Biological & pharmaceutical bulletin最新文献

Evaluation of Readthrough Efficiency of Negamycin Derivatives against Nonsense Mutations in Muscular Dystrophy Genes. 负霉素衍生物对肌营养不良基因无义突变的读透效率评价。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00728

Noriko Omura, Akihiro Taguchi, Keisuke Hamada, Sho Konno, Atsuhiko Taniguchi, Yoshio Hayashi

{"title":"Evaluation of Readthrough Efficiency of Negamycin Derivatives against Nonsense Mutations in Muscular Dystrophy Genes.","authors":"Noriko Omura, Akihiro Taguchi, Keisuke Hamada, Sho Konno, Atsuhiko Taniguchi, Yoshio Hayashi","doi":"10.1248/bpb.b25-00728","DOIUrl":"https://doi.org/10.1248/bpb.b25-00728","url":null,"abstract":"Recently, \"readthrough compounds\" have attracted attention as a promising approach to treat human hereditary diseases caused by nonsense mutations. These compounds enable ribosomes to bypass a premature termination codon (PTC) introduced into mRNA by a nonsense mutation, thereby restoring the expression of full-length functional proteins. We performed a structure-activity relationship study focusing on (+)-negamycin, a known readthrough compound, and identified potent derivatives, TCP-304 and TCP-306, featuring a cyclopropane moiety. In this study, we investigated how the nature of PTCs and their surrounding nucleotide sequences influence the readthrough activity of these negamycin derivatives, using nonsense mutation sequences derived from Duchenne muscular dystrophy and congenital muscular dystrophy genes. In cell-based reporter assay systems, TCP-306 exhibited potent readthrough efficiency against several nonsense mutation sequences containing the TGA-A. Moreover, its sequence preference differed from that of the aminoglycoside G418, a representative readthrough compound that preferentially induces readthrough at TGA-C sequences, suggesting that TCP-306 may serve as an alternative therapeutic option for muscular dystrophies associated with TGA-A nonsense mutations. Overall, this study provides valuable insights for the development of readthrough drugs for hereditary diseases such as muscular dystrophy caused by nonsense mutations.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"346-354"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275585","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

Foreword. 前言。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-ctf4903

Takashi Kitahara

引用次数: 0

Inhibitory Effects of Lansoprazole and Omeprazole on the CYP2C19-Mediated Metabolism of Arachidonic Acid to Epoxyeicosatrienoic Acids: Implications for Cardiovascular Risk. 兰索拉唑和奥美拉唑对cyp2c19介导的花生四烯酸向环氧二十碳三烯酸代谢的抑制作用：对心血管风险的影响

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00738

Risa Kobayashi, Keita Shibata, Daichi Hayakawa, Yuki Nishimura, Ayako Watanabe, Kenji Momo, Hiroaki Gouda, Koji Nobe

{"title":"Inhibitory Effects of Lansoprazole and Omeprazole on the CYP2C19-Mediated Metabolism of Arachidonic Acid to Epoxyeicosatrienoic Acids: Implications for Cardiovascular Risk.","authors":"Risa Kobayashi, Keita Shibata, Daichi Hayakawa, Yuki Nishimura, Ayako Watanabe, Kenji Momo, Hiroaki Gouda, Koji Nobe","doi":"10.1248/bpb.b25-00738","DOIUrl":"10.1248/bpb.b25-00738","url":null,"abstract":"Proton pump inhibitors (PPIs), such as lansoprazole and omeprazole, are associated with an increased risk of cardiovascular events; however, the underlying mechanisms remain unclear. We investigated the inhibitory effects of lansoprazole and omeprazole on the formation of cardioprotective epoxyeicosatrienoic acids (EETs) and their downstream metabolites, dihydroxyeicosatrienoic acids (DHETs), from arachidonic acid catalyzed by CYP enzymes. In vitro incubation studies were conducted using human liver microsomes (HLMs), recombinant CYP2C19 (rCYP2C19), and recombinant CYP2C9 (rCYP2C9). IC50 values and R values (a clinical drug-drug interaction risk predictor) were estimated. In HLMs, lansoprazole inhibited the formation of 5,6-, 8,9-, and 11,12-EETs. Omeprazole showed limited inhibition in comparison. In experiments using recombinant enzymes, lansoprazole and omeprazole strongly inhibited EET formation via rCYP2C19, but not rCYP2C9. Lansoprazole exhibited more potent inhibition than omeprazole. Notably, R values for lansoprazole in rCYP2C19 exceeded 1.1 for total EET and DHET formation. Molecular docking analysis suggested that both PPIs may bind to CYP2C19 in a similar pose to a known inhibitor. Docking scores also supported the stronger inhibitory potential of lansoprazole compared to omeprazole. In conclusion, lansoprazole and omeprazole suppress EET formation primarily via CYP2C19 inhibition. The predicted high risk (R > 1.1) for lansoprazole observed in the rCYP2C19 assay suggests a potential mechanism for the increased cardiovascular risk. Further clinical studies are warranted to validate these findings.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"380-391"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147302036","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

