Folia Pharmacologica Japonica最新文献_第8页

[Prediction of the drug intestinal absorption and drug-induced intestinal toxicity with the use of cultured human/animal crypt-derived intestinal stem cells]. [利用培养的人类/动物隐窝衍生肠干细胞预测药物的肠道吸收和药物引起的肠道毒性]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23097

Kazuya Maeda

{"title":"[Prediction of the drug intestinal absorption and drug-induced intestinal toxicity with the use of cultured human/animal crypt-derived intestinal stem cells].","authors":"Kazuya Maeda","doi":"10.1254/fpj.23097","DOIUrl":"https://doi.org/10.1254/fpj.23097","url":null,"abstract":"Prediction of intestinal drug absorption and drug-induced intestinal toxicity is critical for the development of orally-administered drugs. However, it is difficult to accurately predict these events because of large species differences and a lack of appropriate in vitro assay. Then, we proposed the use of human crypt-derived intestinal cells for the prediction of intestinal absorption and the risk of intestinal toxicity. 3D human intestinal spheroids were established from fresh surgical specimens of proximal jejunum and terminal ileum using the conditioned media containing Wnt3a, R-spondin 3, and noggin. To generate 2D monolayer, spheroids were enzymatically dissociated into single cells and plated onto Matrigel-precoated culture plates/inserts. We have confirmed the activities of typical drug-metabolizing enzymes and uptake/efflux transporters in human jejunal spheroid-derived differentiated cells. Intestinal availability (Fg) estimated from the apical-to-basal permeation clearance across the jejunal monolayer showed a good correlation with in vivo human Fg values for five CYP3A substrate drugs. As for the prediction of intestinal toxicity, we found that the degree of ATP decreases in intestinal spheroids incubated with different EGFR-TKIs varied greatly depending on the drugs and the rank order of the extent of ATP decrease corresponded with that of frequency of clinically-observed diarrhea. We also constructed enterochromaffin (EC) cell-rich spheroids and quantified serotonin release from EC cells upon exposure to drugs for the prediction of drug-induced nausea and vomiting. As a result, we found that the serotonin release was related to the high/low risk of nausea and vomiting of each ALK/ROS1 kinase inhibitors.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 5","pages":"295-299"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105893","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

[Multiplexed epigenetic analysis at single-cell resolution]. [单细胞分辨率的多重表观遗传分析]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24027

Kazuki Nagayasu

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24015

Akemichi Baba

引用次数: 0

[Cardiotoxicity risk assessment of anti-cancer drugs and future perspectives]. [抗癌药物的心脏毒性风险评估及未来展望]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23094

Shota Yanagida, Hiroyuki Kawagishi, Yasunari Kanda

{"title":"[Cardiotoxicity risk assessment of anti-cancer drugs and future perspectives].","authors":"Shota Yanagida, Hiroyuki Kawagishi, Yasunari Kanda","doi":"10.1254/fpj.23094","DOIUrl":"10.1254/fpj.23094","url":null,"abstract":"Cardiotoxicity is a serious adverse effect of anti-cancer drugs. Anti-cancer drug-induced cardiotoxicity are arrhythmia, cardiac contractile dysfunction, coronary artery disease, and hypertension, which affect to the quality of life in patients with cancer. In particular, cardiac contractile dysfunction is a life-threatening symptom leading to heart failure, suggesting that it is very important to predict the risk of developing the contractile dysfunction by anti-cancer drugs. Recently, human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) can be used to assess the risk of drug-induced arrhythmias. This prompts us to evaluate other cardiotoxic effects such as contractility dysfunction and structural toxicity with hiPSC-CMs. Since anti-cancer drug-induced contractility dysfunction are considered to be induced by chronic exposure, we have developed a method to assess chronic contractility dysfunction by imaging analysis of hiPSC-CMs. BMS-986094, which failed in clinical trials due to the occurrence of heart failure, was used as a positive compound. We found that chronic exposure to BMS-986094 decreased the contraction and relaxation velocity in hiPSC-CMs. Doxorubicin was observed to decrease cytotoxicity and both contraction and relaxation velocities in hiPSC-CMs. We are currently further evaluating other anti-cancer drugs with different mode-of-actions using hiPSC-CMs and assess the predictivity and utility of contractile assessment using hiPSC-CMs by comparing with real-world data. Here, we introduce our novel method to assess the chronic contractility of hiPSC-CMs by imaging analysis and discuss the future perspectives for assessing the anti-cancer drug-induced cardiotoxicity.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 2","pages":"83-89"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021324","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

