Folia Pharmacologica Japonica最新文献_第5页

[Development of drug discovery support system using chemoinformatics and generative AI technology]. [利用化学信息学和生成式人工智能技术开发药物发现支持系统]。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24094

Atsushi Yoshimori

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

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24105

Takahiro Iwamoto, Takayuki Nemoto

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Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24107

Junichi Kurihara

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Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24101

Minoru Narita, Naoko Kuzumaki

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[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

[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.25020

Kenzo Hirose

引用次数: 0

[Myofibroblast differentiation induced by mechanical stimulation]. 机械刺激诱导的肌成纤维细胞分化。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.25016

Hiroki Mieno, Michio Nakaya

引用次数: 0

[Analysis of the therapeutic efficacy of bacterial infections through medical big data]. 【利用医疗大数据分析细菌感染的治疗效果】。

Folia Pharmacologica Japonica Pub Date : 2025-01-01 DOI: 10.1254/fpj.24086

Mitsuhiro Goda, Takahiro Niimura, Keisuke Ishizawa

{"title":"[Analysis of the therapeutic efficacy of bacterial infections through medical big data].","authors":"Mitsuhiro Goda, Takahiro Niimura, Keisuke Ishizawa","doi":"10.1254/fpj.24086","DOIUrl":"https://doi.org/10.1254/fpj.24086","url":null,"abstract":"In recent years, many studies have been conducted on various diseases to evaluate clinical efficacy reflecting actual clinical conditions through comprehensive analysis using medical big data, which include various patient groups and factors in clinical practice. On the other hand, there are still very few research reports in the world related to the treatment of infectious diseases using medical big data. This is due to the fact that much medical big data lacks information on the causative organisms of infectious diseases and on determining the effectiveness of infectious disease treatment. In this paper, we introduce a research case study in which analysis on the effectiveness of infectious disease treatment was conducted using medical big data. In this study, we performed a retrospective analysis of two real databases with the aim of validating the usefulness of cefmetazole and flomoxef in urinary tract infections (UTI) in which broad-spectrum β-lactamase (ESBL)-producing bacteria are the primary initiating organisms. Third-generation cephalosporin-resistant E. coli and K. pneumoniae, including ESBL-producing strains, were similarly susceptible to flomoxef and cefmetazole. JMDC Claims data analysis showed that the median time of hospital stay duration was significantly shorter in the flomoxef group than in the cefmetazole group. Flomoxef exhibits effectiveness that is comparable to cefmetazole in treating UTI. When using currently available medical big data to conduct analyses related to infectious disease treatment, valuable analysis results may be obtained by understanding the characteristics of the database and collaborating with clinicians who are familiar with infectious disease treatment.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"160 3","pages":"191-194"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970609","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