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Identification of Bioactive Compounds and Potential Mechanisms of Fuzi in the Treatment of Ulcerative Colitis by Integrating Network Pharmacology and Experimental Validation. 结合网络药理学和实验验证鉴定附子治疗溃疡性结肠炎的活性成分及其作用机制。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00590
Miaomiao Ma, Leshi Liang, Meihong Lin, Canhua Luo, Xingfeng Deng, Changhui Yu
{"title":"Identification of Bioactive Compounds and Potential Mechanisms of Fuzi in the Treatment of Ulcerative Colitis by Integrating Network Pharmacology and Experimental Validation.","authors":"Miaomiao Ma, Leshi Liang, Meihong Lin, Canhua Luo, Xingfeng Deng, Changhui Yu","doi":"10.1248/bpb.b24-00590","DOIUrl":"10.1248/bpb.b24-00590","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a chronic inflammatory bowel disease without efficient treatment. Fuzi has anti-inflammatory and immunomodulatory properties. However, the bioactive compounds and mechanisms of fuzi in the treatment of UC are not completely understood. The active components of fuzi were retrieved from Traditional Chinese Medicine Database System Pharmacology and Analysis Platform; PharmMapper was used to predict the targets of the active components of fuzi; UC-related disease targets were obtained from Online Mendelian Inheritance in Man and Genecards databases, and Venny 2.1 was used to obtain common targets; Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses were performed on the common targets using R 4.0.2. STRING and Cytoscape 3.9.0 was used to construct a protein-protein interaction (PPI) network for the intersection targets. We then determined the role of the candidate molecule from fuzi, Higenamine (Hig), in a mouse model of dextran sulfate sodium (DSS)-induced colitis. In total, 21 active components and 420 corresponding targets of fuzi were obtained, of which 224 common targets were identified by intersecting with UC-related targets. The GO, KEGG, and PPI results suggested that fuzi and Hig may target RAC-alpha serine/threonine-protein kinase (AKT) to regulate the phosphoinositide-3-kinase (PI3K)/AKT pathway in UC. Animal experiments have shown that Hig treatment greatly reduced DSS-induced colitis, as measured by the disease activity index score, colonic inflammation, and intestinal barrier integrity. Mechanistically, Hig downregulated the DSS-induced PI3K-AKT signaling pathway by inhibiting AKT phosphorylation. Altogether, Hig alleviated DSS-induced colitis in mice, possibly by inhibiting colon inflammation and improving the intestinal barrier by regulating the PI3K-AKT signaling pathway. The active component Hig from fuzi is likely to play a role in the treatment of UC.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"246-261"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143655970","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
Evaluating the Efficacy of Premedication in Preventing Hypersensitivity Reactions to Nonionic Contrast Agents. 评价用药前预防非离子造影剂超敏反应的疗效。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00808
Shinya Suzuki, Shungo Imai, Akinori Omata, Tadamasa Kamimura, Hayato Kizaki, Takuma Koinuma, Satoko Hori
{"title":"Evaluating the Efficacy of Premedication in Preventing Hypersensitivity Reactions to Nonionic Contrast Agents.","authors":"Shinya Suzuki, Shungo Imai, Akinori Omata, Tadamasa Kamimura, Hayato Kizaki, Takuma Koinuma, Satoko Hori","doi":"10.1248/bpb.b24-00808","DOIUrl":"10.1248/bpb.b24-00808","url":null,"abstract":"<p><p>Iodine-based contrast agents can induce various acute hypersensitivity reactions ranging from mild itching or vomiting shortly after administration to severe hypotension or loss of consciousness. In Japan, steroid premedication is commonly used to prevent acute hypersensitivity reactions. However, little clear evidence supporting its efficacy is available. In this study, we evaluated the effectiveness of premedication for acute hypersensitivity reactions induced by nonionic iodine contrast agents using propensity score matching. The participants included patients who were administered nonionic iodine contrast agents at Yokohama City Minato Red Cross Hospital between April 1, 2016 and March 31, 2022. Only first-time patients with no history of hypersensitivity reactions to contrast agents were included. The patients were classified into premedication and non-premedication groups, and the incidence proportions of acute hypersensitivity reactions were compared after matching. Of the 19976 patients, 422 (211 in each group) were matched. In the premedication group, 7 cases (3.32%) of hypersensitivity reactions occurred. In contrast, only 2 cases (0.95%) were observed in the non-premedication group. The odds ratio for the occurrence of hypersensitivity reactions in the premedication group was 3.500 (95% confidence interval, 0.727-16.848), with no significant difference. Therefore, premedication did not demonstrate the efficacy in preventing acute hypersensitivity reactions induced by nonionic iodine contrast agents. Based on the results of this study and guidelines, a recommendation for premedication was not reached for patients with a history of allergies, including asthma and atopy, as well as those with a history of drug or food allergies.