Biological & pharmaceutical bulletin最新文献_第10页

Structural Impact Assessment of Cytochrome P450 2A13 Polymorphisms Using Molecular Dynamics Simulations. 利用分子动力学模拟评估细胞色素 P450 2A13 多态性的结构影响。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00908

Koichi Kato, Tomoki Nakayoshi, Sho Hioki, Masahiro Hiratsuka, Yoshinobu Ishikawa, Eiji Kurimoto, Akifumi Oda

{"title":"Structural Impact Assessment of Cytochrome P450 2A13 Polymorphisms Using Molecular Dynamics Simulations.","authors":"Koichi Kato, Tomoki Nakayoshi, Sho Hioki, Masahiro Hiratsuka, Yoshinobu Ishikawa, Eiji Kurimoto, Akifumi Oda","doi":"10.1248/bpb.b23-00908","DOIUrl":"10.1248/bpb.b23-00908","url":null,"abstract":"One of the members of CYP, a monooxygenase, CYP2A13 is involved in the metabolism of nicotine, coumarin, and tobacco-specific nitrosamine. Genetic polymorphisms have been identified in CYP2A13, with reported loss or reduction in enzymatic activity in CYP2A13 allelic variants. This study aimed to unravel the mechanism underlying the diminished enzymatic activity of CYP2A13 variants by investigating their three-dimensional structures through molecular dynamics (MD) simulations. For each variant, MD simulations of 1000 ns were performed, and the obtained results were compared with those of the wild type. The findings indicated alterations in the interaction with heme in CYP2A13.4, .6, .8, and .9. In the case of CYP2A13.5, observable effects on the helix structure related to the interaction with the redox partner were identified. These conformational changes were sufficient to cause a decrease in enzyme activity in the variants. Our findings provide valuable insights into the molecular mechanisms associated with the diminished activity in the CYP2A13 polymorphisms.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 3","pages":"620-628"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140118687","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

Substrate-Dependent Alteration in the C- and O-Prenylation Specificities of Cannabis Prenyltransferase. 大麻异戊烯基转移酶 C-和 O-异戊烯基特异性的底物依赖性改变

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00868

Ryosuke Tanaya, Takeshi Kodama, Juthamart Maneenet, Yoko Yasuno, Atsushi Nakayama, Tetsuro Shinada, Hironobu Takahashi, Takuya Ito, Hiroyuki Morita, Suresh Awale, Futoshi Taura

{"title":"Substrate-Dependent Alteration in the C- and O-Prenylation Specificities of Cannabis Prenyltransferase.","authors":"Ryosuke Tanaya, Takeshi Kodama, Juthamart Maneenet, Yoko Yasuno, Atsushi Nakayama, Tetsuro Shinada, Hironobu Takahashi, Takuya Ito, Hiroyuki Morita, Suresh Awale, Futoshi Taura","doi":"10.1248/bpb.b23-00868","DOIUrl":"10.1248/bpb.b23-00868","url":null,"abstract":"CsPT4 is an aromatic prenyltransferase that synthesizes cannabigerolic acid (CBGA), the key intermediate of cannabinoid biosynthesis in Cannabis sativa, from olivetolic acid (OA) and geranyl diphosphate (GPP). CsPT4 has a catalytic potential to produce a variety of CBGA analogs via regioselective C-prenylation of aromatic substrates having resorcylic acid skeletons including bibenzyl 2,4-dihydroxy-6-phenylethylbenzoic acid (DPA). In this study, we further investigated the substrate specificity of CsPT4 using phlorocaprophenone (PCP) and 2',4',6'-trihydroxydihydrochalcone (THDC), the isomers of OA and DPA, respectively, and demonstrated that CsPT4 catalyzed both C-prenylation and O-prenylation reactions on PCP and THDC that share acylphloroglucinol substructures. Interestingly, the kinetic parameters of CsPT4 for these substrates differed depending on whether they underwent C-prenylation or O-prenylation, suggesting that this enzyme utilized different substrate-binding modes suitable for the respective reactions. Aromatic prenyltransferases that catalyze O-prenylation are rare in the plant kingdom, and CsPT4 was notable for altering the reaction specificity between C- and O-prenylations depending on the skeletons of aromatic substrates. We also demonstrated that enzymatically synthesized geranylated acylphloroglucinols had potent antiausterity activity against PANC-1 human pancreatic cancer cells, with 4'-O-geranyl THDC being the most effective. We suggest that CsPT4 is a valuable catalyst to generate biologically active C- and O-prenylated molecules that could be anticancer lead compounds.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 2","pages":"449-453"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139899289","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

