Effectiveness of Tolvaptan in the Treatment for Patients with Autosomal Dominant Polycystic Kidney Disease: A Meta-analysis.

AIMS AND OBJECTIVE: Autosomal Dominant Polycystic Kidney Disease (ADPKD) is a common chronic kidney disease that leads to End-Stage Renal Disease (ESRD). The key target of this therapy is to prevent the progression of kidney failure. Tolvaptan could slow kidney cyst growth and are proven highly effective. The aims of this analysis are to perform a systematic review, estimate and evaluate the efficacy and safety of tolvaptan in ADPKD patients. MATERIALS AND METHODS: Randomized controlled trials of tolvaptan in ADPKD were identified in PubMed, Ovid, Web of Science and the Cochrane Library electronic database. The changes observed in kidney function, treatment efficiency and the incidence of adverse events between the tolvaptan and placebo groups were compared. Data were analyzed by the RevMan software. RESULTS: Eight trials, including 7 double-blinded randomised controlled trials and 1 quasi RCT involving 1,536 patients were extracted. Significant differences in the annual rate of change in the total kidney volume TKV at any stages of CKD (MD = -3.32, 95%CI =-4.57,-2.07, I2 =70%) and the glomerular filtration rate (MD = 1.4, 95%CI = 0.83,1.97, I2 =0%) were observed between the tolvaptan group and the placebo group. Subgroup analysis of patients in different CKD stages also showed the same conclusion. There was an increase in the urine osmolality, and 24-hour urine volume in patients receiving tolvaptan. Tolvaptan reduced the rate of serious hypertension and kidney pain events in ADPKD patients. At higher doses, it increased the rate of adverse events (liver injuries, thirst, pollakiuria, and nocturia). There was no significant risk of bias in the included studies. CONCLUSION: Tolvaptan has a beneficial effect on ADPKD, but is associated with an increase in adverse events at high doses when compared with the placebo. Further RCTs on tolvaptan may be required to support this conclusion.

Individual diversity between interdependent networks promotes the evolution of cooperation by means of mixed coupling.

Along with the rapid development of network-based information technology, such as cloud computing, big data, the IoT, and so on, human society has stepped into a new era of complex networks. People's life and production activities depend more and more on various complex networks to ensure security and reliability. The complex interrelationships between human and nature establish a link to explain the cooperation of individual behaviour, especially for individual diversity. However, existing researches mostly ignore the influence of individual diversity on networks involved in individual behaviour to strategy selection. Therefore, it needs further research on how to consider both individual diversity and independent networks in the evolution of cooperative behaviour. To address this issue, we extend a simple game model into the interdependent networks through the mixed coupling (i.e., utility and probability) in this work. Also, we divide the kinds of strategic behaviour of a player in one layer concerning individual diversity. Moreover, there exists an optimal region of mixed coupling between networks such that cooperation can be promoted. Finally, experimental results can open the path to understanding the emergence and maintenance of cooperation within various interconnected and interrelated real-world systems newly.

Differential Expression of TXNIP Isoforms in the Peripheral Leukocytes of Patients with Acute Myocardial Infarction.

BACKGROUND: Acute myocardial infarction (AMI) is the most serious type of coronary atherosclerotic heart disease (CAD). The pathological changes are characterized by atherosclerosis. Oxidative stress plays an important role in atherosclerosis. Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor and regulator of thioredoxin, could bind thioredoxin to regulate its expression and antioxidant activity negatively. The NCBI data show that there are two isoforms in TXNIP gene, namely, TXNIP1 and TXNIP2. Our previous studies have shown that TXNIP expression levels in patients with unstable angina pectoris (UAP) were increased compared with controls (CTR). However, no upregulation of TXNIP was detected in AMI patients. METHODS: The leucocytes were isolated from peripheral venous blood, and total RNA of the leucocytes was extracted. Then, real-time quantitative PCR was performed. RESULTS: mRNA levels of TXNIP2 in AMI were significantly increased compared with CTR (P < 0.05). However, the expression of TXNIP1 was downregulated in AMI, but the difference was not statistically significant (P > 0.05). Logistic regression analysis showed that TXNIP2 mRNA levels were significantly associated with AMI (OR = 2.207, P < 0.05). CONCLUSIONS: The expression of TXNIP2, not TXNIP1, is upregulated in leukocytes of AMI patients, indicating that only TXNIP2 in circulating leucocytes may be involved in the pathogenesis of AMI.

Altered Expression of TXNIP in the peripheral leukocytes of patients with coronary atherosclerotic heart disease.

BACKGROUND: Coronary atherosclerotic heart disease (CAD) is mainly caused by atherosclerosis, an inflammatory disease characterized by plaque formation in arteries. Reactive oxygen species caused structural damage and dysfunction of arterial endothelial cells. Thioredoxin-interacting protein (TXNIP) is the endogenous inhibitor and regulator of thioredoxin, a major cellular antioxidant and antiapoptotic system. In order to explore the role of TXNIP in the occurrence and development of CAD, we detected the TXNIP expression and discussed its molecular mechanisms in CAD. METHODS: The mRNA levels of TXNIP gene in peripheral leucocytes were detected in CAD and healthy controls (CTR) by quantitative real-time polymerase chain reaction. And TXNIP proteins were detected by western blotting. RESULTS: TXNIP gene expression levels in patients with unstable angina pectoris (UAP, n = 96) were significantly increased compared with those of CTR (n = 192, P < .05). However, the situation is different in acute myocardial infarction (n = 96, P > .05). Logistic regression analysis showed that TXNIP levels were significantly positive correlated with UAP (OR = 1.728, P < .05). CONCLUSIONS: TXNIP gene expression in the peripheral leucocytes was increased in patients with UAP, indicating that TXNIP in circulating leucocytes may be involved in the pathogenesis of UAP.

Response of human periodontal ligament cells to baicalin.

BACKGROUND: Periodontitis is the most common cause of tooth loss in adults. Periodontal ligament cell (PLC)-based therapy is considered one of the most promising methods in periodontal tissue regeneration. The traditional Chinese medicine baicalin has been shown to possess antimicrobial and anti-inflammatory activities and enhance cell proliferation and alkaline phosphatase activity. The aim of this study is to investigate the response of human PLCs (HPLCs) to baicalin. METHODS: The effect of baicalin on cultured HPLC proliferation was measured with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. The effect of baicalin on the expression of osteoprotegerin (OPG), receptor activator of nuclear factor-κB ligand (RANKL), core binding factor α1 (Cbfα1), and osteocalcin (OC) was determined by quantitative real-time polymerase chain reaction and immunodetection. RESULTS: Baicalin at a concentration of 0.01 µg/mL promoted HPLC proliferation, upregulated OPG messenger RNA (mRNA) and protein expression, and downregulated RANKL mRNA and protein expression. In addition to reducing the RANKL/OPG expression ratio significantly, it also increased Cbfα1 and OC mRNA and protein expression. CONCLUSION: Baicalin showed multifaceted regulation of genes with important roles in tissue growth and differentiation, and thus it has the potential to be a promising candidate for HPLC-based periodontal regeneration therapy.