Folia Pharmacologica Japonica最新文献_第5页

[A remarkable advancement in structural biology aimed at elucidating the ‍mechanism of synovial sarcoma development]. [结构生物学的一个显著进展，旨在阐明‍滑膜肉瘤发展的机制]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25013

Kenji Iwasaki, Satoshi Takenaka

{"title":"[A remarkable advancement in structural biology aimed at elucidating the ‍mechanism of synovial sarcoma development].","authors":"Kenji Iwasaki, Satoshi Takenaka","doi":"10.1254/fpj.25013","DOIUrl":"https://doi.org/10.1254/fpj.25013","url":null,"abstract":"Synovial sarcoma is a type of soft tissue sarcoma that predominantly occurs near the joints of the extremities in young adults. Its hallmark is a recurrent and pathogenic chromosomal translocation, t(X;18)(p11.2;q11.2), which results in the fusion of the SSX1 or SSX2 gene with SS18. The expressed SS18-SSX fusion protein induces abnormalities in the SWItch/Sucrose Non-Fermentable (SWI/SNF) complex, a chromatin remodeling complex. In this paper, we refer specifically to the human SWI/SNF complex as mSWI/SNF. Since 2020, significant progress has been made in elucidating the molecular mechanisms underlying the initial event in synovial sarcomagenesis, particularly in structural biology, thereby opening new possibilities for structure-based drug design (SBDD). SS18-SSX1 replaces the wild-type SS18, an essential subunit of mSWI/SNF, and in turn ejects SMARCB1, another core subunit of the complex. This aberrant mSWI/SNF complex (ssSWI/SNF) is then relocated to nucleosomes containing H2A K119Ub. H2A is one of the core histone proteins, and its 119th lysine residue is ubiquitinated to form H2A K119Ub. Chromatin domains harboring nucleosomes with this modification typically exhibit suppressed gene expression patterns. Furthermore, this region is occupied by polycomb complexes, but ssSWI/SNF competes with them, leading to gene activation, which constitutes the initial event in synovial sarcomagenesis. Given that SSX1 is normally expressed primarily in the testes, it is plausible that its ectopic expression leads to aberrant function within the chromatin remodeling complex. Ultimately, the C-terminal region of SSX1 was found to bind to the acidic patch within the nucleosome, and its structural details have been elucidated through cryo-electron microscopy.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 3","pages":"167-171"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143974055","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

[Nationwide survey of practice after COVID-19 pandemic conducted in medical schools]. [新冠肺炎大流行后全国医学院实践情况调查]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25010

Masaki Mogi, Shung Liu

引用次数: 0

[Physiologically-based pharmacokinetic model analysis of antipsychotic risperidone and its active metabolite paliperidone in perinatal period]. [抗精神病药物利培酮及其活性代谢物帕利哌酮在围产期的生理药代动力学模型分析]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24065

Ikuko Yano

{"title":"[Physiologically-based pharmacokinetic model analysis of antipsychotic risperidone and its active metabolite paliperidone in perinatal period].","authors":"Ikuko Yano","doi":"10.1254/fpj.24065","DOIUrl":"10.1254/fpj.24065","url":null,"abstract":"Pregnancy can affect the absorption, distribution, metabolism, and excretion of several drugs due to pregnancy-induced physiological changes. Risperidone, a second-generation antipsychotic, is prescribed to pregnant women when the benefits outweigh the risks to the fetus. Serum concentrations of risperidone and its active metabolite paliperidone in a pregnant woman as well as her newborn were measured, and physiologically-based pharmacokinetic (PBPK) models of both drugs were developed. The effects of pregnancy on pharmacokinetic parameters of both drugs were quantitively assessed by the developed PBPK model. As a result, serum concentrations of risperidone and paliperidone decrease in the pregnant status and abruptly recover to the non-pregnant level after delivery mainly due to cytochrome P450 (CYP) 2D6 activity changes, and therefore, close and careful monitoring of clinical symptoms should be considered during pregnancy and after delivery. In the 10 different models for estimating the renal function of children, the Flanders metadata equation showed the lowest absolute bias and the greatest precision in predicting paliperidone serum concentration in the neonate. PBPK model-informed approach could help with the precision dosing in special populations, such as pregnant women and neonates.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 2","pages":"103-107"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537006","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

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25027

Ichiro Kawahata

引用次数: 0

[Roles of extracellular vesicles in allergen-specific immunotherapy]. [细胞外囊泡在过敏原特异性免疫治疗中的作用]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25007

Masaya Matsuda, Takeshi Nabe

{"title":"[Roles of extracellular vesicles in allergen-specific immunotherapy].","authors":"Masaya Matsuda, Takeshi Nabe","doi":"10.1254/fpj.25007","DOIUrl":"10.1254/fpj.25007","url":null,"abstract":"The prevalence of allergic diseases has been increasing, and sensitization to allergens such as cedar pollen and house dust mites has become a social issue. Allergic inflammation is primarily driven by type 2 inflammation, which is mediated by interleukin (IL)-4, IL-5, and IL-13 produced by Th2 cells and group 2 innate lymphoid cells (ILC2s). Recent studies have suggested that extracellular vesicle (EV) also plays critical roles in the pathogenesis of allergic diseases. EVs are lipid bilayer-enclosed particles containing proteins, mRNA, and microRNA (miRNA), which function as carriers of cytokines, antigens, and miRNAs, thereby activating Th2 cells and ILC2s and contributing to the progression of various inflammatory diseases. In contrast, we demonstrated that EVs contributed to the regression of allergic disease: EVs derived from the serum of allergen immunotherapy-treated mice exhibited suppression of ILC2 activation. Given their dual roles in both promoting and suppressing immune responses, EVs are emerging as promising targets and tools for novel treatment strategies. Understanding the immunomodulatory mechanisms mediated by EVs will be a crucial step toward developing safer and more effective therapies for allergic diseases. This review provides an overview of the role of EVs in allergic inflammation and highlights our recent findings on how allergen immunotherapy influences the properties and functions of EVs, thereby contributing to the regulation of immune responses and alleviation of allergic symptoms.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"235-238"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552783","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

