Folia Pharmacologica Japonica最新文献_第6页

[Distinct prefrontal neuronal circuits determine repeated stress-induced behavioral styles in mice]. [不同的前额神经回路决定了小鼠反复应激诱导的行为方式]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25040

Shusaku Uchida

{"title":"[Distinct prefrontal neuronal circuits determine repeated stress-induced behavioral styles in mice].","authors":"Shusaku Uchida","doi":"10.1254/fpj.25040","DOIUrl":"10.1254/fpj.25040","url":null,"abstract":"Stressful experiences can initiate or exacerbate mental health conditions, including depression. Depression is a complex and diverse syndrome characterized by varying symptom profiles, progression patterns, and responses to treatment. Despite this, the specific mechanisms by which prolonged stress leads to individual differences in behavior remain poorly understood. A major obstacle in advancing our understanding of the neurobiological and pathological consequences of psychosocial stress is the absence of subtype-based approaches in preclinical models. To address this gap, we implemented a behavioral subtyping strategy in preclinical research to explore how stress-induced behavioral variability is shaped by neural circuits, cellular processes, and molecular mechanisms. Using this approach, we classified stressed male mice into four distinct behavioral subtypes, based on their manifestations of social withdrawal and anhedonia-key features of many psychiatric disorders. Our findings revealed that three neural projection pathways originating from the prefrontal cortex play crucial roles in mediating these stress-related behaviors. In particular, the pathway connecting the medial prefrontal cortex (mPFC) to the anterior paraventricular thalamus (aPVT) was shown to influence a behavioral subtype marked by both social deficits and anhedonia. Moreover, we uncovered a molecular mechanism at the circuit level that underlies this specific phenotype: epigenetic repression of the Shisa2 gene by KDM5C within aPVT-projecting neurons in the mPFC contributes to the emergence of these behavioral impairments. Our research thus highlights distinct biological factors-spanning cellular, molecular, and epigenetic levels-that contribute to individual differences in stress-induced behavioral outcomes.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 2","pages":"89-91"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147325078","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 progress in brain organoid research for human biology]. [人类生物学类脑器官研究进展]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26057

Yurika Ohnishi, Yoshiho Ikeuchi

{"title":"[Current progress in brain organoid research for human biology].","authors":"Yurika Ohnishi, Yoshiho Ikeuchi","doi":"10.1254/fpj.26057","DOIUrl":"https://doi.org/10.1254/fpj.26057","url":null,"abstract":"Understanding human brain development, function, disease, and drug responses remains a central challenge in neuroscience and medicine. However, detailed analyses of living human brain tissue are technically and ethically difficult, and conventional studies have therefore relied largely on animal models and two-dimensional culture systems. Nevertheless, substantial differences exist between humans and animals in developmental processes, cellular composition, neural circuit, and pharmacological responses. Brain organoids are three-dimensional neural tissues generated from human embryonic stem cells or induced pluripotent stem cells, and they can recapitulate aspects of neural progenitor differentiation, cellular diversity, tissue architecture, and neuronal activity. Owing to these properties, brain organoids provide a valuable platform for human biology research. In this article, we review the development of brain organoid research and discuss recent advances including neuronal activity measurements, neural circuit models using assembloids and connectoids, reconstruction of human-enriched cell types and gene programs, analyses of inter-individual variability, toxicological studies, disease modeling, and drug evaluation. Furthermore, we outline the current status and future perspectives of human biology research using brain organoids, with particular attention to challenges such as heterogeneity, limited maturation, the absence of vascular and immune systems, standardization, quality control, and ethical considerations.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 5","pages":"363-369"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879599","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

[Astrocyte research in complex brains]. [复杂大脑中的星形胶质细胞研究]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26046

Yohei Shinmyo

引用次数: 0

[Pharmacology practice in understaffed local university medical schools]. [在人手不足的地方大学医学院的药理学实践]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25068

Masaki Mogi, Shuang Liu

{"title":"[Pharmacology practice in understaffed local university medical schools].","authors":"Masaki Mogi, Shuang Liu","doi":"10.1254/fpj.25068","DOIUrl":"https://doi.org/10.1254/fpj.25068","url":null,"abstract":"Pharmacology department in medical schools performs an introductory practical training program where medical students first experience the medical practice of using drugs in a university setting. However, recent university budget cuts have led to a shortage of human resources, insufficient funding for practical training, and the simplification or promotion of online training due to the COVID-19 pandemic, as well as changes in student attitudes, creating a significant turning point. In this symposium, I presented the results of a survey on the current state of pharmacology laboratory courses at medical schools nationwide, discussed the challenges and difficulties faced by universities across the country. While new forms of practical training, such as joint role-play with other universities and VR practical training that is more accessible to students, have been identified, on the other hand, fewer universities are conducting practical training using animals to cultivate an understanding of the dangers of actual drugs, the importance of life, and the uncertainty of drug administration and the ability to respond to it. Reasons include the decreasing number of staff capable of conducting such experiments, the rising costs of experimental animals, and the limited participation of only some students. However, the educational and ethical benefits of such experiments remain high. Some universities show implementing various innovative training programs. It is essential to gather such insights and collaborate nationwide to develop training formats that, while efficient and rational for faculty, also benefit students in terms of ethical and humanistic development.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 5","pages":"330-334"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879709","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

