Biological & pharmaceutical bulletin最新文献_第2页

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

IF 1.7 4区医学

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

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

{"title":"Identification of 3,5-Bis (2-Ethoxybenzylidene) Piperidin-4-one as a Monocarbonyl Curcumin Analog Inhibiting Cell-Intrinsic NF-κB Activity in 4T1 Breast Cancer Cells.","authors":"Sana Jabbar, Sisca Ucche, Farooq Muhammad Irshad, Suthasinee Seephan, So-Ichiro Sasaki, Retno Murwanti, Ritmaleni, Yoshihiro Hayakawa","doi":"10.1248/bpb.b25-00785","DOIUrl":"https://doi.org/10.1248/bpb.b25-00785","url":null,"abstract":"Although numerous biological properties of curcumin, a bioactive polyphenol from the rhizome of turmeric (Curcuma longa), have been documented, its poor bioavailability limits clinical application. Therefore, identifying new analogs with improved pharmacokinetics and pharmacological properties is essential. Given that curcumin and its related compounds are known to inhibit cancer cell progression and metastasis through nuclear factor-kappaB (NF-κB) signaling inhibition, we investigated 58 newly synthesized, structurally diverse monocarbonyl curcumin analogs. Their inhibitory effects on intrinsic NF-κB activity were assessed in breast cancer cells using the 4T1 cell line expressing a luciferase NF-κB reporter. Among the 58 monocarbonyl curcumin analogs, 3,5-bis(2-ethoxybenzylidene)piperidin-4-one (E145) exhibited potent inhibition of NF-κB activity in 4T1 breast cancer cells. Based on the structure-activity relationship analysis, the central heterocyclic monocarbonyl linker structure of E145 contributed to its increased potency in NF-κB inhibition.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"725-731"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721710","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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

IF 1.7 4区医学

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

Tetsuya Saita, Miyabi Teramoto

{"title":"Immunohistochemical Localization of Sotorasib-Protein Conjugates in the Rat Gastrointestinal Tract.","authors":"Tetsuya Saita, Miyabi Teramoto","doi":"10.1248/bpb.b26-00033","DOIUrl":"https://doi.org/10.1248/bpb.b26-00033","url":null,"abstract":"Sotorasib is a molecularly targeted drug that exerts antitumor effects by selectively binding to KRAS G12C through a Michael addition reaction, irreversibly inhibiting KRAS. However, the frequent occurrence of adverse events, such as gastrointestinal and hepatic disorders, has raised major concerns. These toxicities are thought to arise from interactions between sotorasib and proteins other than KRAS in normal cells. In this study, we generated a specific antibody against sotorasib and established an immunohistochemical method capable of detecting sotorasib-protein conjugates. Using this technique, we clarified the localization of sotorasib-protein conjugates in the digestive tract of rats, including the duodenum, jejunum, ileum, and colon. Sotorasib-protein conjugates were strongly localized to the villous epithelial cells of the small intestine but were scarcely detected in the colon, highlighting regional differences. This study elucidates the localization of sotorasib-protein conjugates in the gastrointestinal tract of rats and provides important insights into the mechanisms underlying sotorasib-induced gastrointestinal disorders.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"732-737"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147721738","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

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

IF 1.7 4区医学

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

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

{"title":"Ganoderic Acid A Derived from Reishi Mushroom Ganoderma lucidum Protects against Intestinal Immunity Reduction Due to Oxidative Stress in Rat.","authors":"Atsuhito Kubota, Keisuke Okamoto, Genki Yasuda, Katsuya Narumi, Yuji Suzuki, Hinata Ueda, Ayako Mori, Natsuko Takahashi-Suzuki, Takashi Satoh, Ken Iseki, Masaki Kobayashi","doi":"10.1248/bpb.b25-00688","DOIUrl":"https://doi.org/10.1248/bpb.b25-00688","url":null,"abstract":"Reishi (Ganoderma lucidum) is known to enhance intestinal immunity, with ganoderic acid A (GA-A) identified as one of its active constituents. However, the specific role of GA-A in regulating immune components such as immunoglobulin A (IgA) from Peyer's patches (PPs) and α-defensin 5 from Paneth cells remains unclear. Additionally, the ability of Reishi to counteract oxidative stress-induced intestinal immune suppression has not been fully elucidated. Therefore, in this study, we aimed to examine the effects of Reishi and GA-A on intestinal immunity in a rat model of ischemia-reperfusion (I/R) injury. Oral administration of GA-A increased IgA secretion from PP cells isolated from rat small intestine and upregulated the mRNA expression of rat α-defensin 5 (RD-5) and toll-like receptor 4 (TLR4) in the ileum, similar to Reishi. In contrast, GA-A did not exhibit immunostimulatory effects in TLR4-deficient mice. In the I/R rat model, both Reishi and GA-A significantly restored IgA secretion and RD-5 mRNA expression, mitigating immune suppression. They were also associated with changes in superoxide dismutase 1 (SOD1) and SOD3 mRNA expression under I/R conditions and prevented villus shedding and Paneth cell loss, indicating protection against I/R-induced intestinal immune decline. These results were comparable to those observed with caffeic acid, the positive control. Overall, these findings suggest that Reishi mitigates intestinal immune suppression caused by I/R injury, with GA-A serving as a key active component mediating these protective effects.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 4","pages":"701-707"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cardioprotective Role of Neuregulin1-ErbB2 Signaling Pathway: Its Physiological and Onco-Cardiological Roles in the Heart. 神经调节蛋白1- erbb2信号通路的心脏保护作用：其在心脏中的生理和肿瘤学作用。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00481

