Autophagy, a double-edged sword for cell survival, is the research object on 2016 Nobel Prize in Physiology or Medicine. Autophagy is a molecular mechanism for maintaining cellular physiology and promoting survival. Defects in autophagy lead to the etiology of many diseases, including diabetes mellitus (DM), cancer, neurodegeneration, infection disease and aging. DM is a metabolic and chronic disorder and has a higher prevalence in the world as well as in Taiwan. The character of diabetes mellitus is hyperglycemia resulting from defects in insulin secretion, insulin action, or both. Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance and failure of producing insulin on pancreatic beta cells. In T2DM, autophagy is not only providing nutrients to maintain cellular energy during fasting, but also removes damaged organelles, lipids and miss-folded proteins. In addition, autophagy plays an important role in pancreatic beta cell dysfunction and insulin resistance. In this review, we summarize the roles of autophagy in T2DM.

Outbreaks of food-associated renal failure in pets occurred in Asia and the United States of America in 2004 and 2007. They were related to the combined intoxication of cyanuric acid and melamine. Our aims were to investigate cyanuric acid and melamine contamination of pet food and to examine subchronic toxicity in rats. Levels of 10%, 20%, 50%, and 50%–100% (w/w) of contaminated pet food were fed to rats for three months. Analytical results revealed that the tainted food contained significant levels of cyanuric acid and melamine in a ratio of 1:6.8. Rats fed the diet of 50%–100% for three months exhibited elevated serum blood urea nitrogen and creatinine, as well as dose-dependent melamine/cyanuric acid crystal-induced nephrotoxicity. The melamine/cyanuric acid crystals of various sizes were mixed with necrotic cell debris and inflammatory cells, accompanied by tubular dilation and interstitial fibrosis. The immunohistochemistry index of proliferative cellular nuclear antigen and osteopontin in the kidney of the 50%–100% group were elevated, indicating regeneration of renal cells and the formation of crystals. In conclusion, the combination ratio of cyanuric acid to melamine and the acidic urine content were two factors that, upon repeated exposure, determined the severity of the nephrotoxicity.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Ming-Yu Lien1, 2, Chiao-Wen Lin3, 4, Hsiao-Chi Tsai1, Yng-Tay Chen5, Ming-Hsui Tsai6, Chun-Hung Hua7, Shun-Fa Yang8, 9 and Chih-Hsin Tang1, 10 1Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan 2Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan 3Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 4Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 5Department of Pediatrics, Medical Research and Medical Genetics, China Medical College Hospital, Taichung, Taiwan 6Department of Otolaryngology, China Medical University Hospital, Taichung, Taiwan 7Department of Otorhinolaryngology, China Medical University Hospital, Taichung, Taiwan 8Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan 9Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan 10Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan Correspondence to: Chih-Hsin Tang, email: chtang@mail.cmu.edu.tw Shun-Fa Yang, email: ysf@csmu.edu.tw Keywords: oral cancer, CCL4, single-nucleotide polymorphism Received: October 20, 2016 Accepted: January 22, 2017 Published: February 22, 2017 ABSTRACT In Taiwan, oral cancer has causally been associated with environmental carcinogens. CCL4 (C-C chemokine ligand 4), a macrophage inflammatory protein with a key role in inflammation and immune-regulation, was implicated in carcinogenesis by facilitating instability in the tumor environment. The purpose of this study was to identify gene polymorphisms of CCL4 specific to patients with oral squamous cell carcinoma (OSCC) susceptibility and clinicopathological characteristics. A total of 2,053 participants, including 1192 healthy people and 861 patients with oral cancer, were recruited for this study. Three single-nucleotide polymorphisms (SNPs) of the CCL4 gene were analyzed by a real-time PCR. We found that the T/T homozygotes of CCL4 rs1634507 G/T polymorphism and the GG haplotype of 2 CCL4 SNPs (rs1634507 and rs10491121) combined were associated with oral-cancer susceptibility. In addition, TA haplotype significantly decreased the risks for oral cancer by 0.118 fold. Among 1420 smokers, CCL4 polymorphisms carriers with the betel-nut chewing habit had a 15.476–20.247-fold greater risk of having oral cancer compared to CCL4 wild-type (WT) carriers without the betel-nut chewing habit. Finally, patients with oral cancer who had A/G heterozygotes of CCL4 rs10491121 A/G polymorphism showed a lower risk for an advanced tumor size (> T2) (p=0.046), compared to those patients with AA homozygotes. Our results suggest that the CCL4 rs1634507 SNP have potential predictive significance in oral carcinogenesis. Gene-environment interactions of CCL4 polymorphisms might influence oral-cancer susceptibility. CCL4 rs10491121 may be a factor to predict the tumor size in OSCC patients.

Inhibition of DNA methyltransferase 1 increases nuclear receptor subfamily 4 group A member 1 expression and decreases blood glucose in type 2 diabetes

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Yng-Tay Chen1, Wei-De Lin1, 2, Wen-Lin Liao3, 4, Ying-Ju Lin1, 5, Jan-Gowth Chang6, 7, 8, Fuu-Jen Tsai1, 9, 10, 11 1Human Genetic Center, Department of Medical Research, China Medical University Hospital, China Medical University, Taichung, Taiwan 2School of Post Baccalaureate Chinese Medicine, China Medical University, Taichung, Taiwan 3Center for Personalized Medicine, China Medical University Hospital, Taichung, Taiwan 4Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan 5Graduate Institute of China Medical Science, China Medical University, Taichung, Taiwan 6Epigenome Research Center, China Medical University Hospital, Taichung, Taiwan 7Department of Laboratory Medicine, China Medical University Hospital, Taichung, Taiwan 8School of Medicine, China Medical University, Taichung, Taiwan 9Department of Medical Genetics, China Medical University Hospital, Taichung, Taiwan 10School of Chinese Medicine, China Medical University, Taichung, Taiwan 11Department of Health and Nutrition Biotechnology, Asia University, Taichung, Taiwan Correspondence to: Fuu-Jen Tsai, e-mail: d0704@mail.cmuh.org.tw Keywords: DNA methylation, DNMT1, PTPRD, type 2 diabetes Received: March 19, 2015 Accepted: May 11, 2015 Published: May 25, 2015 ABSTRACT Genome-wide association study (GWAS) data showed that the protein tyrosine phosphatase receptor type delta (PTPRD) is associated with increased susceptibility to type 2 diabetes (T2D) in Han Chinese. A replication study indicated that PTPRD is involved in the insulin signaling pathway; however, the underlying mechanism remains unclear. We evaluated PTPRD expression in patients with T2D and controls. PTPRD expression levels were lower in patients and were correlated with the duration of the disease. Overexpression of the human insulin receptor PPARγ2 in HepG2 cells induced overexpression of PTPRD and the insulin receptor. PTPRD knockdown, using a shRNA, resulted in down-regulation of the insulin receptor. These results indicate that PTPRD activates PPARγ2 in the insulin signaling pathway. Similar results for PTPRD expression were found using a T2D mouse model. Silencing of PTPRD was caused by DNA methylation in T2D mice and patients, and correlated with DNMT1 expression. Furthermore, we showed that a DNMT1 SNP (rs78789647) was correlated with susceptibility to T2D. This study shows for the first time that DNMT1 caused PTPRD DNA hypermethylation and induced insulin signaling silencing in T2D patients. Our findings contribute to a better understanding of the crucial roles of these regulatory elements in human T2D.