Meta-analysis of the association between sclerostin level and adverse clinical outcomes in patients undergoing maintenance haemodialysis.

BACKGROUND: Studies regarding the relationship of sclerostin (Scl) with clinical outcomes in patients undergoing maintenance haemodialysis have yielded controversial findings. This meta-analysis was performed to investigate the predictive role of Scl in this patient population. METHODS: Several electronic medical databases (e.g. PubMed, Embase, Web of Science and Cochrane Library) were searched for eligible studies through December 20, 2019. Summary hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated based on Scr level (high or low) using a random or fixed effects model. RESULTS: From among 641 initially screened publications, 16 eligible studies were included in this meta-analysis. A high Scl level was not associated with cardiovascular events [HR = 0.8 (95% CI, 0.42-1.35)] or all-cause mortality [HR = 0.93 (95% CI, 0.56-1.54)]. There was high heterogeneity, but no evidence of publication bias. Interestingly, a high Scl level was associated with reduced cardiovascular events [HR = 0.44 (95% CI, 0.29-0.69)] in the subgroup by shorter follow-up period or all-cause mortality [pooled HR = 0.58 (95% CI, 0.36-0.91)] by shorter dialysis vintage. CONCLUSION: This meta-analysis indicated that a high Scl level did not predict total clinical outcomes in patients undergoing maintenance haemodialysis despite survival benefits in the subgroups. The predictive role of Scl in these patients should be further evaluated in large prospective studies.

Nano-Graphene Enclosed Multi Nitrogen: Dynamic Hierarchical Self-Assemble Property for Lithium Ion Storage.

Led to significant capacity improvement to 1800 mA/h after 100 cycles for nano-graphene-N4, which is the first report for a carbonaceous materials anode. In addition, the doping level, id est, number of nitrogen atoms, had a significant influence on the molecular self-assembled structures through hierarchical self-assembly. As the nitrogen concentration increased, the d-space between the nanosheets increased from 3.4 to 4.3. The capacity of the nano-graphene increased greatly from 500 mAh/g for nano-graphene without N-doping to 1800 mAh/g for nano-graphene with nanographene-N4, indicating that the capacity is related to the structures, and was defined and the relationship between performance and structure was determined.

A Novel Process for the Preparation of ZnO Nanoparticles and ZnO/Ni0.5Zn0.5Fe2O4 Nanocomposites.

A novel solution combustion and gel calcination process for the preparation of ZnO nanoparticles and ZnO/Ni0.5Zn0.5Fe2O4 nanocomposites was introduced. The phase identification, morphologies and magnetic properties of ZnO nanoparticles and ZnO/Ni0.5Zn0.5Fe2O4 nanocomposites were confirmed by X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscope (TEM), vibrating sample magnetometer (VSM). The results showed that the concentration of zinc nitrate and the calcination temperature were two key factors for the grain size, crystallinity and properties of ZnO nanoparticles, while, the mass ratio of ZnO and Ni0.5Zn0.5Fe2O4 in ZnO/Ni0.5Zn0.5Fe2O4 nanocomposites was the important factor for the specific magnetizations (Ms) of ZnO/Ni0.5Zn0.5Fe2O4 nanocomposites.

Ginsenoside-Rg1 Protects against Renal Fibrosis by Regulating the Klotho/TGF-ß1/Smad Signaling Pathway in Rats with Obstructive Nephropathy.

Ginsenoside-Rg1 (G-Rg1) is an agent isolated from Panax ginseng that exerts anti-fibrotic effects; however, the mechanism is still unclear. Herein, we investigated whether G-Rg1 administration can mitigate or reverse unilateral ureteral obstruction (UUO)-induced renal fibrosis by regulating the Klotho/transforming growth factor (TGF)-ß1/Smad signaling pathway in rats. Sprague-Dawley male rats were subjected to UUO, and rats in the treatment group were administered G-Rg1 or G-Rg1 plus Klotho short hairpin RNA interference (shRNA), while rats in the control and model groups were administered vehicle for 14 d. Epithelial-mesenchymal transition (EMT) biomarkers and Klotho/TGF-ß1 signaling molecules were examined by immunohistochemistry, quantitative real-time PCR and Western blotting. Immunohistochemistry showed that UUO induced increased pro-fibrotic TGF-ß1 expression, overexpression of the mesenchymal marker, α-smooth muscle actin (α-SMA), and suppression of the epithelial marker, E-cadherin. Moreover, Western blotting analysis indicated that UUO promoted TGF-ß1 and phosphorylated Smad3 (p-Smad3) expression (p<0.01), but blocked Klotho and Smad7 expression (p<0.01). After G-Rg1 administration, the UUO-induced TGF-ß1 and p-Smad3 expression was suppressed (p<0.01), whereas the reduced Klotho and Smad7 expression was reversed (p<0.05), followed by amelioration of the EMT process. Intriguingly, the G-Rg1 effects were largely abrogated by Klotho knockdown. Furthermore, Klotho expression was upregulated by G-Rg1 treatment at the mRNA and protein levels. Our results suggest that G-Rg1 may be beneficial for ameliorating renal fibrosis by targeting Klotho/TGF-ß1/Smad signaling in UUO rats.

