Folia Pharmacologica Japonica最新文献_第10页

[Drug developmental strategies based on functional analysis of pain-regulating molecules in astrocytes under chronic pain]. [基于慢性疼痛下星形胶质细胞疼痛调节分子功能分析的药物开发策略]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24038

Norimitsu Morioka

{"title":"[Drug developmental strategies based on functional analysis of pain-regulating molecules in astrocytes under chronic pain].","authors":"Norimitsu Morioka","doi":"10.1254/fpj.24038","DOIUrl":"https://doi.org/10.1254/fpj.24038","url":null,"abstract":"Spinal cord astrocytes are activated in chronic pain models, especially under conditions of prolonged pain. Hence, targeting spinal cord astrocytes for the development of useful analgesics has attracted much attention. In the CNS, connexin43 (Cx43), a membrane protein expressed and functioning exclusively in astrocytes, is well known to be involved in intercellular signaling as a component of gap junction, but also interacts with intracellular molecules via its characteristically long C-terminal region, thereby affecting cellular function. Previously, we found that Cx43 expression was markedly reduced in spinal dorsal horn astrocytes from a mouse model of neuropathic pain. In order to investigate the relationship between reduced Cx43 expression in spinal astrocytes and the onset of pain, we showed that reduced Cx43 expression altered the expression of pain-related molecules such as the glutamate transporter GLT-1 and the pro-inflammatory cytokine interleukin-6 (IL-6). In particular, we focused on the regulation of IL-6 expression by reduced Cx43 expression in both in vivo and in vitro analyses, and found that IL-6 expression is increased through the Akt- glycogen synthase kinase-3β (GSK-3β) signaling system driven by reduced Cx43 expression during neuropathic pain, which in turn triggers pain. These findings suggest that astrocyte Cx43 is involved in pain prolongation by regulating gene expression of nociceptive factors through interactions with intracellular signaling molecules, which is different from its previously known function, and thus raises expectations for its potential as a new drug target for chronic pain.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 6","pages":"363-366"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575608","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

[Effects of JAL-TA9 on cognitive deficits in Alzheimer's disease model mouse]. [JAL-TA9对阿尔茨海默病模型小鼠认知障碍的影响］

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24076

Suo Zou

{"title":"[Effects of JAL-TA9 on cognitive deficits in Alzheimer's disease model mouse].","authors":"Suo Zou","doi":"10.1254/fpj.24076","DOIUrl":"https://doi.org/10.1254/fpj.24076","url":null,"abstract":"Many studies have been conducted to find an effective drug for Alzheimer's disease (AD) treatment. However, no effective drug applicable for clinical use has been developed. Recently, the FDA approved Lecanemab, an antibody drug that acts as an aggregation inhibitor against Amyloid-beta (Aβ), for AD treatment. However, there are still no fundamental drugs for AD. In this study, we present a strategy for AD treatment that removes Aβ by cleavage reaction using one of the Catalytides, JAL-TA9 (YKGSGFRMI). A single dose of JAL-TA9 administered into the CA1 region of the hippocampus and the intraventricular space improved the deficits in short-term memory of APP-knock-in mice. It also improved the memory of Aβ25-35-induced model mice, as evaluated by the Y-maze and objective recognition tests. These data strongly suggest that JAL-TA9 could be effective in treating AD. However, these administration methods are difficult to apply clinically due to their high invasiveness. Thus, we tested the improvement effects of dementia by administering JAL-TA9 nasally. It is very interesting and exciting that the dementia of Aβ25-35 induced AD model mice was improved by four applications once every three days. These results strongly suggest that JAL-TA9 is the best candidate for AD treatment because it is effective even in the late stage of AD.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 6","pages":"391-395"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575609","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

[Creating a place for open innovation among diverse players - a perspective from practitioners at a science park]. [为不同参与者之间的开放式创新创造场所--来自科学园从业者的视角]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.24001

Haruka Hibino, Keiko Ishigami

引用次数: 0

[Pharmacogenetic testing for prevention of severe cutaneous adverse drug reactions]. [预防严重皮肤药物不良反应的药物基因检测]。

Folia Pharmacologica Japonica Pub Date : 2024-01-01 DOI: 10.1254/fpj.23092

Taisei Mushiroda

{"title":"[Pharmacogenetic testing for prevention of severe cutaneous adverse drug reactions].","authors":"Taisei Mushiroda","doi":"10.1254/fpj.23092","DOIUrl":"10.1254/fpj.23092","url":null,"abstract":"Pharmacogenetic testing benefits patients by predicting drug efficacy and risk of adverse drug reactions (ADRs). Pharmacogenetic biomarkers useful in clinical practice include drug-metabolizing enzyme and drug transporter genes and human leukocyte antigen (HLA) genes. HLA genes, which are important molecules involved in human immunity, have long been analyzed for associations with ADRs, such as skin rash, drug-induced liver injury, and agranulocytosis. HLA is composed of many genes, each of which has dozens of different types (alleles), and many HLA alleles associated with ADRs have been reported. The odds ratios in the association of HLA alleles range from approximately 5 to several thousand, indicating a very large impact on the risk of ADRs. Thus, HLA genetic testing prior to initiation of drug therapy is expected to make a significant contribution to avoiding ADRs, but to demonstrate the clinical utility, it is necessary to prospectively show the effects of medical interventions based on the test results. We conducted the GENCAT study, a prospective, multicenter, single-arm clinical trial to investigate the impact of a therapeutic intervention based on the HLA-A*31:01 test on the incidence of carbamazepine-induced skin rash. HLA-A*31:01-positive patients were treated with an alternative drug such as valproic acid, and the study showed an approximately 60% reduction in the incidence of carbamazepine-induced skin rash. It is expected that the genetic test, which has demonstrated clinical utility, will lead to the establishment of safer and more appropriate stratified medicine by reflecting the information in clinical practice guidelines.","PeriodicalId":12208,"journal":{"name":"Folia Pharmacologica Japonica","volume":"159 2","pages":"90-95"},"PeriodicalIF":0.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140021330","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 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