Microparticles from Hyperphosphatemia-Stimulated Endothelial Cells Promote Vascular Calcification Through Astrocyte-Elevated Gene-1.

Endothelial microparticles (EMPs) can be released in chronic kidney disease (CKD). Plasma concentration of high inorganic phosphate (HP) is considered as a decisive determinant of vascular calcification in CKD. We therefore explored the role of HP-induced EMPs (HP-EMPs) in the vascular calcification and its potential mechanism. We observed the shape of HP-EMPs captured by vascular smooth muscle cells (VSMCs) dynamically changed from rare dots, rosettes, to semicircle or circle. Our results demonstrated that HP-EMPs could directly promote VSMC calcification, or accelerate HP-induced calcification through signal transducers and activators of transcription 3 (STAT3)/bone morphogenetic protein-2 (BMP2) signaling pathway. AEG-1 activity was increased through HP-EMPs-induced VSMC calcification, in arteries from uremic rats, or from uremic rats treated with HP-EMPs. AEG-1 deficiency blocked, whereas AEG-1 overexpression exacerbated, the calcium deposition of VSMCs. AEG-1, a target of miR-153-3p, could be suppressed by agomiR-153-3p. Notably, VSMC-specific enhance of miR-153-3p by tail vein injection of aptamer-agomiR-153-3p decreased calcium deposition in both uremia rats treated with HP-EMPs or not. HP-EMPs could directly induce VSMCs calcification and accelerate Pi-induced calcification, and AEG-1 may act as crucial regulator of HP-EMPs-induced vascular calcification. This study sheds light on the therapeutic agents that influence HP-EMPs production or AEG-1 activity, which may be of benefit to treat vascular calcification.

Long non­coding RNA ZSCAN16­AS1 promotes the malignant properties of hepatocellular carcinoma by decoying microRNA­451a and consequently increasing ATF2 expression.

The importance of long noncoding RNAs (lncRNAs) in the oncogenicity of hepatocellular carcinoma (HCC) has been widely studied. However, the detailed functions of ZSCAN16 antisense RNA 1 (ZSCAN16­AS1) have seldom been explored in HCC until the present study. In the present study, experiments were performed to clarify whether ZSCAN16­AS1 is implicated in the oncogenesis and progression of HCC and to explore the possible underlying mechanisms. ZSCAN16­AS1 expression was analyzed using reverse transcription­quantitative PCR. The effects of ZSCAN16­AS1 on the biological behavior of HCC cells were demonstrated by functional experiments. The direct binding capacity of ZSCAN16­AS1 with microRNA­451a (miR­451a) was indicated by the luciferase reporter assay and RNA immunoprecipitation. The high expression of ZSCAN16­AS1 was confirmed in HCC by The Cancer Genome Atlas database and the cohort of the present study. Survival data revealed that patients with a high ZSCAN16­AS1 level had worse prognosis compared with those with a low ZSCAN16­AS1 level. Following ZSCAN16­AS1 knockdown, HCC cell proliferation, migration and invasion were curbed, whereas cell apoptosis was promoted in vitro. The absence of ZSCAN16­AS1 restricted tumor growth of HCC cells in vivo. Mechanistically, ZSCAN16­AS1 acted as a competing endogenous RNA by decoying miR­451a in HCC cells. Furthermore, activating transcription factor 2 (ATF2), a direct target of miR­451a, was under the regulation of ZSCAN16­AS1, which was exerted by sequestering miR­451a. In addition, miR­451a knockdown or ATF2 resumption reversed the proliferation suppression, apoptosis promotion and migration and invasion inhibition triggered by ZSCAN16­AS1 silencing. In conclusion, ZSCAN16­AS1, a pro­oncogenic lncRNA, aggravated the malignancy of HCC by controlling the miR­451a/ATF2 axis. An understanding of the competing endogenous RNA network of ZSCAN16­AS1/miR­451a/ATF2 in HCC might be instrumental in the development of attractive targets for molecular therapy.

Multi-objective location-scale optimization model and solution methods for large-scale emergency rescue resources.