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"241-245"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143613328","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
Change in Vancomycin Absorption after Intraperitoneal Injection and Correlation between Intraperitoneal Vancomycin Absorption and Peritoneal Equilibration Test Score in Mice with Peritoneal Injuries. 腹膜损伤小鼠腹腔注射万古霉素吸收变化及腹腔注射万古霉素吸收与腹膜平衡测试评分的关系
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00687
Akihiro Moritsuka, Hirotaka Miyamoto, Yukina Takahashi, Haruna Hirata, Yuki Kawauchi, Shintaro Fumoto, Koyo Nishida
{"title":"Change in Vancomycin Absorption after Intraperitoneal Injection and Correlation between Intraperitoneal Vancomycin Absorption and Peritoneal Equilibration Test Score in Mice with Peritoneal Injuries.","authors":"Akihiro Moritsuka, Hirotaka Miyamoto, Yukina Takahashi, Haruna Hirata, Yuki Kawauchi, Shintaro Fumoto, Koyo Nishida","doi":"10.1248/bpb.b24-00687","DOIUrl":"10.1248/bpb.b24-00687","url":null,"abstract":"<p><p>Peritonitis is a serious complication in peritoneal dialysis patients and requires antibiotic administration. Intraperitoneal vancomycin is an empiric therapy for peritonitis caused by Gram-positive cocci; however, there is no way to predict vancomycin absorption after intraperitoneal administration. Therefore, we aimed to evaluate the changes in vancomycin absorption after intraperitoneal injection into mice with chlorhexidine gluconate (CG) induced peritoneal injuries. Additionally, we examined the correlation between intraperitoneal vancomycin absorption and peritoneal equilibration test (PET) score. PET score was determined using glucose concentration in the peritoneal dialysis fluid at each dwell time (D<sub>t</sub>) and D<sub>2</sub> (2 h of dwell time)/D<sub>0</sub> (0 h of dwell time) glucose ratio. Vancomycin was injected into the peritoneal cavity of mice, blood was collected after 1-8 h, and peritoneal fluid was recovered. The residual ratio of intraperitoneal vancomycin was significantly decreased in the CG group at all time points compared to that in the vehicle group. CG group significantly exhibited higher serum vancomycin concentrations than the vehicle group, and the maximum serum concentration increased depending on CG concentration, with 0.05 and 0.1% CG groups showing 3.9- and 6.1-times higher vancomycin concentrations, respectively, than the vehicle group. A significant correlation was observed between the D<sub>t</sub>/D<sub>0</sub> glucose ratios and residual vancomycin ratios in the peritoneal fluid 2 or 6 h after intraperitoneal injection. A good correlation was observed between the D<sub>2</sub>/D<sub>0</sub> glucose and residual vancomycin ratios 6 h after intraperitoneal vancomycin injection. Thus, PET score can predict residual intraperitoneal vancomycin, aiding in dosing decisions.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"80-85"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078561","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
Longitudinal Trend in Antimicrobial Susceptibility among Haemophilus influenzae: A Single-Centre Study in Japan. 流感嗜血杆菌抗菌素敏感性的纵向趋势:日本的单中心研究。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00715
Takeaki Wajima, Naoki Hara, Emi Tanaka, Atsuko Shirai, Kei-Ichi Uchiya
{"title":"Longitudinal Trend in Antimicrobial Susceptibility among Haemophilus influenzae: A Single-Centre Study in Japan.","authors":"Takeaki Wajima, Naoki Hara, Emi Tanaka, Atsuko Shirai, Kei-Ichi Uchiya","doi":"10.1248/bpb.b24-00715","DOIUrl":"10.1248/bpb.b24-00715","url":null,"abstract":"<p><p>Haemophilus influenzae presents significant concerns regarding antimicrobial resistance. The circumstances surrounding H. influenzae have been changing owing to changes in antimicrobial usage. In the present study, to determine the current situation of H. influenzae, the antimicrobial susceptibility trends were investigated. In total, 21 clinical isolates were analyzed. Antimicrobial susceptibility measured using the broth dilution method was compared with that reported in previous studies at the same hospital. Quinolone low-susceptible