Roxadustat reduces left ventricular mass index compared to rHuEPO in haemodialysis patients in a randomized controlled trial.

BACKGROUND: Left ventricular hypertrophy (LVH) is highly prevalent in haemodialysis (HD) patients and is associated with an increased risk of death. Roxadustat and recombinant human erythropoietin (rHuEPO, abbreviated as EPO) are the main treatment strategies for renal anaemia in HD patients, but it has not been clear whether there is a difference in their effect on LVH. METHODS: In this multi-centre, prospective, randomized trial of 12-month duration, study participants were randomized in a 1:1 ratio to the roxadustat group or the EPO group. The doses of both treatment regimens were adjusted so that the patients had a haemoglobin level of 10.0-12.0 g per dL. The primary study endpoint was the change from baseline to 12 months in the left ventricular mass index (LVMI, g/m2) measured by echocardiography. RESULTS: In total, 114 patients were enrolled. The mean age was 50 years, and the median dialysis duration was 33 months. Sixty-one patients were men, and 24 were diabetic. LVMI decreased from 116.18 ± 27.84 to 110.70 ± 25.74 g/m2 in the roxadustat group. However, it increased from 109.35 ± 23.41 to 114.99 ± 28.46 g/m2 in the EPO group, with a significant difference in the change in LVMI between the two groups [-5.48 (-11.60 to 0.65) vs. 5.65 (0.74 to 10.55), p < 0.05]. Changes in left ventricular mass, end-diastolic volume and 6-min walk test seemed superior in the roxadustat group. There were no significant differences in other cardiac geometry, biochemical parameters and major adverse cardiovascular events between the two groups. CONCLUSIONS: Compared to EPO, roxadustat is more helpful in the regression of LVH in HD patients.

Effect of Salicylic Acid Treatment on Disease Resistance to Coleosporium zanthoxyli in Chinese Pepper (Zanthoxylum armatum).

The fungus Coleosporium zanthoxyli causes leaf rust in Chinese pepper (Zanthoxylum armatum). To investigate the control effect of elicitor treatment on leaf rust in this species, the impact of salicylic acid (SA) on the spores and growth of C. zanthoxyli and the induced resistance to leaf rust by Z. armatum were analyzed, and the possible defense mechanisms involved in SA induction were evaluated. The results showed that SA had no effect on C. zanthoxyli spore germination and growth; however, rust resistance was induced in Z. armatum. The optimal SA treatment concentration was 0.4 mg/ml, and the relative cure effect reached 44.56%. SA-induced disease resistance was evident for up to 10 days, while the optimal induction interval was 48 h after stimulation. Consistent with the induced resistance, H2O2, total protein, total phenol, and lignin concentrations and polyphenol oxidase (PPO), peroxidase (POD), phenylalanine ammonia lyase (PAL), superoxide dismutase (SOD), and catalase (CAT) activities were significantly increased with the SA treatment, whereas the malondialdehyde content was significantly decreased. In addition, exogenous SA promoted defense-related enzyme activities, including those of POD, CAT, and PAL, and increased H2O2, lignin, and endogenous SA contents. Furthermore, SA induced the expression of SA signaling pathway genes such as ZaPR1 and ZaNPR1, and silencing ZaPR1 enhanced the sensitivity of Z. armatum to leaf rust. Our results demonstrated that 0.4 mg/ml SA priming increased the activities of CAT, POD, and PAL, elevated the contents of H2O2, lignin, and endogenous SA, and upregulated the expression of the SA-related gene ZaPR1, thereby enhancing the resistance of Z. armatum to leaf rust.

Association of single nucleotide polymorphisms in ADIPOQ gene with risk of hypertension: a systematic review and meta-analysis.

BACKGROUND: Hypertension has been continuing to be a major contributor to the global burden of disease and to the global mortality, leading to over 10 million deaths each year. The purpose of this study was to investigate the association between Adiponectin gene polymorphism with Essential hypertension (EH). METHODS: PubMed, EMbase, the Cochrane Library, and China National Knowledge Infrastructure (CNKI) were searched independently by two investigators. Pooled odds ratios and 95% confidence intervals were calculated to estimate the associations of Adiponectin polymorphism with EH. RESULTS: Thirteen studies with 3198 cases and 3076 controls for meta-analysis (MA) were included in present study. Pooled results showed that rs2241766 polymorphism is associated with the risk of EH in the allelic model (G vs. T: OR=1.10; 95% CI, 1.01-1.21). In the <40 years subgroup, rs2241766 polymorphism is associated with the risk of EH in allele model (G vs. T: OR=1.43; 95% CI, 1.06-1.94), recessive model (GG vs. GT + TT: OR=5.26, 95% CI=1.47-18.76), homozygous model of GG (GG vs.TT: OR=5.27, 95% CI=1.47-18.95), and rs266729 in recessive model (GG vs. GT + TT: OR=2.33, 95% CI=1.33-4.08). CONCLUSIONS: Our meta-analysis results show that the rs2241766 polymorphism is associated with the risk of hypertension. There still need a larger sample with better design to verify.

