Fluorescent biosensors have become essential tools in life sciences, enabling the visualization of the spatiotemporal dynamics of signaling molecules at the cellular level. In particular, intensity-based sensors-where changes in the concentrations of signaling molecules are detected as changes in fluorescence intensity-are widely used due to their versatility. However, such sensors are often affected by several factors, including variations in biosensor concentration, photobleaching, optical path settings, and focus drift, which hamper quantitative analysis. To overcome these challenges, we have been developing fluorescence lifetime imaging microscopy (FLIM)-based biosensors that utilize fluorescence lifetime-a parameter independent of probe concentration and imaging conditions-as a robust and reliable readout. Our research has focused on the quantitative visualization of physiological parameters, particularly those relevant to skeletal muscle homeostasis and ion channel activity. One example is a small-molecule fluorescent temperature sensor designed to quantify temperature changes in subcellular compartments. This sensor, based on an organic dye, enables targeting to organelle membranes and provides high spatial resolution, allowing precise detection of local heat production, such as that occurring in the mitochondria of brown adipocytes. In parallel, we have developed genetically encoded fluorescent protein-based sensors that correlate fluorescence lifetime values with the concentrations of signaling molecules such as ATP. These sensors have enabled the quantitative imaging of ATP dynamics in various cell types and multicellular systems. Furthermore, we are constructing a flexible sensor development platform, paving the way for the creation of diverse biosensors that can contribute to comprehensive studies in muscle physiology.

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.

Skeletal muscle channelopathies are rare genetic disorders caused by mutations in voltage-gated ion channel genes that regulate sarcomere excitability, including the CLCN1 gene encoding ClC-1, the KCNJ2 gene encoding Kir2.1, the SCN4A gene encoding Nav1.4, and the CACNA1S gene encoding Cav1.1. More than one hundred heterozygous missense mutations have been identified in SCN4A, representing a broad spectrum of clinical phenotypes, including sodium channel myotonia (SCM), paramyotonia congenita (PMC), hyperkalemic periodic paralysis (HyperPP) and hypokalemic periodic paralysis (HypoPP). In addition, recent case reports have shown that compound heterozygous mutations or homozygous mutations in SCN4A are associated with congenital myopathy or congenital myasthenic syndrome. Regarding the pathological mechanisms of SCM/PMC and HyperPP, a large number of electrophysiological analyses have shown an association between the functional alteration of the mutant Nav1.4 and the clinical phenotype. On the other hand, HypoPP has long been a mysterious disorder. In 2007, the recent discovery of aberrant leak currents, called "gating pore currents", brought a breakthrough in the field of HypoPP research and contributed to the elucidation of the structure-function relationship of the voltage sensing domain of voltage-gated ion channels. However, there has been little progress in the discovery of the therapeutics. Recently, we have generated HEK293T-based HypoPP model cell lines aiming to establish the in vitro platform for the high-throughput drug screening. Our HypoPP model cells would provide new insight into the development of novel therapeutics for channelopathies.

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.

Steroid hormone receptors (SRs) play pivotal roles in the fundamental biological functions related to reproduction, development, and homeostasis. They are also closely associated with various pathophysiologies, including hormone-dependent cancers, metabolic syndromes, and neuropsychiatric disorders. SRs are ligand-dependent transcription factors belonging to the nuclear receptor superfamily. This superfamily also includes orphan nuclear receptors, such as estrogen-related receptors (ERRs) comprising three subtypes of α, β, and γ. Despite their high homology with estrogen receptors (ERs), ERRs cannot bind any endogenous steroid hormones and can activate gene transcription in a ligand-independent manner. Recently, ERRs have attracted considerable attention for their involvement in stem cell pluripotency, senescence, and other poorly understood biological processes. Although subcellular and subnuclear dynamics are crucial for SR function, how ERRs behave in living cells to activate or repress their target genes remains incompletely understood. We have investigated the behaviors of ERRs using fluorescent protein labeling, focusing on whether ERRs exhibit dynamic changes similar to SRs and whether these changes relate to their functional activity. In this review, we summarize findings from studies of molecular behavior, highlighting the coregulation of estrogen signaling by ERs and ERRs, the subnuclear movement of ERRs related to transcriptional repression, and the promotion of lactate metabolism by a novel lactate-responsive protein, LRPGC1, through interaction with ERRγ. We hope these insights contribute to elucidating fundamental biomedical processes and the pathological mechanisms linked to aberrant nuclear receptor signaling pathways.

Pharmacology role-play is a participatory learning exercise in which students take on the roles of healthcare providers and patients or family members, explaining diseases and pharmacological treatments based on presented case scenarios, and actively learning through mutual communication. Traditionally conducted face-to-face within a single university, this exercise has shifted to online formats during the COVID-19 pandemic, and more recently, attempts have been made to implement inter-university online sessions that utilize remote collaborative learning. In this study, we compared the educational outcomes of online role-play conducted independently at Kochi University and Ehime University in 2020 with those of an inter-university online role-play jointly conducted by both universities in 2021. Participants were third-year medical students at Kochi University and second-year medical students at Ehime University. After completing all assignments, students were asked to complete a post-session questionnaire. Five-point Likert scale responses were analyzed, and free-text comments were further examined using text mining with co-occurrence network analysis. The results indicated that inter-university role-play, compared with single-university sessions, facilitated the recognition of diverse perspectives and promoted deeper reflection through discussion. This experience contributed to enhanced understanding of patients' perspectives, increased motivation for becoming physicians, and improved learning attitudes. These findings suggest that inter-university online role-play is an effective educational approach for enhancing learning outcomes in pharmacology education.

Skeletal muscle is composed of thousands of myofibers that enable contraction and relaxation. Myofibers are constantly exposed to biophysical stresses during repeated contractile processes; nevertheless, skeletal muscle maintains its "resilience" through both structural robustness and the ability to sense and adapt to biophysical forces. Regulation of intra- and extracellular ionic concentrations is a critical determinant for cell growth, fate determination, and death. In myofibers, Ca2+ release from sarcoplasmic reticulum is well established as the trigger for myofiber contraction, whereas accumulating evidence suggests the importance of Ca2+ influx across sarcolemma in myofiber homeostasis. Moreover, other ions such as magnesium ion are increasingly recognized for their roles in skeletal muscle functions. In this review, we summarize the current understandings of adaptive mechanisms dependent on Ca2+ influx in response to biophysical stresses, with a particular focus on membrane repair and myofiber regeneration processes.