isolates were further characterized by multi-locus sequence typing. Upon comparing the susceptibility data in 2022 with those in the past 15 years, the number of β-lactamase nonproducing ampicillin-resistant isolates was decreased. Regarding recent changes, β-lactam-susceptible isolates were found to have gradually increased every year. However, β-lactamase-producing isolates did not decrease. In particular, the ratio of β-lactamase-producing amoxicillin and clavulanic acid-resistant isolates in 2022 was the highest among all the years studied. Moreover, quinolone low-susceptible isolates were still present, suggesting that these isolates could have been indigenized in the community. Furthermore, a β-lactamase-producing amoxicillin and clavulanic acid-resistant isolate was found to have emerged among the quinolone low-susceptibility isolates. At first glance, these findings indicate that antimicrobial resistance has decreased among H. influenzae in clinical settings. However, β-lactamase-producing isolates and quinolone low-susceptible isolates have remained at a constant rate in the community.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"60-64"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078576","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
Continuous Ingestion of a Standardized Extract of Cultured Lentinula edodes Mycelia Suppresses Spontaneous Carcinogenesis in a Murine Model. 连续摄入培养香菇菌丝体的标准提取物可抑制小鼠模型中的自发癌变。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00641
Shigeki Adachi, Takahiro Tougan, Haruko Ryo, Jun Takanari, Koji Wakame, Taiki Aoshi, Taisei Nomura
{"title":"Continuous Ingestion of a Standardized Extract of Cultured Lentinula edodes Mycelia Suppresses Spontaneous Carcinogenesis in a Murine Model.","authors":"Shigeki Adachi, Takahiro Tougan, Haruko Ryo, Jun Takanari, Koji Wakame, Taiki Aoshi, Taisei Nomura","doi":"10.1248/bpb.b24-00641","DOIUrl":"https://doi.org/10.1248/bpb.b24-00641","url":null,"abstract":"<p><p>AHCC<sup>®</sup>, a standardized extract of cultured Lentinula edodes mycelia, suppresses the proliferation of both cancer cell line-derived and patient-derived xenografts transplanted into mice. However, the mechanism of action underlying the suppressive effect of AHCC on spontaneous carcinogenesis remains unclear. This study investigated the effects of long-term AHCC ingestion on spontaneous carcinogenesis and the health of C3H/HeJ mice. The mice were divided into three groups: A (2% AHCC ingestion continuously 2 d a week), B (2% AHCC ingestion daily), and C (water ingestion). The ingestion of AHCC or water was started when mice were 5 weeks old and were observed until 24 months of age. The occurrence of the first death was delayed in the AHCC-ingestion groups, and the survival rates were significantly higher in the AHCC-ingestion groups than in the control group. The proportion of \"healthy mice\" with no morphological abnormalities in their organs was also significantly higher in the AHCC-ingestion groups than in the control group. Furthermore, the incidence of cancer-bearing mice, particularly breast cancer and liver cancer, was significantly reduced in the AHCC-ingestion groups. The reduced rates of breast cancer were particularly higher among females of the AHCC-ingestion groups, whereas the reduced rates of liver cancer were higher among males of the AHCC-ingestion groups. These results suggest that continuous AHCC ingestion maintains health and prevents spontaneous carcinogenesis.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"687-693"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141157","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
Evaluating Signal Peptide Efficiency for Extracellular Protein Secretion for mRNA Vaccine Design. mRNA疫苗设计中细胞外蛋白分泌的信号肽效率评价
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00155
Shinya Sato, Naoki Minagawa, Yuro Hirata, Masanori Sasaki, Takumi Okamoto, Mariko Kamiya, Koji Matsuhisa, Shigeru Kawakami, Masayuki Kaneko
{"title":"Evaluating Signal Peptide Efficiency for Extracellular Protein Secretion for mRNA Vaccine Design.","authors":"Shinya Sato, Naoki Minagawa, Yuro Hirata, Masanori Sasaki, Takumi Okamoto, Mariko Kamiya, Koji Matsuhisa, Shigeru Kawakami, Masayuki Kaneko","doi":"10.1248/bpb.b25-00155","DOIUrl":"https://doi.org/10.1248/bpb.b25-00155","url":null,"abstract":"<p><p>mRNA vaccines have emerged as promising platforms for the prevention of infectious diseases and cancer treatment. The antigenic protein has a signal peptide added to the N-terminus for extracellular secretion. However, it remains unclear whether the optimization of signal peptides has been sufficiently compared and examined for antigen