Biological & pharmaceutical bulletin最新文献_第3页

Evaluation of the Effect of Aldehyde Oxidase Inhibitors on 6-Mercaptopurine Metabolism. 醛氧化酶抑制剂对6-巯基嘌呤代谢影响的评价。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00083

Hinata Ueda, Katsuya Narumi, Ayako Furugen, Keisuke Okamoto, Yoshitaka Saito, Masaki Kobayashi

{"title":"Evaluation of the Effect of Aldehyde Oxidase Inhibitors on 6-Mercaptopurine Metabolism.","authors":"Hinata Ueda, Katsuya Narumi, Ayako Furugen, Keisuke Okamoto, Yoshitaka Saito, Masaki Kobayashi","doi":"10.1248/bpb.b25-00083","DOIUrl":"https://doi.org/10.1248/bpb.b25-00083","url":null,"abstract":"Thiopurines, such as 6-mercaptopurine (6-MP) and azathioprine, are converted to the inactive metabolites 6-thioxanthin (6-TX) and 6-thiouric acid (6-TUA). Molybdenum-containing oxidoreductases, aldehyde oxidase (AOX) and xanthine oxidase (XO), are involved in the oxidation of 6-MP to 6-TX; XO inhibitors affect the therapeutic efficacy of thiopurines and the incidence of adverse effects, such as liver and blood disorders. However, the role of AOX in the pharmacokinetics of 6-MP remains unclear. To clarify the clinical importance of AOX-mediated drug-drug interactions, we evaluated whether drugs that inhibit AOX affect 6-MP metabolism. The metabolism of 6-MP to 6-TX was strongly inhibited by AOX inhibitors (amitriptyline, chlorpromazine, clomipramine, clozapine, hydralazine, quetiapine, and raloxifene) in a reaction mixture containing human liver cytosol. The inhibition of 6-TX production rate by each AOX inhibitor was 60-70% at high concentrations, although the XO inhibitor febuxostat showed an inhibition rate of 10-30%. Furthermore, the combination of febuxostat and each AOX inhibitor showed greater inhibition than when each compound was added alone. The AOX inhibitor did not alter 6-MP oxidation by recombinant XO. These results suggest that AOX inhibition may affect the pharmacokinetics of thiopurines. However, because of the lower activity of AOX in rats than that in humans, the contribution of AOX could not be assessed using in vivo experiments. Further studies are needed to evaluate the contribution of AOX to the therapeutic and adverse effects of thiopurines, both in clinical studies and in animal models of liver humanization.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"713-720"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172430","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Antidepressant-Like Effects of Intracerebroventricular Injection of Nociceptin Analogs in Mice. 脑室注射痛觉肽类似物对小鼠的抗抑郁作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00832

Osamu Nakagawasai, Kohei Takahashi, Futa Kuroda, Akihiro Ambo, Mayu Abe, Wataru Nemoto, Koichi Tan-No