Oridonin Suppresses Mast Cell Degranulation and Alleviates Ovalbumin-Induced Allergic Rhinitis. 奥利多宁能抑制肥大细胞脱颗粒并缓解卵清蛋白诱发的过敏性鼻炎

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00594

Sota Kidawara, Shizuki Kimura, Haruka Takano, Wakana Inoue, Kota Iinuma, Michihiro Takahama, Naoki Takemura, Tatsuya Saitoh

{"title":"Oridonin Suppresses Mast Cell Degranulation and Alleviates Ovalbumin-Induced Allergic Rhinitis.","authors":"Sota Kidawara, Shizuki Kimura, Haruka Takano, Wakana Inoue, Kota Iinuma, Michihiro Takahama, Naoki Takemura, Tatsuya Saitoh","doi":"10.1248/bpb.b24-00594","DOIUrl":"https://doi.org/10.1248/bpb.b24-00594","url":null,"abstract":"Incidence of type I allergies, such as hay fever, is continuously increasing in developed countries, including Japan. Type I allergies are triggered by chemical mediators, such as histamine, which are released via immunoglobulin E (IgE)-mediated mast cell degranulation. Therefore, medications inhibiting the synthesis, release, and receptor binding of these mediators are commonly used to manage type I allergy symptoms. As self-care disease prevention practices are gaining attention worldwide, regular consumption of food and supplements containing safe components inhibiting mast cell degranulation is a potential strategy to prevent allergic attacks. Here, we aimed to assess the ability of phytochemicals derived from edible plants to inhibit mast cell degranulation using the β-hexosaminidase release assay and investigate their cytotoxicity and efficiency in alleviating allergic symptoms. We found that oridonin, a diterpenoid isolated from Isodon japonicus Hara, strongly inhibited β-hexosaminidase release from both the RBL-2H3 rat cell line and mouse bone marrow-derived mast cells stimulated with dinitrophenyl (DNP)-conjugated human serum albumin after sensitization with DNP-IgE. Oridonin also inhibited β-hexosaminidase release induced by the calcium ionophore, A23187, in both cell types. Notably, oridonin did not adversely affect cell survival at concentrations necessary to inhibit β-hexosaminidase release. In a mouse model of ovalbumin (OVA)-induced allergic rhinitis, intraperitoneal administration of oridonin significantly reduced the nasal rubbing caused by intranasal OVA administration without affecting the serum levels of OVA-specific IgE. Therefore, oridonin could be an effective daily intake component to alleviate allergic diseases by inhibiting mast cell degranulation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 11","pages":"1920-1926"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142680646","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

Refining Hepatocyte Models to Capture the Impact of CYP2D6*10 Utilizing a PITCh System. 利用 PITCh 系统完善肝细胞模型以捕捉 CYP2D6*10 的影响

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00202

Ryosuke Negoro, Ayu Ouchi, Sayaka Deguchi, Kazuo Takayama, Takuya Fujita

{"title":"Refining Hepatocyte Models to Capture the Impact of CYP2D6*10 Utilizing a PITCh System.","authors":"Ryosuke Negoro, Ayu Ouchi, Sayaka Deguchi, Kazuo Takayama, Takuya Fujita","doi":"10.1248/bpb.b24-00202","DOIUrl":"https://doi.org/10.1248/bpb.b24-00202","url":null,"abstract":"CYP2D6 variants contain various single nucleotide polymorphisms as well as differing levels of metabolic activity. Among these, one of the less active variants CYP2D6*10 (100C > T) is the most prevalent mutation in East Asians, including Japanese. This mutation leads to an amino acid substitution from proline to serine, which reduces the stability of CYP2D6 and consequently decreases its metabolic activity. In this study, we used a genome editing technology called the Precise Integration into Target Chromosome (PITCh) system to stably express six drug-metabolizing enzymes (CYP3A4, POR, uridine diphosphate glucuronosyltransferase 1A1 (UGT1A1), CYP1A2, CYP2C19, CYP2C9, and CYP2D6*10) in HepG2 (CYP2D6*10 KI-HepG2) cells to examine the effect of CYP2D6*10 on drug metabolism prediction. The protein expression levels of CYP2D6 in CYP2D6*10 KI-HepG2 cells were reduced relative to those in the CYP3A4-POR-UGT1A1-CYP1A2-CYP2C19-CYP2C9-CYP2D6 knock-in-HepG2 (CYPs-UGT1A1 KI-HepG2) cells. Consistent with the CYP2D6 protein expression results, CYP2D6 metabolic activity in CYP2D6*10 KI-HepG2 cells was reduced relative to CYPs-UGT1A1 KI-HepG2 cells. We successfully generated CYP2D6*10 KI-HepG2 cells with highly expressed, functional CYP2D6*10, as well as CYP1A2, 2C9, 2C19 and 3A4. CYP2D6*10 KI-HepG2 cells could be an invaluable model for hepatic metabolism and hepatotoxicity studies in East Asians, including Japanese.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 8","pages":"1422-1428"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141900891","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