Yoshinori Mikami, Satomi Adachi-Akahane

{"title":"Cardioprotective Role of Neuregulin1-ErbB2 Signaling Pathway: Its Physiological and Onco-Cardiological Roles in the Heart.","authors":"Yoshinori Mikami, Satomi Adachi-Akahane","doi":"10.1248/bpb.b25-00481","DOIUrl":"https://doi.org/10.1248/bpb.b25-00481","url":null,"abstract":"Neuregulin 1 (NRG1), a member of the epidermal growth factor (EGF) family, regulates the development, differentiation, proliferation, and plasticity in multiple tissues through its binding to ErbB3 and ErbB4 receptors. In the cardiovascular system, NRG1 plays a crucial role in cardiac development, physiological function, and cell survival. Since NRG1 exerts cardioprotective effects through its interaction with ErbB2/ErbB4 and ErbB4 homodimers on cardiomyocytes, the administration of recombinant human NRG1 has the potential for the treatment of heart failure. ErbB2 is known as human epidermal growth factor receptor 2 (HER2), which is overexpressed in approximately 20% of breast cancers. Trastuzumab (TRZ), a humanized monoclonal antibody targeting ErbB2/HER2, is used for the therapy of HER2-positive breast cancer. However, cardiotoxicity has been observed in approximately 5-10% of patients treated with TRZ. Risk factors for the onset of cardiotoxicity include the use of anthracyclines, hypertension, and diabetes. However, the mechanism linking diabetes and TRZ-induced cardiotoxicity remains unclear. Recently, we reported that the serum levels of NRG1 were elevated in the mouse model of diabetic cardiomyopathy. We found that the up-regulated NRG1 compensates for insulin deficiency to maintain systolic function in the early stage of diabetic cardiomyopathy. This review aims to discuss the physiological roles of NRG1-ErbB2 signaling in the cardiovascular system, the cardioprotective effects of NRG1 and its clinical applications, and the molecular mechanisms of TRZ-induced cardiotoxicity through the blockade of the NRG1-ErbB2 signaling pathway.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"24-29"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145899243","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

Evaluation of Drug-Induced Kidney Injury by Primary Culture of Rat Kidney Tissue Slices Using Oxygen-Permeable Polyolefin Plate with Low Drug Adsorption. 低药物吸附性透氧聚烯烃板原代培养大鼠肾组织片评价药物性肾损伤。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00572

Moeno Kadoguchi, Kohei Matsushita, Katsuhiro Esashika, Jingjing Yang, Jun Takahashi, Ikumi Tamai, Hiroshi Arakawa

