Biological & pharmaceutical bulletin最新文献

Actual Use of Budesonide Enteric-Coated Capsules for Crohn's Disease in Japan: Analysis of Health Insurance Big Data. 布地奈德肠溶胶囊在日本治疗克罗恩病的实际使用：健康保险大数据分析

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00435

Keiji Yagisawa, Atsuhito Kubota, Shungo Imai, Shunsuke Nashimoto, Yuki Sato, Hitoshi Kashiwagi, Atsuo Maemoto, Mitsuru Sugawara, Yoh Takekuma

{"title":"Actual Use of Budesonide Enteric-Coated Capsules for Crohn's Disease in Japan: Analysis of Health Insurance Big Data.","authors":"Keiji Yagisawa, Atsuhito Kubota, Shungo Imai, Shunsuke Nashimoto, Yuki Sato, Hitoshi Kashiwagi, Atsuo Maemoto, Mitsuru Sugawara, Yoh Takekuma","doi":"10.1248/bpb.b24-00435","DOIUrl":"10.1248/bpb.b24-00435","url":null,"abstract":"Using a large health insurance database in Japan, we examined the real-world usage of budesonide enteric-coated capsules (BUD) in treating Crohn's disease. We analyzed data from the Japan Medical Data Center claims database for Crohn's disease patients prescribed BUD from April 2016 to March 2021, focusing on prescription status, adverse events (AEs), monitoring tests, and concomitant medications over 2 years following BUD initiation. Patients were categorized into two groups based on BUD usage duration: ≤1 year and >1 year. Of the 7364 registered patients, 1049 (14.2%) were prescribed BUD. Among the 562 followed for 2 years, 505 (89.9%) used BUD for ≤1 year and 57 (10.1%) for >1 year. Over 70% of the patients used at least one biologic, and more than 20% used at least two. The proportions of new thiopurine initiation were 22 and 9% in the ≤1-year and >1-year groups, respectively (p = 0.0181). We did not identify any obvious increase in AEs from long-term BUD use within the confines of our study design. However, regardless of prescription duration, over half of the patients lacked hepatitis B virus screening, glycated hemoglobin measurement, adrenal function quantification, or bone densitometry. Usage of strong CYP3A4 inhibitors was more frequent among patients in the BUD >1-year group. This study revealed that numerous Japanese patients received long-term BUD prescriptions. Although no apparent increase in AEs from long-term BUD was detected, we identified inadequate monitoring of AEs and drug interactions, as well as insufficient use of steroid-sparing agents.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"33-38"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045211","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

Assessment of Risk of Acidosis in Patients with Mild-to-Moderate Chronic Kidney Disease Treated with Intravenous Branched-Chain Amino Acid-Enriched Solution: A Propensity Score Matching Analysis. 静脉注射支链氨基酸浓缩液治疗轻中度慢性肾病患者的酸中毒风险评估：倾向得分匹配分析

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00569

Hiroko Kaji, Tomoharu Yokooji, Takanori Taogoshi, Satoru Izumitani, Eisuke Hida, Hiroaki Matsuo