The location of emergency rescue resources is the basis for the supply of all kinds of materials required for rescue work. Appropriate selection of emergency resource locations can greatly improve the efficiency of emergency supplies. Based on the summary and analysis of the existing research on it, we aim to provide efficient and feasible models and solutions for the location and layout of emergency rescue resources. In optimizing the layout of emergency rescue resources, we have taken into account the dynamic characteristics of emergency demand, the needs of emergency efficiency, cost and fairness, and constructed an optimization model for emergency resource location and construction scale. At the same time, in order to reduce the scale of solving the multi-objective optimization problem under multiple disasters, improve the computational efficiency, and obtain the absolute optimal solution in the feasible region, two types of power function methods are proposed to solve the model: basic efficacy coefficient method and unit cost utility method. Finally, we design a simulation example to verify the feasibility and effectiveness of the proposed emergency resource location model and solution methods. The results show that the model proposed in this paper can maximize the effectiveness of priority emergency rescue resources, while greatly reducing emergency costs. More importantly, it can ensure the fairness of emergency rescue to a certain extent and can optimize resource scale while optimizing location. Our research will provide a practical plan reference for the configuration decision in emergency rescue work.

Role of Vitamin D Receptor Gene Polymorphisms on the Susceptibility to Periodontitis: A Meta-Analysis of a Controversial Issue.

Background: To assess whether vitamin D receptor (VDR) gene polymorphisms influence the susceptibility to periodontitis. Methods: We retrieved 34 relevant studies, comprising a total of 3848 subjects suffering from periodontitis and 3470 controls for this meta-analysis. The pooled data were analyzed using STATA software. Results: Among all ethnic groups examined, the VDR BsmI polymorphism was associated with periodontitis under the recessive model (odds ratio [OR] = 0.722, 95% confidence interval [CI]: 0.532-0.980, p = 0.037). There was also a link between the VDR FokI polymorphism and periodontitis in the overall population (dominant model: OR = 1.459, 95% CI: 1.050-2.028, p = 0.025 and allelic model: OR = 1.386, 95% CI: 1.026-1.874, p = 0.034) and in Chinese participants (dominant model: OR = 1.813, 95% CI: 1.185-2.774, p = 0.006; allelic model: OR = 1.602, 95% CI: 1.044-2.459, p = 0.031) when stratified by race. The FokI variant was also correlated with aggressive periodontitis (AP) (dominant model: OR = 2.204, 95% CI: 1.148-4.231, p = 0.018; allelic model: OR = 2.017, 95% CI: 1.365-2.980, p = 0.000; and recessive model: OR = 2.903, 95% CI: 1.520-5.542, p = 0.001). We also showed a correlation between the VDR TaqI variant and periodontitis susceptibility in Caucasian populations (dominant model: OR = 0.525, 95% CI: 0.318-0.866, p = 0.012). The results revealed that there was no relationship between the VDR ApaI gene polymorphism and periodontitis. Conclusions: There was a link between the VDR BsmI and FokI gene polymorphisms and periodontitis in the overall population. In addition, the FokI polymorphism was correlated with AP. There was a link between the TaqI polymorphism and periodontitis in the Caucasian population. The VDR Apal variant, however, was not correlated with periodontitis.

Impact of Vitamin D Receptor Gene Polymorphism on Chronic Renal Failure Susceptibility.

