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 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

In Vitro Anti-inflammatory Activity of Tyrosol and Tryptophol: Metabolites of Yeast via the Ehrlich Pathway. 酵母通过埃利希途径代谢产物酪氨酸和色氨酸的体外抗炎活性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00625

Toshio Niwa, Yoji Kato, Toshihiko Osawa

引用次数: 0

Impact of Bridged Nucleic Acid Positions within Blocking Oligonucleotides on DNA Amplification Inhibition in Wild-Type Blocking PCR. 阻断寡核苷酸桥接核酸位置对野生型阻断PCR中DNA扩增抑制的影响。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00113

Takuma Yamashita, Yoshinori Tsukumo, Takenori Yamamoto, Eriko Uchida, Tokuyuki Yoshida, Yasunori Uchida, Takao Inoue

{"title":"Impact of Bridged Nucleic Acid Positions within Blocking Oligonucleotides on DNA Amplification Inhibition in Wild-Type Blocking PCR.","authors":"Takuma Yamashita, Yoshinori Tsukumo, Takenori Yamamoto, Eriko Uchida, Tokuyuki Yoshida, Yasunori Uchida, Takao Inoue","doi":"10.1248/bpb.b25-00113","DOIUrl":"https://doi.org/10.1248/bpb.b25-00113","url":null,"abstract":"Detecting low-frequency genetic mutations is crucial for genetic testing, especially in cancer diagnostics. Wild-type blocking PCR identifies these genetic mutations using a blocking oligonucleotide that is fully complementary to wild-type DNA. The blocking oligonucleotide selectively binds to wild-type DNA, inhibiting its amplification by DNA polymerase and allowing preferential amplification of mutant DNA. Bridged nucleic acids (BNAs), with high binding affinities for cDNA, are often incorporated into the blocking oligonucleotide to enhance inhibition. However, the effects of BNA positioning within the blocking oligonucleotide on wild-type DNA amplification inhibition are poorly understood. To address this issue, we evaluated the effects of different BNA positions on amplification inhibition efficacy by comparing blocking oligonucleotides with varying numbers of BNAs at the 5' end, 3' end, and central region. Results indicated that BNAs at the 5' end enhanced the inhibition efficacy, whereas BNAs at the 3' end notably diminished the inhibition efficacy. Likewise, increasing the number of BNAs in the central region generally decreased the inhibition efficacy. This is one of the first studies to report the importance of BNA positioning in the amplification inhibition efficacy of blocking oligonucleotides.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"606-612"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144075712","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