[Comprehensive characterization of primary ciliated cells in inflammatory skin diseases]. 【炎性皮肤病原发性纤毛细胞的综合表征】。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25073

Mikihito Ike, Manami Toriyama

{"title":"[Comprehensive characterization of primary ciliated cells in inflammatory skin diseases].","authors":"Mikihito Ike, Manami Toriyama","doi":"10.1254/fpj.25073","DOIUrl":"10.1254/fpj.25073","url":null,"abstract":"Primary cilia are non-motile organelles that act as cellular \"antennas\" to sense extracellular signals. As functional studies of primary cilia across various organs and tissues have progressed, it has become clear that primary cilia are also formed in skin-resident cells, including keratinocytes. Keratinocytes maintain skin homeostasis by producing cytokines and chemokines in response to external stimuli, and supporting skin tissue homeostasis through interactions with surrounding cells. Therefore, dysregulation of keratinocyte signaling leads to the development of inflammatory skin diseases. We revealed that ciliated cells are markedly increased in atopic dermatitis (AD) and psoriasis. However, their functional roles remain unclear. We combined immunofluorescence staining and spatial transcriptomics (Visium HD), which provides single-cell-level spatial resolution within tissue sections. Immunostaining of healthy skin, AD lesions, and psoriatic skin before and after phototherapy revealed that, even after phototherapy-when epidermal thickening and inflammation were alleviated-the number of ciliated cells remained higher than in healthy skin. Transcriptomic analysis revealed that ciliated cells retained features of undifferentiated keratinocytes and exhibited upregulation of metabolic, cell-cycle, and signaling pathways compared to post-treatment cells. These findings suggest that disease-associated primary cilia may disrupt keratinocyte signaling and skin barrier maturation, and could promote disease relapse by facilitating rapid inflammatory responses upon re-stimulation. Our findings suggest that modulating cilia formation or cilia-associated signaling could provide a potential therapeutic strategy for inflammatory skin diseases.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 3","pages":"177-182"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835808","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

[Modality strategy in Eisai drug discovery: challenges toward next-generation therapeutics using proximity-inducing compound]. [卫材药物发现的模式策略：使用邻近诱导化合物的下一代治疗方法的挑战]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25095

Kazunobu Kira

{"title":"[Modality strategy in Eisai drug discovery: challenges toward next-generation therapeutics using proximity-inducing compound].","authors":"Kazunobu Kira","doi":"10.1254/fpj.25095","DOIUrl":"10.1254/fpj.25095","url":null,"abstract":"In recent years, the concept of \"modality\" has attracted significant attention in drug discovery, encompassing diverse approaches such as small molecules, antibodies, nucleic acids, and cell-based therapies. Eisai has leveraged its long-standing expertise in small-molecule drug design to focus on proximity-inducing compound (PIC), which induces novel pharmacological effects by bringing two distinct proteins into close proximity. PIC form ternary complexes between a target protein and an effector protein, enabling mechanisms such as targeted degradation, post-translational modification, and modulation of protein-protein interactions. This strategy allows intervention in previously \"undruggable\" targets that lack suitable binding pockets for conventional inhibitors. Among PIC, targeted protein degraders such as proteolysis targeting chimera (PROTAC) and molecular glue degrader (MGD) have advanced rapidly into clinical development worldwide. Eisai's entry into this field was driven by the discovery of the unique mechanism of action of Indisulam and E7820, which function as MGD to degrade RBM39 via DCAF15 recruitment. Building on this foundation, Eisai is pursuing tumor-selective strategies, including the development of a CEACAM6-targeted degrader antibody conjugate (DAC) and PROTAC utilizing tumor-selective E3 ligases. These approaches aim to achieve both efficacy and safety by restricting degradation activity to cancer cells. PIC represent a transformative modality that expands the druggable proteome and offers new therapeutic options for intractable diseases. This article outlines Eisai's efforts in PIC-based drug discovery, with a focus on targeted protein degradation and future perspectives.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 3","pages":"145-149"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835750","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 properties and clinical efficacy of sphingosine 1-phosphate (S1P) receptor modulator, Etrasimod (Velsipity^® 2 mg tablets)]. [鞘氨醇1-磷酸（S1P）受体调节剂Etrasimod （Velsipity®2 mg片）的药理特性及临床疗效]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26041

Satoko Nonaka-Hashida, Hirotoshi Yuasa, Ryosuke Ono, Hiroshi Hirano, Koki Fukuta, Masanori Hizue

