Biological & pharmaceutical bulletin最新文献

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

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

Lipopolysaccharide-Induced Changes in Facial Expression and Orofacial Movement in Mice. 脂多糖诱导小鼠面部表情和口面部运动的变化。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00142

Ren Tatematsu, Ryosuke Yoshida, Nobuyoshi Matsumoto, Yuji Ikegaya

{"title":"Lipopolysaccharide-Induced Changes in Facial Expression and Orofacial Movement in Mice.","authors":"Ren Tatematsu, Ryosuke Yoshida, Nobuyoshi Matsumoto, Yuji Ikegaya","doi":"10.1248/bpb.b26-00142","DOIUrl":"https://doi.org/10.1248/bpb.b26-00142","url":null,"abstract":"Sickness behavior is defined by a coordinated set of behavioral changes that emerge during infection and other inflammatory states. A major challenge for assessment, however, is the broad suppression of behavioral output, which hampers the dissociation of specific affective states from generalized motor inhibition. In this study, we applied facial expression analysis to characterize the sickness state in lipopolysaccharide (LPS)-injected male mice, leveraging the well-established capacity of rodents to express affective states through facial action units. LPS induced changes in both movement-related and grimace-like facial features. Inter-feature correlation analysis revealed that grimace-like features, including orbital tightening and nose bulging, showed LPS-specific temporal correlations in a subset of time bins. Furthermore, grimace-like readouts showed greater inter-individual variability than movement-related measures. Together, these findings support the viability of facial expression analysis as a noninvasive readout for behavioral states in inflammatory models that induce hypoactivity.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 6","pages":"996-1000"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315520","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 1.8 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":"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":1.8,"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

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 1.8 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":1.8,"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 1.8 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":"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":1.8,"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

Ganoderic Acid A Derived from Reishi Mushroom Ganoderma lucidum Protects against Intestinal Immunity Reduction Due to Oxidative Stress in Rat. 从灵芝中提取的灵芝酸A对氧化应激引起大鼠肠道免疫力下降的保护作用。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00688

Atsuhito Kubota, Keisuke Okamoto, Genki Yasuda, Katsuya Narumi, Yuji Suzuki, Hinata Ueda, Ayako Mori, Natsuko Takahashi-Suzuki, Takashi Satoh, Ken Iseki, Masaki Kobayashi

{"title":"Ganoderic Acid A Derived from Reishi Mushroom Ganoderma lucidum Protects against Intestinal Immunity Reduction Due to Oxidative Stress in Rat.","authors":"Atsuhito Kubota, Keisuke Okamoto, Genki Yasuda, Katsuya Narumi, Yuji Suzuki, Hinata Ueda, Ayako Mori, Natsuko Takahashi-Suzuki, Takashi Satoh, Ken Iseki, Masaki Kobayashi","doi":"10.1248/bpb.b25-00688","DOIUrl":"10.1248/bpb.b25-00688","url":null,"abstract":"Reishi (Ganoderma lucidum) is known to enhance intestinal immunity, with ganoderic acid A (GA-A) identified as one of its active constituents. However, the specific role of GA-A in regulating immune components such as immunoglobulin A (IgA) from Peyer's patches (PPs) and α-defensin 5 from Paneth cells remains unclear. Additionally, the ability of Reishi to counteract oxidative stress-induced intestinal immune suppression has not been fully elucidated. Therefore, in this study, we aimed to examine the effects of Reishi and GA-A on intestinal immunity in a rat model of ischemia-reperfusion (I/R) injury. Oral administration of GA-A increased IgA secretion from PP cells isolated from rat small intestine and upregulated the mRNA expression of rat α-defensin 5 (RD-5) and toll-like receptor 4 (TLR4) in the ileum, similar to Reishi. In contrast, GA-A did not exhibit immunostimulatory effects in TLR4-deficient mice. In the I/R rat model, both Reishi and GA-A significantly restored IgA secretion and RD-5 mRNA expression, mitigating immune suppression. They were also associated with changes in superoxide dismutase 1 (SOD1) and SOD3 mRNA expression under I/R conditions and prevented villus shedding and Paneth cell loss, indicating protection against I/R-induced intestinal immune decline. These results were comparable to those observed with caffeic acid, the positive control. Overall, these findings suggest that Reishi mitigates intestinal immune suppression caused by I/R injury, with GA-A serving as a key active component mediating these protective effects.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"701-707"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687369","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

Identification of 3,5-Bis (2-Ethoxybenzylidene) Piperidin-4-one as a Monocarbonyl Curcumin Analog Inhibiting Cell-Intrinsic NF-κB Activity in 4T1 Breast Cancer Cells. 3,5-双（2-乙氧基苄基）Piperidin-4-one作为单羰基姜黄素类似物抑制4T1乳腺癌细胞内生性NF-κB活性的鉴定

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00785

Sana Jabbar, Sisca Ucche, Farooq Muhammad Irshad, Suthasinee Seephan, So-Ichiro Sasaki, Retno Murwanti, Ritmaleni, Yoshihiro Hayakawa