Structural and Functional Diversity of Mitochondria Isolated from Different Cell Types. 从不同细胞类型分离的线粒体结构和功能多样性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00716

Yusei Endo, Mai Kanai, Masaki Kobayashi, Yoshikazu Higami, Shoko Itakura, Makiya Nishikawa, Kosuke Kusamori

{"title":"Structural and Functional Diversity of Mitochondria Isolated from Different Cell Types.","authors":"Yusei Endo, Mai Kanai, Masaki Kobayashi, Yoshikazu Higami, Shoko Itakura, Makiya Nishikawa, Kosuke Kusamori","doi":"10.1248/bpb.b25-00716","DOIUrl":"https://doi.org/10.1248/bpb.b25-00716","url":null,"abstract":"Mitochondria are essential organelles responsible for energy production, autophagy, and apoptosis, and mitochondrial dysfunction has been implicated in various diseases affecting the heart, liver, and kidneys. Mitochondrial transplantation, wherein isolated mitochondria are administered into cells or tissues, has recently emerged as a promising therapeutic approach for restoring cellular functions by enhancing ATP generation and reducing oxidative stress. However, the characteristics and functional diversity of the mitochondria isolated from different cell types remain poorly understood. Here, we aimed to identify the optimal mitochondrial source for transplantation therapy by comparing mitochondria isolated from several mammalian cell types, including mesenchymal stromal, hepatic, muscular, and pluripotent stem cells. Mitochondria were isolated using a streptolysin O-based isolation method and characterized through particle size, zeta potential, protein content, and ATP content. The isolated mitochondria exhibited uniform morphology, negative surface charge, sufficient protein yield, and ATP content, indicating successful preparation of functionally competent organelles suitable for comparative analysis. The mitochondria derived from mesenchymal stromal cells exhibited the highest bioenergetic activity. Adding these mitochondria enhanced cellular proliferation, oxygen consumption, and resistance to oxidative stress in recipient cells. Collectively, these findings demonstrate that mitochondria isolated from autologous mesenchymal stromal cells possess superior bioenergetic properties, highlighting their potential as an optimal source for mitochondrial transplantation therapy and providing new insights into the design of mitochondria-based therapeutics.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"457-466"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147376008","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

SMTP-44D Improves High Glucose-Induced Vascular Endothelial Dysfunction. SMTP-44D改善高糖诱导的血管内皮功能障碍。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00619

Shiori Jono, Ryosuke Shinouchi, Takashi Obama, Hiroyuki Itabe, Keiji Hasumi, Koji Nobe

{"title":"SMTP-44D Improves High Glucose-Induced Vascular Endothelial Dysfunction.","authors":"Shiori Jono, Ryosuke Shinouchi, Takashi Obama, Hiroyuki Itabe, Keiji Hasumi, Koji Nobe","doi":"10.1248/bpb.b25-00619","DOIUrl":"https://doi.org/10.1248/bpb.b25-00619","url":null,"abstract":"Chronic diabetic complications are mostly caused by vascular disorders, with only a few effective treatments or preventive measures currently available. In this study, we investigated the effects of Stachybotrys microspora triprenyl phenol-44D (SMTP-44D), a fungus-derived compound that inhibits both the epoxide hydrolase and phosphatase activities of soluble epoxide hydrolase (sEH), using human umbilical vein endothelial cells (HUVECs) in a high glucose treatment model. When HUVECs were treated with high glucose (30 mM) for 24 h, cell viability decreased to 69% compared with that under normal glucose (5.6 mM) conditions. When SMTP-44D was added, cell viability increased to 111%. In addition, nitric oxide levels in HUVECs decreased to 52% after 24 h of high-glucose treatment but increased to 82% after SMTP-44D treatment. Under the same conditions, high-glucose treatment increased intracellular reactive oxygen species levels and reduced Akt activation. SMTP-44D significantly improved both these changes, compared with the high glucose group. Under high glucose conditions, it is likely that oxidative stress and the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway are involved in endothelial dysfunction, and that SMTP-44D restores vascular function by acting on these pathways. In this study, we demonstrated, for the first time, SMTP-44D improves diabetic vascular endothelial dysfunction, suggesting that it may be a novel therapeutic and preventive candidate for the treatment of chronic complications of diabetes.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"74-83"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145958563","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

