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Aims: Type 2 diabetes is a rising problem and a significant risk factor for small and large vessel disease. The present study aims to investigate the effect of a 6-week aerobic exercise program on High-mobility Group Box 1 (HMGB1) gene expression in aortic tissue of diabetic rats. Methods & Materials: In this experimental study, 40 male rats aged 8 weeks were randomly selected. Once familiarized with the exercise protocol, they were divided into four groups of healthy-control (n=10), diabetic-control (n=10), healthy-exercise (n=10), and diabetic-exercise (n=10). Type 2 diabetes was first induced, and then the rats run on a treadmill for 6 weeks, 5 sessions per week. After 12-14 h of fasting and 72 h after the last session, aortic tissue sampling was performed for HMGB1 analysis by quantitative real-time polymerase chain reaction (q-RT PCR) technique. Data analysis was performed using 1-way ANOVA and Tukey post hoc test at the significant level of P

// Chiao-Wen Lin 1, 2 , Ying-Erh Chou 3, 4 , Chia-Ming Yeh 4, 5 , Shun-Fa Yang 4, 5 , Chun-Yi Chuang 3, 6 and Yu-Fan Liu 7, 8 1 Institute of Oral Sciences, Chung Shan Medical University, Taichung, Taiwan 2 Department of Dentistry, Chung Shan Medical University Hospital, Taichung, Taiwan 3 School of Medicine, Chung Shan Medical University, Taichung, Taiwan 4 Department of Medical Research, Chung Shan Medical University Hospital, Taichung, Taiwan 5 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan 6 Department of Otolaryngology, Chung Shan Medical University Hospital, Taichung, Taiwan 7 Department of Biomedical Sciences, College of Medicine Sciences and Technology, Chung Shan Medical University, Taichung, Taiwan 8 Division of Allergy, Department of Pediatrics, Chung Shan Medical University Hospital, Taichung, Taiwan Correspondence to: Yu-Fan Liu, email: yfliu@csmu.edu.tw Keywords: HMGB1, polymorphism, OSCC, bioinformatics analysis, haplotypes Received: January 04, 2017 Accepted: February 15, 2017 Published: March 11, 2017 ABSTRACT Oral squamous cell carcinoma (OSCC) is a common malignancy that has been causally associated with both hereditary and acquired factors. The high mobility group box 1 ( HMGB1 ) gene plays an important role as a DNA chaperone to help maintain nuclear homeostasis. Altered expression of HMGB1 has been implicated in a wide range of pathological processes, including inflammation and cancer. The present study explores the impact of HMGB1 gene polymorphisms, combined with environmental risks regarding susceptibility to oral tumorigenesis. Four single-nucleotide polymorphisms (SNPs) of the HMGB1 gene, rs1412125, rs2249825, rs1045411, and rs1360485, were evaluated in 1,200 normal controls and 772 patients with OSCC. We found an association between the wild-type allele of rs1045411 and genotypes CT and CT/TT (AOR=0.754, 95% CI=0.582-0.978 and AOR=0.778, 95% CI=0.609-0.995, respectively). Additionally, bioinformatics analysis was used to characterize the functional relevance of these variants for the miRNA-505-5p binding site and transcriptional regulation by the HMGB1 3’-UTR and promoter regions. Moreover, in considering behavioral exposure to environmental carcinogens, the presence of the four HMGB1 SNPs, combined with/without betel quid chewing and smoking showed, profoundly synergistic effects on the risk of OSCC. In conclusion, we present a potential clinical relevance for HMGB1 variants in OSCC, as well as associations between HMGB1 polymorphisms, haplotypes and environmental risk factors. The finding may help in development of optimal therapeutic approaches for OSCC patients.

BACKGROUND High-mobility group box 1 (HMGB1) plays a crucial role in a variety of diseases, including neonatal necrotizing enterocolitis (NEC). The purpose of this study was to investigate the association of HMGB1 gene single-nucleotide polymorphisms (SNPs) with susceptibility and survival prognosis in Chinese Han neonates with NEC. MATERIAL AND METHODS The HMGB1 gene rs1360485, rs1045411, and rs2249825 site SNPs were genotyped in all participants. The mRNA expression of serum HMGB1 was examined using quantitative reverse transcription-polymerase chain reaction. The correlation of the HMGB1 rs1360485 SNP with NEC neonatal survival prognosis was evaluated by univariate analysis and logistic multivariate regression analysis. RESULTS The TC and CC genotype and C allele distribution frequencies of the rs1360485 SNP were lower in the NEC group, and the differences were statistically significant (all P0.05). Individuals carrying the TC and CC genotype or C allele had a low risk of being affected by NEC. However, the genotype and allele distributions of rs1045411 and rs2249825 were not significantly different between the patient and control groups (P0.05). NEC neonates with HMGB1 gene rs1360485 site mutations had lower mRNA levels of serum HMGB1 than those with rs1360485 site wild-type, and the rs1360485 genotypes TC and CC could independently predict better survival outcomes in NEC neonates. CONCLUSIONS This study demonstrated that the rs1360485 SNP of the HMGB1 gene is associated with susceptibility of NEC in neonates, and the rs1360485 genotypes TC and CC may affect HMGB1 expression and are associated with the survival prognosis of neonates with NEC.

High mobility group box protein 1 (HMGB1) has been considered as a ubiquitous nuclear protein with an architectural function, but even early reports have described its presence outside of the nucleus. Today, we have only started to understand the extranuclear and extracellular functions of HMGB1: we know that it participates in developmental and differentiation processes, triggers and modulates many of the inflammatory cascades in the body, and may even be involved in the metastatic invasion programme of cancer cells. Given such diverse roles, it is important to know which cells express HMGB1, where, and how much. The present review deals with the expression pattern of HMGB1 and provides evidence that, far from being housekeeping, the HMGB1 gene is tightly regulated. This can have implications for therapeutic intervention on inflammatory diseases as well as cancer.