{"title":"Assessment of Risk of Acidosis in Patients with Mild-to-Moderate Chronic Kidney Disease Treated with Intravenous Branched-Chain Amino Acid-Enriched Solution: A Propensity Score Matching Analysis.","authors":"Hiroko Kaji, Tomoharu Yokooji, Takanori Taogoshi, Satoru Izumitani, Eisuke Hida, Hiroaki Matsuo","doi":"10.1248/bpb.b24-00569","DOIUrl":"10.1248/bpb.b24-00569","url":null,"abstract":"Intravenous administration of branched-chain amino acid (BCAA)-enriched solution is contraindicated in patients with severe chronic kidney disease (CKD). However, there have been no reports on its risks in patients with mild-to-moderate CKD. In this study, we compared the incidence of acidosis between patients with mild-to-moderate CKD (estimated glomerular filtration rate [eGFR] ≥30 and <60 mL/min/1.73 m2) and patients without CKD (eGFR ≥60 mL/min/1.73 m2) who received intravenous BCAA-enriched solution after propensity score matching (PSM). A retrospective analysis of the medical records at Hiroshima University Hospital identified 608 patients who were treated with intravenous BCAA-enriched solutions between January 2005 and December 2010. The laboratory data for these patients were analyzed. After PSM, the incidence of acidosis was compared between 91 pairs of patients with mild-to-moderate CKD or no CKD using Fisher's exact test. The incidence of acidosis was significantly higher in the mild-to-moderate CKD group than in the non-CKD group (36.3 vs. 18.7%, p <0.05). The odds ratio for the incidence of acidosis in patients with mild-to-moderate CKD was 2.48 (95% confidence interval 1.26-4.88). Kaplan-Meier curves showed that the cumulative incidence of acidosis increased soon after initiation of intravenous BCAA-enriched solution in both groups. In conclusion, intravenous BCAA-enriched solution can cause acidosis even in patients without CKD, with an increased risk in patients with mild-to-moderate CKD, in whom this agent is not contraindicated. Therefore, intravenous BCAA-enriched solution should be administered with caution in patients with CKD, regardless of its severity.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"46-50"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045323","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

Esaxerenone Improves Vascular Endothelial Dysfunction by Reducing Serum and Glucocorticoid-Regulated Kinase 1 Activity and Enhancing the Akt Pathway in Type 2 Diabetic Mice. Esaxerenone通过降低2型糖尿病小鼠血清和糖皮质激素调节的激酶1活性以及增强Akt通路改善血管内皮功能障碍

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00009

Kumiko Taguchi, Tomoya Furukawa, Takayuki Matsumoto, Tsuneo Kobayashi

{"title":"Esaxerenone Improves Vascular Endothelial Dysfunction by Reducing Serum and Glucocorticoid-Regulated Kinase 1 Activity and Enhancing the Akt Pathway in Type 2 Diabetic Mice.","authors":"Kumiko Taguchi, Tomoya Furukawa, Takayuki Matsumoto, Tsuneo Kobayashi","doi":"10.1248/bpb.b25-00009","DOIUrl":"https://doi.org/10.1248/bpb.b25-00009","url":null,"abstract":"Mineralocorticoid receptor (MR) blockers reduce cardiovascular complications as MRs play a crucial role in cardiovascular regulation. Diabetic cardiovascular complications are caused by vascular endothelial dysfunction. This study used a type 2 diabetic mouse model (DM) to investigate whether esaxerenone (ESAX), an MR blocker, ameliorates vascular endothelial dysfunction. ESAX (3 mg/kg/d) was administered via diet to KK-Ay mice or C57BL/6J mice, a nondiabetic control (Control), for 8 weeks, and metabolic parameters and blood pressure were measured. Vascular responses of the aortic segments were analyzed with acetylcholine, sodium nitroprusside, UK14304, or phenylephrine (PE). The other aortas were used for Western blot analysis. DM mice exhibited higher plasma glucose, insulin, metabolic parameters, and blood pressure levels than those of the Control mice. Parameters that did not include blood pressure were unaltered by DM or ESAX-administered DM (DM + ESAX). However, DM impaired UK14304-induced endothelial-dependent relaxation and nitric oxide production and elevated PE-induced contraction. ESAX administration ameliorated endothelial dysfunction and improved the protein kinase B (Akt) phosphorylation under α2-agonist UK14304 stimulation in the aorta from DM mice compared with that of the Control mice. However, ESAX did not recover the increased G protein-coupled receptor kinase 2 (GRK2) expression and activity in the DM aorta. Furthermore, the DM-induced phosphorylation of serum and glucocorticoid-regulated kinase 1 (SGK1) was inhibited by ESAX. Overall, ESAX attenuates the development of DM-induced endothelial dysfunction by reducing SGK1 activity and enhancing Akt activity without affecting the GRK2 pathway. These results suggest that the vascular protective effects of ESAX could be employed for diabetic vascular complications.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"422-431"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143963136","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