{"title":"Antidepressant-Like Effects of Intracerebroventricular Injection of Nociceptin Analogs in Mice.","authors":"Osamu Nakagawasai, Kohei Takahashi, Futa Kuroda, Akihiro Ambo, Mayu Abe, Wataru Nemoto, Koichi Tan-No","doi":"10.1248/bpb.b24-00832","DOIUrl":"https://doi.org/10.1248/bpb.b24-00832","url":null,"abstract":"Opioid receptors and their endogenous ligands are novel targets for the treatment of depression. The nociception (NOP) receptor is structurally similar to the opioid receptor, but NOP is known to have a low affinity for the opioid receptor subtypes μ, δ, and κ. In previous studies, we synthesized peptides with a high affinity for opioid receptors and investigated their antidepressant-like effects in mice. However, we have not yet examined whether NOP-related analogs have antidepressant-like effects. Herein, we synthesized NOP analogs (peptide-1-peptide-8) by solid-phase peptide synthesis using the 9-fluorenylmethyloxycarbony (Fmoc) method with Acetyl-Arg-Tyr-Tyr-Arg-Ile-Arg-NH2 (Ac-RYYRIR-NH2) as the lead compound. We examined the affinities and antagonistic activities of the analogs for the NOP receptor using receptor-binding and mouse vas deferens assays, and their effects on the duration of immobile behavior in a tail suspension test. Peptide-6 showed a high affinity and antagonistic activity for the NOP receptor. The intracerebroventricular administration of peptide-6 in mice shortened the duration of immobile behavior, whereas the co-administration of NOP inhibited this effect. Moreover, intracerebroventricular administration of the selective NOP receptor antagonist J-113397 showed antidepressant-like effects in mice. These data suggest that peptide-6 exerts an antidepressant-like effect via inactivation of the central NOP receptor in mice and may represent a lead compound for the development of antidepressant drugs in the future.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"682-686"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Irinotecan-Induced Site-Specific Pigmentation in the Plantar Region of Mice. 伊立替康诱导小鼠足底部位特异性色素沉着。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00662

Masashi Imai, Keiichi Hiramoto, Shota Tanaka, Mei Okayama, Kazuya Ooi

{"title":"Irinotecan-Induced Site-Specific Pigmentation in the Plantar Region of Mice.","authors":"Masashi Imai, Keiichi Hiramoto, Shota Tanaka, Mei Okayama, Kazuya Ooi","doi":"10.1248/bpb.b24-00662","DOIUrl":"10.1248/bpb.b24-00662","url":null,"abstract":"Skin pigmentation is a widely recognized side effect of cancer chemotherapy that can negatively affect patient QOL. However, although numerous case reports have documented pigmentation caused by anticancer drugs, the precise mechanisms remain unclear. Among such pigmentation, that induced by 5-fluorouracil (5-FU) has garnered considerable attention, whereas reports on irinotecan-induced pigmentation are comparatively limited. In this study, we investigated the pigmentation-related effects of irinotecan in colored hairless mice. Mice received intraperitoneal injections of 20 mg/kg irinotecan, and we subsequently examined the pigmentation of the plantar and buttock regions. The results indicated that irinotecan specifically induces pigmentation in the plantar region, with no pigmentation observed on the buttocks. In contrast, pigmentation was noted on the buttocks, although not in the plantar region, in the control mice treated with 5-FU and cytarabine. Furthermore, irinotecan treatment promoted a marked elevation in the expression of tyrosinase, cAMP response element binding protein (CREB), and microphthalmia-associated transcription factor (MITF) in the plantar region, whereas no significant changes were observed in the buttocks. These findings indicate that irinotecan leads to site-specific pigmentation in the sole of the foot, thereby highlighting the potential for anticancer drugs to cause localized pigmentation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"108-114"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Purification of Recombinant Monoclonal Antibodies from Transgenic Chicken Eggs and Removal of Egg-White Proteins. 转基因鸡蛋中重组单克隆抗体的纯化及蛋白的去除。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00078

Takehiro Mukae, Kyoko Yoshii, Isao Oishi

引用次数: 0

Development of Low-Density Lipoprotein Receptor-Targeted Liposomes for Enhanced Accumulation in Ischemia/Reperfusion Environment. 低密度脂蛋白受体靶向脂质体在缺血/再灌注环境中增强积累的研究进展。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00118

