical evidence. METHODS AND ANALYSIS: The systematic review will be performed according to the Cochrane Handbook for Systematic Reviews of Interventions. The protocol is being reported in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols Statement. An literature search strategy will be developed and adapted for 9 databases. Searches will be run from the database inception until the date of the search implementation and be updated before the review is completed. Randomized controlled trials that investigate the effects of O. sinensis for dialysis patients (peritoneal dialysis and hemodialysis) will be included. We will focus on outcomes recommended by the core outcome measures in effectiveness trials, including mortality, cardiovascular disease, infection, vascular access problems, dialysis adequacy, hyperkalaemia, life participation. Two researchers will independently screen the studies, extract data and evaluate study quality using the Risk of Bias 2 tool. Subgroup analysis will be performed according to peritoneal dialysis and hemodialysis. Sensitivity analyses will be conducted based on the Leave-1-Out Method. The Grading of Recommendations Assessment, Development, and Evaluation approach will be used to rate the quality of the evidence. Meta analysis will be performed using Review Manager 5.3 and R packages. OBJECTIVES: Studies have reported positive results of O. sinensis as adjuvant treatment for patients with dialysis. This review will synthesis current evidence on how O. sinensis can improve dialysis. Thus, it is expected that robust and conclusive evidence of the effects of O. sinensis during or after treatment can be obtained. These findings can inform future research and the selection of O. sinensis to promote quality of life for people with dialysis.

New-onset glucose disorders in peritoneal dialysis patients: a meta-analysis and systematic review.

BACKGROUND: Peritoneal dialysis (PD) patients are at high risk of developing glucose metabolism disturbance (GMD). The incidence and prevalence of new-onset GMD, including diabetes mellitus (DM), impaired glucose tolerance (IGT) and impaired fast glucose (IFG), after initiation of PD, as well as their correlated influence factors, varies among studies in different areas and of different sample sizes. Also, the difference compared with hemodialysis (HD) remained unclear. Thus we designed this meta-analysis and systematic review to provide a full landscape of the occurrence of glucose disorders in PD patients. METHODS: We searched the MEDLINE, Embase, Web of Science and Cochrane Library databases for relevant studies through September 2018. Meta-analysis was performed on outcomes using random effects models with subgroup analysis and sensitivity analysis. RESULTS: We identified 1124 records and included 9 studies involving 13 879 PD patients. The pooled incidence of new-onset DM (NODM) was 8% [95% confidence interval (CI) 4-12; I2 = 98%] adjusted by sample sizes in PD patients. Pooled incidence rates of new-onset IGT and IFG were 15% (95% CI 3-31; I2 = 97%) and 32% (95% CI 27-37), respectively. There was no significant difference in NODM risk between PD and HD [risk ratio 0.99 (95% CI 0.69-1.40); P = 0.94; I2 = 92%]. PD patients with NODM were associated with an increased risk of mortality [hazard ratio 1.06 (95% CI 1.01-1.44); P < 0.001; I2 = 92.5%] compared with non-DM PD patients. CONCLUSIONS: Around half of PD patients may develop a glucose disorder, which can affect the prognosis by significantly increasing mortality. The incidence did not differ among different ethnicities or between PD and HD. The risk factor analysis did not draw a definitive conclusion. The glucose tolerance test should be routinely performed in PD patients.

Microarray analysis reveals gene and microRNA signatures in diabetic kidney disease.