{"title":"Evaluation of Drug-Induced Kidney Injury by Primary Culture of Rat Kidney Tissue Slices Using Oxygen-Permeable Polyolefin Plate with Low Drug Adsorption.","authors":"Moeno Kadoguchi, Kohei Matsushita, Katsuhiro Esashika, Jingjing Yang, Jun Takahashi, Ikumi Tamai, Hiroshi Arakawa","doi":"10.1248/bpb.b25-00572","DOIUrl":"https://doi.org/10.1248/bpb.b25-00572","url":null,"abstract":"Rat kidney tissue slices are expected to be useful for an in vitro evaluation of drug-induced kidney injury (DIKI). We previously established a primary culture of rat kidney tissue slices using gas-permeable plates. However, polydimethylsiloxane (PDMS) exhibits a significant adsorption of lipophilic drugs, leading to limitations in DIKI evaluation. The aim of the present study was to evaluate a gas-permeable InnoCell™ non-treated plate made of polyolefin with low adsorption of lipophilic compounds for the primary culture of rat kidney tissue slices as an in vitro DIKI evaluation system. Drug concentrations in the medium were measured 24 h after the addition of 9 drugs to PDMS plates and InnoCell™ non-treated plates. Intra-tissue ATP levels and histopathology of rat kidney tissue slices were examined on Day 3 of culture. As a result, the InnoCell™ non-treated plates exhibited lower adsorption rates for sunitinib, cyclosporine A, and alectinib than the PDMS plates. Intra-tissue ATP levels were maintained, and immunohistochemical staining of megalin and aquaporin 1 was observed for up to 3 d. Furthermore, exposure to nephrotoxic lipophilic drugs reduced the ATP content in slices compared to that in non-treated slices. These results suggest that the primary culture of rat kidney tissue slices using InnoCell™ non-treated plates is useful for the DIKI evaluation of lipophilic drugs compared with conventional PDMS plates.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"122-129"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146017107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Identification of Inhibitors for eIF5A2-Dependent Translation Elongation by Monitoring the Translational Efficiency of Polyproline Motif in Mitochondrial Fission Regulator 1. 通过检测线粒体裂变调节因子中聚脯氨酸基序的翻译效率鉴定eif5a2依赖性翻译延伸抑制剂1。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00720

Masato Suzuki, Masahiro Komeno, Ryosuke Yasumura, Ayuna Miwa, Misaki Enomoto, Hitoshi Kotani, Ken Matsumoto, Kazunori Akimoto, Chiaki Takahashi, Kazuei Igarashi, Kyohei Higashi

{"title":"Identification of Inhibitors for eIF5A2-Dependent Translation Elongation by Monitoring the Translational Efficiency of Polyproline Motif in Mitochondrial Fission Regulator 1.","authors":"Masato Suzuki, Masahiro Komeno, Ryosuke Yasumura, Ayuna Miwa, Misaki Enomoto, Hitoshi Kotani, Ken Matsumoto, Kazunori Akimoto, Chiaki Takahashi, Kazuei Igarashi, Kyohei Higashi","doi":"10.1248/bpb.b25-00720","DOIUrl":"https://doi.org/10.1248/bpb.b25-00720","url":null,"abstract":"We previously reported that eukaryotic translation initiation factor 5A2 (eIF5A2), rather than eIF5A1, is important for the proliferation of HeLa S3 and MDA-MB-231 cells, despite the 84% amino acid sequence identity between eIF5A1 and eIF5A2. In addition, individual upregulated genes, including mitochondrial fission regulator 1 (MTFR1), which has a proline-rich motif, by eIF5A2 were different from those in eIF5A1. Thus, eIF5A2-dependent translational elongation is a promising target for cancer treatment with minimal side effects. In this study, we constructed a high-throughput screening system to identify eIF5A2-dependent translation elongation inhibitors by monitoring the translation efficiency of the MTFR1-luciferase fusion protein in HeLa S3 cells. Orlistat and andrographolide (AGP) were suggested as inhibitors of eIF5A2-dependent translation elongation among 1744 compounds from libraries. In addition to the findings related to AGP, the present study revealed that orlistat and the silencing of eIF5A2 suppressed the invasive activity of MDA-MB-231 cells. Downregulation of heparanase 1 expression, but not of matrix metalloproteinase-2 (MMP2) and MMP9, by eIF5A2 silencing was similar to that by treatment with orlistat and AGP, suggesting that orlistat and AGP were, at least in part, capable of attenuating eIF5A2-dependent translation elongation through the repression of eIF5A2 expression. Based on these observations, monitoring the translational efficiency of MTFR1 synthesis may be useful for identifying new eIF5A2 inhibitors.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"355-363"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275629","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 Chronic Kidney Disease on the Onset of Sepsis: A Systematic Review. 慢性肾脏疾病对脓毒症发病的影响：一项系统综述。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00585

Sumika Osa, Yuki Enoki, Ayuka Endo, Kanako Kumamoto, Keita Kobayashi, Chihiro Komiya, Natsuki Satake, Junichi Kawakami, Tatsuya Yagi, Kazuaki Taguchi, Kazuaki Matsumoto

