Biological & pharmaceutical bulletin最新文献

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":"https://doi.org/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

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":"https://doi.org/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

Actual Use of Budesonide Enteric-Coated Capsules for Crohn's Disease in Japan: Analysis of Health Insurance Big Data.

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":"https://doi.org/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

Activated Fibroblast Growth Factor Receptor 1 Mitigated Poly-PR-Induced Oxidative Stress and Protein Translational Impairment.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00794

Taisei Ito, Kazuki Ohuchi, Hisaka Kurita, Takanori Murakami, Shinnosuke Takizawa, Ayaka Fujimaki, Junya Murata, Yasuhisa Oida, Isao Hozumi, Kiyoyuki Kitaichi, Masatoshi Inden

{"title":"Activated Fibroblast Growth Factor Receptor 1 Mitigated Poly-PR-Induced Oxidative Stress and Protein Translational Impairment.","authors":"Taisei Ito, Kazuki Ohuchi, Hisaka Kurita, Takanori Murakami, Shinnosuke Takizawa, Ayaka Fujimaki, Junya Murata, Yasuhisa Oida, Isao Hozumi, Kiyoyuki Kitaichi, Masatoshi Inden","doi":"10.1248/bpb.b24-00794","DOIUrl":"https://doi.org/10.1248/bpb.b24-00794","url":null,"abstract":"Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterized by selective motor neuron cell death. A GGGGCC hexanucleotide repeat expansion (HRE) within the chromosome 9 open reading frame 72 (C9orf72) gene is a major causative factor in ALS. This abnormal HRE triggers five types of dipeptide repeat protein (DPR), each composed of two alternating amino acid expressions. Among the DPRs, arginine-rich Poly-PR localizes predominantly to the nucleus, exerting particularly strong toxicity on motor and cortical neurons. Several mechanisms have been proposed for poly-PR-induced neurotoxicity. In this study, poly-PR-expressing NSC34 motor neuron-like cells showed an increase in oxidative stress. Fibroblast growth factor receptor 1 (FGFR1) is known to promote neurogenesis and inhibit apoptosis in neurons. However, its neuroprotective effects against DPR-induced toxicity have not been previously reported. Here, we demonstrated that FGFR1 activation reduced oxidative stress by upregulating nuclear factor erythroid 2-related factor 2 (NRF2) expression. Furthermore, we propose that the increase in NRF2 through FGFR1 activation may result from the alleviation of protein translation impairment. Overall, these findings suggest that FGFR1 activation provides neuroprotection against poly-PR toxicity and may represent a potential therapeutic strategy for ALS.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"93-100"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078594","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

Potentiation of Nicotine-Induced Currents by QO58, a Kv7 Channel Opener, in Intracardiac Ganglion Neurons of Rats.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00498

Shiho Arichi, Kei Eto, Masanori Ogata, Sachie Sasaki-Hamada, Hitoshi Ishibashi

{"title":"Potentiation of Nicotine-Induced Currents by QO58, a Kv7 Channel Opener, in Intracardiac Ganglion Neurons of Rats.","authors":"Shiho Arichi, Kei Eto, Masanori Ogata, Sachie Sasaki-Hamada, Hitoshi Ishibashi","doi":"10.1248/bpb.b24-00498","DOIUrl":"https://doi.org/10.1248/bpb.b24-00498","url":null,"abstract":"QO58 (5-(2,6-dichloro-5-fluoropyridin-3-yl)-3-phenyl-2-(trifluoromethyl)-1H-[1,5-a] pyrimidin-7-one) is currently used as a specific activator of the Kv7 (KCNQ) family of K+ channels. Here, we report an unexpected potentiating effect of this drug on nicotinic acetylcholine receptors. We recorded the whole-cell responses to the rapid application of nicotine with the Cs+-based pipette solution in intracardiac ganglion neurons freshly dissociated from the rat heart. Nicotine-induced inward currents were concentration-dependently blocked by mecamylamine, but not by 1 μM atropine at a holding potential of -60 mV. While the application of QO58 per se evoked a persistent inward current at this holding potential, 10 μM QO58 potentiated the peak amplitude of the nicotine-induced current. The QO58-induced inward currents were inhibited by the Kv7 channel blockers XE991 and Ba2+, but not by mecamylamine. On the other hand, the nicotine-induced current potentiated by QO58 was fully inhibited by mecamylamine. The facilitatory action of QO58 on the nicotinic response was unaffected by Ba2+. QO58 did not affect the reversal potential of the nicotine-induced current. QO58 apparently shifted the concentration-response curve of nicotine to the left. The half-maximal effective concentrations for nicotine in the absence and presence of 10 μM QO58 were 10.2 and 4.3 μM, respectively. These results suggest that QO58 acts as a positive allosteric modulator of nicotinic acetylcholine receptors. Given the prevalence of nicotinic receptor signaling, the present observations should be considered in future studies on the roles of Kv7 channels in the function of neural circuits and diseases.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"101-107"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254194","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