Shintaro Yoneda, Kentaro Kogure

{"title":"Development of Low-Density Lipoprotein Receptor-Targeted Liposomes for Enhanced Accumulation in Ischemia/Reperfusion Environment.","authors":"Shintaro Yoneda, Kentaro Kogure","doi":"10.1248/bpb.b25-00118","DOIUrl":"https://doi.org/10.1248/bpb.b25-00118","url":null,"abstract":"Cerebral ischemia/reperfusion (I/R) injury caused by resumed blood flow to an infarcted area contributes to poor patient prognosis due to a lack of treatment strategies. While the blood-brain barrier (BBB) is the greatest barrier for drug delivery to the brain, temporary disruption to the BBB after brain I/R injury allows for delivery of cerebroprotective drug-encapsulated nanoparticles into the brain parenchyma. However, issues remain with delivering drugs to the I/R region using nanoparticles, such as the limited therapeutic time window due to BBB repair over time. To overcome these challenges, we developed nanoparticles specifically targeting the I/R environment. Human umbilical vein endothelial cells (HUVECs) were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), an in vitro I/R model. Low-density lipoprotein receptor (LDLR) mRNA was upregulated early during the reoxygenation process. Furthermore, immunostaining of OGD/R-treated cells showed an increase in LDLR expression. Next, we constructed a peptide that mimics the LDLR binding recognition site on LDL, and modified liposomes to display the peptide on their surface. Peptide-modified liposomes showed targeting ability to the LDLR on cells. Accumulation of peptide-modified liposomes was significantly increased in OGD/R treated cells compared with controls, and was reduced by blocking LDLR using its antibody. These results demonstrate upregulation of LDLR and LDLR-mediated liposome uptake in OGD/R stressed cells. In conclusion, LDLR binding recognition site mimicking peptide-modified liposomes are a useful drug carrier that can recognize I/R injured endothelial cells.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 7","pages":"1008-1015"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144625354","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Anisotropic Mesenchymal Stem Cell Sheet Composed of Adipose-Tissue- and Umbilical-Cord-Derived Mesenchymal Stem Cells. 由脂肪组织和脐带来源的间充质干细胞组成的各向异性间充质干细胞片。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00364

Kenichi Nagase, Hasumi Kuramochi, Hironobu Takahashi

引用次数: 0

Development of Research Foundation for Comprehensive Articulation of Drug Effects. 药物效应综合表达研究基金的建立。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00509

Tadahaya Mizuno

{"title":"Development of Research Foundation for Comprehensive Articulation of Drug Effects.","authors":"Tadahaya Mizuno","doi":"10.1248/bpb.b24-00509","DOIUrl":"https://doi.org/10.1248/bpb.b24-00509","url":null,"abstract":"As unexpected adverse events and successful drug repositioning have shown, drug effects are complex and include aspects not recognized by developers. How can we understand these unrecognized drug effects? Drug effects can be numerized by encompassing biological responses to drugs. For instance, the transcriptome data of cultured cells and toxicopathological images of mice treated with a compound represent the effects of the compound in vitro and in vivo, respectively. As a next step, we focused on pattern recognition, a data science framework to extract essentially important low-dimensional latent variables from high-dimensional observed data such as latent variable models. Latent variables are low-dimensional, allowing us to visualize drug effects in an easily recognizable form, such as a radar chart. This bird's-eye view of drug effects enables us to compare them with existing knowledge, potentially articulating the effects of drugs as the known knowns and known unknowns. We believe that the three-step strategy of numerization, visualization, and articulation will allow us to understand drug effects comprehensively, and we are currently verifying this approach. In this review, we will introduce these candidate studies and hope to share our interest in \"pattern recognition of biological responses,\" the pillar of our group.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"1-5"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930619","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Stress Response Kinase MK2 Induces Non-canonical Activation of EphA2 in EML4-ALK Lung Cancer Cells. 应激反应激酶MK2诱导EML4-ALK肺癌细胞中EphA2的非规范激活

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00747

Fang Zhang, Yue Zhou, Naru Hamada, Akihiro Tanaka, Satoru Yokoyama, Seiji Yano, Kunio Matsumoto, Hiroyuki Mano, Hiroaki Sakurai

引用次数: 0

Vitamin D Receptor rs2228570 Gene Polymorphism Is Associated with Asthma Severity and Exacerbations. 维生素D受体rs2228570基因多态性与哮喘严重程度和恶化有关

