Journal of Toxicological Sciences最新文献_第6页

Ontogeny of schooling behavior and stage-specific vulnerability to valproic acid in Xenopus laevis larvae. 非洲爪蟾幼虫对丙戊酸的群体行为和阶段特异性易损性的个体发生。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.463

Momoka Yamashita, Hayase Horie, Akinori Ishihara

{"title":"Ontogeny of schooling behavior and stage-specific vulnerability to valproic acid in Xenopus laevis larvae.","authors":"Momoka Yamashita, Hayase Horie, Akinori Ishihara","doi":"10.2131/jts.51.463","DOIUrl":"https://doi.org/10.2131/jts.51.463","url":null,"abstract":"Perinatal exposure to chemicals such as valproic acid (VPA) increases the risk of neurodevelopmental disorders, including autism spectrum disorder (ASD). Because maternal drug metabolism complicates the assessment of fetal impacts in mammalian models, Xenopus laevis tadpoles have emerged as an effective alternative for neurotoxicology. Tadpoles exhibit \"schooling,\" a polarized social aggregation behavior. Previous studies, which exposed tadpoles to VPA continuously from stage NF42 to NF49, suggested that VPA-induced social behavior abnormalities are triggered during this period. In this study, we re-evaluated the ontogeny of schooling behavior and its vulnerability to VPA by administering short-term exposures at specific developmental stages. Using computational modeling and statistical analyses, we compared the spatial distribution of live tadpoles with computer-simulated random models. Untreated tadpoles exhibited significant, non-random social aggregation as early as stage NF42, indicating that the sensorimotor circuitry for schooling is established earlier than previously assumed. Furthermore, tadpoles exposed to VPA for 4 days starting at stages NF42 and NF48 maintained schooling behavior, whereas VPA exposure starting at stage NF52 significantly disrupted spatial cohesion. These findings indicate that while social behavior is acquired prior to NF42, NF52 represents a critical window of heightened pharmacological vulnerability to teratogens, providing new insights into the etiology of environmentally induced neurodevelopmental disorders.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 9","pages":"463-469"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148881065","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

Whole-genome sequencing-based profiling of CYP2D6 structural variants in Japanese patients with solid tumors. 基于全基因组测序的日本实体瘤患者CYP2D6结构变异分析

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2026-01-01 DOI: 10.2131/jts.51.549

Sumiko Ohnami, Takeshi Nagashima, Keiichi Hatakeyama, Kouji Maruyama, Maki Mizuguchi, Sou Nakatani, Fukumi Kamada, Yuji Shimoda, Keiichi Ohshima, Kenichi Urakami, Shumpei Ohnami, Ken Yamaguchi

{"title":"Whole-genome sequencing-based profiling of CYP2D6 structural variants in Japanese patients with solid tumors.","authors":"Sumiko Ohnami, Takeshi Nagashima, Keiichi Hatakeyama, Kouji Maruyama, Maki Mizuguchi, Sou Nakatani, Fukumi Kamada, Yuji Shimoda, Keiichi Ohshima, Kenichi Urakami, Shumpei Ohnami, Ken Yamaguchi","doi":"10.2131/jts.51.549","DOIUrl":"https://doi.org/10.2131/jts.51.549","url":null,"abstract":"Cytochrome P450 2D6 (CYP2D6), a key enzyme involved in the metabolism of a wide range of pharmaceuticals, exhibits extensive genetic variants, including copy number variations (CNVs) and structural alterations. Hybrid alleles formed between CYP2D6 and its highly homologous pseudogene CYP2D7 frequently result in reduced or absent enzymatic activity and show marked interethnic variability. However, accurate characterization of CNVs and hybrid structures in the Japanese population remains technically challenging. In this study, we performed a comprehensive analysis of CYP2D6 genetic and structural variants in 1,287 Japanese patients with solid tumors using whole-genome sequencing (WGS). CNVs and diplotypes were inferred using Sequenza and Aldy, visually inspected with Integrative Genomics Viewer (IGV), and validated using quantitative PCR and Sanger sequencing. A total of 68 distinct diplotypes were identified. The most frequent diplotype was *1/36+*10 (0.2176), followed by *1/*1 (0.1919), *1/*2 (0.0940), *1/*10 (0.0653), *2/*36+*10 (0.0645), and *36/*36+*10 (0.0513). Complete gene deletion (*5/*5) was detected in three cases, and heterozygous deletion (*5/-) in 86 cases. Given that functional annotations for CYP2D6 alleles are well established, WGS-based comprehensive detection represents a practical and scalable strategy for pharmacogenomic profiling. This approach is expected to support optimized drug selection and advance personalized medicine.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"51 10","pages":"549-555"},"PeriodicalIF":1.8,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149111533","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

Assessing the Impact of Firm Age and Location on SME Growth Potential in Namibian Markets 评估公司年龄和地点对纳米比亚市场中小企业增长潜力的影响