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24087

Eiichi Taira

引用次数: 0

[Drug discovery using iPS cells and in silico model]. [利用iPS细胞和计算机模型发现药物]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24046

Yuya Fujiwara, Yoshinori Yoshida

{"title":"[Drug discovery using iPS cells and in silico model].","authors":"Yuya Fujiwara, Yoshinori Yoshida","doi":"10.1254/fpj.24046","DOIUrl":"https://doi.org/10.1254/fpj.24046","url":null,"abstract":"Human induced pluripotent stem cells derived cardiomyocytes (hiPSC-CMs) can recapitulate the properties of human cardiomyocyte and exhibit disease phenotypes in vitro, attributable to their healthy- or patient-specific genetic backgrounds. Therefore, hiPSC-CMs are a crucial tool for developing therapeutic agents for cardiovascular diseases, and regenerative medicine using hiPSC-CMs is expected to be an alternative therapy to heart transplantation. Moreover, the development of organoid models has been advanced to replicate the complex structure of heart tissue in vitro, thereby effectively facilitating drug discovery. On the other hand, current methods for advancing drug discovery using hiPSC-CMs face limitations, including the difficulty of quantifying characteristics such as cell structure and predicting the risk and efficacy of candidate drug in clinical practice. In the field of regenerative medicine, challenges include quality control and the verification of safety of transplanted cells in human. In silico model, including artificial intelligence (AI) and simulation, have been developed in the field of drug discovery using hiPSC-CMs. These advancements encompass phenotype scoring via AI and risk prediction through simulations. This review outlines the current status and challenges of drug discovery using hiPSC-CMs and in silico model, based on the published reports.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 1","pages":"13-17"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931070","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 75th Regional Meeting (Kita Area)]. [第75届区域会议（北区）]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.S24087

引用次数: 0

[Real-time measurement of neuromodulators using GRAB sensors]. [利用GRAB传感器实时测量神经调节剂]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24111

Rentaro Higuchi, Yasutaka Mukai, Hiroaki Norimoto

{"title":"[Real-time measurement of neuromodulators using GRAB sensors].","authors":"Rentaro Higuchi, Yasutaka Mukai, Hiroaki Norimoto","doi":"10.1254/fpj.24111","DOIUrl":"https://doi.org/10.1254/fpj.24111","url":null,"abstract":"To advance our understanding of the neuronal mechanisms underpinning animal behavior, it is important to integrate traditional electrophysiological methodologies with cutting-edge technologies capable of providing detailed insights into the dynamics of neuromodulators. However, achievement of high spatial and temporal resolution in neuromodulator measurements has presented significant challenges, particularly in the context of real-time observations within freely behaving animals. Recent innovations, exemplified by the development of genetically encoded fluorescent indicator, commonly referred to as \"GRAB sensors,\" have addressed these limitations. These tools enable the real-time, high-precision quantification of neuromodulators, representing a transformative advancement in the field. Notably, GRAB sensors have been designed to target a broad spectrum of neuromodulators, including dopamine (DA), acetylcholine (ACh), noradrenaline/norepinephrine (NE), and neuropeptides, offering unparalleled specificity, sensitivity, and temporal resolution. This review provides an overview of the features and advantages of GRAB sensors, highlights their diverse applications, and discusses key considerations pertinent to their implementation in contemporary neuroscience research.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 3","pages":"195-200"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144063156","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

[Regulation of myeloid-derived suppressor cells by glutamate]. 谷氨酸对髓源性抑制细胞的调控。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25009

Masashi Tachibana

{"title":"[Regulation of myeloid-derived suppressor cells by glutamate].","authors":"Masashi Tachibana","doi":"10.1254/fpj.25009","DOIUrl":"https://doi.org/10.1254/fpj.25009","url":null,"abstract":"Myeloid-derived suppressor cells (MDSCs) suppress anti-tumor immunity in tumor bearers, which leads to tumor progression. Immune checkpoint blockers (ICBs) demonstrated significant efficiency against various cancers; however, their success rate is limited to approximately 20-30% in patients with cancer. To address this limitation, predictive biomarkers and combination therapies are required. Since MDSCs are supposed to be crucial for the resistance to ICBs, targeting MDSCs could be a promising approach for cancer immunotherapy. Granulocyte colony-stimulating factor (G-CSF), widely used as prophylaxis and therapy for febrile neutropenia (FN), has been shown to significantly reduce its incidence. However, G-CSF has been reported to promote tumor progression caused by the enhancing the proliferation of MDSCs. We found that G-CSF enhances the immunosuppressive activity of MDSCs through the upregulation of γ-glutamyltransferase 1 (GGT1). GGT1, an enzyme hydrolyzing extracellular glutathione, is reported to be a marker for early-stage cancers and promote tumor progression. It is suggested that GGT1 increases glutamate levels through glutathione hydrolysis and that metabotropic glutamate receptor signaling enhances the immunosuppressive activity of MDSCs. Moreover, in FN mouse models, we observed that G-CSF promoted tumor progression, while the inhibition of GGT abolished. Together, the inhibition of GGT can mitigate the tumor-promoting effects of MDSCs without compromising the beneficial effect of G-CSF. These insights should lead to the safer and more effective cancer immunotherapy.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 3","pages":"158-162"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143993062","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