MicroRNA-223 ameliorates alcoholic liver injury by inhibiting the IL-6–p47phox–oxidative stress pathway in neutrophils

Objectives Chronic-plus-binge ethanol feeding activates neutrophils and exacerbates liver injury in mice. This study investigates how recent excessive drinking affects peripheral neutrophils and liver injury in alcoholics, and how miR-223, one of the most abundant microRNAs (miRNAs) in neutrophils, modulates neutrophil function and liver injury in ethanol-fed mice. Designs Three hundred alcoholics with (n=140) or without (n=160) recent excessive drinking and 45 healthy controls were enrolled. Mice were fed an ethanol diet for 10 days followed by a single binge of ethanol. Results Compared with healthy controls or alcoholics without recent drinking, alcoholics with recent excessive drinking had higher levels of circulating neutrophils, which correlated with serum levels of alanine transaminase (ALT) and aspartate transaminase (AST). miRNA array analysis revealed that alcoholics had elevated serum miR-223 levels compared with healthy controls. In chronic-plus-binge ethanol feeding mouse model, the levels of miR-223 were increased in both serum and neutrophils. Genetic deletion of the miR-223 gene exacerbated ethanol-induced hepatic injury, neutrophil infiltration, reactive oxygen species (ROS) and upregulated hepatic expression of interleukin (IL)-6 and phagocytic oxidase (phox) p47phox. Mechanistic studies revealed that miR-223 directly inhibited IL-6 expression and subsequently inhibited p47phox expression in neutrophils. Deletion of the p47phox gene ameliorated ethanol-induced liver injury and ROS production by neutrophils. Finally, miR-223 expression was downregulated, while IL-6 and p47phox expression were upregulated in peripheral blood neutrophils from alcoholics compared with healthy controls. Conclusions miR-223 is an important regulator to block neutrophil infiltration in alcoholic liver disease and could be a novel therapeutic target for the treatment of this malady

On Reconstruction of Teacher Professional Identity in Curriculum Reform for Vocational Education

Vocational education curriculum is being reformed nationwide less than compulsory education. It sources from demonstrating college construction in higher vocational education, and imports design-oriented curriculum idea from German. To teachers, it is necessary to reconstruct their rights to utterance

Research on Exploratory English Teaching Methods in Art Colleges

English teaching has met troubles in students specialized in arts who can’t understand the teachers’ explanation. Force feeding duck teaching in classroom hasn’t completed the task of teaching. Inquiry English teaching is introduced in this article to improve the status

On Reconstruction of Teacher Professional Identity in Curriculum Reform for Vocational Education

Vocational education curriculum is being reformed nationwide less than compulsory education. It sources from demonstrating college construction in higher vocational education, and imports design-oriented curriculum idea from German. To teachers, it is necessary to reconstruct their rights to utterance

Exploring and Construction On Practicality Instruction System in Engineering Education Based On CDIO Concept

Choosing a faculty of the college as an attempt, the author analyzed the CDIO concept and its necessity in practicality instruction system, discussed the construction of practicality instruction system in engineering education under the direct of CDIO concept

Exploring and Construction On Practicality Instruction System in Engineering Education Based On CDIO Concept

Choosing a faculty of the college as an attempt, the author analyzed the CDIO concept and its necessity in practicality instruction system, discussed the construction of practicality instruction system in engineering education under the direct of CDIO concept