The current study aimed to identify therapeutic gene and microRNA (miRNA) biomarkers for diabetic kidney disease (DKD). The public expression profile GSE30122 was used. Following data preprocessing, the limma package was used to select differentially-expressed genes (DEGs) in DKD glomeruli samples and tubuli samples and they were compared with corresponding controls. Then overlapping DEGs in glomeruli and tubuli were identified and enriched analysis was performed. In addition, protein­protein interaction (PPI) network analysis as well as sub­network analysis was conducted. miRNAs of the overlapping DEGs were investigated using WebGestal. A total of 139 upregulated and 28 downregulated overlapping DEGs were selected, which were primarily associated with pathways involved in extracellular matrix (ECM)­receptor interactions and cytokine­cytokine receptor interactions. CD44, fibronectin 1, C­C motif chemokine ligand 5 and C­X­C motif chemokine receptor 4 were four primary nodes in the PPI network. miRNA (miR)­17­5p, miR­20a and miR­106a were important and nuclear receptor subfamily 4 group A member 3 (NR4A3), protein tyrosine phosphatase, receptor type O (PTPRO) and Kruppel like factor 9 (KLF9) were all predicted as target genes of the three miRNAs in the integrated miRNA­target network. Several genes were identified in DKD, which may be involved in pathways such as ECM­receptor interaction and cytokine­cytokine receptor interaction. Three miRNAs may also be used as biomarkers for therapy of DKD, including miR­17­5p, miR­20a and miR­106a, with the predicted targets of NR4A3, PTPRO and KLF9.

Roles of MicroRNA-195 in cardiomyocyte apoptosis induced by myocardial ischemia-reperfusion injury.

This study aims to investigate microRNA-195 (miR-195) expression in myocardial ischaemia-reperfusion (I/R) injury and the roles of miR-195 in cardiomyocyte apoptosis though targeting Bcl-2. A mouse model of I/R injury was established. MiR- 195 expression levels were detected by real-time quantitative PCR (qPCR), and the cardiomyocyte apoptosis was detected by TUNEL assay. After cardiomyocytes isolated from neonatal rats and transfected with miR-195 mimic or inhibitor, the hypoxia/reoxygenation (H/R) injury model was established. Cardiomyocyte apoptosis and mitochondrial membrane potential were evaluated using flow cytometry. Bcl-2 and Bax mRNA expressions were detected by RT-PCR. Bcl-2, Bax and cytochrome c (Cyt-c) protein levels were determined by Western blot. Caspase-3 and caspase-9 activities were assessed by luciferase assay. Compared with the sham group, miR-195 expression levels and rate of cardiomyocyte apoptosis increased significantly in I/R group (both P < 0.05). Compared to H/R + negative control (NC) group, rate of cardiomyocyte apoptosis increased in H/R + miR-195 mimic group while decreased in H/R + miR-195 inhibitor group (both P <0.05). MiR-195 knockdown alleviated the loss of mitochondrial membrane potential (P <0.05). MiR-195 overexpression decreased Bcl-2 mRNA and protein expression, increased BaxmRNA and protein expression, Cyt-c protein expression and caspase-3 and caspase-9 activities (all P <0.05).While, downregulated MiR-195 increased Bcl-2 mRNA and protein expression, decreased Bax mRNA and protein expression, Cyt-c protein expression and caspase-3 and caspase-9 activities (all P < 0.05). Our study identified that miR-195 expression was upregulated in myocardial I/R injury, and miR-195 overexpression may promote cardiomyocyte apoptosis by targeting Bcl-2 and inducing mitochondrial apoptotic pathway.

Association between glucose transporter 1 rs841853 polymorphism and type 2 diabetes mellitus risk may be population specific (1rs8418532).

BACKGROUND: So far, studies on the association between the glucose transporter 1 (GLUT1) rs841853 polymorphism and type 2 diabetes mellitus (T2DM) risk have generated considerable controversy. The present study was performed to clarify the association of this genetic variation with T2DM. METHODS: A comprehensive literature search of electronic databases was conducted to obtain articles focused on the relationship between the GLUT1 rs841853 polymorphism and T2DM, followed by a systemic meta-analysis. RESULTS: Fourteen articles and 19 individual studies were included for analysis. Main analyses revealed extreme heterogeneity and random effect pooled odds ratios (OR) were weakly significant in allele contrast (OR 1.28; 95% confidence interval [CI] 1.01, 1.63; P=0.04) and dominant model (OR 1.52; 95% CI 1.19, 1.94; P=0.0008) for T allele. Subgroup analyses for Caucasians showed marginal positive results in the dominant model. However, analyses for Asians yielded an obvious relationship to T2DM risk in all genetic models. Interestingly, T allele even seemed to be a protective factor against the development of T2DM in Blacks in allele contrast. Sensitivity analyses did not alter materially for most comparisons and no publication bias was found in this meta-analysis. CONCLUSIONS: The results of the present meta-analysis provide evidence that the GLUT1 rs841853 polymorphism may confer increased susceptibility to T2DM in Asians. However, there is no currently available strong evidence supporting the association between this genetic variation and T2DM in Caucasians, Blacks, or the overall population.

