Biological & pharmaceutical bulletin最新文献_第5页

Simple Cytosolic and Nuclear Introduction of Boron Compounds Using Cationic Lipids to Enhance Cancer Cell-Killing Activity in Boron Neutron Capture Therapy.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00651

Shiori Hirase, Yurina Araki, Yoshihide Hattori, Ayako Aoki, Daisuke Fujiwara, Masataka Michigami, Tomoka Takatani-Nakase, Ikuo Fujii, Shiroh Futaki, Mitsunori Kirihata, Ikuhiko Nakase

{"title":"Simple Cytosolic and Nuclear Introduction of Boron Compounds Using Cationic Lipids to Enhance Cancer Cell-Killing Activity in Boron Neutron Capture Therapy.","authors":"Shiori Hirase, Yurina Araki, Yoshihide Hattori, Ayako Aoki, Daisuke Fujiwara, Masataka Michigami, Tomoka Takatani-Nakase, Ikuo Fujii, Shiroh Futaki, Mitsunori Kirihata, Ikuhiko Nakase","doi":"10.1248/bpb.b24-00651","DOIUrl":"https://doi.org/10.1248/bpb.b24-00651","url":null,"abstract":"Boron neutron capture therapy (BNCT), a type of nuclear capture-based radiotherapy, has received extensive attention because of its strong anticancer effects, especially in head and neck cancers. This therapy was approved for clinical use in 2020 in Japan. This study demonstrated a technique that effectively uses the electrostatic interactions of negatively charged borane cage (polyhedral borane anion) of disodium mercaptoundecahydro-closo-dodecaborate (BSH) and positively charged cationic lipids or arginine-rich cell-penetrating peptides as carriers to enhance the efficiency of cellular uptake. Mixing of fluorescein isothiocyanate (FITC)-labeled BSH (FITC-BSH) with the cationic lipids led to increased cytosolic release and nuclear accumulation of FITC-BSH, resulting in superior cancer cell-killing activity following thermal neutron irradiation. This simple technique and our experimental results provide essential insights for the further development of BNCT.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"344-354"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143794505","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

Safety Assessment of Medications during Pregnancy and Breastfeeding Based on Quantitative and Toxicological Analyses.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00016

Ayako Furugen

{"title":"Safety Assessment of Medications during Pregnancy and Breastfeeding Based on Quantitative and Toxicological Analyses.","authors":"Ayako Furugen","doi":"10.1248/bpb.b25-00016","DOIUrl":"10.1248/bpb.b25-00016","url":null,"abstract":"The potential risks to the fetus or infant should be evaluated before initiating pharmacotherapy during pregnancy and breastfeeding. However, safety information and experiences during pregnancy and breastfeeding are often lacking because these populations are generally excluded from clinical drug development studies. Perinatal mental health is important. Based on quantitative and toxicological analyses, we focused on medications used in psychiatry and neurology during the perinatal period. As the placenta serves as a temporary but crucial organ for ensuring successful pregnancy and appropriate fetal growth, we assessed the effects of antiepileptic drugs (AEDs) on placental functions such as transport mechanisms, nutrient transport, and trophoblast differentiation. Several AEDs have been suggested to be transported to the placenta via carrier-mediated pathways in a series of studies. Valproic acid, known to pose several risks to the fetus, affects the gene expression of nutrient transporters and trophoblast differentiation. Furthermore, we established several quantitative methods, such as those for antianxiety and hypnotic drugs, to evaluate the safety of pharmacotherapy during breastfeeding using liquid chromatography-tandem mass spectrometry. The validated methods were applied to clinical samples donated by lactating women. In a series of studies, the importance of choosing a suitable method for sample preparation for each biological matrix has been highlighted. The results obtained from the clinical samples suggest the possibility of differences in transfer properties among drugs categorized in the same class. Furthermore, this research emphasizes the critical need to assess breast milk transfer in human studies because species differences have been suggested in some cases.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"337-343"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771314","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

A 3D Cell-Culture System That Uses Nano-Fibrillated Bacterial Cellulose to Prepare a Spherical Formulation of Culture Cells.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00804

Shunsuke Akagi, Hidenori Ando, Cristina Nana Amorim Matsuo, Kenji Tajima, Haruka Takata, Tokuo Matsushima, Takatomo Kusano, Tatsuhiro Ishida