Irinotecan-Induced Site-Specific Pigmentation in the Plantar Region of Mice.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00662

Masashi Imai, Keiichi Hiramoto, Shota Tanaka, Mei Okayama, Kazuya Ooi

{"title":"Irinotecan-Induced Site-Specific Pigmentation in the Plantar Region of Mice.","authors":"Masashi Imai, Keiichi Hiramoto, Shota Tanaka, Mei Okayama, Kazuya Ooi","doi":"10.1248/bpb.b24-00662","DOIUrl":"https://doi.org/10.1248/bpb.b24-00662","url":null,"abstract":"Skin pigmentation is a widely recognized side effect of cancer chemotherapy that can negatively affect patient QOL. However, although numerous case reports have documented pigmentation caused by anticancer drugs, the precise mechanisms remain unclear. Among such pigmentation, that induced by 5-fluorouracil (5-FU) has garnered considerable attention, whereas reports on irinotecan-induced pigmentation are comparatively limited. In this study, we investigated the pigmentation-related effects of irinotecan in colored hairless mice. Mice received intraperitoneal injections of 20 mg/kg irinotecan, and we subsequently examined the pigmentation of the plantar and buttock regions. The results indicated that irinotecan specifically induces pigmentation in the plantar region, with no pigmentation observed on the buttocks. In contrast, pigmentation was noted on the buttocks, although not in the plantar region, in the control mice treated with 5-FU and cytarabine. Furthermore, irinotecan treatment promoted a marked elevation in the expression of tyrosinase, cAMP response element binding protein (CREB), and microphthalmia-associated transcription factor (MITF) in the plantar region, whereas no significant changes were observed in the buttocks. These findings indicate that irinotecan leads to site-specific pigmentation in the sole of the foot, thereby highlighting the potential for anticancer drugs to cause localized pigmentation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 2","pages":"108-114"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254264","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

Colistin Resistance in Acinetobacter baumannii: Basic and Clinical Insights.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b23-00642

Go Kamoshida, Noriteru Yamada, Daiki Yamaguchi, Kinnosuke Yahiro, Yuji Morita

{"title":"Colistin Resistance in Acinetobacter baumannii: Basic and Clinical Insights.","authors":"Go Kamoshida, Noriteru Yamada, Daiki Yamaguchi, Kinnosuke Yahiro, Yuji Morita","doi":"10.1248/bpb.b23-00642","DOIUrl":"https://doi.org/10.1248/bpb.b23-00642","url":null,"abstract":"The emergence of drug-resistant bacteria has posed a significant problem in medical institutions worldwide. Colistin, which targets lipopolysaccharide (LPS), serves as a last-resort antimicrobial agent against multidrug-resistant Gram-negative bacteria. Nevertheless, Acinetobacter baumannii, a pathogen with a worldwide prevalence of antimicrobial resistance, has been reported to develop resistance to colistin frequently. In this review, we discuss how A. baumannii acquires resistance to colistin, focusing on modification as well as loss of LPS present in its outer membrane, which is the primary mechanism of A. baumannii's resistance to colistin. Basic and clinical insights regarding colistin resistance in A. baumannii have been discussed in isolation. Therefore, we discuss the relationship between these 2 colistin resistance mechanisms in terms of the frequency and fitness of genetic mutations based on the insights from basic studies and clinical settings. We concluded that understanding the detailed mechanisms of colistin drug resistance requires a comprehensive understanding of both the frequency of mutations and the effects of selection pressure. Finally, we highlight the importance of promoting research from both basic science and clinical perspectives.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 3","pages":"213-221"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143536429","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

Comparison of Oncology Drug Lag in Japan and South Korea Based on the Interval between the U.S. Approval and the Local Approval. 基于美国批准与本土批准间隔的日韩肿瘤药物滞后性比较

