Ulcerative colitis (UC) is a chronic inflammatory bowel disease caused by multiple factors, and its etiology and pathogenesis are not fully understood. Janus kinases (JAK) are non‑transmembrane tyrosine kinases that play a key role in many immune‑related cytokine signaling pathways. JAK‑STATs signaling pathway is a cytokine‑mediated signaling pathway, which is involved in many important biological processes such as cell proliferation, differentiation, apoptosis and immune regulation. JAK inhibitors are small molecule drugs that can be administered orally and are relatively inexpensive, therefore, JAK inhibitors may become a new target for the treatment of UC. This article reviewed progress of research on the efficacy and safety of small molecule JAK inhibitors in treatment of UC.

The arginyl-tRNA synthetase (ArgRS) catalyzes the esterification reaction between L-arginine and its cognate tRNA(Arg). Previously reported structures of ArgRS shed considerable light on the tRNA recognition mechanism, while the aspect of amino acid binding in ArgRS remains largely unexplored. Here we report the first crystal structure of E. coli ArgRS (eArgRS) complexed with L-arginine, and a series of mutational studies using isothermal titration calorimetry (ITC). Combined with previously reported work on ArgRS, our results elucidated the structural and functional roles of a series of important residues in the active site, which furthered our understanding of this unique enzyme.
Arginine ; chemistry ; Arginine-tRNA Ligase ; chemistry ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Escherichia coli ; Ligands ; Mutagenesis, Site-Directed ; Protein Binding ; Protein Conformation ; RNA, Transfer ; chemistry ; Structure-Activity Relationship

Background: Inflammatory bowel disease (IBD) is a chronic recurrent inflammatory disease of gastrointestinal tract including ulcerative colitis (UC) and Crohn's disease (CD). It is unclear whether there is a causal association between unsaturated fatty acids and IBD. Aims: A two⁃sample Mendelian randomization analysis was used to explore the causal association between unsaturated fatty acids and IBD. Methods: The data of the genome⁃wide association study (GWAS) of unsaturated fatty acids and IBD were obtained from web⁃based public databases. Two⁃sample Mendelian randomization analysis was performed by using inverse⁃variance weighted analysis, and weight median estimator and MR⁃Egger regression were conducted to validate the association of the causal effect. The causality of unsaturated fatty acids on the risk of IBD was evaluated by OR and 95% CI. Results: No direct causal association was found between ω⁃6 fatty acids and CD, and a direct causal association was found with UC. Inverse⁃variance weighted analysis showed a 16% increase in the risk of UC for each standard deviation increase in ω⁃6 fatty acid gene levels (OR=1.16, 95% CI: 1.00⁃1.36, P=0.04). However, no causal association was found between ω⁃3 fatty acids, monounsaturated fatty acids and IBD. Conclusions: ω⁃6 fatty acids may be only causally associated with UC, and no causal association is found between ω⁃3 fatty acids, monounsaturated fatty acids and IBD.