{"title":"Impact of Chronic Kidney Disease on the Onset of Sepsis: A Systematic Review.","authors":"Sumika Osa, Yuki Enoki, Ayuka Endo, Kanako Kumamoto, Keita Kobayashi, Chihiro Komiya, Natsuki Satake, Junichi Kawakami, Tatsuya Yagi, Kazuaki Taguchi, Kazuaki Matsumoto","doi":"10.1248/bpb.b25-00585","DOIUrl":"10.1248/bpb.b25-00585","url":null,"abstract":"Patients with chronic kidney disease (CKD) who develop sepsis experience worse prognoses; however, the impact of CKD on the incidence of sepsis has not been systematically investigated. A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A comprehensive search of Medical Literature Analysis and Retrieval System Online, Web of Science, the Cochrane Register of Controlled Trials, and ClinicalTrials.gov was performed for literature published prior to May 22, 2025, comparing the onset of sepsis in patients with or without CKD. The risk of bias was determined using the Risk of Bias in Nonrandomized Studies of Interventions tool. This study was registered with the International Prospective Register of Systematic Reviews (CRD42023465075). A total of 14 studies met the inclusion criteria for the systematic review. Of these, 5 examined community-acquired sepsis, 2 focused on intensive care unit-acquired sepsis, and the rest investigated surgery-acquired sepsis. Most studies enrolled populations aged over 65 years; 2 assessed age-related sepsis risk. One study evaluated sepsis occurrence in patients with end-stage CKD, while 3 studies stratified this association by estimated glomerular filtration rate (eGFR). Nearly all studies demonstrated an increased risk of sepsis among patients with CKD, with the risk progressively increasing as eGFR declined. Additionally, 2 studies reported that CKD elevated the risk of sepsis regardless of age, and all included studies indicated a low risk of bias. We indicate that patients with CKD may have a higher risk of developing sepsis than individuals without CKD.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 1","pages":"99-107"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145997195","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

Enhanced Therapeutic Efficacy of Photodynamic Therapy Using Hybrid Liposomes Containing Indocyanine Green in a Triple-Negative Breast Cancer Mouse Model. 含有吲哚菁绿的混合脂质体在三阴性乳腺癌小鼠模型中的光动力治疗效果增强。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00745

Masaki Okumura, Hinano Otsuka, Junna Takai, Koichi Goto, Yoko Matsumoto, Hideaki Ichihara

{"title":"Enhanced Therapeutic Efficacy of Photodynamic Therapy Using Hybrid Liposomes Containing Indocyanine Green in a Triple-Negative Breast Cancer Mouse Model.","authors":"Masaki Okumura, Hinano Otsuka, Junna Takai, Koichi Goto, Yoko Matsumoto, Hideaki Ichihara","doi":"10.1248/bpb.b25-00745","DOIUrl":"https://doi.org/10.1248/bpb.b25-00745","url":null,"abstract":"Triple-negative breast cancer (TNBC) is characterized by the absence of hormone receptors and human epidermal growth factor receptor 2 (HER2) expression, rendering hormone therapy and HER2-targeted treatments ineffective. Consequently, conventional chemotherapy remains the primary therapeutic option, despite its severe side effects and poor prognosis. Hybrid liposomes (HL) composed of phospholipids and polyethylene glycol (PEG)-based surfactants have been reported to have therapeutic effects on various cancers without containing anticancer drugs. In this study, we investigated whether photodynamic therapy (PDT) with HL containing indocyanine green (HL/ICG) enhanced the therapeutic effect of HL alone in a mouse model of subcutaneous implantation of triple-negative breast cancer (TNBC) cells in vivo. HL/ICG selectively accumulated in tumors in mice implanted with 4T1-Luc cells, a TNBC cell line. Histological analysis of resected tumor tissues following HL/ICG-mediated PDT revealed a significant increase in cells positive for oxidative stress markers, indicating elevated intracellular oxidative damage. Additionally, a marked presence of apoptotic cells was observed, suggesting that PDT effectively induced programmed cell death in tumor tissues. These results indicate that PDT with HL/ICG induces oxidative stress-mediated apoptosis in tumors derived from 4T1-Luc cells and significantly enhances the therapeutic efficacy of HL alone in vivo, highlighting its potential as a promising strategy for the treatment of TNBC.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"310-315"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146200094","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

Risk Factor of Persistent Hypotension Associated with 5-Aminolevulinic Acid: A Single-Institution Retrospective Study. 5-氨基乙酰丙酸与持续性低血压相关的危险因素：一项单机构回顾性研究

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00474

Naoto Okada, Hikaru Kimura, Masakazu Ozaki, Miho Tamura, Fumiya Ochi, Takaaki Sasaki, Tomoyo Takimoto, Takashi Kitahara

