Biological & pharmaceutical bulletin最新文献_第5页

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

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 1.8 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":"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":1.8,"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

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 1.8 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":"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":1.8,"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

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 1.8 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":"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":1.8,"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

Hypertonicity and Piezo1 Activation Enhance Radiosensitivity of B16 Melanoma. 高渗性和Piezo1激活增强B16黑色素瘤的放射敏感性。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00214

Yusei Yagi, Kazuki Kitabatake, Mitsutoshi Tsukimoto

{"title":"Hypertonicity and Piezo1 Activation Enhance Radiosensitivity of B16 Melanoma.","authors":"Yusei Yagi, Kazuki Kitabatake, Mitsutoshi Tsukimoto","doi":"10.1248/bpb.b26-00214","DOIUrl":"https://doi.org/10.1248/bpb.b26-00214","url":null,"abstract":"Radiation therapy is widely used for cancer treatment; however, radioresistance remains a major obstacle, particularly in malignant melanoma. In this study, we investigated the effects of hypertonicity and activation of the mechanosensitive ion channel Piezo1 on the radiation response of B16 mouse melanoma cells. Hypertonic conditions significantly impaired radiation-induced DNA damage signaling and/or repair, as evidenced by reduced γH2AX and 53BP1 foci formation, and increased the number of unrepaired DNA damage sites at later time points. Consistently, hypertonicity enhanced radiation-induced reproductive cell death. These effects were attenuated by the Piezo1 inhibitor GsMTx4 and by Piezo1 knockdown, suggesting that Piezo1 partially mediates hypertonicity-induced radiosensitization. Pharmacological activation of Piezo1 using Yoda1 similarly impaired DNA damage responses and enhanced radiation-induced cell death. In addition, the combination of Yoda1 and irradiation significantly suppressed tumor growth in B16 melanoma-bearing mice. Collectively, these findings suggest that hypertonicity and activation of Piezo1 enhance the radiosensitivity of B16 melanoma cells, at least in part through impairment of DNA damage responses, and highlight Piezo1 as a potential target for improving radiotherapy efficacy.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 7","pages":"1049-1059"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390090","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 Nucleic Acid-Loaded Nanobubbles for Ultrasound-Mediated Therapeutic Applications. 核酸负载纳米气泡在超声介导治疗中的应用进展。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00224

Yoko Endo-Takahashi

{"title":"Development of Nucleic Acid-Loaded Nanobubbles for Ultrasound-Mediated Therapeutic Applications.","authors":"Yoko Endo-Takahashi","doi":"10.1248/bpb.b26-00224","DOIUrl":"https://doi.org/10.1248/bpb.b26-00224","url":null,"abstract":"Ultrasound has attracted considerable attention not only as a diagnostic imaging modality but also as a physical trigger for drug delivery system (DDS). Ultrasound irradiation applied in combination with gas-filled bubbles can induce cavitation and transiently increase the permeability of cellular membranes, thereby enhancing the intracellular delivery of therapeutic molecules. Our research group has developed ultrasound-responsive gas-containing lipid nanoparticles, initially termed bubble liposomes (BLs) and later referred to as nanobubbles (NBs), as carriers for nucleic acid delivery. Early studies indicated that BLs facilitated the efficient cytoplasmic delivery of small interfering RNA under ultrasound irradiation. Subsequent investigations expanded the platform to include diverse nucleic acids, including plasmid DNA and microRNA, and revealed therapeutic efficacy in disease models such as hindlimb ischemia. Further developments include strategies for brain-targeted gene delivery mediated via blood-brain barrier modulation and the design of stable anionic NBs with the capacity to load nucleic acids via cationic intermediates. More recently, polysaccharide-coated NBs and microfluidic preparatory methods have been assessed with a view to improving delivery performance and particle uniformity. These advances highlight the potential utility of nucleic acid-loaded NBs as theranostic platforms for the integration of ultrasound imaging and gene delivery. The continued development of this technology may contribute to the advancement of next-generation ultrasound-mediated DDS.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 7","pages":"1038-1042"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366800","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 Deuterated Drugs on Safety: Insights from Pharmacovigilance Data Analysis. 氘化药物对安全性的影响：来自药物警戒数据分析的见解。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00768

Kohei Kitagawa, Hideki Nawa, Shota Asai, Naohiro Iwata, Takahiro Niimura, Hirofumi Hamano, Mitsuhiro Goda, Yoshito Zamami, Keisuke Ishizawa