protein secretion and immunogenicity. This study investigated the effects of various signal peptides on the extracellular secretion of a model protein, NanoLuc luciferase (Nluc), in different cell lines. We compared the secretion efficiency of Nluc fused to artificial (#38 and #34) and natural signal peptides (cystatin S, lactotransferrin, and tissue plasminogen activator) in human embryonic kidney 293, C2C12, and HepG2 cells. Luciferase assays and Western blot analysis revealed that the cystatin S signal peptide consistently induced the highest secretion of Nluc among all cell types tested. Notably, the cystatin S signal peptide outperformed previously reported tissue plasminogen activator signal peptides in terms of secretion efficiency. Furthermore, we observed no correlation between Nluc secretion and mRNA expression levels for each signal peptide, suggesting that enhanced secretion was not attributable to increased transcription. Our findings highlight the potential of the cystatin S signal peptide in enhancing the extracellular secretion of antigenic proteins in mRNA vaccines by improving the efficiency of protein translation.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"706-712"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144141161","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 Progress in Drug Development Based on Functional Molecules Involved in Pathogenesis and Analysis of Their Mechanisms. 基于功能分子参与发病机制的药物开发研究进展。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00069
Hideaki Hara
{"title":"Research Progress in Drug Development Based on Functional Molecules Involved in Pathogenesis and Analysis of Their Mechanisms.","authors":"Hideaki Hara","doi":"10.1248/bpb.b25-00069","DOIUrl":"https://doi.org/10.1248/bpb.b25-00069","url":null,"abstract":"<p><p>Ocular diseases that result in blindness impair the QOL of patients as well as cause significant socioeconomic losses. Glaucoma is the leading cause of blindness, followed by retinitis pigmentosa, diabetic retinopathy, and age-related macular degeneration (AMD). Although the pathogeneses of these ocular diseases differ, they are all retinal diseases that lead to blindness owing to progressive retinal damage. However, the mechanisms underlying the pathogenesis and progression of these diseases have not yet been fully elucidated. In addition, treatment methods for these diseases have not yet been fully established, and their pathophysiology should be elucidated to establish novel treatment methods and drugs. Rodent pathological models, particularly mice and rats, have been established to elucidate the pathogenesis of these diseases. However, anatomical differences between the eyes of humans and rodents suggest that differences in pathogenic mechanisms may exist. In addition, species differences in drug responsiveness have become an issue in various respects, making it increasingly difficult to directly extrapolate the results obtained in rodents to humans. Therefore, evaluations using non-human primates, which are physiologically similar to humans, are required. This review outlines the basic research of AMD and glaucoma models using mice and non-human primates and their therapeutic strategies, focusing on the research findings.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"744-758"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144198244","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
Vaseline Coating on Paw Soles Alters the Spontaneous Gait of Rats. 脚掌涂敷凡士林改变大鼠自发步态。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00116
Yuga Kimura, Kotaro Yamashiro, Yuji Ikegaya, Nobuyoshi Matsumoto
{"title":"Vaseline Coating on Paw Soles Alters the Spontaneous Gait of Rats.","authors":"Yuga Kimura, Kotaro Yamashiro, Yuji Ikegaya, Nobuyoshi Matsumoto","doi":"10.1248/bpb.b25-00116","DOIUrl":"https://doi.org/10.1248/bpb.b25-00116","url":null,"abstract":"<p><p>Spontaneous walking behavior is modulated by various factors, but it remains almost unknown whether and how moisturizing paw soles of rats alters their gait. To this end, we allowed rats to spontaneously walk on a disk-shaped treadmill before and after their paw soles were coated with white petrolatum (vaseline) and monitored the rat's walking. Using DeepLabCut- and DeepEthogram-based pipelines offline, we calculated the shoulder-elbow-wrist angle and defined the distance as the trajectory of the wrist. The distance was shorter in the stance phase but longer in the swing phase after vaseline was treated than before. The duration of the stance and swing phases was shorter in the vaseline-treated period. The angle at forepaw landing and takeoff was smaller and larger, respectively, in the vaseline period. These findings underscore the dominance of moisturizing sole skins over the well-organized dynamics of a spontaneous gait.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"843-848"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144301060","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