4区医学

Journal of Toxicological Sciences Pub Date : 2025-11-30 DOI: 10.64375/6cxecn38

Adetunji Anthony Adeyanju, Shihaleni E. Ndjaba, Mary Onjefu

{"title":"Assessing the Impact of Firm Age and Location on SME Growth Potential in Namibian Markets","authors":"Adetunji Anthony Adeyanju, Shihaleni E. Ndjaba, Mary Onjefu","doi":"10.64375/6cxecn38","DOIUrl":"https://doi.org/10.64375/6cxecn38","url":null,"abstract":"This study investigates the impact of business age and location on the growth of small and medium-sized enterprises (SMEs) in Namibia. Using a cross-sectional survey design and descriptive-analytical approach, data were collected from SMEs operating in five key towns. A stratified sampling technique ensured robust representation, yielding a high response rate of 94.5% from 189 questionnaires. The findings reveal that a substantial majority of SMEs are in their early stages, with 66% of firms operating for less than five years, indicating limited operational experience and resource bases that may hinder their rapid growth. Favourable environmental conditions, including proximity to customers, safe neighbourhoods, and advantageous lease terms, were identified as key enablers of operational efficiency and competitive advantage. These insights highlight the need for targeted policy interventions and innovative management practices that support young SMEs and leverage locational benefits to foster sustainable growth. This study contributes to the understanding of SME dynamics in emerging markets and offers actionable strategies for enhancing business performance in a competitive landscape.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"6 3","pages":"318-330"},"PeriodicalIF":0.0,"publicationDate":"2025-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://journals.ium.edu.na/index.php/njms/article/download/91/170","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147919982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Dose-dependent metabolic and oviposition effects of lithium cobalt oxide in Drosophila 氧化钴锂对果蝇代谢和产卵的剂量依赖性影响

4区医学

Journal of Toxicological Sciences Pub Date : 2025-11-02 DOI: 10.1080/02772248.2025.2580609

Hui Jin, Feiyue Feng, Fanhao Kong, Xiangyü Li, Jie Shen

引用次数: 0

Quality and biochemical assessment of apple ( Malus pumila L. var. Red Delicious) grown around brick kilns in Budgam District of Kashmir 克什米尔Budgam地区砖窑周围种植的苹果（Malus pumila L. var. Red Delicious）的质量和生化评价

4区医学

Journal of Toxicological Sciences Pub Date : 2025-05-20 DOI: 10.1080/02772248.2025.2503762

Javeed Iqbal Ahmad Bhat, Humayun Azad, Tariq Ahmad Bhat, Immad A. Shah

引用次数: 0

Carbon nanotubes induce autophagy, apoptosis, and S-phase cell cycle arrest in HeLa cells 碳纳米管诱导HeLa细胞自噬、凋亡和s期细胞周期阻滞

4区医学

Journal of Toxicological Sciences Pub Date : 2025-05-02 DOI: 10.1080/02772248.2025.2498380

Haiyan Peng, Min Wu, Chao Yan, Jian Wan, Hongmao Zhang, Shumao Ding

引用次数: 0

Developmental toxicity of novel alternatives to perfluorooctanoic acid in zebrafish embryos 全氟辛酸新替代品对斑马鱼胚胎的发育毒性

4区医学

Journal of Toxicological Sciences Pub Date : 2025-04-21 DOI: 10.1080/02772248.2025.2493683

Dan Yang, Xiaohui Zhao, Shasha Dong, Cong Liu, Jianhui Xu, Xiaohui Li, Jing Xing, Yawei Shi, Ya Sun, Guanghui Ding

引用次数: 0

Per- and polyfluoroalkyl substances: toxicokinetics, exposure and health risks. 全氟和多氟烷基物质：毒性动力学、接触和健康风险。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.97

Yukiko Fujii, Kouji H Harada

{"title":"Per- and polyfluoroalkyl substances: toxicokinetics, exposure and health risks.","authors":"Yukiko Fujii, Kouji H Harada","doi":"10.2131/jts.50.97","DOIUrl":"10.2131/jts.50.97","url":null,"abstract":"Per- and polyfluoroalkyl substances (PFAS) are a group of chemicals containing stable per- or polyfluoroalkyl groups. Recent epidemiological studies have shown that PFAS cause health risks even at low concentrations. This review outlines the toxicokinetics, exposure and health risks of PFAS, with a focus on perfluorooctane sulfonic acid (PFOS), perfluorooctanoic acid (PFOA), and long-chain perfluoroalkyl carboxylic acids (LC-PFCAs). These compounds are known to interact with various proteins in vivo, including the peroxisomal proliferator-activated receptor-α (PPARα). PFOA and PFOS have been identified as carcinogenic. It is known that PFOA and PFOS are transported by transporters such as organic anion transporter. Significant species differences in the behavior of these compounds exist, with much longer half-lives in humans than in mice and rats. One of the reasons that the half-lives of PFOA and PFOS are long in humans is that their renal clearance is low in humans. For animal toxicity experiments, it is essential that the doses in animal experiments are converted to equivalent doses in humans using pharmacokinetic models. Compared with PFOA, some LC-PFCAs have longer half-lives and accumulate more in the liver. Although tap water is a source of exposure to PFAS, the most common exposure source is food, with seafood being an important source for exposure to PFAS in Japan. PFOS and PFOA concentrations in human blood in Japan have been decreasing in recent years. However, according to clinical guidance published in 2022 by the United States National Academies, most Japanese residents are still in the medium risk group (PFAS concentration in plasma or serum is greater than 2 ng/mL and less than 20 ng/mL) or above. Further research is needed to help reduce exposure, and further risk assessments are required.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"97-104"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537433","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