{"title":"A 3D Cell-Culture System That Uses Nano-Fibrillated Bacterial Cellulose to Prepare a Spherical Formulation of Culture Cells.","authors":"Shunsuke Akagi, Hidenori Ando, Cristina Nana Amorim Matsuo, Kenji Tajima, Haruka Takata, Tokuo Matsushima, Takatomo Kusano, Tatsuhiro Ishida","doi":"10.1248/bpb.b24-00804","DOIUrl":"https://doi.org/10.1248/bpb.b24-00804","url":null,"abstract":"A 3-dimensional (3D) cell culture is now being actively pursued to accomplish the in vivo-like cellular morphology and biological functions in cell culture. We recently obtained nano-fibrillated bacterial cellulose (NFBC). In this study, we developed a novel NFBC-based 3D cell-culture system, the OnGel method, and the Suspension method. HepG2 human liver cancer cells were cultured via these methods and formed spherical formulations in the optimized condition, 1.0% (w/v) of NFBC in the OnGel method, and 0.06-0.10% (w/v) of NFBC in the Suspension method. Non-cancerous cells such as human-induced pluripotent stem (iPS) cells and human mesenchymal stem cells (MSCs) also formed spherical formulations. It is noteworthy that both the size and cell viability of spheroids prepared via these methods were comparable to those cultured using commercially available 3D cell-culture systems. Both OnGel and Suspension methods are less complicated than the existing 3D cell-culture systems, which is an invaluable advantage for the preparation of cancer spheroids. The NFBC-based 3D cell-culture systems introduced here show great promise as a tool to prepare cultures for cell-derived spheroids for the progress of both in vitro and in vivo studies of the biological functioning of cells.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"23-32"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045203","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

α₁-Adrenoceptor Blockade by Class I Antiarrhythmic Drugs in Guinea Pig Thoracic Aorta as Revealed by Mechanical and Fluorescence Displacement Analysis.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00797

Iyuki Namekata, Maika Seki, Hiro Igarashi, Kohei Tsukada, Ayaka Kawazoe, Kuniaki Shirai, Marina Miyahara, Shogo Hamaguchi, Hikaru Tanaka

{"title":"α1-Adrenoceptor Blockade by Class I Antiarrhythmic Drugs in Guinea Pig Thoracic Aorta as Revealed by Mechanical and Fluorescence Displacement Analysis.","authors":"Iyuki Namekata, Maika Seki, Hiro Igarashi, Kohei Tsukada, Ayaka Kawazoe, Kuniaki Shirai, Marina Miyahara, Shogo Hamaguchi, Hikaru Tanaka","doi":"10.1248/bpb.b24-00797","DOIUrl":"https://doi.org/10.1248/bpb.b24-00797","url":null,"abstract":"The effects of thirteen Vaughn Williams class I antiarrhythmic drugs on the α1-adrenergic receptor-mediated contraction were examined in thoracic aorta tissue preparations isolated from the guinea pig. Cibenzoline, quinidine, aprindine, and ranolazine, as well as prazosin, inhibited the phenylephrine-induced contraction with pA2 values of 5.64, 5.59, 5.61, 5.08, and 8.50, respectively, but not prostaglandin F2α-induced. These drugs reduced the staining of the smooth muscle layer by fluorescent prazosin. Propafenone inhibited the phenylephrine-induced contraction with an apparent pA2 value of 5.31 and reduced the staining by fluorescent prazosin, but also inhibited the prostaglandin F2α-induced contraction. Other class I antiarrhythmic drugs, disopyramide, pirmenol, procainamide, lidocaine, mexiletine, flecainide, pilsicainide, and GS-458967, affected neither the contraction by phenylephrine nor the fluorescent staining by prazosin. These results indicate that among the class I antiarrhythmic drugs, cibenzoline, aprindine, and propafenone, as well as quinidine and ranolazine, have α1-adrenoceptor-blocking activity at therapeutically relevant concentrations.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"144-150"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490670","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

Functional Analysis of Modified Caco-2 Cells Carrying CES2A1 as a Model for Intestinal Absorption of Prodrugs.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00645

Teruko Imai, Masanari Isasaka, Yusuke Oyama, Yusuke Takagi, Kayoko Ohura, Shunsuke Kotani, Yuichiro Nakada