Influence of Size, Flexibility, Hydrophobicity, Surface Charge, and Surface Chemistry on the Biodistribution of Orally Administered Polymer Nanoparticles. 尺寸、柔韧性、疏水性、表面电荷和表面化学对口服聚合物纳米颗粒生物分布的影响。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00005

Go Yasuno, Hiroyuki Koide, Shinya Hirata, Takumi Okamoto, Midori Watanabe, Kaito Saito, Keijiro Sato, Katsuki Matayoshi, Sei Yonezawa, Tomohiro Asai

{"title":"Influence of Size, Flexibility, Hydrophobicity, Surface Charge, and Surface Chemistry on the Biodistribution of Orally Administered Polymer Nanoparticles.","authors":"Go Yasuno, Hiroyuki Koide, Shinya Hirata, Takumi Okamoto, Midori Watanabe, Kaito Saito, Keijiro Sato, Katsuki Matayoshi, Sei Yonezawa, Tomohiro Asai","doi":"10.1248/bpb.b25-00005","DOIUrl":"https://doi.org/10.1248/bpb.b25-00005","url":null,"abstract":"The optimal pharmacokinetics (PK) of orally administered nanoparticles (NPs) varies depending on their application (e.g., drug delivery, adsorbent, and adjuvant). Therefore, engineering NPs to achieve optimal PK is essential for the development of drug designs. Some studies have demonstrated that individual NP factors change the intestinal absorption of NPs; however, no technology has been established to control the biodistribution of orally administered NPs. In this study, a database about the influence of NP characteristics on biodistribution after oral administration was provided. A library of N-isopropylacrylamide polymer NPs with various characteristics that could influence the biodistribution after oral administration, such as size, flexibility, hydrophobicity, surface charges, and surface chemistries, were prepared. NPs with various sizes were synthesized by tuning the surfactant concentration only during synthesis, whereas NPs with different flexibility, hydrophobicity, surface charge, and surface chemistry were synthesized by feeding the corresponding functional monomer. The total amount of NPs accumulated in the organs decreased with increasing NP size, rigidity, hydrophobicity, electric potential (whether positive or negative), and polyethylene glycol modification. The results indicated that the absorption of orally administered NPs can be controlled by optimizing the characteristics of NP such as size, flexibility, hydrophobicity, surface charge, and surface chemistry. The results of this study will provide useful information to design NP formulations.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 4","pages":"399-409"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143972588","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

Impact of Daily High Ergosterol Intake for 14 Weeks in Ovariectomized Rats on Cholesterol and Vitamin D₃ Biosynthesis Pathways. 卵巢切除大鼠连续 14 周每天摄入大量麦角甾醇对胆固醇和维生素 D3 生物合成途径的影响

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00536

Naoko Kuwabara, Junkichi Kanda, Shinji Sato, Saori Nakagawa

{"title":"Impact of Daily High Ergosterol Intake for 14 Weeks in Ovariectomized Rats on Cholesterol and Vitamin D3 Biosynthesis Pathways.","authors":"Naoko Kuwabara, Junkichi Kanda, Shinji Sato, Saori Nakagawa","doi":"10.1248/bpb.b24-00536","DOIUrl":"10.1248/bpb.b24-00536","url":null,"abstract":"Postmenopausal women are at a higher risk of developing dyslipidemia and osteoporosis due to estrogen deficiency, necessitating regular vitamin D supplementation and the use of cholesterol inhibitors, respectively, to prevent these conditions. Despite current treatments, alternatives are needed to address both conditions simultaneously. Ergosterol, a precursor of vitamin D2, is a fungal sterol converted to brassicasterol by 7-dehydrocholesterol reductase, a cholesterol biosynthesis enzyme that converts 7-dehydrocholesterol (a precursor of vitamin D3) into cholesterol. Our previous research demonstrated that ergosterol decreases cholesterol levels and increases 7-dehydrocholesterol levels in human HepG2 hepatoma cells. Furthermore, we reported that ergosterol increases vitamin D2 levels, inhibits the cholesterol biosynthetic pathway, and potentially promotes vitamin D3 biosynthesis in male rats fed a high-fat and high-sucrose diet. In this study, we investigated the effects of daily high ergosterol intake on cholesterol, vitamin D2, and D3 biosynthetic pathways in ovariectomized (OVX) rats using GC-MS and LC with tandem mass spectrometry. OVX rats treated with ergosterol for 14 weeks exhibited significantly decreased plasma cholesterol levels and markers of cholesterol absorption, such as the plant sterol sitosterol. Furthermore, 7-dehydrocholesterol levels increased in these rats compared to untreated OVX rats. We observed that 1α, 25-dihydroxyvitamin D3 levels slightly increased in OVX rats treated with ergosterol. Additionally, ergosterol improved bone strength and increased OVX-induced bone resorption. These results indicate that daily ergosterol intake may aid in the simultaneous prevention of dyslipidemia and osteoporosis in postmenopausal women.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"39-45"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143045324","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

