Folia Pharmacologica Japonica最新文献_第8页

[Elucidation of the pathogenesis of optic nerve diseases and new therapeutic strategies to protect visual function]. [阐明视神经疾病的发病机制和保护视力功能的新治疗策略]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24049

Chikako Harada, Kazuhiko Namekata, Xiaoli Guo, Takayuki Harada

{"title":"[Elucidation of the pathogenesis of optic nerve diseases and new therapeutic strategies to protect visual function].","authors":"Chikako Harada, Kazuhiko Namekata, Xiaoli Guo, Takayuki Harada","doi":"10.1254/fpj.24049","DOIUrl":"10.1254/fpj.24049","url":null,"abstract":"Approximately 80% of all the information we receive about the world comes through the visual pathways and visual function deterioration causes severe decline in QOL. Glaucoma is the leading cause of blindness in the world, in which visual field deficit deteriorates as the optic nerve degeneration progresses. Hence, the development of fundamental cure is needed. Our research focuses on the signaling of brain-derived neurotrophic factor (BDNF), one neurotrophic factor reduced with aging and glaucoma patients. We generated modified tropomyosin receptor kinase B (TrkB) which can be constitutively activated in the absence of its ligand BDNF. The active site of TrkB is localized to the plasma membrane, allowing for constitutive activation of intracellular signaling. Gene therapy with the modified TrkB in a mouse model of glaucoma was proven to be protective. In addition, our group reported that apoptosis signal-regulating kinase 1 (ASK1), one of the stress response factors, is related to the severity of optic neuritis and myelitis in model mice of multiple sclerosis. We generated four lines of cell type specific ASK1 conditional knockout mice and found that ASK1 in glial cells increased the severity of neuroinflammation while ASK1 deficiency in immune cells had no significant effects. Further, we found that ASK1 is required in microglia and astrocytes to cause and maintain neuroinflammation by a feedback loop between these two cell types. Our results suggest that ASK1 might be a promising therapeutic target for reducing neuroinflammation including optic neuritis.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 2","pages":"68-72"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536992","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

[Analysis for acquiring and overriding oral tolerance in food allergy to use murine models]. [用小鼠模型分析食物过敏获得和克服口服耐受的情况]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24104

Hirotaka Yamashita

{"title":"[Analysis for acquiring and overriding oral tolerance in food allergy to use murine models].","authors":"Hirotaka Yamashita","doi":"10.1254/fpj.24104","DOIUrl":"https://doi.org/10.1254/fpj.24104","url":null,"abstract":"Oral tolerance is an immune regulatory system for foods. Eating foods gives healthy people nutrition. However, foods are immune exclusion material in patients of food allergy. We thought possibilities for immune intolerance for foods, failing acquisition of oral tolerance and breaking acquired tolerance. Then, we made murine models for the possibilities. First, we made the food allergy model and oral tolerance model for ovalbumin (OVA). Experimental oral tolerance was induced by previously oral treatment with OVA solution before the sensitization by intraperitoneal injection of OVA. In the oral tolerance model, elevation of OVA-specific IgE was suppressed completely and anaphylaxis was not induced. Next, as the model of failing acquisition of oral tolerance, we used the food additives into the OVA solution for tolerance. As results, intake of the OVA solution with food additives prevented acquiring oral tolerance and induced anaphylaxis for OVA. Recently, \"dual-allergen exposure hypothesis\" was suggested. The hypothesis proposed allergic sensitization to food could occur through cutaneous sensitization and that consumption of food protein induced oral tolerance. We attempted to override oral tolerance for the food by sensitization via skin. We found that epicutaneous sensitization and sensitization by intradermal injection of OVA could override acquired oral tolerance. As two common denominators for immune intolerance for foods, we confirmed the change of migration of dendritic cells and prevention of inducing regulatory T cells.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"230-234"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552751","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

[Mechanism of pathogenesis by a gain-of-function variant of STAT6 causing severe allergic diseases and potential for development of molecularly targeted drugs]. 【STAT6的功能获得性变异引起严重过敏性疾病的发病机制及分子靶向药物的开发潜力】。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25008

Kumiko Yanagi, Tadashi Kaname

{"title":"[Mechanism of pathogenesis by a gain-of-function variant of STAT6 causing severe allergic diseases and potential for development of molecularly targeted drugs].","authors":"Kumiko Yanagi, Tadashi Kaname","doi":"10.1254/fpj.25008","DOIUrl":"https://doi.org/10.1254/fpj.25008","url":null,"abstract":"Allergic diseases have been considered multifactorial diseases. However, comprehensive genome sequencing, such as whole exome analysis, is revealing a group of diseases in which single genes are deeply involved in their pathogenesis. We identified a de novo missense variant of STAT6 [NM_003153:c.1255G>A,p.(Asp419Asn)] in a severely allergic patient with atopic dermatitis, hyper IgE, eosinophilic gastroenteritis, and food allergy by whole exome sequencing analysis. STAT6 is known as a transcription factor induced by IL-4 stimulation. Stimulation with IL-4 induces STAT6 phosphorylation via the JAK-STAT pathway and dimer formation. The STAT6 dimer quickly translocates into the nucleus and ultimately activates the expression of genes specific for TH2-type immune responses. Our experiments in vitro showed that nuclear translocation of mutant STAT6 (p.Asp419Asn) is enhanced compared to wild-type STAT6. In addition, even in the absence of IL-4 stimulation, we observed the translocation of mutant STAT6 in its unphosphorylated state, which activated gene expression. Mutant STAT6 knock-in mice elicited an abnormal TH2-dominant immune response in vivo, with findings similar to those observed in patients. Our findings suggest that mutant STAT6 is a gain-of-function variant. Currently, anti-IL-4Rα monoclonal antibodies, JAK inhibitors that block the JAK-STAT pathway, and non-specific anti-inflammatory drugs such as steroids are shown to be effective in treating this disease. The pathogenesis of immune dysregulation caused by gain-of-function variants of the STAT6 gene is being elucidated. Further efforts are required to elucidate the detailed mechanisms of this disease and it will hopefully lead to the development of more essential agents that specifically regulate STAT6 activity.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 4","pages":"244-249"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144552755","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.24101