Our pooled analysis aimed to assess the impact of vitamin D receptor (VDR) gene polymorphism on chronic renal failure (CRF) susceptibility. Relevant studies were searched from multiple databases, then pooled-analyses were performed using Stata software. Eighteen studies involving 2512 CRF patients and 3630 healthy controls were included. Pooled analysis showed that VDR ApaI and TaqI gene polymorphism were not associated with CRF susceptibility either in Asian or in Caucasians populations, and VDR BsmI and FokI gene polymorphism were not associated with CRF susceptibility in overall populations. The subgroup analysis showed that VDR BsmI gene polymorphism was associated with CRF susceptibility in Chinese under the Allele model (OR = 0.76, 95% CI: 0.59-0.97, P = 0.029). In Spanish individuals, VDR BsmI gene polymorphism was associated with CRF: Recessive model (BB vs. Bb + bb): OR = 1.60, 95% CI: 1.09-2.35, P = 0.016; Additive model (BB + bb vs. Bb): OR = 1.60, 95% CI: 1.21-2.12, P = 0.001). In addition, in the Asian subgroup, VDR FokI gene polymorphism was associated with CRF risk: Allele model (F vs. f): OR = 0.31, 95% CI: 0.16-0.59, P = 0.000; Dominant model (FF + Ff vs. ff): OR = 0.12, 95% CI: 0.03-0.59, P = 0.009 and Recessive model (FF vs. Ff + ff): OR = 0.32, 95% CI: 0.13-0.75, P = 0.009. This pooled analysis showed that VDR BsmI gene polymorphism was associated with CRF risk in the Chinese and Spanish individuals, and, VDR FokI gene polymorphism was associated with CRF risk in Asian subjects. But VDR ApaI and TaqI gene polymorphism were not associated with CRF risk either in Asian or in Caucasian individuals.

Impact of Statins on Arteriovenous Fistulas Outcomes: A Meta-Analysis.

Statins are effective lipid-lowering drugs with beneficial pleiotropic effects for vascular remodeling processes, statins may have a beneficial effect on the function of arteriovenous fistulas (AVFs) in hemodialysis (HD) patients. Therefore, we performed this systematic review to assess the protective effects of statin therapy in HD patients. The randomized controlled trials (RCTs) or quasi-RCTs and retrospective cohort studies (RCS) of statin therapy for the function of AVFs in HD patients were searched from multiple databases. Relevant studies were screened according to predefined inclusion criteria and then pooled-analyses were performed using RevMan 5.2 software. One RCT and six RCS containing 20 246 HD patients were included in this meta-analysis, of whom 9847 were treated with statins and 10 399 were treated with placebo. Our meta-analysis showed that there was no significant difference between statins and placebo groups, with those who received statin therapy showing similar AVF failure rates compared to control (pooled risk ratio = 0.89; 95% CI, 0.70 to 1.12, P = 0.32), and there was obvious evidence of statistical heterogeneity (P = 0.005; I2  = 68%). In addition, subgroup pooled analyses revealed that statin therapy did not ameliorate AVF failure in participants from the same racial background or similar sample size trials. There was no evidence that statins therapy could reduce the AVFs failure. However, due to methodological limitations and obvious statistical heterogeneity, high-quality, long-term and multicenter trials are required to fully elucidate the clinical value of statins administration for the outcomes of AVFs in HD patients.

Effects of far infrared therapy on arteriovenous fistulas in hemodialysis patients: a meta-analysis.

BACKGROUND: Far infrared (FIR) therapy may have a beneficial effect on maturity and function of arteriovenous fistulas (AVFs) in hemodialysis (HD) patients. Therefore, we performed this pooled analysis to assess the protective effects of FIR therapy in HD patients. METHODS: The randomized controlled trials (RCTs) and quasi-RCTs of FIR therapy for HD patients were searched from multiple databases. Relevant studies were screened according to the predefined inclusion criteria. The meta-analyses were performed using RevMan 5.2 software (The Cochrane Collaboration, Oxford, UK). RESULTS: Meta-analysis showed that FIR therapy could significantly increase the vascular access blood flow level (MD, 81.69 ml/min; 95% CI, 46.17-117.21; p < .001), AVFs diameter level (MD, 0.36 mm; 95% CI, 0.22-0.51; p < .001), and the primary AVFs patency (pooled risk ratio = 1.24; 95% CI, 1.12-1.37, p < .001). In addition, therapy with FIR ray radiation could decrease AVFs occlusion rates (pooled risk ratio = 0.20; 95% CI, 0.08-0.46; p < .001) and the level of needling pain (pooled risk ratio = 0.08; 95% CI, 0.06-0.10, p < .001). CONCLUSIONS: FIR therapy can reduce AVFs occlusion rates and needling pain level, while significantly improve the level of vascular access blood flow, AVFs diameter and the primary AVFs patency.