{"title":"Effect of Deuterated Drugs on Safety: Insights from Pharmacovigilance Data Analysis.","authors":"Kohei Kitagawa, Hideki Nawa, Shota Asai, Naohiro Iwata, Takahiro Niimura, Hirofumi Hamano, Mitsuhiro Goda, Yoshito Zamami, Keisuke Ishizawa","doi":"10.1248/bpb.b25-00768","DOIUrl":"https://doi.org/10.1248/bpb.b25-00768","url":null,"abstract":"Huntington's disease (HD) is a progressive neurodegenerative disorder characterized by motor, cognitive, and psychiatric symptoms. Tetrabenazine (TBZ), a vesicular monoamine transporter 2 inhibitor, is commonly used to manage chorea; however, it may exhibit fluctuating plasma levels and elicit frequent adverse events. In this study, we aimed to clarify the effects of TBZ deuteration on its safety profile. We compared the safety profiles of TBZ and deutetrabenazine (DTBZ) in real-world clinical practice using disproportionality analysis and the large-scale pharmacovigilance database, VigiBase-the WHO's global database of adverse drug reactions. Adverse event signals were assessed using the information component (IC). Seriousness was classified according to clinical outcome, and time to onset (TTO) was analyzed for selected events. TBZ showed signals for disorientation, dystonia, and sleep disorders (IC025 > 0), whereas DTBZ did not. Serious adverse events were reported in 54.7% of TBZ cases and 37.9% of DTBZ cases. The TTO of sleep disorder was also evaluated; however, the number of cases with available TTO information was limited. DTBZ showed fewer adverse event signals and a lower proportion of serious adverse events than TBZ. These findings suggest potential differences in the safety profiles of the two drugs, which may influence tolerability in the treatment of HD.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 6","pages":"983-988"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293350","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 the Ligand-Dependent Coactivator Recruitment of the Nuclear Receptor Pregnane X Receptor Using Its Three-Alanine Residues-Inserted Mutant. 利用3 -丙氨酸残基插入突变体评估核受体孕烷X受体的配体依赖性共激活子募集。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00155

Ayaka Sugawara, Ryota Shizu, Hikaru Nishiguchi, Kotona Motokatsu, Takuomi Hosaka, Takamitsu Sasaki, Kouichi Yoshinari

{"title":"Evaluation of the Ligand-Dependent Coactivator Recruitment of the Nuclear Receptor Pregnane X Receptor Using Its Three-Alanine Residues-Inserted Mutant.","authors":"Ayaka Sugawara, Ryota Shizu, Hikaru Nishiguchi, Kotona Motokatsu, Takuomi Hosaka, Takamitsu Sasaki, Kouichi Yoshinari","doi":"10.1248/bpb.b26-00155","DOIUrl":"https://doi.org/10.1248/bpb.b26-00155","url":null,"abstract":"The pregnane X receptor (PXR) is a nuclear receptor that regulates the expression of drug-metabolizing enzymes in response to various chemicals. Ligand binding to PXR induces a conformational alteration of the C-terminal coactivator-binding motif activation function 2 (AF2), leading to the recruitment of coactivators. The contribution of each coactivator to PXR-mediated transcription may vary depending on the ligand. Therefore, identifying ligand-dependent differences in coactivator recruitment is important for understanding the biological functions of PXR. In this study, we investigated the ligand-dependent recruitment of coactivators using a PXR mutant containing a three-alanine insertion immediately upstream of AF2 (PXR-3A). Mammalian two-hybrid assays showed that PXR-3A recruited coactivators in a ligand-dependent manner. Treatment with the PXR ligand SR12813 induced the interaction of PXR-3A with coactivator peptides. Using reporter assays with the PXR-binding motifs from CYP3A4, CYP2C19, and CYP2C9 promoters, we evaluated the influences of coactivator overexpression on ligand-dependent reporter activity. In assays with the CYP3A4 promoter, rifampicin, rifaximin, or SR12813 induced reporter activity, and overexpression of peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α) or nuclear receptor coactivator 1 (NCoA1) enhanced rifaximin- and SR12813-dependent transactivation. In assays using the CYP2C19 promoter, rifampicin and rifaximin induced reporter activity, whereas SR12813 did not. PGC1α enhanced rifaximin- or SR12813-induced transcription, whereas NCoA1, NCoA2, and activating signal cointegrator-2 (ASC2) did not exhibit clear ligand-dependent effects. NCoA3 knockdown in HepaRG cells attenuated SR12813-dependent induction of CYP2C19. Taken together, using the PXR-3A mutant, we demonstrated ligand-dependent recruitment of coactivators by PXR.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 6","pages":"974-982"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293360","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A Quantitative in Vitro Framework Reveals State-Dependent Pharmacological Responses to Repeated Inflammatory Stimulation in Synovial Fibroblasts. 定量体外框架揭示滑膜成纤维细胞对反复炎症刺激的状态依赖性药理学反应。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b26-00213