Minoru Narita, Naoko Kuzumaki

引用次数: 0

[Cardiotoxicity risk assessment of anticancer drugs by focusing on mitochondrial quality of human iPS cell-derived cardiomyocytes]. [通过关注人类iPS细胞衍生心肌细胞的线粒体质量来评估抗癌药物的心脏毒性风险]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24056

Yuri Kato, Yuya Nakamura, Moe Kondo, Yasunari Kanda, Motohiro Nishida

{"title":"[Cardiotoxicity risk assessment of anticancer drugs by focusing on mitochondrial quality of human iPS cell-derived cardiomyocytes].","authors":"Yuri Kato, Yuya Nakamura, Moe Kondo, Yasunari Kanda, Motohiro Nishida","doi":"10.1254/fpj.24056","DOIUrl":"https://doi.org/10.1254/fpj.24056","url":null,"abstract":"Currently, a variety of anticancer agents are used in the treatment of cancer. Since anticancer agents are used continuously over a long time, they carry the risk of side effects. One of the major side effects is cardiac dysfunction. For example, doxorubicin, an anthracycline-type anticancer agent, is clinically restricted because of its dose-dependent cardiotoxicity. Cardiotoxicity includes decreased ejection fraction, arrhythmias, and congestive heart failure, all of which are associated with high mortality rates. Therefore, it is important to assess the risk of cardiotoxicity of anticancer agents in advance. Cardiomyocytes require energy to beat and retain an abundance of mitochondria. We established quantitative measurements of mitochondrial length and respiratory activities using cardiomyocytes. We found that exposure of human iPS cell-derived cardiomyocytes (hiPSC-CMs) to anticancer agents with reported cardiotoxicity enhanced mitochondrial hyperfission and the oxygen consumption rate was significantly reduced. Knockdown of dynamin-related protein 1 (Drp1), mitochondrial fission-accelerating GTP-binding protein, suppressed mitochondrial hyperfission in hiPSC-CMs. This indicates that visualizing mitochondrial functions in hiPSC-CMs will be helpful in assessing the risk of cardiotoxicity caused by anticancer agents and that maintaining mitochondrial quality will become a new strategy to reduce anticancer agents-induced cardiotoxicity. In this review, we present the evaluation of cardiotoxicity targeting mitochondrial quality in anticancer agents, using osimertinib, a non-small cell lung cancer drug, as an example.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 1","pages":"9-12"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142931035","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

[A novel drug target VIPR2 to regulate migration and proliferation in breast cancer]. [一种新的药物靶向VIPR2调节乳腺癌的迁移和增殖]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25006

Satoshi Asano, Kotaro Sakamoto, Yukio Ago

{"title":"[A novel drug target VIPR2 to regulate migration and proliferation in breast cancer].","authors":"Satoshi Asano, Kotaro Sakamoto, Yukio Ago","doi":"10.1254/fpj.25006","DOIUrl":"https://doi.org/10.1254/fpj.25006","url":null,"abstract":"Molecularly targeted drugs currently used in breast cancer target the epidermal growth factor receptors, and are less effective when used against breast cancer subtypes with low levels of these receptors. There is therefore an urgent need to identify a new target molecule for such breast cancer subtypes. Vasoactive intestinal peptide (VIP) receptor 2 (VIPR2) is a G-protein-coupled receptor that binds to Gαs, Gαi, and Gαq proteins to regulate their downstream signaling. VIPR2 is known to be highly expressed in the suprachiasmatic nucleus of the brain, but is also expressed in many peripheral organs. VIPR2 expression has also been reported in thyroid cancer, gastric cancer, lung cancer, pancreatic adenocarcinoma, sarcoma, and neuroendocrine tumors, and VIPR2 mRNA expression and VIPR2 gene copy number are particularly elevated in breast cancer. We therefore investigated the involvement of VIPR2 in the proliferation and migration of breast cancer cells. We showed that VIP-VIPR2 is a novel molecular mechanism that controls cell migration by activating phosphatidylinositol-3 kinaseγ (PI3Kγ), promoting the production of phosphatidylinositol 3,4,5-triphosphate, and then regulating the formation and extension of pseudopodia. VIP-VIPR2 also regulated cyclin D1 levels through the cAMP/PKA/extracellular signal-regulated kinase and PI3K/AKT/Akt-glycogen synthase kinase-3β signaling pathways, thereby controlling cell proliferation by regulating the G1/S transition in the cell cycle. Treatment with a selective VIPR2 antagonist peptide KS-133 suppressed VIP-induced cell proliferation and migration. These results suggest that VIPR2 is a novel target molecule associated with breast cancer and that KS-133 is a potential molecular targeted drug for breast cancer.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 3","pages":"163-166"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143984841","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.25052

Motohiro Nishida

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25020

Kenzo Hirose

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25022

Koh Nakayama, Takashi Nakagawa

引用次数: 0

[Preface]. [序言]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24099

Osamu Kaminuma, Keiko Yasumatsu

引用次数: 0