Oxaliplatin-Induced Liver Toxicity: Hepatic Transglutaminase 7 Upregulation Associates with Oxidative Stress, Inflammation, and Apoptosis. 奥沙利铂诱导的肝毒性：肝脏转谷氨酰胺酶7上调与氧化应激、炎症和细胞凋亡相关。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00689

Husah M Alowss, Ibtesam S Almami, Heba F Gomaa

{"title":"Oxaliplatin-Induced Liver Toxicity: Hepatic Transglutaminase 7 Upregulation Associates with Oxidative Stress, Inflammation, and Apoptosis.","authors":"Husah M Alowss, Ibtesam S Almami, Heba F Gomaa","doi":"10.1248/bpb.b25-00689","DOIUrl":"https://doi.org/10.1248/bpb.b25-00689","url":null,"abstract":"Transglutaminases (TGs) are calcium-dependent enzymes that cross-link proteins, contributing to apoptosis, extracellular matrix (ECM) stabilization, and inflammation. While TG2 has been extensively studied in hepatic injury, the role of TG7 in oxaliplatin-induced liver responses remains unclear. Oxaliplatin, a third-generation platinum chemotherapeutic, effectively treats solid tumors but can induce hepatic stress through oxidative and pro-inflammatory signaling. Adult rats received intraperitoneal oxaliplatin (10 mg/kg weekly) for 6 weeks. qRT-PCR, immunohistochemistry (IHC), immunofluorescence (IF), and a TG activity assay assessed hepatic TG7 expression, localization, and activity. Oxidative stress indicators (serum malondialdehyde [MDA] and reduced glutathione [GSH]) and pro-inflammatory cytokine transcription (CASP3, interleukin-6 (IL-6), tumor necrosis factor α (TNF-α)) were evaluated. Oxaliplatin exposure markedly increased TG7 mRNA and protein levels, elevated TG enzymatic activity, raised MDA (+49.4%), depleted GSH (-18.6%), and upregulated CASP3, IL-6, and TNF-α. DNA fragmentation and microscopic observations from IHC- and IF-processed sections were consistent with apoptosis-associated DNA degradation and subtle stress-related structural variations. Immunostaining revealed altered TG7 distribution within hepatocytes and sinusoidal regions. In this oxaliplatin-exposed rat liver model, TG7 upregulation and increased TG activity were associated with oxidative stress, inflammatory cytokine induction, and apoptotic signaling. These findings identify TG7 as a stress-associated marker during oxaliplatin exposure and support further studies to clarify its mechanistic role and evaluate its potential as utility as a biomarker under chemotherapy-associated hepatic stress conditions.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"316-326"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200076","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

Dynamic Feature of Oxidized LDL in Vivo. 体内氧化LDL的动态特征。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00628

Hiroyuki Itabe

引用次数: 0

Investigation of the Effects of Calcium Alginate on Blood Sodium Concentration and the Suppression of Blood Pressure Elevation in Rats. 海藻酸钙对大鼠血钠浓度及血压升高抑制作用的研究。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00592

Yusuke Namiki, Kenji Ida, Yoko Homma, Namino Tomimori, Ken Sato, Chihaya Kakinuma, Hidehisa Tachiki, Takuo Ogihara