One-step surface modification of poly(lactide-co-glycolide) microparticles with heparin.

PURPOSE: The aim of this study was to modify the surface of poly(lactide-co-glycolide) (PLGA) microparticles with heparin. The heparin-coated PLGA may enhance blood and tissue compatibility of PLGA devices and provide a novel approach to deliver growth factors. MATERIALS AND METHODS: A one-step method using heparin to replace traditional emulsifiers (e.g., PVA) during emulsion-solvent evaporation process was employed to surface-entrap heparin in PLGA microspheres. The emulsifying activity of heparin was modified via varying counter ion form, including univalent (Na(+), K(+), Li(+), and [Formula: see text]) and divalent (Ca(2+), Mg(2+), Ba(2+), and Zn(2+)) cations, and complexation with amino acids (Arg, Lys, Leu, Val, Gly and Glu). Surface accessible and total heparin loading were determined by a modified toluidine blue assay and elemental analysis, respectively. RESULTS: Heparin bound with univalent counter ions and amino acids exhibited emulsifying activity to varying degrees, whereas divalent heparin salts tended to cause complete aggregation of the PLGA o/w emulsion. Increasing pH (>or=7.4) of hardening medium enhanced heparin adsorption and significantly stabilized the PLGA o/w emulsion. The initial surface density of heparin on the PLGA microspheres prepared using univalent heparin salts was around 8-33 mg/m(2). Surface associated heparin desorbed quickly; potassium heparin showed the best retention, with approximately 0.2 and 0.1 mg/m(2) detected on PLGA microsphere surface following 1- and 14-day incubation in PBST at 37 degrees C, respectively. CONCLUSIONS: PLGA microparticles were successfully surface-modified with heparin. Univalent salts and amino acid complexes of heparin, as effective emulsifiers, can become surface-immobilized in PLGA microspheres.

Injectable polymer microspheres enhance immunogenicity of a contraceptive peptide vaccine.

Advanced contraceptive peptide vaccines suffer from the unavailability of adjuvants capable of enhancing the antibody response with acceptable safety. We sought to overcome this limitation by employing two novel poly(lactic-co-glycolic acid) (PLGA) microsphere formulations to deliver a synthetic human chorionic gonadotropin (hCG) peptide antigen co-synthesized with a T-cell epitope from tetanus toxoid (TT), C-TT2-CTP35: surface-conjugated immunogen to induce phagocytosis; and encapsulated peptide to provide a depot effect, with MgCO(3) co-encapsulated in the polymer to neutralize acidity from the biodegrading PLGA polyester. A single immunization of encapsulated peptide in rabbits elicited a stronger antibody response with equivalent duration relative to a positive control--three injections of the peptide administered in a squalene-based water-in-oil emulsion. Surface-conjugated peptide was less effective but enhanced antibody levels at 1/5 the dose, relative to soluble antigen. Most remarkable and unexpected was the finding that co-encapsulation of base was essential to attain the powerful adjuvant effect of the PLGA-MgCO(3) system, as the MgCO(3)-free microspheres were completely ineffective. A promising contraceptive hCG peptide vaccine with acceptable side effects (i.e., local tissue reactions) was achieved by minimizing PLGA and MgCO(3) doses, without significantly affecting antibody response.