Folia Pharmacologica Japonica最新文献_第9页

[A new treatment option for complex perianal fistulas in Crohn's disease patients; development of darvadstrocel (allogeneic expanded adipose-derived mesenchymal stem cells) in Japan]. [克罗恩病患者复杂肛周瘘的新治疗方案；darvadstrocel（异体扩增脂肪间充质干细胞）在日本的发展]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23046

Takayoshi Yamaguchi

{"title":"[A new treatment option for complex perianal fistulas in Crohn's disease patients; development of darvadstrocel (allogeneic expanded adipose-derived mesenchymal stem cells) in Japan].","authors":"Takayoshi Yamaguchi","doi":"10.1254/fpj.23046","DOIUrl":"https://doi.org/10.1254/fpj.23046","url":null,"abstract":"Crohn's disease (CD) is a chronic and relapsing inflammatory bowel disease affecting the entire gastrointestinal tract. The prevalence of CD among Japanese people is increasing. One of the most frequent complications of CD is perianal fistulas. People living with CD may experience complex perianal fistulas, which can cause intense pain, bleeding, swelling, infection, and anal discharge. Despite medical and surgical advancements, complex perianal fistulas in CD remain challenging for clinicians to treat. CD patients living with perianal fistulas reported a negative impact on many aspects of their quality of life. Darvadstrocel is a cell therapy product containing a suspension of allogeneic expanded adipose-derived mesenchymal stem cells. It has been approved in Europe and Japan for the treatment of complex perianal fistulas that have shown an inadequate response to at least one conventional or biologic therapy in adult patients with non-active/mildly active luminal CD. By exhibiting immunomodulatory and local anti-inflammatory effects at the site of inflammation, it offers a new treatment option for complex perianal fistulas in CD patients. In this manuscript, the characteristic of darvadstrocel, the summary of results from the pivotal phase 3 studies in Europe and Japan, and the development strategy in Japan were introduced.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 3","pages":"150-155"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140860431","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

[Enhancement of mast cells activation by ATP via P2X4 receptor]. [ATP 通过 P2X4 受体增强肥大细胞的活化]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23083

Kazuki Yoshida, Masa-Aki Ito, Isao Matsuoka

{"title":"[Enhancement of mast cells activation by ATP via P2X4 receptor].","authors":"Kazuki Yoshida, Masa-Aki Ito, Isao Matsuoka","doi":"10.1254/fpj.23083","DOIUrl":"10.1254/fpj.23083","url":null,"abstract":"Adenosine-5'-triphosphate (ATP) is an important intracellular energy currency, but it is released extracellularly in response to various stimuli and acts as an intercellular signaling molecule by stimulating various P2 receptors. ATP and ADP are stored in synaptic vesicles and secretory granules, and are released extracellularly upon stimulation, playing important roles in neurotransmission and platelet aggregation. Furthermore, considerable amount of ATP is released by mechanical stimuli such as skin scraping or by cell damage, which in turn activates immune cells to promote inflammatory responses. Mast cells (MCs) are derived from hematopoietic stem cells and play a central role in type I allergic reactions. MCs are activated by IgE-mediated antigen recognition, leading to type I allergic reactions. MCs express P2X7 receptors that are activated by high concentrations of ATP (>0.5 ‍mM), and reported to aggravate inflammatory bowel disease and dermatitis. In contrast, role of MC P2 receptors that respond to lower concentrations of ATP remains to be investigated. We investigated in detail the effects of ATP in mouse bone marrow-derived MCs, and found that lower concentrations of ATP (<100 ‍μM) promotes IgE-dependent and GPCR-mediated degranulation via the ionotropic P2X4 receptor. In mouse allergic models, P2X4 receptor signal promote MC-mediated allergic responses through comprehensively increasing the sensitivity of MCs to different stimuli. Since ATP is known to be released from various cells upon mechanical stimuli such as cell damage or scratching, inhibition of P2X4 receptor signaling may represent a novel strategy to abrogate allergic reaction.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 1","pages":"39-43"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139086526","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 development of innovative therapeutic drugs targeting hypoxia responses]. [开发针对缺氧反应的创新治疗药物]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23090