Preventive Effects of Psoraleae Semen Extracts on Cognitive Dysfunction in Alzheimer's Disease Model AppNL-P-F Mice. 补骨脂精提取物对老年痴呆症模型AppNL-P-F小鼠认知功能障碍的预防作用
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00773
Genki Hiramatsu, Reina Mizutani, Kazufumi Toume, Yosuke Inada, Masahito Sawahata, Daisuke Uta, Katsuko Komatsu, Toshiaki Kume
{"title":"Preventive Effects of Psoraleae Semen Extracts on Cognitive Dysfunction in Alzheimer's Disease Model App<sup>NL-P-F</sup> Mice.","authors":"Genki Hiramatsu, Reina Mizutani, Kazufumi Toume, Yosuke Inada, Masahito Sawahata, Daisuke Uta, Katsuko Komatsu, Toshiaki Kume","doi":"10.1248/bpb.b24-00773","DOIUrl":"10.1248/bpb.b24-00773","url":null,"abstract":"<p><p>Oxidative stress and neuroinflammation accompanied by microglial activation are increased in Alzheimer's disease (AD) and contribute to the pathogenesis of AD. Nuclear factor erythroid-derived 2-related factor 2 (Nrf2) is a master transcription factor that acts as an endogenous defense mechanism against oxidative stress and inflammation and is a potential target for preventing AD. Psoraleae Semen (PS) reportedly has antioxidant and anti-inflammatory effects. This study aimed to examine the effects of PS extract (PSE) on Nrf2 activation and prevention of cognitive dysfunction in App<sup>NL-P-F</sup> AD model mice. The effects of PSE on antioxidant response element (ARE) activity and cytoprotection in PC12 cells and on microglial activation in BV-2 cells were evaluated. PSE showed high ARE activity and prevented 6-hydroxydopamine-induced cytotoxicity in PC12 cells. Moreover, PSE suppressed lipopolysaccharide-induced nitric oxide production in BV-2 cells. Oral administration of PSE prevented cognitive dysfunction in App<sup>NL-P-F</sup> mice without affecting motor function. Our results support that PSE can contribute to the development of new preventive and therapeutic agents for AD focusing on Nrf2 activation.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"75-79"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078580","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
Involvement of the Na+/Ca2+ Exchanger in the Automaticity of the Cardiomyocytes from the Guinea Pig Pulmonary Vein but Not the Sinus Node. Na+/Ca2+交换参与豚鼠肺静脉而非窦结心肌细胞的自动性。
IF 1.7 4区 医学
Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00725
Ryosuke Odaka, Kana Sekiguchi, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka
{"title":"Involvement of the Na<sup>+</sup>/Ca<sup>2+</sup> Exchanger in the Automaticity of the Cardiomyocytes from the Guinea Pig Pulmonary Vein but Not the Sinus Node.","authors":"Ryosuke Odaka, Kana Sekiguchi, Shogo Hamaguchi, Iyuki Namekata, Hikaru Tanaka","doi":"10.1248/bpb.b24-00725","DOIUrl":"10.1248/bpb.b24-00725","url":null,"abstract":"<p><p>Fluorescence imaging analysis was performed in cardiomyocytes from the sinus node, the orthotopic pacemaker, and the pulmonary vein, a potential ectopic pacemaker that may cause atrial fibrillation, focusing on the role of the Na<sup>+</sup>/Ca<sup>2+</sup> exchanger (NCX). Isolated cardiomyocytes from the guinea pig pulmonary vein and sinus node showing automaticity were loaded with fluorescence probes for analysis. Inhibition of NCX by SEA0400 decreased the Ca<sup>2+</sup> transient frequency in the pulmonary vein cardiomyocytes but not in the sinus node. The basal intracellular Ca<sup>2+</sup> concentration, as well as the number of Ca<sup>2+</sup> sparks in the subsarcolemmal region, was higher in the pulmonary vein cardiomyocytes than in the sinus node. By contrast, the intracellular Na<sup>+</sup> concentration was not different between the pulmonary vein and sinus node cardiomyocytes. The equilibrium potential for NCX (E<sub>NCX</sub>) was estimated to be less negative in the pulmonary vein cardiomyocytes than in the sinus node. In conclusion, the forward mode NCX is involved in spontaneous activity in the pulmonary vein cardiomyocytes but not in the sinus node; this is probably because the Ca<sup>2+</sup> supply and the driving force for the forward mode NCX are both larger in the pulmonary vein cardiomyocytes than in the sinus node.</p>","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"151-161"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143490669","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
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