FXR Antagonist FLG249 Lowers Hepatic Triacylglycerol and Serum Cholesterol Level in High-Fat Diet-Induced Obese Mice. FXR拮抗剂FLG249可降低高脂饮食诱发肥胖小鼠的肝脏三酰甘油和血清胆固醇水平

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00311

Yusuke Iguchi, Yukiko Yamashita, Keigo Gohda, Keisuke Oda, Ko Fujimori, Yukihiro Sera, Tsuneo Imanaka, Masafumi Yamaguchi, Mizuho Une, Naoki Teno

引用次数: 0

Exploring IDI2-AS1, OIP5-AS1, and LITATS1: Changes in Long Non-coding RNAs Induced by the Poly I:C Stimulation. 探索 IDI2-AS1、OIP5-AS1 和 LITATS1：Poly I:C 刺激诱导的长非编码 RNA 的变化

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00037

Yuka Yagi, Rina Abe, Hidenori Tani

{"title":"Exploring IDI2-AS1, OIP5-AS1, and LITATS1: Changes in Long Non-coding RNAs Induced by the Poly I:C Stimulation.","authors":"Yuka Yagi, Rina Abe, Hidenori Tani","doi":"10.1248/bpb.b24-00037","DOIUrl":"10.1248/bpb.b24-00037","url":null,"abstract":"Long non-coding RNAs (lncRNAs) are sequences longer than 200 nucleotides, but they do not encode proteins. Nevertheless, they have significant roles in diverse biological functions. It remains unclear how viral infections trigger the expression of lncRNAs. In our previous research, we revealed a distinct type of lncRNAs with a lifespan under 4 h in human HeLa cells. These short-lived lncRNAs might be associated with numerous regulatory roles. Given their potential impact on human physiology, these short-lived lncRNAs could be key indicators to measure polyinosinic:polycytidylic acid (poly I:C) stimulation. In our recent work, we discovered three lncRNAs: IDI2-AS1, OIP5-AS1, and LITATS1. After exposure to poly I:C, imitating viral assault in human A549 cells, IDI2-AS1 levels dropped significantly while OIP5-AS1 and LITATS1 levels rose markedly. Our results indicate that short-lived lncRNAs respond to poly I:C stimulation, exhibiting substantial changes in expression. This indicates that the understanding the role of lncRNAs in the host response to viral infection and the potential for these molecules to serve as novel therapeutic targets.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 6","pages":"1144-1147"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309874","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

EphA4 Induces the Phosphorylation of an Intracellular Adaptor Protein Dab1 via Src Family Kinases. EphA4通过Src家族激酶诱导细胞内适配蛋白Dab1磷酸化

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b24-00273

Mitsuki Hara, Keisuke Ishii, Mitsuharu Hattori, Takao Kohno

{"title":"EphA4 Induces the Phosphorylation of an Intracellular Adaptor Protein Dab1 via Src Family Kinases.","authors":"Mitsuki Hara, Keisuke Ishii, Mitsuharu Hattori, Takao Kohno","doi":"10.1248/bpb.b24-00273","DOIUrl":"10.1248/bpb.b24-00273","url":null,"abstract":"Dab1 is an intracellular adaptor protein essential for brain formation during development. Tyrosine phosphorylation in Dab1 plays important roles in neuronal migration, dendrite development, and synapse formation by affecting several downstream pathways. Reelin is the best-known extracellular protein that induces Dab1 phosphorylation. However, whether other upstream molecule(s) contribute to Dab1 phosphorylation remains largely unknown. Here, we found that EphA4, a member of the Eph family of receptor-type tyrosine kinases, induced Dab1 phosphorylation when co-expressed in cultured cells. Tyrosine residues phosphorylated by EphA4 were the same as those phosphorylated by Reelin in neurons. The autophosphorylation of EphA4 was necessary for Dab1 phosphorylation. We also found that EphA4-induced Dab1 phosphorylation was mediated by the activation of the Src family tyrosine kinases. Interestingly, Dab1 phosphorylation was not observed when EphA4 was activated by ephrin-A5 in cultured cortical neurons, suggesting that Dab1 is localized in a different compartment in them. EphA4-induced Dab1 phosphorylation may occur under limited and/or pathological conditions in the brain.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 7","pages":"1314-1320"},"PeriodicalIF":1.7,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141632523","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