Male rat-specific fatty change in liver by DS-1971a: Elevation in phospholipids and adenosine as early responses to the fatty change in male rat-derived primary hepatocytes. DS-1971a 对雄性大鼠肝脏特异性脂肪变化的影响：磷脂和腺苷的升高是雄性大鼠原代肝细胞对脂肪变化的早期反应。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.125

Kazunori Fujimoto, Hiroyuki Kishino, Jun Hirao, Takanori Maejima, Kazuhiko Mori, Yoshimi Tsuchiya

{"title":"Male rat-specific fatty change in liver by DS-1971a: Elevation in phospholipids and adenosine as early responses to the fatty change in male rat-derived primary hepatocytes.","authors":"Kazunori Fujimoto, Hiroyuki Kishino, Jun Hirao, Takanori Maejima, Kazuhiko Mori, Yoshimi Tsuchiya","doi":"10.2131/jts.50.125","DOIUrl":"10.2131/jts.50.125","url":null,"abstract":"In a 3-month repeated oral dose toxicity study of DS-1971a, a selective inhibitor of the Nav1.7 voltage-gated sodium channel, fatty change of hepatocytes was observed only in male rats at doses of 100 mg/kg and above. However, this change was not observed in female rats even at the highest dose of 1500 mg/kg. Furthermore, fatty change was not observed in mice and monkeys administered the highest dose of 1000 mg/kg for 6 and 9 months, respectively. To further investigate species differences of this fatty change, lipid accumulation was evaluated by staining with the LipidTOX dye in primary cultured hepatocytes derived from male and female rats, male monkeys, and male and female humans. After exposure to DS-1971a for 72 hr, the staining showed an increase in intensity specifically in male rat-derived hepatocytes in a concentration-dependent manner. Metabolomic analysis using rat-derived primary cultured hepatocytes exposed to DS-1971a for 24 and 72 hr revealed that phospholipids, not neutral lipids like triacylglycerols, and adenosine were elevated in the male-derived hepatocytes. These results suggest that the elevation of phospholipids and adenosine in the hepatocytes may contribute to the specific fatty change observed in male rats.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"125-134"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537432","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

Induction of VEGF-A expression by methylmercury is mediated by the EGFR-p38 MAPK-COX-2-PKA pathway in cultured human brain microvascular pericytes. 甲基汞介导的EGFR-p38 MAPK-COX-2-PKA通路在培养的人脑微血管周细胞中诱导VEGF-A表达。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.199

Eiko Yoshida, Kenta Sakurai, Akishige Hirata, Tomoko Sasaoka, Takashi Hirooka, Tomoya Fujie, Takato Hara, Chika Yamamoto, Yasuyuki Fujiwara, Yo Shinoda, Komyo Eto, Toshiyuki Kaji

{"title":"Induction of VEGF-A expression by methylmercury is mediated by the EGFR-p38 MAPK-COX-2-PKA pathway in cultured human brain microvascular pericytes.","authors":"Eiko Yoshida, Kenta Sakurai, Akishige Hirata, Tomoko Sasaoka, Takashi Hirooka, Tomoya Fujie, Takato Hara, Chika Yamamoto, Yasuyuki Fujiwara, Yo Shinoda, Komyo Eto, Toshiyuki Kaji","doi":"10.2131/jts.50.199","DOIUrl":"10.2131/jts.50.199","url":null,"abstract":"Methylmercury is the causative organometallic compound of Minamata disease. Pathological changes in the cerebrum of patients are localized along the deep sulci and fissures of the cerebral cortex such as the calcarine fissure. It has been suggested that the occurrence of brain edema is important for the cerebral damage caused by methylmercury. Previously, we found that methylmercury induces vascular endothelial growth factor-A in cultured human brain microvascular pericytes, which may increase permeability of the brain microvasculature. In the present study, our findings suggest that this induction is mediated via the epidermal growth factor receptor-p38 mitogen-activated protein kinase-cyclooxygenase-2-protein kinase A pathway in cultured human brain microvascular pericytes. These results partly support our hypothesis that methylmercury causes neurotoxicity by activation of intracellular signaling pathways in various cell types, including neurons, macrophages, vascular endothelial cells, and pericytes.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 4","pages":"199-204"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772578","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