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High-mobility group box 1 (HMGB1) is an abundant architectural chromosomal protein that has multiple biologic functions: gene transcription, DNA replication, DNA-damage repair, and cell signaling for inflammation. HMGB1 can be released passively by necrotic cells or secreted actively by activated immune cells into the extracellular milieu after injury. Extracellular HMGB1 acts as a damage-associated molecular pattern to initiate the innate inflammatory response to infection and injury by communicating with neighboring cells through binding to specific cell-surface receptors, including Toll-like receptors (TLRs) and the receptor for advanced glycation end products (RAGE). Numerous studies have suggested HMGB1 to act as a key protein mediating the pathogenesis of chronic and acute liver diseases, including nonalcoholic fatty liver disease, hepatocellular carcinoma, and hepatic ischemia/reperfusion injury. Here, we provide a detailed review that focuses on the role of HMGB1 and HMGB1-mediated inflammatory signaling pathways in the pathogenesis of liver diseases.

Objectives: An environment-wide association study (EWAS) may be useful to comprehensively test and validate associations between environmental factors and cardiovascular disease (CVD) in an unbiased manner. Approach and results: Data from National Health and Nutrition Examination Survey (1999–2014) were randomly 50:50 spilt into training set and testing set. CVD was ascertained by a self-reported diagnosis of myocardial infarction, coronary heart disease or stroke. We performed multiple linear regression analyses associating 203 environmental factors and 132 clinical phenotypes with CVD in training set (false discovery rate

An environment-wide association study (EWAS) may be useful to comprehensively test and validate associations between environmental factors and peripheral arterial disease (PAD) in an unbiased manner.Data from cross-sectional cohorts from the US National Health and Nutrition Examination Survey (1999-2004) were randomly 50:50 split into training set and testing set. A value of ankle-brachial index (ABI)1.0 or1.4 defined PAD. We performed multiple linear regression analyses associating each of the 417 environmental and self-reported factors with PAD in the training set (false discovery rate5%). Significant findings were validated in the testing set (p0.05) and entered into a logistic regression model with penalized likelihood based on the Akaike Information Criterion (AIC).Overall, 6819 participants40 years old were included. The validated factors comprised positive associations with smoking-associated factors (cigarette smoker, family smoker and smoked100 cigarettes, urinary cotinine), cadmium, urinary albumin, C-reactive protein, blood o-xylene and thyroxine 4, and inverse associations with α-carotene and trans-/cis-β-carotene for PAD. Finally, only 4 of these factors were nominally significant in the AIC-selected model: cadmium (OR 1.27, 95% CI 1.12-1.45), cis-β-carotene (OR 0.81, 95% CI 0.72-0.91), CRP (OR 1.19, 95% CI 1.03-1.38) and urinary albumin (OR 1.20, 95% CI 1.04-1.38).Our systematic evaluation provides new knowledge on the complex array of environmental correlates of PAD. These identified correlates need to be probed in further observational and interventional studies.

An environment-wide association study may be useful to test and validate associations between environmental factors and peripheral arterial disease (PAD) in an unbiased manner. Data from cross-sectional cohorts from National Health and Nutrition Examination Survey (1999-2004) were randomly spilt