Astragaloside IV alleviates puromycin aminonucleoside-induced podocyte cytoskeleton injury through the Wnt/PCP pathway.

Podocyte injury is a common cause of massive proteinuria. Astragaloside IV (AS-IV) has been reported to protect podocytes in diabetic models. However, the effects and potential mechanism of AS-IV on puromycin aminonucleoside (PAN)-induced podocyte injury remains unclear. The aim of the present study was to investigate the protective effect of AS-IV on PAN-induced podocyte injury both in vivo and in vitro. In vivo, we induced a podocytic-injury model in rats via a single tail vein injection of PAN. The rats in the treatment group received AS-IV intragastrically (i.g.) at a dose of 40 mg/kg/day for 10 days. At the end of the experiment, 24 h urine, serum and kidney samples were collected for examination. In vitro, we injured podocytes with 30 µg/ml PAN and treated them with AS-IV at concentrations of 5, 25 and 50 µg/ml. Next, we analyzed podocyte protein expression and the Wnt/planar-cell polarity (PCP) pathway using western blot and immunofluorescence (IF). Our results showed that AS-IV decreased proteinuria in PAN-injured rats, and restored specific protein expression in podocytes. In PAN-induced injuries to human podocytes, AS-IV restored the expression and distribution of F-actin and synaptopodin, and repaired the morphology of the actin-based cytoskeleton. Notably, AS-IV could activate the Wnt/PCP pathway by promoting expression of Wnt5a, protein tyrosine kinase 7 (PTK7), Rho-associated coiled-coil-containing protein kinase 1 (ROCK1), Ras-related C3 botulinum toxin substrate 1 (Rac1) and phospho-SAPK/JNK (Thr183/Tyr185) (p-JNK) in vivo and in vitro. In conclusion, we demonstrated that AS-IV alleviated PAN-induced injury to the podocyte cytoskeleton, partially by activating the Wnt/PCP pathway.

Transcription profiling of artemisinin-treated diabetic nephropathy rats using high-throughput sequencing.

Artemisinin (Art) plays a renoprotective role in diabetic nephropathy (DN) rats. However, the differential gene expression profile and underlying molecular mechanism of Art treatment in DN is not well understood. We constructed an animal model of DN by injection of streptozotocin (STZ) in rats. We then examined the profile of differentially expressed genes following administration of Art using RNA-sequencing (KANGCH&EN, Shanghai, China). Five genes identified by RNA-sequencing were randomly selected and validated by qRT-PCR. Bioinformatic analyses were performed to study these differentially expressed genes. We identified a total of 31 genes that were significantly up-regulated in DN samples compared to both normal and Art treatment samples, and 38 genes that were significantly down-regulated in DN samples compared to both normal and Art treatment samples. The identified genes were associated with a list of gene ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and may be involved in the mechanism underlying Art treatment of DN. Thus, the results from the current study demonstrate that genes are aberrantly expressed after Art treatment and identify promising targets in the treatment of DN with artemisinin.

Trichosanthes kirilowii lectin alleviates diabetic nephropathy by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway.

Trichosanthes kirilowii lectin (TKL) has been reported to exert hypoglycemic effects in alloxan-induced diabetic mice. However, there is no evidence showing that it helps to prevent diabetic nephropathy (DN). We used a high glucose (HG)-induced HK-2 cell model and a streptozocin (STZ)-induced Wistar rat model to investigate the effects of TKL on DN, as well as the mechanisms for those effects. Our results showed that TKL significantly increased the viability of HG-treated HK-2 cells and inhibited cell apoptosis. In vivo experiments demonstrated that TKL attenuated STZ-induced histopathological damage and the inflammatory response in rat kidney tissues. Pre-treatment of HK-2 cells or STZ-treated rats with polyinosinic acid (Poly IC), an inhibitor of lectin-like oxLDL receptor 1 (LOX1), blocked the protective effect of TKL against HG- or STZ-induced damage to kidney tissue, indicating that TKL might exert its effect via LOX1-mediated endocytosis. Additional results suggested that TKL inhibits the phosphorylation of IκB kinase ß (IKKß) and the nuclear factor-κB (NF-κB) inhibitor protein (IκBα), and thereby reduces the nuclear translocation of NF-κB (p65). ChIP assay data indicated that TKL markedly inhibits the binding of p65 to the CASP9 gene in HG-treated HK-2 cells, subsequently suppressing transcription of the CASP9 gene. In the dual-luciferase reporter assay, TKL significantly inhibited luciferase activity in cells co-transfected with p65 and a wild-type capase-9 construct instead of mutated caspase-9 constructs.Taken together, our results show that TKL helps to protect against DN by inhibiting the LOX1/NF-κB/caspase-9 signaling pathway, suggesting TKL as a promising agent for treating DN.