{"title":"Functional Analysis of Modified Caco-2 Cells Carrying CES2A1 as a Model for Intestinal Absorption of Prodrugs.","authors":"Teruko Imai, Masanari Isasaka, Yusuke Oyama, Yusuke Takagi, Kayoko Ohura, Shunsuke Kotani, Yuichiro Nakada","doi":"10.1248/bpb.b24-00645","DOIUrl":"https://doi.org/10.1248/bpb.b24-00645","url":null,"abstract":"Carboxylesterase (CES) plays an important role in the metabolism of ester-containing drugs such as prodrugs and is highly expressed in the human intestine and liver. The ideal prodrug is barely hydrolyzed by human intestinal CES (CES2A1) but is extensively converted to an active drug by human hepatic CES (CES1A). It is, therefore, important to evaluate CES2A1-mediated hydrolysis during intestinal absorption. Unfortunately, Caco-2 cells, the most common enterocyte model for drug permeability, are not suitable for permeability studies of prodrugs due to their high and extremely low expression of CES1A and CES2A1, respectively. Previously, we have prepared CES2/Caco-2CES1KD cells with reduced human CES1A and highly expressed CES2A1. In the present study, the metabolic and transport properties of CES2/Caco-2CES1KD cells were characterized. The expression of transporters and metabolizing enzymes other than CESs was similar in CES2/Caco-2CES1KD and Caco-2 cells. However, the expression of CES2A1 in CES2/Caco-2CES1KD was about 7-10 fold higher than that of CES1A in Caco-2 cells and comparable to levels found in the human intestine. Hydrolysis during transport across cell monolayers was analyzed using ethyl and butyl esters of p-aminobenzoic acid (PABA). Ethyl PABA, a better substrate for CES1A than CES2A1, was similarly hydrolyzed in Caco-2 and CES2/Caco-2CES1KD cell monolayers due to the high expression of CES2A1 in CES2/Caco-2CES1KD cells. Butyl PABA, a good substrate for CES2A1, was substantially hydrolyzed in CES2/Caco-2CES1KD cell monolayers, in contrast to negligible hydrolysis in Caco-2 cell monolayers. N-Acetylation of PABA derived from PABA esters showed similar activity in Caco-2 and CES2/Caco-2CES1KD cell monolayers.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"162-171"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143514599","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

Effect of (p)ppGpp on the Expression of the Vibrioferrin-Mediated Iron Acquisition System in Vibrio parahaemolyticus.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00624

Tomotaka Tanabe, Katsushiro Miyamoto, Kenjiro Nagaoka, Hiroshi Tsujibo, Tatsuya Funahashi

{"title":"Effect of (p)ppGpp on the Expression of the Vibrioferrin-Mediated Iron Acquisition System in Vibrio parahaemolyticus.","authors":"Tomotaka Tanabe, Katsushiro Miyamoto, Kenjiro Nagaoka, Hiroshi Tsujibo, Tatsuya Funahashi","doi":"10.1248/bpb.b24-00624","DOIUrl":"https://doi.org/10.1248/bpb.b24-00624","url":null,"abstract":"Bacteria have a stringent response system mediated by guanosine pentaphosphate and tetraphosphate ((p)ppGpp), which suppresses the expression of genes involved in cell growth and promotes the expression of genes involved in nutrient uptake and metabolism under nutrient-limited stress. In environments with limited availability of iron, an essential trace element, bacteria generally produce and secrete siderophores to efficiently utilize water-insoluble ferric iron (Fe3+) in the environment. In Vibrio parahaemolyticus, Fur (iron-responsive repressor) and RyhB (Fur-regulated small RNA) regulate the expression of genes involved in the utilization of vibrioferrin (VF), a siderophore produced by this bacterium. In this study, we examined whether (p)ppGpp is also involved in regulating the expression of genes related to the VF utilization system. Results of the chrome azurol S plate assay revealed that the strain in which 3 (p)ppGpp synthetases were deleted (∆relA∆spoT∆relV) produced less VF than the parental strain. Growth test results showed that the growth rate of ∆relA∆spoT∆relV in an iron-limited medium was suppressed compared with that of the parental strain but was restored with the addition of VF. Furthermore, RT-quantitative (q)PCR results showed that the expression levels of pvsA (VF biosynthesis gene) and pvuA2 (ferric VF receptor gene) in ∆relA∆spoT∆relV under iron limitation were significantly reduced compared with those in the parental strain. Western blot results demonstrated that the expression level of PvuA2 in ∆relA∆spoT∆relV was lower than that in the parental strain. These results suggest that (p)ppGpp promotes the expression of genes related to VF biosynthesis and the ferric VF uptake system under iron limitation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"188-194"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536420","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

Point Mutation Analysis of the Drug Efflux Pump MexB in Clinical Isolates of Pseudomonas aeruginosa.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b23-00190

Seiji Yamasaki, Naoki Koga, Ryosuke Nakashima, Mitsuko Hayashi-Nishino, Kunihiko Nishino