{"title":"Investigation of the Effects of Calcium Alginate on Blood Sodium Concentration and the Suppression of Blood Pressure Elevation in Rats.","authors":"Yusuke Namiki, Kenji Ida, Yoko Homma, Namino Tomimori, Ken Sato, Chihaya Kakinuma, Hidehisa Tachiki, Takuo Ogihara","doi":"10.1248/bpb.b25-00592","DOIUrl":"https://doi.org/10.1248/bpb.b25-00592","url":null,"abstract":"The effects of calcium alginate (Ca-Alg) on the suppression of blood sodium (Na+) concentration and blood pressure elevation in rats were investigated. In a single-dose administration test, oral administration of a 0.3% sodium chloride (NaCl) solution (5 mg/kg) resulted in a significant increase in the difference in the area under the blood Na+ concentration-time curve (ΔAUC). When the finest Ca-Alg particles (8 mg/body, 270 mesh) were simultaneously administered orally under the same conditions, a significant decrease in ΔAUC and a tendency for a decrease in the maximum blood concentration difference (ΔCmax) were observed. In a repeated administration test, rats were allowed to freely ingest a 3.0% Ca-Alg-containing feed for 5 weeks, and an increase in Na+ excretion in feces was observed. Furthermore, in spontaneously hypertensive rats (SHR), when the same Ca-Alg-containing feed was freely consumed for 15 weeks, a significant inhibition of blood pressure elevation was observed after 10 weeks. Additionally, blood biochemical tests and renal histopathological examination of these rats confirmed the safety of Ca-Alg. Based on these results, it was concluded that Ca-Alg suppresses Na+ absorption and blood pressure elevation in rats.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"564-571"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147509560","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

Mechanisms of Skin Aging and the Interventional Effects of Plant Polysaccharides: A Review Based on Signaling Pathways. 植物多糖对皮肤衰老的干预作用及其机制研究进展

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00733

Xinyu Hou, Ziyi Chen, Jie Wang, Huailong Yu, Biyao Liu, Yue Zhang, Huarong Shao, Fei Liu

引用次数: 0

Establishment of Irinotecan-Induced Oral Mucositis Hamster Model and Evaluation of Therapeutic Agents. 伊立替康致口腔黏膜炎仓鼠模型的建立及药物疗效评价。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00018

Shinichi Watanabe, Natsumi Mori, Sakura Toyooka, Kaede Utsunomiya, Yukiro Kurokawa, Yasuhiro Nakagami, Takumi Yamaguchi

{"title":"Establishment of Irinotecan-Induced Oral Mucositis Hamster Model and Evaluation of Therapeutic Agents.","authors":"Shinichi Watanabe, Natsumi Mori, Sakura Toyooka, Kaede Utsunomiya, Yukiro Kurokawa, Yasuhiro Nakagami, Takumi Yamaguchi","doi":"10.1248/bpb.b26-00018","DOIUrl":"https://doi.org/10.1248/bpb.b26-00018","url":null,"abstract":"Chemotherapy-induced oral mucositis is a frequent and debilitating adverse effect that impairs nutritional status and interrupts cancer therapy. Although 5-fluorouracil-induced animal models of oral mucositis are well established, irinotecan, widely used for colorectal, lung, and pancreatic cancers, has also been associated with oral mucosal injury; however, no standardized preclinical model exists. This study aimed to establish a reproducible hamster model of irinotecan-induced oral mucositis and evaluate the prophylactic and therapeutic efficacy of topical hangeshashinto (HST) compared with dexamethasone. Male Syrian hamsters received intraperitoneal irinotecan (100, 150, or 200 mg/kg) on Day 0, followed by localized mucosal injury induced by 50% acetic acid. Ulcer area, body weight, histopathology, peripheral blood count, and myeloperoxidase (MPO) activity were evaluated. HST (10% aqueous solution) or dexamethasone (0.01% elixir) was administered topically once daily either prophylactically (Days -3 to 0) or therapeutically (from Day 0 onward). Ulcer area increased in a dose-dependent manner, peaking on Day 4. The 200 mg/kg dose yielded consistent lesion formation with transient weight loss. Histopathological examination revealed dense neutrophilic infiltration and epithelial disruption. MPO activity was significantly elevated on Days 4 and 7. Prophylactic HST significantly reduced the peak and cumulative ulcer areas, whereas dexamethasone delayed healing. The 200 mg/kg irinotecan plus acetic acid hamster model thus provides a reliable platform for investigating oral mucositis. HST, particularly when administered prophylactically, exhibited better efficacy than dexamethasone, potentially through modulation of inflammatory responses and attenuation of oxidative stress. This model may facilitate further mechanistic studies and the development of preventive strategies for chemotherapy-induced oral mucositis.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 3","pages":"572-577"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147572086","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