Kiyotsugu Yoshikawa, Hiroki Hagimoto, Eijiro Nakamura

引用次数: 0

[Nav1.7 as a target for the first disease-modifying drugs for osteoarthritis]. [Nav1.7作为治疗骨关节炎的首批改变疾病药物的靶点]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24010

Yoshiaki Suzuki

引用次数: 0

[Recent advances in capillary electrophoresis-mass spectrometry analysis of ‍trace biomolecules]. [毛细管电泳-质谱分析‍痕量生物大分子的最新进展]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24036

Takayuki Kawai

{"title":"[Recent advances in capillary electrophoresis-mass spectrometry analysis of ‍trace biomolecules].","authors":"Takayuki Kawai","doi":"10.1254/fpj.24036","DOIUrl":"https://doi.org/10.1254/fpj.24036","url":null,"abstract":"In recent years, various trace bioanalysis methods have been developed, including single-cell transcriptome analysis methods. As the sample volume and amount of biomolecules contained therein are extremely limited, development of new single-cell analysis methods require extremely high-level techniques. It is necessary to design an appropriate analysis system that integrates a highly sensitive detection system and a pretreatment protocol for minimizing sample loss, where separation method is especially important for analyzing diverse mixtures of biomolecules. Among them, capillary electrophoresis (CE) can separate biomolecules in nanoliter-scale solutions with high resolution, making it highly compatible with trace samples such as single cells. By combining with highly sensitive nano-electrospray ionization-mass spectrometry (MS), it is possible to detect nanomolar to sub-nanomolar biomolecules, which can be further improved by using online sample preconcentration methods. These highly sensitive analytical techniques have made it possible to analyze trace amounts of metabolites, proteins, lipids, etc. This review paper summarizes the research on CE-MS trace bioanalysis that has been reported to date, with a focus on single-cell analysis.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 5","pages":"321-326"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105896","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 mechanisms of diseases and global approaches]. [疾病的机制和全球方法]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24033

Shihori Tanabe, Tae-Young Kim, Rosalía Rodríguez-Rodríguez, Chang-Beom Park

引用次数: 0

[The discovery of JAL-TA9 which cleaves amyloid-β with proteolytic activity]. [发现具有蛋白分解活性的 JAL-TA9]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24074

Rina Nakamura

{"title":"[The discovery of JAL-TA9 which cleaves amyloid-β with proteolytic activity].","authors":"Rina Nakamura","doi":"10.1254/fpj.24074","DOIUrl":"https://doi.org/10.1254/fpj.24074","url":null,"abstract":"Amyloid-β (Aβ) 42, one of the causes of Alzheimer's disease (AD), is produced by the cleavage of amyloid precursor protein (APP) by β- or γ-secretases. Since Aβ42 oligomers exhibit strong neurotoxicity, Aβ42 is predicted to be a potentially efficient target for drug therapies. Recently, we screened peptides that activate MMP7 using our peptide library and found that the synthetic peptide JAL-TA9 (YKGSGFRMI), which is derived from the BoxA region of Tob1 protein, showed proteolytic activity. It is generally accepted that an enzyme should be a large molecular protein consisting of more than thousands of amino acids. Thus, this is the first finding that a small synthetic peptide has protease activity, and we termed Catalytide as the general name of peptides with protease activity. In this study, we demonstrate the cleavage activity of JAL-TA9 not only against the authentic soluble form of Aβ42 but also against the solid type of Aβ42 in the central region. In addition, we demonstrated the cleavage activity using brain slices of AD patients. JAL-TA9 decreased the amount of accumulated Aβ42 in the brain of Alzheimer's patients. Taken together, JAL-TA9 is an attractive seed for the development of peptide drugs with a new strategy for Alzheimer's disease.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 6","pages":"386-390"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575628","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 characteristics and clinical study results of ensitrelvir fumaric acid (XOCOVA^® Tablets 125 ‍mg)]. [富马酸依西曲韦（XOCOVA® 125 ‍mg 片剂）的药理特性和临床研究结果]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24017