{"title":"Identification of 3,5-Bis (2-Ethoxybenzylidene) Piperidin-4-one as a Monocarbonyl Curcumin Analog Inhibiting Cell-Intrinsic NF-κB Activity in 4T1 Breast Cancer Cells.","authors":"Sana Jabbar, Sisca Ucche, Farooq Muhammad Irshad, Suthasinee Seephan, So-Ichiro Sasaki, Retno Murwanti, Ritmaleni, Yoshihiro Hayakawa","doi":"10.1248/bpb.b25-00785","DOIUrl":"10.1248/bpb.b25-00785","url":null,"abstract":"Although numerous biological properties of curcumin, a bioactive polyphenol from the rhizome of turmeric (Curcuma longa), have been documented, its poor bioavailability limits clinical application. Therefore, identifying new analogs with improved pharmacokinetics and pharmacological properties is essential. Given that curcumin and its related compounds are known to inhibit cancer cell progression and metastasis through nuclear factor-kappaB (NF-κB) signaling inhibition, we investigated 58 newly synthesized, structurally diverse monocarbonyl curcumin analogs. Their inhibitory effects on intrinsic NF-κB activity were assessed in breast cancer cells using the 4T1 cell line expressing a luciferase NF-κB reporter. Among the 58 monocarbonyl curcumin analogs, 3,5-bis(2-ethoxybenzylidene)piperidin-4-one (E145) exhibited potent inhibition of NF-κB activity in 4T1 breast cancer cells. Based on the structure-activity relationship analysis, the central heterocyclic monocarbonyl linker structure of E145 contributed to its increased potency in NF-κB inhibition.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"725-731"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721710","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

Immunohistochemical Localization of Sotorasib-Protein Conjugates in the Rat Gastrointestinal Tract. sotorasib蛋白偶联物在大鼠胃肠道中的免疫组织化学定位。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00033

Tetsuya Saita, Miyabi Teramoto

{"title":"Immunohistochemical Localization of Sotorasib-Protein Conjugates in the Rat Gastrointestinal Tract.","authors":"Tetsuya Saita, Miyabi Teramoto","doi":"10.1248/bpb.b26-00033","DOIUrl":"10.1248/bpb.b26-00033","url":null,"abstract":"Sotorasib is a molecularly targeted drug that exerts antitumor effects by selectively binding to KRAS G12C through a Michael addition reaction, irreversibly inhibiting KRAS. However, the frequent occurrence of adverse events, such as gastrointestinal and hepatic disorders, has raised major concerns. These toxicities are thought to arise from interactions between sotorasib and proteins other than KRAS in normal cells. In this study, we generated a specific antibody against sotorasib and established an immunohistochemical method capable of detecting sotorasib-protein conjugates. Using this technique, we clarified the localization of sotorasib-protein conjugates in the digestive tract of rats, including the duodenum, jejunum, ileum, and colon. Sotorasib-protein conjugates were strongly localized to the villous epithelial cells of the small intestine but were scarcely detected in the colon, highlighting regional differences. This study elucidates the localization of sotorasib-protein conjugates in the gastrointestinal tract of rats and provides important insights into the mechanisms underlying sotorasib-induced gastrointestinal disorders.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"732-737"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721738","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

An Oligodeoxynucleotide from Lactic Acid Bacteria Promotes the Differentiation of Endothelial Cells from Induced Pluripotent Stem Cells. 来自乳酸菌的寡脱氧核苷酸促进内皮细胞从诱导多能干细胞分化。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00016

Tomoko Yamaguchi-Shibano, Misae Nishijima, Tomohide Takaya, Kenji Kawabata

{"title":"An Oligodeoxynucleotide from Lactic Acid Bacteria Promotes the Differentiation of Endothelial Cells from Induced Pluripotent Stem Cells.","authors":"Tomoko Yamaguchi-Shibano, Misae Nishijima, Tomohide Takaya, Kenji Kawabata","doi":"10.1248/bpb.b26-00016","DOIUrl":"10.1248/bpb.b26-00016","url":null,"abstract":"Bacterial genome-derived oligodeoxynucleotides (ODNs) are recognized as pathogen-associated molecular patterns by Toll-like receptors. They induce inflammatory responses by activating the innate immune response. Recently, ODNs reported to regulate stem cell differentiation have garnered attention owing to the discovery of new functions. In this study, we aimed to investigate the effects of a myogenic ODN (iSN04), derived from the Lactobacillus genome sequence and reported to enhance myoblast differentiation, on the differentiation of vascular endothelial cells and other mesodermal lineages derived from the human induced pluripotent stem cell lines iMR90-4 and 201B7. The addition of iSN04 to the differentiation induction medium increased the proportion of CD31+CD144+ endothelial cells in the cell population. Furthermore, quantitative RT-PCR showed that the addition of iSN04 increased the gene expression of vascular endothelial cell markers such as von Willebrand factor. Analysis of cells on Day 3 after the addition of iSN04 revealed an increase in the expression of Brachyury-T, a marker of the mesoderm. These results suggest that iSN04 may improve the differentiation efficiency of cells, such as vascular endothelial cells, into other mesodermal cells by promoting mesoderm differentiation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 5","pages":"802-808"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147926114","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