Efficacy of De-Escalation to Cefmetazole in Patients with Bacteremic Urinary Tract Infections Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli. 头孢美唑降压治疗广谱产β-内酰胺酶大肠杆菌所致菌血症性尿路感染的疗效。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00834

Takaya Namiki, Yuta Yokoyama, Motonori Kimura, Shogo Fukuda, Shoji Seyama, Osamu Iketani, Yoshifumi Uwamino, Aya Jibiki, Hitoshi Kawazoe, Hisakazu Ohtani, Naoki Hasegawa, Kazuaki Matsumoto, Rentaro Oda, Hideki Hashi, Sayo Suzuki, Tomonori Nakamura

{"title":"Efficacy of De-Escalation to Cefmetazole in Patients with Bacteremic Urinary Tract Infections Caused by Extended-Spectrum β-Lactamase-Producing Escherichia coli.","authors":"Takaya Namiki, Yuta Yokoyama, Motonori Kimura, Shogo Fukuda, Shoji Seyama, Osamu Iketani, Yoshifumi Uwamino, Aya Jibiki, Hitoshi Kawazoe, Hisakazu Ohtani, Naoki Hasegawa, Kazuaki Matsumoto, Rentaro Oda, Hideki Hashi, Sayo Suzuki, Tomonori Nakamura","doi":"10.1248/bpb.b24-00834","DOIUrl":"https://doi.org/10.1248/bpb.b24-00834","url":null,"abstract":"This study aimed to clarify the optimal value for the unbound cefmetazole concentration to remain above the minimum inhibitory concentration (MIC) (fT ≥ MIC) for efficacy of de-escalation to cefmetazole in patients with bacteremic urinary tract infection by extended-spectrum β-lactamase-producing Escherichia coli. This double-center retrospective observational study was conducted at Tokyo Bay Urayasu Ichikawa Medical Center and Keio University Hospital from January 2012 to October 2022. Efficacy was determined via clinical evaluation (mortality rate, recurrence rate, vital changes) and bacteriological evaluation, and the optimal fT ≥ MIC was calculated via receiver operating characteristic curve analysis. As a result, the number of patients evaluated were 40 (35 and 5 in the treatment success and treatment failure groups, respectively). Univariate analysis showed that fT ≥ MIC, recurrence rate, and MIC for cefmetazole against bacteria were significantly different for the two groups (p < 0.05). Receiver operating characteristic curve analysis showed that the optimal fT ≥ MIC indicating efficacy was 57% (area under the curve: 0.94, 95% confidence interval: 0.86-1.00, p = 0.002). All patients with fT ≥ MIC ≥ 57% had successful treatment, whereas the frequency of treatment failure was high among those with fT ≥ MIC <57%. The optimal fT ≥ MIC for the clinical efficacy of de-escalation to cefmetazole in patients with bacteremic urinary tract infection by extended-spectrum β-lactamase-producing E. coli was fT ≥ MIC ≥ 57%. This finding would be useful for optimal dosing of cefmetazole.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"537-544"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971364","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

External Validation of Population Pharmacokinetic Models for Unbound Cefazolin in Patients Receiving Prophylactic Dosing. 接受预防性给药的非结合头孢唑林人群药代动力学模型的外部验证。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00027