Research on the Development of Methods for Detection of Substandard and Falsified Medicines by Clarifying Their Pharmaceutical Characteristics Using Modern Technology. 利用现代技术通过阐明药品特征来开发假冒伪劣药品检测方法的研究。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00749

Naoko Yoshida

{"title":"Research on the Development of Methods for Detection of Substandard and Falsified Medicines by Clarifying Their Pharmaceutical Characteristics Using Modern Technology.","authors":"Naoko Yoshida","doi":"10.1248/bpb.b23-00749","DOIUrl":"10.1248/bpb.b23-00749","url":null,"abstract":"The existence of substandard and falsified medicines threatens people's health and causes economic losses as well as a loss of trust in medicines. As the distribution of pharmaceuticals becomes more globalized and the spread of substandard and falsified medicines continues worldwide, pharmaceutical security measures must be strengthened. To eradicate substandard and falsified medicines, our group is conducting fact-finding investigations of medicines distributed in lower middle-income countries (LMICs) and on the Internet. From the perspective of pharmaceutics, such as physical assessment of medicines, we are working to clarify the actual situation and develop methods to detect substandard and falsified medicines. We have collected substandard and falsified medicines distributed in LMICs and on the Internet and performed pharmacopoeial tests, mainly using HPLC, which is a basic analytic method. In addition to quality evaluation, we have evaluated the applicability of various analytic methods, including observation of pharmaceuticals using an electron microscope, Raman scattering analysis, near-IR spectroscopic analysis, chemical imaging, and X-ray computed tomography (CT) to detect substandard and falsified medicines, and we have clarified their limitations. We also developed a small-scale quality screening method using statistical techniques. We are engaged in the development of methods to monitor the distribution of illegal medicines and evolve research in forensic and policy science. These efforts will contribute to the eradication of substandard and falsified medicines. Herein, I describe our experience in the development of detection methods and elucidation of the pharmaceutical status of substandard and falsified medicines using novel technologies.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 5","pages":"878-885"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140849286","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

Phosphatidylcholine-Plasmalogen-Oleic Acid Reduces BACE1 Expression in Human SH-SY5Y Cells. 磷脂酰胆碱-质原油酸可降低人 SH-SY5Y 细胞中 BACE1 的表达。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00787

Haruka Okabayashi, Miki Yasuda, Chinatsu Nii, Ryo Sugishita, Keijo Fukushima, Kouki Yuasa, Satoshi Kotoura, Hiromichi Fujino

引用次数: 0

Wild-Type DCTN1 Suppresses the Aggregation of DCTN1 Mutants Associated with Perry Disease. 野生型 DCTN1 可抑制与佩里病有关的 DCTN1 突变体的聚集。

IF 2 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-01-01 DOI: 10.1248/bpb.b23-00828

Yuto Fukui, Hisashi Shirakawa, Shuji Kaneko, Kazuki Nagayasu

{"title":"Wild-Type DCTN1 Suppresses the Aggregation of DCTN1 Mutants Associated with Perry Disease.","authors":"Yuto Fukui, Hisashi Shirakawa, Shuji Kaneko, Kazuki Nagayasu","doi":"10.1248/bpb.b23-00828","DOIUrl":"10.1248/bpb.b23-00828","url":null,"abstract":"Perry disease, a rare autosomal dominant neurodegenerative disorder, is characterized by parkinsonism, depression or apathy, unexpected weight loss, and central hypoventilation. Genetic analyses have revealed a strong association between point mutations in the dynactin I gene (DCTN1) coding p150glued and Perry disease. Although previous reports have suggested a critical role of p150glued aggregation in Perry disease pathology, whether and how p150glued mutations affect protein aggregation is not fully understood. In this study, we comprehensively investigated the intracellular distribution of the p150glued mutants in HEK293T cells. We further assessed the effect of co-overexpression of the wild-type p150glued protein with mutants on the formation of mutant aggregates. Notably, overexpression of p150glued mutants identified in healthy controls, which is also associated with amyotrophic lateral sclerosis, showed a thread-like cytoplasmic distribution, similar to the wild-type p150glued. In contrast, p150glued mutants in Perry disease and motor neuron disease caused aggregation. In addition, the co-overexpression of the wild-type protein with p150glued mutants in Perry disease suppressed aggregate formation. In contrast, the p150glued aggregation of motor neuron disease mutants was less affected by the wild-type p150glued. Further investigation of the mechanism of aggregate formation, contents of the aggregates, and biological mechanisms of Perry disease could help develop novel therapeutics.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"47 1","pages":"253-258"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139545352","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