{"title":"Point Mutation Analysis of the Drug Efflux Pump MexB in Clinical Isolates of Pseudomonas aeruginosa.","authors":"Seiji Yamasaki, Naoki Koga, Ryosuke Nakashima, Mitsuko Hayashi-Nishino, Kunihiko Nishino","doi":"10.1248/bpb.b23-00190","DOIUrl":"https://doi.org/10.1248/bpb.b23-00190","url":null,"abstract":"The rapid emergence of drug-resistant microbes has recently become a major concern in the medical field. In Pseudomonas aeruginosa, one of the most important mechanisms underlying antibiotic resistance is MexAB-OprM system, increases in this efflux system result in greater resistance to a wide range of drugs, and genetic mutations have been identified as a contributing factor. Thus, this study characterized point mutations in the mexB gene that are common to 39 clinical P. aeruginosa isolates obtained from The Pseudomonas Genome Database. Basic Local Alignment Search Tool (BLAST) was used to compare the mexB gene sequences of those 39 strains with PAO1. The majority of these point mutations were silent mutations without amino acid mutations. Mutations 2730, 495, and 2280, which were abundant in the strains examined, were characterized by greater codon usage after the mutation. A positive correlation has been reported between tRNA levels and codon usage in Escherichia coli, and the same relationship may be present in P. aeruginosa. In this study, the silent mutations observed in many strains mainly involved the substitution of C or G, which resulted in a higher codon usage and stronger binding power after than before the mutation. This change is considered advantageous for survival in the human body by increasing the translation efficiency of the MexB protein. Thus, combining the silent mutation identified in this study with information on the expression level of mexB is expected to be used as an indicator to identify multidrug-resistant P. aeruginosa.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"230-233"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536438","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

Usefulness of an Intermittently Scanned Continuous Glucose Monitoring System for Risk Management of Individuals without Diabetes in Japan.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00340

Aya Torii-Goto, Seiji Fukaya, Katsuo Amioka, Rei Shibata, Masae Yoshikawa

{"title":"Usefulness of an Intermittently Scanned Continuous Glucose Monitoring System for Risk Management of Individuals without Diabetes in Japan.","authors":"Aya Torii-Goto, Seiji Fukaya, Katsuo Amioka, Rei Shibata, Masae Yoshikawa","doi":"10.1248/bpb.b24-00340","DOIUrl":"https://doi.org/10.1248/bpb.b24-00340","url":null,"abstract":"We examined whether the glucose levels and awareness of individuals without diabetes changed after using a sensor-based intermittently scanned continuous glucose monitoring (isCGM) system in their daily lives. Japanese individuals without a diabetes diagnosis wore the isCGM system while maintaining a normal lifestyle during the baseline period. A certified diabetes educator coached them on how to improve their lifestyle based on information from sensor data, food journals, and body composition. The participants subsequently consumed a specific diet, exercised for 2 months, and wore a new sensor after the intervention period. A total of 36 Japanese participants were eligible for analysis in this study. The time above range and the area under the curve did not change between before and after the intervention in overall participants. The visual analogue scale scores significantly increased from before to after the intervention in the overall participants. Stratified analysis was performed by dividing the participants into 18 control participants (glycated hemoglobin level <5.7%) and 18 participants with prediabetes (glycated hemoglobin level 5.7-6.4%). The time in range and the area under the curve significantly increased and decreased after the intervention in participants with prediabetes but not in control participants. The visual analogue scale scores significantly increased from before to after the intervention in both control and prediabetes groups individually. Lifestyle modification, along with the use of an isCGM system, is highly effective at preventing type 2 diabetes mellitus, potentially reducing the individual and public health burdens of diabetes, particularly for individuals with prediabetes.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"234-240"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613330","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

Evidence Showing Bombesin-Like Peptides Contract Guinea Pig Vas Deferens Smooth Muscle.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00721

Ge Liu, Hiryu Fujita, Hayato Agui, Ayu Kato, Miwa Enomoto, Futaba Makino, Nana Yamada, Kento Yoshioka, Keisuke Obara, Yoshio Tanaka

