Metformin directly binds the alarmin HMGB1 and inhibits its proinflammatory activity

Metformin is the first-line drug in the treatment of type 2 diabetes. In addition to its hypoglycemic effect, metformin has an anti-inflammatory function, but the precise mechanism promoting this activity remains unclear. High mobility group box 1 (HMGB1) is an alarmin that is released from necrotic cells and induces inflammatory responses by its cytokine-like activity and is, therefore, a target of anti-inflammatory therapies. Here we identified HMGB1 as a novel metformin-binding protein by affinity purification using a biotinylated metformin analogue. Metformin directly bound to the C-terminal acidic tail of HMGB1. Both in vitro and in vivo, metformin inhibited inflammatory responses induced by full-length HMGB1 but not by HMGB1 lacking the acidic tail. In an acetaminophen-induced acute liver injury model in which HMGB1 released from injured cells exacerbates the initial injury, metformin effectively reduced liver injury and had no additional inhibitory effects when the extracellular HMGB1 was blocked by anti-HMGB1-neutralizing antibody. In summary, we report for the first time that metformin suppresses inflammation by inhibiting the extracellular activity of HMGB1. Because HMGB1 plays a major role in inflammation, our results suggest possible new ways to manage HMGB1-induced inflammation

Sustainable transportation pros, cons, and self-efficacy as predictors of 6-month stage transitions in a Chinese sample

Sustainable transportation (ST) refers to any form of commuting other than single occupancy vehicle usage. This study prospectively examined the pros, cons, and self-efficacy for ST as predictors of stage transitions over a period of 6 months. Participants included 656 Chinese college students and workers. They completed a translated questionnaire on their ST stage (from Precontemplation to Maintenance), pros, cons, and self-efficacy. Six months later, the participants completed another questionnaire on their stage of change. The data on the participants in the pre-Action and post-Action stages were combined to predict forward transitions out of the pre-Action stages and backward transitions from the post-Action stages. Logistic regression analyses were conducted predicting 6-month stage transitions, either forward or backward, using baseline stage, pros, cons, and self-efficacy. Higher ST pros and, unexpectedly, lower ST self-efficacy predicted forward stage transitions among baseline participants who were not using ST. In contrast, lower ST pros and higher ST cons predicted backward stage transitions (regression) among those who at baseline were using ST. This study provides a preliminary understanding of predictive mechanisms of stage transitions for ST

Sustainable transportation stage of change, decisional balance, and self-efficacy scale development and validation in two university samples

Single occupancy vehicle (SOV) transportation is a key contributor to climate change and air pollution. Sustainable transportation (ST), commuting by any means other than SOV, could both slow climate change and enhance public health. The transtheoretical model (TTM) provides a useful framework for examining how people progress towards adopting ST. Short valid and reliable measures for ST decisional balance, self-efficacy, and climate change doubt were developed and their relationship with stages of change was examined. Two large university-based volunteer samples participated in measurement studies. Using multiple procedures, three brief internally consistent measures were developed: decisional balance, self-efficacy, and climate change doubt. The stages of change correctly discriminated both decisional balance and self-efficacy, as well as replicated hypothesized relationships. Climate change doubt did not vary by stages; however, it may prove useful in future studies. Results support the validation of these measures and the application of the TTM to ST