Toshiaki Komatsu, Yuka Kawai, Yoko Takayama, Yuto Akamada, Mayuko Miyagawa, Masaomi Ikeda, Hideyasu Tsumura, Daisuke Ishii, Kazumasa Matsumoto, Masatsugu Iwamura, Hirotsugu Okamoto, Hideaki Hanaki, Katsuya Otori

{"title":"External Validation of Population Pharmacokinetic Models for Unbound Cefazolin in Patients Receiving Prophylactic Dosing.","authors":"Toshiaki Komatsu, Yuka Kawai, Yoko Takayama, Yuto Akamada, Mayuko Miyagawa, Masaomi Ikeda, Hideyasu Tsumura, Daisuke Ishii, Kazumasa Matsumoto, Masatsugu Iwamura, Hirotsugu Okamoto, Hideaki Hanaki, Katsuya Otori","doi":"10.1248/bpb.b25-00027","DOIUrl":"https://doi.org/10.1248/bpb.b25-00027","url":null,"abstract":"This study aimed to evaluate published population pharmacokinetic models of unbound cefazolin to assess their predictive performance using an independent dataset. A systematic literature search was conducted on PubMed to identify studies evaluating the population pharmacokinetics of unbound cefazolin in patients. Subsequently, the selected models were used for external validation. Predictive bias was visually assessed by plotting the prediction errors (PEs) and relative PEs. Predictive precision was evaluated by calculating the mean absolute error (MAE), root mean square error (RMSE), and mean relative error (MRE). The predictive performance of the 4 unbound population pharmacokinetic models was evaluated using clinical data from 64 patients and 218 unbound concentration samples. The PEs for unbound cefazolin concentrations in the Komatsu model indicated a positive bias, while the RPEs demonstrated similar predictive distributions along the y = 0 line, regardless of the predicted values. In contrast, the other 3 models showed a negative bias for both PE and RPE at unbound cefazolin concentrations. The best MAE, RMSE, and MRE (%) values were 4.71, 9.02, and 30.2 in Komatsu et al.'s model, while the next best values were 11.5, 16.1, and 107.2 in Chung et al.'s model. Both models, which performed best regarding bias and accuracy, were also utilized in studies on unbound concentrations and the correlation between total concentrations and protein-binding sites. This study identified these models as the most suitable for predicting unbound cefazolin concentration profiles in surgical patients.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"650-656"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144118627","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

Systemic mRNA Delivery into the Muscle of Duchenne Muscular Dystrophy Model Mice Using Alpha-Dystroglycan Binding Peptide Modified Lipid Nanoparticles. 利用α -糖醛酸结合肽修饰的脂质纳米颗粒将mRNA传递到杜氏肌营养不良模型小鼠的肌肉中。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00898

Eri Sasaki, Yuki Itaya, Yoko Endo-Takahashi, Yusuke Yano, Nobuhito Hamano, Keisuke Hamada, Yamato Kikkawa, Kosuke Nakashima, Rui Tada, Tsuyoshi Miura, Hiroki Tanaka, Hidetaka Akita, Motoyoshi Nomizu, Yoichi Negishi

