メタボロミクス:オープンアクセス

MicroRNAs play key regulatory roles in many different biological processes, including development, differentiation, homeostasis and inflammation. The latest version of miRBase lists over 1100 distinct microRNA sequences in mice and over 1800 in humans. One pair of mature microRNAs whose 3’ regions differ by only 2 nucleotides, miR-146a and miR- 146b, is involved in metabolism, differentiation and immunity. NF-κB directly induces miR-146a, while both miR-146a and miR-146b target NF-κB pathway components interleukin-1 receptor-associated kinase 1 (Irak1) and tumor necrosis factor receptor-associated factor-6 (Traf6) for repression. Inhibition of miR-146a increases glucose-stimulated insulin secretion and promotes differentiation of mouse spermatogonia. Muscle-specific inactivation of mediator complex subunit 1 (Med1), another miR-146a target, enhances insulin sensitivity and improves glucose tolerance in mice. This review highlights the role of miR-146a in metabolic regulation, hematopoietic and spermatogenic differentiation, and induction of the immune response.

Protein Arginine Deiminase type 4 (PAD4) is a new therapeutic target for the treatment of rheumatoid arthritis. In this study, ligand-based virtual screening with the integration with drug repurposing strategy was applied to the discovery of PAD4 inhibitors. Ultrafast Shape Recognition (USR) was used to search for compounds with similar shape to a previously reported inhibitor with harmful side-effects, i.e., streptonigrin. Thirty five lead-like compounds and two existing drugs were obtained from virtual screening and their inhibitory activity was tested at fixed concentration of 100 μM. Five lead-like compounds showed significant inhibition on the enzymatic activity of PAD4. The potency of the best compound was investigated by carrying out IC50 study. Importantly, the structure of the best of these new active molecules was strikingly different from that of streptonigrin. Furthermore, this new PAD4 inhibitor is the most potent to date found by a computational approach and its structure can be optimized in the future for the design of an even better inhibitor of PAD4.

Metabolomics, the global study of metabolites, has recently emerged as a promising approach for identification of potential diagnostic and treatment response biomarkers for psychotic disorders. To date, numerous studies have utilised metabolomics to better understand psychotic disorders and findings from these studies have begun to converge. In this review, we briefly describe the metabolomics approach including the different platforms used to analyse metabolites in biological samples from patients. We also summarise promising metabolic and pharmaco-metabolic biomarkers reported in the current psychotic disorder literature, which point to the dysregulation of fatty acid metabolism and the imbalance in oxidants/antioxidants that is present at illness onset. Finally, we conclude with a commentary on the challenges and future contribution of the metabolomics approach within the larger biomarker discovery framework currently being utilised in the field of psychiatry.

Many autoimmune diseases and cancers have an underlying immune basis, and these include Systemic Lupus Erythematosus (SLE), rheumatoid arthritis, systemic sclerosis, ankylosing spondylitis, as well as breast cancer. Biological therapies are monoclonal antibodies and fusion proteins which contain specific recognition components that have antibody function. This principle takes advantage of antigen specificity to produce monoclonal antibodies to the desired antigen. Problems of biological therapies include ethical, regulatory, and licensing issues, documentation of trials, funding, adverse effects, media attention and publicity, selection issues, time considerations and risk-benefit analysis. Therefore, proper and strict regulation of research on humans as well as use of these biological agents should be carefully enforced and monitored by the authorities, to ensure maintenance of transparency and good standards.