Folia Pharmacologica Japonica最新文献

Ozanimod hydrochloride (Product name: ZEPOZIA^® Capsule Starter Pack, ZEPOZIA^® Capsules 0.92 mg; Nonproprietary name: ozanimod hydrochloride, hereinafter referred to as ozanimod) is an orally available receptor modulator that acts on the sphingosine 1-phosphate (S1P) receptor and selectively binds with high affinity to S1P₁ and S1P₅ receptors. Following binding to and activation of S1P₁ receptors, ozanimod acts as a functional S1P₁ receptor antagonist by inducing internalization of S1P₁ receptors expressed on the surface of cells such as lymphocytes through agonism of S1P₁ receptors. These effects may ameliorate the pathologic changes of the autoimmune disease ulcerative colitis (UC). The Japanese phase II/III study (Study RPC01-3103) demonstrated the efficacy and safety of this drug in Japanese patients with moderate to severe ulcerative colitis. In Japan, it was approved by the Ministry of Health, Labour and Welfare (MHLW) in December 2024 for the treatment of moderate to severe UC in patients who have had an inadequate response to conventional therapies, and was launched in March 2025. Existing UC treatments show significant therapeutic effects, but medications for moderate to severe UC have respective advantages and disadvantages in efficacy, safety, and administration routes. No treatment meets all criteria. Ozanimod, with a novel mechanism, offers sustained high efficacy in improving clinical symptoms and mucosal damage in moderate to severe UC patients. It has a favorable safety profile, high medication compliance, and is a convenient oral treatment for long-term use. Thus, providing Ozanimod as a new UC treatment option is of high clinical significance.

The cerebellum has historically been viewed as a key center for motor control and motor learning, with research primarily focusing on Purkinje cells as the core elements of its circuitry. However, accumulating evidence suggests a broader role for the cerebellum, extending to non-motor functions such as emotion, cognition, autonomic regulation, and metabolic control. Recent technical advances in neuroscience have facilitated the functional analysis of the deep cerebellar nuclei (DCN), which integrate signals from the cerebellar cortex and transmit them to the rest of the brain. This review will focus on the DCN, summarizing current findings on their involvement in psychiatric disorders and metabolic regulation.

Interleukin (IL)-19, a member of the IL-10 cytokine family, has been recognized for its anti-inflammatory functions in conditions such as inflammatory bowel disease and dermatitis. However, its role in liver diseases remains largely unexplored. In this study, we investigated the pathophysiological significance of IL-19 using a murine model of nonalcoholic fatty liver disease (NAFLD/NASH). Mice lacking IL-19 fed a customized CDAHFD diet exhibited delayed weight recovery, exacerbated inflammatory cell infiltration, enhanced fibrosis, and elevated serum liver injury markers and pro-inflammatory cytokines compared with wild-type mice. IL-19 was primarily produced by Kupffer cells in the liver and acted on hepatocytes to activate STAT3 signaling, suppress lipogenic gene expression, and enhance ATP production and PPARα activity. These actions shifted fatty acid utilization toward energy metabolism, thereby attenuating lipid accumulation and hepatocellular injury. Collectively, our findings suggest that IL-19 functions as a protective regulator suppressing steatosis and fibrogenesis. Future studies integrating steatosis and fibrosis models are warranted to further delineate its mechanisms and to evaluate the potential of IL-19 as a biomarker and therapeutic target in chronic liver diseases.

The etiology of psychiatric disorders such as schizophrenia, autism spectrum disorder (ASD), and depression remains largely unknown, and to date, no clear diagnostic criteria or curative pharmacological treatments have been established. One contributing factor is that patients with psychiatric disorders actually represent a heterogeneous population, yet are treated as a single group in clinical trials, which lowers the success rate of drug development. Against this background, there has been growing advocacy for stratification based on objective biomarkers, such as those proposed in the Research Domain Criteria (RDoC), rather than relying solely on syndrome-based classifications such as the DSM-5 or ICD-11 for diagnosis and therapeutic development. Furthermore, the elucidation of psychiatric pathophysiology and the development of effective pharmacological and therapeutic interventions require common objective indices that can bridge human and animal studies to enable translational research between preclinical and clinical domains. In patients with schizophrenia, sleep disturbances are consistently observed with high reproducibility, and abnormalities in sleep spindle generation during non-REM sleep have recently attracted attention as a novel biomarker. Moreover, spindle abnormalities have also been reported not only in schizophrenia but in subsets of patients with Alzheimer's disease, ASD, and Parkinson's disease, suggesting the possibility of shared pathophysiological mechanisms across distinct psychiatric and neurological disorders. In this article, I highlight electroencephalographic markers such as non-REM sleep spindles and gamma oscillations-objective neurophysiological indices measurable in both humans and experimental animals-that may deepen our understanding of the pathophysiology of psychiatric disorders and ultimately contribute to the development of novel therapeutics.