Yuko Tsuge, Yasuko Ariwa, Kentarou Shibata

{"title":"[Pharmacological characteristics and clinical study results of ensitrelvir fumaric acid (XOCOVA® Tablets 125 ‍mg)].","authors":"Yuko Tsuge, Yasuko Ariwa, Kentarou Shibata","doi":"10.1254/fpj.24017","DOIUrl":"10.1254/fpj.24017","url":null,"abstract":"Ensitrelvir fumaric acid (Xocova® hereafter ensitrelvir) is a novel anti-SARS-CoV-2 drug for COVID-19. Hokkaido University and Shionogi & Co., Ltd. engaged in joint research targeting SARS-CoV-2 3C-like (3CL) protease at an early stage and started clinical trials in July 2021. In February 2022, an application was filed for manufacture and sales approval for the indication of \"SARS-CoV-2 infection,\". Ensitrelvir recieved the first emergency regulatory approval from the Ministry of Health, Labour and Welfare (MHLW) in Japan in November 2022, and has obtained standard approval in March 2024. This emergency approval was based on the confirmed safety in a Phase 2/3 study (T1221) conducted in Japan and other Asian countries (Korea and Vietnam) in patients with mild/moderate COVID-19 and the presumed efficacy in Phase 3 Part (SCORPIO-SR), and the standard approval is based on efficacy from the Phase 3 part. In the Phase 3 part, ensitrelvir administered orally 375/125 ‍mg once daily for five days, in patients with irrespective of risk factors for severe complications and vaccination status, demonstrating a significant reduction vs placebo in the time to resolution of five typical Omicron-related symptoms (stuffy or runny nose, sore throat, cough, feeling hot or feverish, and low energy or tiredness), and also showed a significant reduction in viral RNA on day 4 relative to placebo (P < 0.001). In the Phase 2/3 study, there were no serious adverse events or deaths, indicating good tolerability and safety. We hope that ensitrelvir will contribute as a new treatment option for patients suffering from COVID-19 symptoms.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 4","pages":"264-281"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467233","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.24016

Hisaharu Yamada, Kohei Kikkawa

引用次数: 0

[Underlying mechanisms for psychotropic effects of delta opioid receptor agonists]. [δ类阿片受体激动剂精神作用的基本机制]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24011

Toshinori Yoshioka, Akiyoshi Saitoh

{"title":"[Underlying mechanisms for psychotropic effects of delta opioid receptor agonists].","authors":"Toshinori Yoshioka, Akiyoshi Saitoh","doi":"10.1254/fpj.24011","DOIUrl":"https://doi.org/10.1254/fpj.24011","url":null,"abstract":"Growing evidence has indicated that delta opioid receptor (DOP) agonists are potential psychotropic drugs such as for depression, anxiety, and PTSD. In rodent studies, we have also demonstrated that DOP agonists exhibit potent anxiolytic-like effects via the inhibition of the excitatory neuronal activity which projects to the amygdala from the prelimbic prefrontal cortex and facilitate extinction learning of contextual fear memory through PI3K-Akt signaling pathway in the infralimbic prefrontal cortex and MEK-ERK signaling pathway in the amygdala. In this article, we introduce the functional mechanisms underlying antidepressant-like effects and anti-stress effects of DOP agonists. Then, we employed a valid animal model of depression, chronic vicarious social defeat stress (cVSDS) mice, and investigated that the influence of DOP activation on pathopsychological factors in depression such as the adult hippocampal neurogenesis, hypothalamic-pituitary-adrenal (HPA) axis, and neuroinflammation. First, repeated administrations after the stress period to cVSDS mice with a selective DOP agonist, KNT-127, improved social interaction behaviors and reduced hyperactivation of the HPA axis without affecting hippocampal neurogenesis. Meanwhile, repeated KNT-127 administrations during the cVSDS period prevented the exacerbation of social interaction behaviors, dysregulation of the HPA axis, and excessive new-born neuronal cell death in the hippocampal dentate gyrus. Moreover, in both administration paradigms, KNT-127 suppressed microglial overactivation in the dentate gyrus of cVSDS mice. These results indicate that the underlying mechanism of DOP-induced antidepressant-like effects differ from those of conventional monoaminergic antidepressants. Furthermore, we propose that DOP agonists might have prophylactic effects as well as therapeutic effects on pathophysiological changes in depression.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 4","pages":"225-228"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141467238","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