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00555

Yoshifumi Tachibana, Jangsoo Yoon, Mamoru Narukawa

{"title":"Comparison of Oncology Drug Lag in Japan and South Korea Based on the Interval between the U.S. Approval and the Local Approval.","authors":"Yoshifumi Tachibana, Jangsoo Yoon, Mamoru Narukawa","doi":"10.1248/bpb.b24-00555","DOIUrl":"https://doi.org/10.1248/bpb.b24-00555","url":null,"abstract":"Drug lag is a serious issue for patients with life-threatening diseases such as cancer. Japan and Korea have been facing a large drug lag, despite having a large market and a good clinical trial environment. We analyzed drug lags for anticancer drugs between these countries, using the information on 82 anticancer drugs approved in the United States between 2017 and 2022. The national health insurance coverage status was also investigated. The approval lag, defined as the number of days from the date of approval in the United States to the date of approval in the country of interest, was used as the indicator of drug lag and was calculated for each drug. The median for all drugs was estimated using the Kaplan-Meier method, with the lag for locally unapproved drugs treated as censored data. The median approval lag in Japan and Korea for all drugs, including locally unapproved drugs, were 1547 d (4.2 years) and 1000 d (2.7 years), respectively. The approval lags for the approved drugs were 216 and 655 d in Japan and Korea, respectively. All drugs approved in Japan were covered by national health insurance whereas many drugs recently approved in Korea were not yet covered. The overall drug lag in Japan was greater than that in Korea due to the high number of unapproved drugs in Japan. In Korea, more drugs have been approved; however, it generally takes longer for them to become widely available to the public.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"11-16"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142977468","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

Development of Research Foundation for Comprehensive Articulation of Drug Effects. 药物效应综合表达研究基金的建立。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00509

Tadahaya Mizuno

{"title":"Development of Research Foundation for Comprehensive Articulation of Drug Effects.","authors":"Tadahaya Mizuno","doi":"10.1248/bpb.b24-00509","DOIUrl":"https://doi.org/10.1248/bpb.b24-00509","url":null,"abstract":"As unexpected adverse events and successful drug repositioning have shown, drug effects are complex and include aspects not recognized by developers. How can we understand these unrecognized drug effects? Drug effects can be numerized by encompassing biological responses to drugs. For instance, the transcriptome data of cultured cells and toxicopathological images of mice treated with a compound represent the effects of the compound in vitro and in vivo, respectively. As a next step, we focused on pattern recognition, a data science framework to extract essentially important low-dimensional latent variables from high-dimensional observed data such as latent variable models. Latent variables are low-dimensional, allowing us to visualize drug effects in an easily recognizable form, such as a radar chart. This bird's-eye view of drug effects enables us to compare them with existing knowledge, potentially articulating the effects of drugs as the known knowns and known unknowns. We believe that the three-step strategy of numerization, visualization, and articulation will allow us to understand drug effects comprehensively, and we are currently verifying this approach. In this review, we will introduce these candidate studies and hope to share our interest in \"pattern recognition of biological responses,\" the pillar of our group.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"1-5"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930619","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

Vitamin D Receptor rs2228570 Gene Polymorphism Is Associated with Asthma Severity and Exacerbations.

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2025-01-01 DOI: 10.1248/bpb.b24-00684

Sekiko Uehara, Keita Hirai, Toshihiro Shirai, Hinako Otaki, Taisuke Akamatsu, Kunihiko Itoh

{"title":"Vitamin D Receptor rs2228570 Gene Polymorphism Is Associated with Asthma Severity and Exacerbations.","authors":"Sekiko Uehara, Keita Hirai, Toshihiro Shirai, Hinako Otaki, Taisuke Akamatsu, Kunihiko Itoh","doi":"10.1248/bpb.b24-00684","DOIUrl":"https://doi.org/10.1248/bpb.b24-00684","url":null,"abstract":"Vitamin D plays a crucial role in immune system function. Several studies have indicated that genetic variations in the vitamin D receptor (VDR) and vitamin D binding protein (VDBP, encoded by GC gene) increase the risk of developing asthma. However, the effect of these variations on the prognosis and clinical outcomes of asthma remains unclear. This study, involving 152 adult patients with asthma, aimed to assess the influence of VDR and GC polymorphisms on asthma severity and its exacerbation. Gene polymorphisms previously associated with asthma risk were analyzed, and VDR mRNA expression levels were evaluated in peripheral blood mononuclear cells. The AA genotype of the VDR rs2228570 polymorphism was associated with an elevated risk of severe asthma compared to the AG/GG genotype (odds ratio, 3.20; 95% confidence interval [CI], 1.24-8.28). Furthermore, patients with the rs2228570 AA genotype showed an elevated risk of exacerbation during the 1-year follow-up period (hazard ratio, 4.01; 95% CI, 1.75-9.15). VDR mRNA expression was significantly reduced in patients with the AA genotype. Furthermore, the mRNA expression levels of GLCCI1, HDAC2, NR3C1, and NFE2L2, which are associated with steroid response, were reduced in patients with the AA genotype. Our findings indicate that patients with the AA genotype of VDR rs2228570 are more likely to experience severe asthma and exacerbations. This polymorphism has the potential to reduce vitamin D efficacy by altering VDR function and expression, potentially resulting in increased inflammation and reduced steroid responsiveness in patients with asthma.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"48 1","pages":"86-92"},"PeriodicalIF":1.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143078582","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