Plasma s-Klotho is related to kidney function and predicts adverse renal outcomes in patients with advanced chronic kidney disease.

To investigate whether the soluble Klotho (s-Klotho) level in patients with chronic kidney disease (CKD) is related to kidney function and whether a low s-Klotho level can predict adverse renal outcomes or CKD progression in patients with advanced CKD. 112 patients with CKD stages 3-5 and 30 healthy volunteers were enrolled. Blood samples were collected to measure serum creatinine, calcium, phosphorus, intact parathyroid hormone, and hemoglobin. s-Klotho and fibroblast growth factor 23 (FGF23) were determined by ELISA. We first conducted a cross-sectional study to investigate correlations between s-Klotho and estimated glomerular filtration rate (eGFR) and other parameters. Patients were then followed prospectively for 20.1±10.1 months according to s-Klotho median level until serum creatinine doubled, or initiation of renal replacement therapy, or death. s-Klotho levels inpatients with CKD were significantly lower than that in the control group. For patients with CKD, there were no differences in age distribution among subgroups. However, s-Klotho level differed significantly across CKD stages, and it was lower in the advanced CKD group compared with the moderate CKD group. Correlation analysis revealed that s-Klotho was positively associated with eGFR, but inversely associated with FGF23. During the follow-up of 20.1±10.1 months, patients with higher s-Klotho levels showed a reduced risk of kidney adverse outcomes, including serum creatinine doubling and initiation of renal replacement therapy. Cox regression analysis revealed that low s-Klotho was an independent risk factor for CKD progression. s-Klotho level was closely correlated with kidney function, further, low s-Klotho level could predict adverse kidney disease outcomes in patients with progressive CKD.

Tranilast attenuates TGF-ß1-induced epithelial-mesenchymal transition in the NRK-52E cells.

We previously reported that tranilast can halt the pathogenesis of chronic cyclosporine nephrotoxicity in rats via the transforming growth factor-ß (TGF-ß) /Smad pathway, an important signaling system involved in epithelial-mesenchymal transition (EMT), but the exact underlying cellular mechanisms are not yet clear. Thus, by selecting TGF-ß1-induced normal rat kidney proximal tubular epithelial cells (NRK-52E) as a model, we demonstrated potential modifying effect of tranilast on EMT-induced by TGF-ß1 in vitro. NRK-52E cells were incubated with the blank vehicle (Dulbecco's modified Eagle's medium and F-12 (DMEM/F12) added with 10% fetal bovine serum (FBS)), 10 ng/ml TGF-ß1 alone or together with 100, 200 or 400µM tranilast for 48 h after incubation in medium containing 1% FBS for 24 h. Cell morphological changes were observed to confirm occurrence of EMT. Protein expressions of two typical markers of EMT, E-cadherin and α-smooth muscle actin (α-SMA), were assessed by western blotting and flow cytometry, respectively. Our results showed that TGF-ß1 induced spindle-like morphological transition, the loss of E-cadherin protein and upregulation of expression of α-SMA. However, the TGF-ß1-produced changes in cellular morphology, E-cadherin and α-SMA were inversed by tranlilast in concentration-dependent manner. Our findings indicate that tranilast can directly inhibit EMT. Thus, it may be implied that regulation of EMT be the target to prevent renal tubulointerstitial fibrosis.

[Research on the effects of PIAS3 expression on the invasion of glioma TJ905 cells].

OBJECTIVES: To investigate the function and possible mechanisms of PIAS3 expression on the invasion of TJ905 cells. METHODS: PIAS3 overexpression vectors were constructed and PIAS3 siRNA were chemically synthesized, which were separately transfected into TJ905 cells for upregulation or downregulation of PIAS3 expression levels in TJ905 cells. After that, the invasive effects of TJ905 cells were measured by Transwell assay, and the expression of PIAS3, tissue inhibitor of metalloproteinases (TIMP)3, matrix metalloprotease (MMP)-2, and MMP-9 were identified by Western blot. RESULTS: In vitro transfection efficiency of plasmids and oligonucleotides were separately 85.3% ± 3.1% and 95.1% ± 2.9%. PIAS3 overexpression plasmid transfection in vitro could effectively improve the expression of PIAS3 protein in TJ905 cells and inhibit the invasion of TJ905 cells (P < 0.05), and cell penetration ratio reduced from 87.9% ± 9.3% to 37.3% ± 7.9% compared with control group, while it upregulated TIMP3 and downregulated MMP-2, MMP-9 protein expression (P < 0.05); PIAS3 siRNA transfection could inhibit the PIAS3 protein expression of TJ905 cells and promote the invasion of TJ905 cells (P < 0.05), and cell penetration ratio increased from 83.9% ± 7.1% to 93.2% ± 3.1% compared with control group, while it downregulated TIMP3 and upregulated MMP-2, MMP-9 protein expression (P < 0.05). CONCLUSION: PIAS3 expression is closely related to the invasion properties of glioma TJ905 cells.