{"title":"Evidence Showing Bombesin-Like Peptides Contract Guinea Pig Vas Deferens Smooth Muscle.","authors":"Ge Liu, Hiryu Fujita, Hayato Agui, Ayu Kato, Miwa Enomoto, Futaba Makino, Nana Yamada, Kento Yoshioka, Keisuke Obara, Yoshio Tanaka","doi":"10.1248/bpb.b24-00721","DOIUrl":"https://doi.org/10.1248/bpb.b24-00721","url":null,"abstract":"In this study, we investigated (1) the functional role of large-conductance Ca2+-activated K+ (BKCa) channels in the regulation of guinea pig vas deferens smooth muscle (VDSM) contractions and (2) the potential contractile effects of 33 physiologically active substances and related chemicals that have not been previously reported to contract VDSM. Iberiotoxin (an inhibitor of BKCa channels, 10-7 M) was the most potent enhancer of both noradrenaline (10-5 M)- and ATP (10-6 M)-induced contractions among the 6 types of K+ channel inhibitors. In addition, BKCa channel mRNA expression was the highest among the 32 types of K+ channel mRNAs. Iberiotoxin also enhanced the contractions induced by acetylcholine (10-6 M), histamine (5 × 10-5 M), bradykinin (10-6 M), neurokinin A (10-6 M), neurokinin B (10-6 M), and substance P (10-6 M). In the 33 tested physiologically active substances and related chemicals (15 peptides, 5 amino acids and their derivatives, 11 prostanoid- and isoprostane-related drugs, 1 endocannabinoid, and 1 phospholipid), we found that 3 bombesin-like peptides, neuromedin B (NMB) (10-6 M), gastrin-releasing peptide (GRP, 10-8 M), and NMC (10-6 M), contracted VDSM in the absence of iberiotoxin, and these contractions were strongly enhanced in the presence of iberiotoxin. Among the 3 bombesin receptor subtypes, the mRNA expression level of Grpr (BB2 receptor) was the highest. These findings suggest that (1) BKCa channels are the most powerful negative regulator of VDSM contractility and (2) NMB, GRP, and NMC are physiologically active substances that contract VDSM.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"298-307"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143699184","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

Epigallocatechin-3-gallate Alleviates Ethanol-Induced Endothelia Cells Injury Partly through Alteration of NF-κB Translocation and Activation of the Nrf2 Signaling Pathway. 表没食子儿茶素-3-没食子酸酯部分通过改变NF-κB转位和激活Nrf2信号通路，减轻乙醇诱导的内皮细胞损伤。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2024-07-05 Epub Date: 2024-06-12 DOI: 10.1248/bpb.b23-00773

Jie Xu, Shouzhu Xu, Jiayin Luo, Shihao Zhang, Dongdong Wu, Qifan Yang, Rourou Fang, Chuandao Shi, Qiling Liu, Jing Zhao

{"title":"Epigallocatechin-3-gallate Alleviates Ethanol-Induced Endothelia Cells Injury Partly through Alteration of NF-κB Translocation and Activation of the Nrf2 Signaling Pathway.","authors":"Jie Xu, Shouzhu Xu, Jiayin Luo, Shihao Zhang, Dongdong Wu, Qifan Yang, Rourou Fang, Chuandao Shi, Qiling Liu, Jing Zhao","doi":"10.1248/bpb.b23-00773","DOIUrl":"10.1248/bpb.b23-00773","url":null,"abstract":"Ethanol (alcohol) is a risk factor that contributes to non-communicable diseases. Chronic abuse of ethanol is toxic to both the heart and overall health, and even results in death. Ethanol and its byproduct acetaldehyde can harm the cardiovascular system by impairing mitochondrial function, causing oxidative damage, and reducing contractile proteins. Endothelial cells are essential components of the cardiovascular system, are highly susceptible to ethanol, either through direct or indirect exposure. Thus, protection against endothelial injury is of great importance for persons who chronic abuse of ethanol. In this study, an in vitro model of endothelial injury was created using ethanol. The findings revealed that a concentration of 20.0 mM of ethanol reduced cell viability and Bcl-2 expression, while increasing cell apoptosis, intracellular reactive oxygen species (ROS) levels, mitochondrial depolarization, and the expression of Bax and cleaved-caspase-3 in endothelial cells. Further study showed that ethanol promoted nuclear translocation of nuclear factor kappa B (NF-κB), increased the secretion of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 in the culture medium, and inhibited nuclear factor-erythroid 2-related factor 2 (Nrf2) signaling pathway. The aforementioned findings suggest that ethanol has a harmful impact on endothelial cells. Nevertheless, the application of epigallocatechin-3-gallate (EGCG) to the cells can effectively mitigate the detrimental effects of ethanol on endothelial cells. In conclusion, EGCG alleviates ethanol-induced endothelial injury partly through alteration of NF-κB translocation and activation of the Nrf2 signaling pathway. Therefore, EGCG holds great potential in safeguarding individuals who chronically abuse ethanol from endothelial dysfunction.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":" ","pages":"1248-1254"},"PeriodicalIF":1.7,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141309873","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