Folia Pharmacologica Japonica最新文献_第8页

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25083

Masahiro Ikeda

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25094

Sho Kubota

引用次数: 0

[Preface]. (前言)。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25079

Toshiko Yamazawa, Yuji Hara

引用次数: 0

[Reducing jet lag by "softening" the circadian clock: a study using transgenic rats expressing BMAL1-dominant negative proteins in the nervous system]. [通过“软化”生物钟来减少时差反应：一项利用在神经系统中表达bmal1显性阴性蛋白的转基因大鼠的研究]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26002

Yoichi Minami, Yasufumi Shigeyoshi

{"title":"[Reducing jet lag by \"softening\" the circadian clock: a study using transgenic rats expressing BMAL1-dominant negative proteins in the nervous system].","authors":"Yoichi Minami, Yasufumi Shigeyoshi","doi":"10.1254/fpj.26002","DOIUrl":"https://doi.org/10.1254/fpj.26002","url":null,"abstract":"The circadian clock is an endogenous oscillator with a period of approximately 24 hours, with the central pacemaker localized in the suprachiasmatic nucleus (SCN). Jet lag occurs because the clock requires several days to entrain to a new environment. To address this, it is common practice to use bright light exposure-a potent zeitgeber-at specific times. Here, we propose an alternative approach based on a mathematical limit cycle model: reducing the amplitude of the circadian oscillator to enhance its responsiveness to timing cues. As a proof of concept, we generated a transgenic rat line expressing a dominant-negative (DN) form of BMAL1 in the nervous system to create a model with weakened circadian function. We developed an expression vector using the mouse Prion protein promoter to express a BMAL1 DN lacking the C-terminus, a region critical for CRY1 interaction. We confirmed that the behavioral rhythms of BMAL1 DN(+) Tg rats exhibited lower amplitudes compared to their DN(-) littermates under both light-dark (LD) and constant darkness (DD) conditions. Furthermore, ex vivo SCN organ cultures from BMAL1 DN(+) rats showed lower amplitude rhythms than those from controls. When exposed to bright light at ZT14 (two hours after lights-off) and released to DD, BMAL1 DN(+) rats showed a significantly greater phase response. Additionally, following an abrupt shift in the LD cycle, BMAL1 DN(+) rats required fewer days to re-entrain to the new environment. These suggest that reducing the amplitude of the circadian oscillator enhances phase responsiveness and accelerates entrainment to new light-dark cycles.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 4","pages":"239-243"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Pharmacological characteristics and clinical outcomes of Rimegepant (Nurtec^® ODT), an oral CGRP receptor antagonist for the acute treatment and prevention of migraine]. [用于急性治疗和预防偏头痛的口服CGRP受体拮抗剂Rimegepant （Nurtec®ODT）的药理学特征和临床结果]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26050

Tomofumi Ishikawa, Saori Morota, Beini Shi, Yinhua Li, Masahiro Iijima

{"title":"[Pharmacological characteristics and clinical outcomes of Rimegepant (Nurtec® ODT), an oral CGRP receptor antagonist for the acute treatment and prevention of migraine].","authors":"Tomofumi Ishikawa, Saori Morota, Beini Shi, Yinhua Li, Masahiro Iijima","doi":"10.1254/fpj.26050","DOIUrl":"https://doi.org/10.1254/fpj.26050","url":null,"abstract":"Migraine is a highly prevalent neurological disorder and is associated with substantial mental, social, and disease burden. Current migraine management comprises acute and preventive treatments; however, conventional acute and preventive medications have been associated with challenges such as contraindications, a delayed onset of efficacy, and adverse drug reactions. Rimegepant is an orally available small molecule calcitonin gene-related peptide (CGRP) receptor antagonist uniquely approved for both acute and preventive treatments. Nonclinical studies have demonstrated its high affinity for the CGRP receptor without inducing vasoconstriction in coronary or intracranial arteries. Consistent with these findings, clinical studies have shown no signals suggestive of cardiovascular risk, indicating a low concern for vasoconstrictive effects as triptans. In Phase 1 studies in healthy Japanese adults, rimegepant showed rapid absorption, supporting a rapid onset of action in acute treatment, and relatively longer half-life (10 h), supporting sustained efficacy. From a preventive perspective, while existing CGRP monoclonal antibodies are administered as injectable formulations, rimegepant can be administered orally as an orally disintegrating (OD) tablet. Drug-drug interaction studies demonstrated co-administration of rimegepant with triptans is possible due to a lack of clinically meaningful blood pressure elevation or pharmacokinetic interactions. Multiple clinical trials have confirmed the efficacy and safety of rimegepant for acute treatment, and every other day (EOD) dosing significantly reduced monthly migraine days. In addition to its favorable safety profile, the flexible use of the same formulation for both acute and preventive treatments represents a clinically meaningful, new option in migraine treatment.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 4","pages":"280-290"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Membrane lipids and galactose-recognizing lectin, galectin]. [膜脂和半乳糖识别凝集素]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26022