[Preface]. [序言]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23031

Naoyuki Matsuda, Yuichi Hattori

引用次数: 0

[Integration of basic and clinical researches to develop the biomarker of ‍depression]. [整合基础与临床研究，开发抑郁症生物标志物]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23029

Shigeo Miyata

引用次数: 0

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24059

Hiroki Ueda

引用次数: 0

[Cefiderocol: a first and novel class of siderophore cephalosporin for Carbapenem-resistant Gram-negative infection]. [Cefiderocol：治疗耐碳青霉烯革兰阴性菌感染的第一类新型嗜苷头孢菌素]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24029

Yoshinori Yamano, Ippei Morita, Mari Ariyasu

{"title":"[Cefiderocol: a first and novel class of siderophore cephalosporin for Carbapenem-resistant Gram-negative infection].","authors":"Yoshinori Yamano, Ippei Morita, Mari Ariyasu","doi":"10.1254/fpj.24029","DOIUrl":"10.1254/fpj.24029","url":null,"abstract":"Antimicrobial resistance is currently recognized as an urgent concern against public health in worldwide. Carbapenem-resistant (CR) Gram-negative bacteria, such as Enterobacterales, Pseudomonas aeruginosa and Acinetobacter baumannii are listed as critical pathogens which are widely spread and can cause severe and often deadly infections in WHO guidance. Cefiderocol (Fetroja®), a novel and first siderophore cephalosporin, was approved for the infections caused by these problematic CR Gram-negative bacteria in Japan on November 30, 2023. Cefiderocol has unique mechanisms to be incorporated into bacterial cells using bacterial iron transportation system and to be highly stable against most β-lactamases, which lead to promising antibacterial activity against these Gram-negative bacteria including CR strains in vitro. In CREDIBLE-CR Ph3 trial, cefiderocol showed the good efficacy and safety for patients with CR Gram-negative bacteria. In APEKS-cUTI and APEKS-NP trials, cefiderocol showed non-inferiority and suggested superiority to imipenem/cilastatin in complicated urinary tract infection (cUTI) patients, and non-inferiority to high dose of meropemen in pneumonia patients, respectively. Cefiderocol is expected to be an optimal treatment for CR Gram-negative infections with limited treatment options and would be an important drug to combat the threat of CR bacteria.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 5","pages":"331-340"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105887","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

[Development of early prediction and discriminating techniques for Lewy body diseases]. [路易体疾病早期预测和鉴别技术的开发]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23065

Ichiro Kawahata, Atsushi Takeda, Kohji Fukunaga

{"title":"[Development of early prediction and discriminating techniques for Lewy body diseases].","authors":"Ichiro Kawahata, Atsushi Takeda, Kohji Fukunaga","doi":"10.1254/fpj.23065","DOIUrl":"10.1254/fpj.23065","url":null,"abstract":"The advent of a super-aged society poses urgent challenges in overcoming age-related neurological disorders and extending a healthy lifespan. Neurodegenerative diseases such as Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease are characterized by the accumulation of pathogenic proteins in the brain, leading to the formation of intracellular aggregates known as pathological hallmarks. In the early stages of protein accumulation, before the onset of clinical symptoms such as cognitive impairment or motor dysfunction, brain inflammation begins to occur. Subsequently, neuronal death progresses, and clinical symptoms manifest as dementia or Parkinson's disease. Therefore, there is a need for early prediction of neurodegeneration and the development of disease-modifying drugs for pre-symptomatic prevention. To address this issue, we have focused on enhancing the degradation of amyloid-β protein by targeting Ca2+/calmodulin-dependent kinase II (CaMKII)/proteasome system and on suppressing the propagation and uptake mechanisms of α-synuclein by targeting fatty acid-binding proteins (FABPs) coupled with the long isoform of dopamine D2 (D2L) receptor. Additionally, our analysis of FABP knockout mice has revealed an increased expression of FABPs in the neurodegenerative process, suggesting their involvement in mitochondrial dysfunction and neuronal death. Based on these findings, this article highlights the physiological significance of FABP family proteins in neurodegeneration and discusses the analysis of plasma biomarkers for predicting neurodegenerative disorders and the discriminatory methods for distinguishing between Alzheimer's disease, dementia with Lewy bodies, and Parkinson's disease. Furthermore, we explore the potential of ultra-early prediction of neurodegenerative disorders.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 1","pages":"2-5"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086523","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

[Development of fluorescent imaging sensors based on proteins]. [基于蛋白质的荧光成像传感器的开发]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23036

Saaya Hario, Shiori Takeuchi, Robert E Campbell, Takuya Terai

引用次数: 0