{"title":"[Pharmacological properties and clinical efficacy of sphingosine 1-phosphate (S1P) receptor modulator, Etrasimod (Velsipity® 2 mg tablets)].","authors":"Satoko Nonaka-Hashida, Hirotoshi Yuasa, Ryosuke Ono, Hiroshi Hirano, Koki Fukuta, Masanori Hizue","doi":"10.1254/fpj.26041","DOIUrl":"10.1254/fpj.26041","url":null,"abstract":"Etrasimod L-arginine (Velsipity® 2 mg tablets) is a small-molecule sphingosine 1-phosphate (S1P) receptor modulator with high selectivity for the S1P receptor subtypes S1P1, S1P4, and S1P5. Through its action on S1P1, etrasimod induces receptor internalization, thereby inhibiting lymphocyte egress from lymph nodes to sites of inflammation. This mechanism is considered to reduce chronic inflammation in the colonic mucosa associated with ulcerative colitis (UC). Nonclinical pharmacology studies have shown that etrasimod preferentially activates the β-arrestin pathway, while relatively weakly activating G protein pathway associated with heart rate reduction compared to other S1P modulators. In clinical trials, first-dose bradycardia was mild and transient, and the magnitude of heart rate reduction after dose titration to 2 mg was comparable to that observed when treatment was initiated directly at 2 mg. Therefore, etrasimod can be initiated at the maintenance dose of 2 mg. In domestic and global Phase III clinical trials, once-daily oral administration of etrasimod 2 mg significantly improved clinical remission and endoscopic outcomes compared with placebo at 12 and 52 weeks in patients with moderately to severely active UC, including those with an inadequate response to biologics or Janus kinase inhibitors. The safety profile was favorable, with adverse event rates comparable to placebo and most events being mild to moderate. Based on these results, etrasimod was approved in Japan in June 2025 for moderate to severe UC with inadequate response to existing therapies. With once-daily oral dosing without titration and a favorable safety profile, etrasimod represents a new therapeutic option for UC.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 5","pages":"383-394"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148879702","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 properties and clinical efficacy of sphingosine 1-phosphate (S1P) receptor modulator, Ozanimod (ZEPOSIA^®)]. [鞘氨醇1-磷酸（S1P）受体调节剂Ozanimod （ZEPOSIA®）的药理特性和临床疗效]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25053

Hiroshi Iwata, Yoko Uchikawa

{"title":"[Pharmacological properties and clinical efficacy of sphingosine 1-phosphate (S1P) receptor modulator, Ozanimod (ZEPOSIA®)].","authors":"Hiroshi Iwata, Yoko Uchikawa","doi":"10.1254/fpj.25053","DOIUrl":"https://doi.org/10.1254/fpj.25053","url":null,"abstract":"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.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 1","pages":"45-54"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899308","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

[Cellular senescence in pulmonary hypertension]. [肺动脉高压的细胞衰老]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.25067

Lin-Hai Kurahara

引用次数: 0

[Pediatric drug development: current landscape, challenges, and future directions]. [儿科药物开发：现状、挑战和未来方向]。

Folia Pharmacologica Japonica Pub Date : 2026-01-01 DOI: 10.1254/fpj.26012

Chie Emoto, Tsuyoshi Fukuda

{"title":"[Pediatric drug development: current landscape, challenges, and future directions].","authors":"Chie Emoto, Tsuyoshi Fukuda","doi":"10.1254/fpj.26012","DOIUrl":"https://doi.org/10.1254/fpj.26012","url":null,"abstract":"Pediatric drug development has seen significant progress through the implementation of extrapolation strategies incorporating modeling and simulation (M&S) techniques. The ICH E11A guideline provides a systematic framework for pediatric extrapolation, advocating for comprehensive assessments of disease characteristics, pharmacology, and therapeutic outcomes to determine the appropriateness of such methodologies. At the 2025 Pharmaceuticals and Medical Devices Agency (PMDA) workshop, stakeholders emphasized the importance of adopting such strategies to address drug lag and loss observed in Japan, as well as the necessity of establishing flexible consultation mechanisms early in the development process. Here, to illustrate M&S capabilities, physiologically-based pharmacokinetic (PBPK) modeling was employed using physiological data from Japanese pediatric populations to simulate PKs, with validation across 14 drugs indicating predictive accuracy within a 0.5-2.0-fold range of observed PK parameters. These results provide a basis for further validation of this population. Ultimately this approach intends to support dosage and administration in preparation for pediatric clinical trials in Japan, as well as to reinforce the scientific justification. Moreover, PBPK modeling enhances theoretical insights into predicting PKs for special pediatric populations with unique disease conditions and assessing drug-drug interaction risks, which are not amenable to prospective clinical trials. Achieving further progress in this field necessitates multidisciplinary collaboration among industry, regulatory agencies, academia, and healthcare institutions, with each party fulfilling its respective responsibilities to collectively advance pediatric drug development.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"161 3","pages":"164-169"},"PeriodicalIF":0.0,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147835768","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