Junko Nio-Kobayashi

{"title":"[Membrane lipids and galactose-recognizing lectin, galectin].","authors":"Junko Nio-Kobayashi","doi":"10.1254/fpj.26022","DOIUrl":"https://doi.org/10.1254/fpj.26022","url":null,"abstract":"Although the main component of cell membrane is phospholipids, there are regions that are rich in glycosphingolipids and cholesterol, called membrane microdomains. Membrane microdomains are densely populated with receptors and intra/extracellular proteins that regulate signal transduction. Membrane microdomains move freely on cell membrane like floating rafts in the sea. In the presence of ligands, they associate with intracellular signaling molecules, regulating cellular functions. Most cell surface proteins including receptors and secreted proteins are glycosylated and interact with lectins that recognize specific glycan structures. Glycan-lectin binding plays an important role in regulating cellular function. Glycans on receptors and ligands and on glycosphingolipids abundant in membrane microdomains are recognized and crosslinked by endogenous lectins, regulating the behavior of cell surface molecules such as receptors. We have been investigating the in vivo function of galactose-recognizing galectins. Fifteen subtypes of galectins exist in mammals, and they are widely distributed throughout the body including the gastrointestinal tract, urogenital tract, and immune system in a tissue- and cell-specific manner. While analyzing the function of galectins in the mechanism controlling the function of the corpus luteum, which produces progesterone essential for the establishment and maintenance of pregnancy, we discovered that cell membrane lipids play a central role in regulating luteal function. Here, we introduce the involvement of cell membrane lipids, particularly a lipid-derived mediator, prostaglandin E, and the qualitative and quantitative changes in glycosphingolipids, as well as galactose-recognizing galectins in the mechanism controlling human corpus luteum function.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 4","pages":"253-256"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148367680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Current perspectives on the deep cerebellar nuclei in research on psychiatric and metabolic disorders]. [在精神和代谢疾病研究中小脑深部核的最新观点]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25081

Taiga Ishimoto, Chitoku Toda

引用次数: 0

[Prediction of drug intestinal absorption and drug-induced intestinal toxicity with the use of human crypt-derived intestinal stem cells and their differentiated cells]. [利用人隐窝来源的肠道干细胞及其分化细胞预测药物肠道吸收和药物诱导的肠道毒性]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26021

Kazuya Maeda

{"title":"[Prediction of drug intestinal absorption and drug-induced intestinal toxicity with the use of human crypt-derived intestinal stem cells and their differentiated cells].","authors":"Kazuya Maeda","doi":"10.1254/fpj.26021","DOIUrl":"https://doi.org/10.1254/fpj.26021","url":null,"abstract":"For the development of orally-administered drugs, quantitative prediction of drug intestinal absorption and drug-induced intestinal toxicity is one of the essential evaluation items. However, the current experimental systems have some critical problems such as large inter-species difference in animal studies and different gene expression levels between Caco-2 cells and human intact intestinal tissue. Thus, the construction of novel experimental systems which can reflect human intestinal physiology has been desired. We established stable 3D culture of intestinal stem cells in Matrigel originally isolated from surgical specimens and novel experimental systems for the prediction of intestinal absorption and toxicity with their differentiated cells. For the prediction of intestinal absorption, intestinal availability and PXR-mediated induction of pharmacokinetics-related genes could be predicted with our differentiated cells, but not Caco-2 cells due to the low expression levels of key molecules. For the prediction of intestinal toxicity, we evaluated the decrease in intracellular ATP level of intestinal stem cells by anticancer drugs to predict the risk of drug-induced severe diarrhea and serotonin release from EC (enterochromaffin) cell-rich spheroids to predict the risk of drug-induced emesis. Based on these in vitro assays, we succeeded in the prediction of the difference in the frequency of diarrhea and emesis in the clinical situation after administration of each tested drug. In this review, we summarized the major problems of current assays and usefulness of human crypt-derived intestinal stem cells and their differentiated cells for the prediction of clinical pharmacokinetics and toxicity of drugs in humans.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 5","pages":"370-375"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[The significance of IL-19 in the liver: crosstalk among inflammation, metabolism, and fibrosis]. [IL-19在肝脏中的意义：炎症、代谢和纤维化之间的串扰]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25061

Yuko Mitani, Takashi Fujita, Yasu-Taka Azuma

{"title":"[The significance of IL-19 in the liver: crosstalk among inflammation, metabolism, and fibrosis].","authors":"Yuko Mitani, Takashi Fujita, Yasu-Taka Azuma","doi":"10.1254/fpj.25061","DOIUrl":"https://doi.org/10.1254/fpj.25061","url":null,"abstract":"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.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 1","pages":"11-14"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899618","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

[Neural basis underlying life-saving-like behavior]. [类似救生行为背后的神经基础]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25104

Takeshi Nagahiro, Kazuki Kakehi, Yuji Ikegaya, Nobuyoshi Matsumoto

引用次数: 0