Takuro Yamada, Takanatsu Hosokawa, Hiroki Mitoma, Natsune Iwasaki, Yoshiki Katayama, Teruki Nii, Markus H Hoffmann, Takeshi Mori

{"title":"A Quantitative in Vitro Framework Reveals State-Dependent Pharmacological Responses to Repeated Inflammatory Stimulation in Synovial Fibroblasts.","authors":"Takuro Yamada, Takanatsu Hosokawa, Hiroki Mitoma, Natsune Iwasaki, Yoshiki Katayama, Teruki Nii, Markus H Hoffmann, Takeshi Mori","doi":"10.1248/bpb.b26-00213","DOIUrl":"https://doi.org/10.1248/bpb.b26-00213","url":null,"abstract":"Rheumatoid arthritis is characterized by chronic synovial inflammation and recurrent flares, which are thought to involve joint-specific inflammatory memory. Synovial fibroblasts (SFs) contribute to this process through altered responses to repeated inflammatory stimulation. However, pharmacological targeting of these state-dependent responses remains limited, partly due to the lack of screening systems that distinguish responses under initial and repeated stimulation conditions. Here, we established a quantitative in vitro system using primary murine SFs. Repeated tumor necrosis factor-α stimulation enhanced interleukin-6 (IL-6) production, recapitulating key features previously reported in human SFs. This system enabled direct comparison of drug effects under single and repeated stimulation conditions, revealing distinct response patterns and identifying compounds that selectively modulate the enhanced response induced by repeated stimulation. Notably, a complement receptor antagonist attenuated the additional increase in IL-6 production observed after repeated stimulation, accompanied by the attenuation of glycolysis-related gene expression, while showing no significant effect under single stimulation conditions. These findings highlight the importance of state-dependent pharmacological evaluation and demonstrate the utility of this experimental framework for analyzing differential responses associated with repeated inflammatory stimulation.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 6","pages":"1011-1015"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315527","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

Sterility Test Conditions for Purified Sodium Hyaluronate Injection Evaluated via Membrane Filtration. 膜过滤法评价透明质酸钠注射液无菌试验条件。

IF 1.8 4区医学

Biological & pharmaceutical bulletin Pub Date : 2026-01-01 DOI: 10.1248/bpb.b25-00818

Katsuhiko Hayashi, Kenji Ohya, Yukiko Hara-Kudo, Takahiro Ohnishi

{"title":"Sterility Test Conditions for Purified Sodium Hyaluronate Injection Evaluated via Membrane Filtration.","authors":"Katsuhiko Hayashi, Kenji Ohya, Yukiko Hara-Kudo, Takahiro Ohnishi","doi":"10.1248/bpb.b25-00818","DOIUrl":"https://doi.org/10.1248/bpb.b25-00818","url":null,"abstract":"Sterile preparations require a sterility test, commonly performed by membrane filtration (MF) or direct inoculation (DI) as specified in pharmacopeias. MF is the preferred method for filterable aqueous preparations because of its high sensitivity, and DI is often used to test devices due to the difficulty in eluting microorganisms from the surfaces. A recent amendment to International Organization for Standardization 11737-2 now permits MF for liquid products of medical devices. Injections of hyaluronic acid (HA) are listed as drugs in the Japanese Pharmacopoeia (JP), but are classified as liquid products of medical devices in Europe and the U.S.A. The JP mandates DI for HA-based injections. HA-based injections for osteoarthritis were recently considered for reclassification as drugs in the United States because of their anti-inflammatory, analgesic, and chondroprotective effects. This study examined the suitability of MF and DI for sterility testing of an HA-based injection product. In DI, the maximum allowable volume of HA-based injection was set at 0.25 mg/mL of HA in the culture medium. All tested bacterial and fungal growths in media supplemented with 0.25 mg/mL of HA were observed within 3 d (bacteria) and 5 d (fungi). In MF, the injection was diluted with 0.1% peptone-0.1% polysorbate 80 solution. The solution was filtered, and the membrane was washed twice. All tested bacterial and fungal growths were observed in the culture medium. For the sterility test of the HA-based injection product, no growth was observed after 14 d of incubation in both methods. In conclusion, both DI and MF are suitable for sterility testing of HA-based injections.","PeriodicalId":8955,"journal":{"name":"Biological & pharmaceutical bulletin","volume":"49 6","pages":"1001-1005"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148315632","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