Ethyl Pyruvate Attenuates CaCl2-Induced Tubular Epithelial Cell Injury by Inhibiting Autophagy and Inflammatory Responses.

BACKGROUND/AIMS: Nephrolithiasis is one of the most prevalent diseases of the urinary system. Approximately 80% of human kidney stones are composed of calcium oxalate (CaOx), and hypercalciuria is one of the most common metabolic disorders. Emerging evidence indicates that autophagy and inflammatory responses are related to the formation of CaOx nephrolithiasis. However, the roles of autophagy and inflammation in patients with hypercalciuria remain unclear. Ethyl pyruvate (EP) displays protective effects in experimental models of many illnesses. In this study, we investigated the protective effects of EP in vitro through its inhibition of autophagy and inflammatory responses after CaCl2-induced tubular epithelial cell injury. METHODS: First, we cultured human tubular epithelial (HK-2) cells in the presence of various concentrations of CaCl2 (0, 0.1, 0.25, 0.5, 1.0, 1.5, and 2.0 mg/ml) for 12 h and EP (0, 1.0, 2.5, 5.0, and 10.0 mM) for 2 h to select the optimum concentration using the Cell Counting Kit-8 assay and lactate dehydrogenase (LDH) assay. Cells in culture were stimulated with CaCl2 (1.0 mg/ml, 12 h) with or without EP pretreatment (2.5 mM, 2 h). After the exposure, we detected the expression of inflammation-related proteins using an enzyme-linked immunosorbent assay and Western blot analysis. Finally, the levels of autophagy-related proteins were determined through Western blot analysis, and the number of GFP-LC3 dots and autophagic vacuoles was detected under confocal microscopy. RESULTS: With the use of the Cell Counting Kit-8 assay and the LDH assay, we identified the optimum concentration for CaCl2 (1.0 mg/ml) treatment and EP pretreatment (2.5 mM). Our research indicated that CaCl2 can induce autophagy and inflammatory responses in HK-2 cells. Furthermore, treatment with EP prior to CaCl2 stimulation attenuated HK-2 cell injury by inhibiting autophagy and inflammation. CONCLUSION: Our results provide evidence that EP attenuates CaCl2-induced injury of HK-2 cells by downregulating the expression of inflammation and autophagy proteins that may be associated with the inhibition of the high-mobility group box-1 (HMGB1)/toll-like receptor 4 (TLR4)/NF-κB pathway and the competitive interaction with Beclin-1 of HMGB1.

Association between insulin-like growth factor 1 gene rs35767 polymorphisms and cancer risk: A meta-analysis.

BACKGROUND: Several studies have been conducted on the relationship between insulin-like growth factor 1 gene (IGF-1) rs35767 polymorphisms and cancer risk, but the results are conflicting. We performed a meta-analysis to investigate the relationship between IGF-1 rs35767 polymorphisms and cancer risk. METHODS: Eight studies (5 for IGF-1 rs35767 C>T and 3 for IGF-1 rs35767 A>G) with a total of 11,257 cases and 16,213 controls were included. The studies were about the association between IGF-1 rs35767 polymorphisms and cancer risk and acquired by searching PubMed, Embase, and Web of Science databases for articles published before January 20, 2019. STATA software was used to analyze the data and identify the strength of the association by using pooled-odds ratios (ORs) with corresponding 95% confidence intervals (CIs). RESULTS: No significant associations were observed between the IGF-1 rs35767 C>T polymorphism and cancer risk in all genetic models. However, the IGF-1 rs35767 A>G polymorphism was significantly associated with increased cancer risk for all genetic models (G vs A: OR = 1.087, 95% CI: 1.036-1.141, Ph = .338; GG vs AA: OR = 1.272, 95% CI: 1.121-1.442, Ph = .359; AG vs AA: OR = 1.187, 95% CI: 1.043-1.351, Ph = .695; AG+GG vs AA: OR = 1.187, 95% CI: 1.043-1.351, Ph = .695; GG vs AA+AG: OR = 1.086, 95% CI: 1.025-1.151, Ph = .275). Begg and Egger tests showed that no publication bias existed. CONCLUSION: Our findings indicated that the IGF-1 rs35767 A>G polymorphism might be a risk factor for cancer development. However, additional well-designed studies with sample sizes larger than ours need to be conducted in the future to verify our findings.