IRF3 regulates cardiac fibrosis but not hypertrophy in mice during angiotensin II-induced hypertension.

Hypertension is a typical modern lifestyle-related disease that is closely associated with the development of cardiovascular disorders. Elevation of angiotensin II (ANG II) is one of several critical factors for hypertension and heart failure; however, the mechanisms underlying the ANG II-mediated pathogenesis are still poorly understood. Here, we show that ANG II-mediated cardiac fibrosis, but not hypertrophy, is regulated by interferon regulatory factor 3 (IRF3), which until now has been exclusively studied in the innate immune system. In a ANG II-infusion mouse model (3.0 mg/kg/d), we compared IRF3-deficient mice (Irf3(-/-)/Bcl2l12(-/-)) with matched wild-type (WT) controls. The development of cardiac fibrosis [3.95 ± 0.62% (WT) vs. 1.41 ± 0.46% (Irf3(-/-)/Bcl2l12(-/-)); P<0.01] and accompanied reduction in left ventricle end-diastolic dimension [2.89 ± 0.10 mm (WT) vs. 3.51 ± 0.15 mm (Irf3(-/-)/Bcl2l12(-/-)); P=0.012] are strongly suppressed in Irf3(-/-)/Bcl2l12(-/-) mice, whereas hypertrophy still develops. Further, we provide evidence for the activation of IRF3 by ANG II signaling in mouse cardiac fibroblasts. Unlike the activation of IRF3 by innate immune receptors, IRF3 activation by ANG II is unique in that it is activated through the canonical ERK signaling pathway. Thus, our present study reveals a hitherto unrecognized function of IRF3 in cardiac remodeling, providing new insight into the progression of hypertension-induced cardiac pathogenesis.

A critical link between Toll-like receptor 3 and type II interferon signaling pathways in antiviral innate immunity.

A conundrum of innate antiviral immunity is how nucleic acid-sensing Toll-like receptors (TLRs) and RIG-I/MDA5 receptors cooperate during virus infection. The conventional wisdom has been that the activation of these receptor pathways evokes type I IFN (IFN) responses. Here, we provide evidence for a critical role of a Toll-like receptor 3 (TLR3)-dependent type II IFN signaling pathway in antiviral innate immune response against Coxsackievirus group B serotype 3 (CVB3), a member of the positive-stranded RNA virus family picornaviridae and most prevalent virus associated with chronic dilated cardiomyopathy. TLR3-deficient mice show a vulnerability to CVB3, accompanied by acute myocarditis, whereas transgenic expression of TLR3 endows even type I IFN signal-deficient mice resistance to CVB3 and other types of viruses, provided that type II IFN signaling remains intact. Taken together, our results indicate a critical cooperation of the RIG-I/MDA5-type I IFN and the TLR3-type II IFN signaling axes for efficient innate antiviral immune responses.

[Implementation of the Latest Scientific Knowledge/Technologies and Activities for International Harmonisation of the Japanese Pharmacopoeia].

The Japanese Pharmacopoeia (JP) is an official document that defines the specifications, criteria, and standard test methods necessary to properly ensure the quality of medicines in Japan. To ensure the efficacy and safety of pharmaceutical products, it is essential to establish standards that ensure their quality. For this purpose, the JP aims to include all drugs that are important from the viewpoint of healthcare and medical treatment, and description of each monograph of medicine is maintained and improved so that those standards can be generally practiced. In addition, to play a key role as the official document in the field of pharmaceutical product quality, JP contents are enhanced by proactively introducing the latest scientific knowledge and technologies. As the international manufacturing of pharmaceutical products and their raw materials that are distributed in Japan is increasing, the JP has recently begun to promote the international harmonisation of pharmaceutical excipients and general tests through the Pharmacopoeial Discussion Group (PDG) and to swiftly implement the harmonised items in the JP. In addition, the JP will implement internationally harmonised concepts and specifications for pharmaceutical products, e.g., the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH), to define the latest concepts of quality control for pharmaceutical products in the official document. We introduce the implementation of the latest scientific knowledge, technologies, and activities for international harmonisation of the JP.

The Asia Pacific Disaster Mental Health Network: Setting a Mental Health Agenda for the Region.

Addressing the psychological mechanisms and structural inequalities that underpin mental health issues is critical to recovery following disasters and pandemics. The Asia Pacific Disaster Mental Health Network was established in June 2020 in response to the current disaster climate and to foster advancements in disaster-oriented mental health research, practice and policy across the region. Supported by the World Health Organization (WHO) Thematic Platform for Health Emergency and Disaster Risk Management (Health EDRM), the network brings together leading disaster psychiatry, psychology and public health experts. Our aim is to advance policy, research and targeted translation of the evidence so that communities are better informed in preparation and response to disasters, pandemics and mass trauma. The first meetings of the network resulted in the development of a regional disaster mental health agenda focused on the current context, with five priority areas: (1) Strengthening community engagement and the integration of diverse perspectives in planning, implementing and evaluating mental health and psychosocial response in disasters; (2) Supporting and assessing the capacity of mental health systems to respond to disasters; (3) Optimising emerging technologies in mental healthcare; (4) Understanding and responding appropriately to addressing the mental health impacts of climate change; (5) Prioritising mental health and psychosocial support for high-risk groups. Consideration of these priority areas in future research, practice and policy will support nuanced and effective psychosocial initiatives for disaster-affected populations within the Asia Pacific region.

Feasibility and psychometric properties of the UCLA PTSD reaction index for DSM-5 in japanese youth: A multi-site study.

The purpose of this study was to determine the reliability and validity of the UCLA PTSD Reaction Index for DSM-5 (PTSD-RI-5) among Japanese youth. This is the first study to explore psychometrics of the DSM-5 version of the PTSD-RI-5, as well as the first multisite study of an Asian population. This article presents psychometric characteristics of the PTSD-RI-5 derived from a sample of Japanese children and adolescents (N = 318). The PTSD-RI-5 total scale displayed good internal consistency reliability (α = 0.85). Correlations of PTSD-RI scores with the posttraumatic stress scores on the TSCC-A for the entire sample provided evidence of convergent validity. The four-factor structure of the PTSD-RI-5 was supported through confirmatory factor analysis in this sample. In conclusion, a DSM-5 version of the PTSD-RI-5 can be regarded as an adequate instrument for clinical and research purposes in Japan.

General Principles for the Education and Training of GCP Inspectors: The Outcome of Discussions by International Regulatory Experts in the Discussion Group on the ICH E6 Guideline.

In response to the globalization of drug development, regulatory inspection of Good Clinical Practice (GCP) has recently been conducted not only by International Conference on Harmonisation (ICH) regions but also non-ICH regions. To promote the international implementation of GCP, consistent understanding and interpretation of its concept among regions are important. This article summarizes the background and past activities of the E6 Discussion Group, established under the Regulators Forum.