{"title":"Risk Factor of Persistent Hypotension Associated with 5-Aminolevulinic Acid: A Single-Institution Retrospective Study.","authors":"Naoto Okada, Hikaru Kimura, Masakazu Ozaki, Miho Tamura, Fumiya Ochi, Takaaki Sasaki, Tomoyo Takimoto, Takashi Kitahara","doi":"10.1248/bpb.b25-00474","DOIUrl":"https://doi.org/10.1248/bpb.b25-00474","url":null,"abstract":"5-Aminolevulinic acid (5-ALA), an amino acid precursor of protoporphyrin IX, is used in the photodynamic diagnosis (PDD) of bladder cancer because it emits fluorescence at specific wavelengths. Severe hypotension has been reported in patients undergoing 5-ALA-based PDD. Previous studies have mainly focused on hypotension occurring immediately after 5-ALA administration. Persistent hypotension lasting beyond the day of administration has also been reported, indicating a need for continued postoperative management. However, the risk factors associated with persistent 5-ALA-induced hypotension remain unclear. This retrospective study aimed to identify the risk factors for persistent hypotension following 5-ALA administration. Among 263 patients who received 5-ALA for PDD of bladder cancer at Yamaguchi University Hospital between April 2018 and March 2022, 183 developed hypotension and were included in the analysis. Patients were classified into a persistent hypotension group (n = 30), comprising those with continued hypotension the following day, and a nonpersistent group (n = 153). Baseline demographics and clinical characteristics were comparable between the groups. In contrast, preoperative hemoglobin levels were significantly lower in the persistent group (p < 0.05). Multivariate logistic regression analysis identified preoperative hemoglobin levels as an independent risk factor for persistent hypotension (odds ratio, 0.76; 95% confidence interval, 0.60-0.97). A hemoglobin concentration of 12.9 g/dL was determined as the cutoff value for predicting the incidence of persistent hypotension using receiver-operating characteristic curve analysis. Although further validation is required, these findings suggest that the preoperative hemoglobin level may serve as a potential indicator for risk stratification of persistent hypotension induced by 5-ALA.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"335-340"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146218403","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 Transport Properties of Human Zinc Transporter 1: Kinetics and pH-Dependency. 人体锌转运蛋白的功能转运特性1：动力学和ph依赖性。

IF 1.7 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00624

Yuma Yoshioka, Takaaki Miyaji

{"title":"Functional Transport Properties of Human Zinc Transporter 1: Kinetics and pH-Dependency.","authors":"Yuma Yoshioka, Takaaki Miyaji","doi":"10.1248/bpb.b25-00624","DOIUrl":"https://doi.org/10.1248/bpb.b25-00624","url":null,"abstract":"Intracellular zinc (Zn2+) homeostasis is essential for physiological and pathological processes and is strictly regulated by Zn2+ transporters. Zinc transporter 1 (ZnT1) is a ubiquitously expressed plasma membrane-localized Zn transporter that exports Zn2+ from the cytoplasm to the extracellular space. However, the functional transport properties regarding kinetics and driving forces of ZnT1 remain debatable. In this study, we established a cell-free proteoliposome assay system and demonstrated that ZnT1 transports Zn2+ with high affinity in pH-dependent and pH-independent manners. The Km and Vmax of pH-dependent Zn2+ transport were 0.40 μM and 15.13 nmol/min/mg protein, and those of pH-independent Zn2+ transport were 0.52 μM and 8.88 nmol/min/mg protein (low concentrations of Zn2+), 3.02 μM and 17.59 nmol/min/mg protein (high concentrations of Zn2+), respectively, suggesting biphasic kinetic components of Zn2+ transport. Even without pH gradient formation, ZnT1 exhibits potent Zn2+ transport activity. In pH dependency, Zn2+ transport activity was higher at an inside pH of 6.0 than at 6.5-7.5 for proteoliposomes, despite the same ΔpH of 0.5-1.5. The Zn2+ transport activity decreased at an outside pH of 8.0, despite an increase in ΔpH. Although previous studies have proposed that ZnT1-mediated Zn2+ transport activity is driven by a calcium (Ca2+) gradient and not by a pH gradient, Ca2+ does not enhance Zn2+ transport activity in the presence or absence of a pH gradient. These results strongly suggest that ZnT1 protein transports Zn2+ optimally at a specific pH and exports excess intracellular Zn2+ even without ΔpH.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 2","pages":"364-370"},"PeriodicalIF":1.7,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147275552","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