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00684

Sekiko Uehara, Keita Hirai, Toshihiro Shirai, Hinako Otaki, Taisuke Akamatsu, Kunihiko Itoh

{"title":"Vitamin D Receptor rs2228570 Gene Polymorphism Is Associated with Asthma Severity and Exacerbations.","authors":"Sekiko Uehara, Keita Hirai, Toshihiro Shirai, Hinako Otaki, Taisuke Akamatsu, Kunihiko Itoh","doi":"10.1248/bpb.b24-00684","DOIUrl":"10.1248/bpb.b24-00684","url":null,"abstract":"Vitamin D plays a crucial role in immune system function. Several studies have indicated that genetic variations in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP, encoded by GC gene) increase the risk of developing asthma. However, the effect of these variations on the prognosis and clinical outcomes of asthma remains unclear. This study, involving 152 adult patients with asthma, aimed to assess the influence of VDR and GC polymorphisms on asthma severity and its exacerbation. Gene polymorphisms previously associated with asthma risk were analyzed, and VDR mRNA expression levels were evaluated in peripheral blood mononuclear cells. The AA genotype of the VDR rs2228570 polymorphism was associated with an elevated risk of severe asthma compared to the AG/GG genotype (odds ratio, 3.20; 95% confidence interval [CI], 1.24-8.28). Furthermore, patients with the rs2228570 AA genotype showed an elevated risk of exacerbation during the 1-year follow-up period (hazard ratio, 4.01; 95% CI, 1.75-9.15). VDR mRNA expression was significantly reduced in patients with the AA genotype. Furthermore, the mRNA expression levels of GLCCI1, HDAC2, NR3C1, and NFE2L2, which are associated with steroid response, were reduced in patients with the AA genotype. Our findings indicate that patients with the AA genotype of VDR rs2228570 are more likely to experience severe asthma and exacerbations. This polymorphism has the potential to reduce vitamin D efficacy by altering VDR function and expression, potentially resulting in increased inflammation and reduced steroid responsiveness in patients with asthma.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"86-92"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Comparison of Oncology Drug Lag in Japan and South Korea Based on the Interval between the U.S. Approval and the Local Approval. 基于美国批准与本土批准间隔的日韩肿瘤药物滞后性比较

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00555

Yoshifumi Tachibana, Jangsoo Yoon, Mamoru Narukawa

{"title":"Comparison of Oncology Drug Lag in Japan and South Korea Based on the Interval between the U.S. Approval and the Local Approval.","authors":"Yoshifumi Tachibana, Jangsoo Yoon, Mamoru Narukawa","doi":"10.1248/bpb.b24-00555","DOIUrl":"10.1248/bpb.b24-00555","url":null,"abstract":"Drug lag is a serious issue for patients with life-threatening diseases such as cancer. Japan and Korea have been facing a large drug lag, despite having a large market and a good clinical trial environment. We analyzed drug lags for anticancer drugs between these countries, using the information on 82 anticancer drugs approved in the United States between 2017 and 2022. The national health insurance coverage status was also investigated. The approval lag, defined as the number of days from the date of approval in the United States to the date of approval in the country of interest, was used as the indicator of drug lag and was calculated for each drug. The median for all drugs was estimated using the Kaplan-Meier method, with the lag for locally unapproved drugs treated as censored data. The median approval lag in Japan and Korea for all drugs, including locally unapproved drugs, were 1547 d (4.2 years) and 1000 d (2.7 years), respectively. The approval lags for the approved drugs were 216 and 655 d in Japan and Korea, respectively. All drugs approved in Japan were covered by national health insurance whereas many drugs recently approved in Korea were not yet covered. The overall drug lag in Japan was greater than that in Korea due to the high number of unapproved drugs in Japan. In Korea, more drugs have been approved; however, it generally takes longer for them to become widely available to the public.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"11-16"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0