{"title":"Systemic mRNA Delivery into the Muscle of Duchenne Muscular Dystrophy Model Mice Using Alpha-Dystroglycan Binding Peptide Modified Lipid Nanoparticles.","authors":"Eri Sasaki, Yuki Itaya, Yoko Endo-Takahashi, Yusuke Yano, Nobuhito Hamano, Keisuke Hamada, Yamato Kikkawa, Kosuke Nakashima, Rui Tada, Tsuyoshi Miura, Hiroki Tanaka, Hidetaka Akita, Motoyoshi Nomizu, Yoichi Negishi","doi":"10.1248/bpb.b24-00898","DOIUrl":"https://doi.org/10.1248/bpb.b24-00898","url":null,"abstract":"Duchenne muscular dystrophy (DMD) is a hereditary disease that requires gene or nucleic acid therapy, which involves muscle-targeted delivery of therapeutic material. We previously developed liposomes targeting muscle tissue in DMD model mice (mdx) using an A2G80 peptide, which has an affinity for α-dystroglycan abundantly expressed on the muscle cell membrane. However, these liposomes did not carry gene or nucleic acids. In this study, we aimed to develop muscle-targeting lipid nanoparticles (LNPs) encapsulating luciferase mRNA and evaluate gene expression levels after systemic administration of these LNPs. We first evaluated the efficiency of mRNA delivery based on luciferase activity using polyethylene glycol (PEG)-dimyristoyl glycerol (DMG) and PEG-distearoyl glycerol (DSG) in mdx systemic administration. PEG-DSG-LNPs showed lower luciferase expression in the liver and spleen and higher expression in mdx muscle tissue than PEG-DMG-LNPs. The addition of the A2G80 peptide to LNPs using PEG-DSG (A2G80-DSG-LNPs) significantly increased their activity in mdx but not in normal mice. These results suggest that A2G80-DSG-LNPs allow for muscle-targeted mRNA delivery and are useful tools for DMD treatment.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 5","pages":"721-727"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144172431","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

CB1 Receptor Agonist ACEA Resists ER Stress-Mediated Apoptosis via CB1R-Independent Mechanism. CB1受体激动剂ACEA通过不依赖cb1r的机制抵抗内质网应激介导的细胞凋亡。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00023

Kazuaki Mori, Akinobu Togo, Keisuke Ohta, Toru Asahi, Chihiro Nozaki, Kosuke Kataoka

{"title":"CB1 Receptor Agonist ACEA Resists ER Stress-Mediated Apoptosis via CB1R-Independent Mechanism.","authors":"Kazuaki Mori, Akinobu Togo, Keisuke Ohta, Toru Asahi, Chihiro Nozaki, Kosuke Kataoka","doi":"10.1248/bpb.b25-00023","DOIUrl":"https://doi.org/10.1248/bpb.b25-00023","url":null,"abstract":"Cannabinoid receptor type 1 (CB1R) plays a key role in neuronal homeostasis, synaptic plasticity, and neuroprotection. CB1R antagonists typically protect against CB1R agonists-induced neurotoxicity. However, we previously found that the CB1R antagonists rimonabant and its analog AM251 can also be neurotoxic: under serum-free conditions, these compounds induce apoptosis in human neuroblastoma SH-SY5Y cells through mitochondrial damage and endoplasmic reticulum (ER) stress. To elucidate the mechanisms of this neurotoxicity, we examined the effects of CB1R agonists. We co-treated SH-SY5Y cells with rimonabant or AM251 in combination with either the CB1R agonist arachidonyl 2-chloroethylamide (ACEA) or WIN 55212-2 mesylate (WIN). ACEA, but not WIN, protected cells from rimonabant- and AM251-induced apoptosis. While ACEA had only a limited effect on mitochondrial damage, it significantly reduced phosphorylation of the eukaryotic initiation factor 2 alpha (eIF2α), a key marker of ER stress. Given that ACEA also functions as an agonist of transient receptor potential vanilloid 1 (TRPV1), we investigated its role in ACEA-mediated neuroprotection. The TRPV1 antagonist capsazepine blocked ACEA's protective effects, suggesting that ACEA acts through TRPV1 rather than CB1R. ACEA also prevented apoptosis induced by camptothecin, a well-established apoptosis inducer, through a similar capsazepine-sensitive mechanism, demonstrating its broader protective effects against apoptosis. These findings indicate that rimonabant and AM251 induce neurotoxicity independently of CB1R under serum-free conditions and that ER stress is likely to be a key target of CB1R-independent neuroprotection by ACEA. Our study highlights the complexity of CB1R ligand-associated neurotoxicity and neuroprotection.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 6","pages":"769-781"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144224191","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 Syk Inhibitory Activity of Vialinin A on Degranulation from Antigen-Stimulated RBL-2H3 Cells. Vialinin A对抗原刺激的RBL-2H3细胞脱粒的抑制作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b25-00121

Ange Murielle Djidjou Tagne, Kouichi Sugaya, Jun-Ichi Onose, Naoki Abe

引用次数: 0