Journal of Toxicological Sciences最新文献

Evaluation of rewarding effects of nitazene analogs: results from conditioned place preference tests and in vivo microdialysis experiments in mice. 评价nitazene类似物的奖励作用：条件位置偏好试验和小鼠体内微透析实验的结果。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.33

Kyoko Hataoka, Motoki Hojo, Sakiko Nomura, Yoshio Nakagawa, Ayaka Kawai, Mari Nakamura, Kiyomi Ikushima, David B Alexander, Jin Suzuki, Toshinari Suzuki, Akiko Inomata

{"title":"Evaluation of rewarding effects of nitazene analogs: results from conditioned place preference tests and in vivo microdialysis experiments in mice.","authors":"Kyoko Hataoka, Motoki Hojo, Sakiko Nomura, Yoshio Nakagawa, Ayaka Kawai, Mari Nakamura, Kiyomi Ikushima, David B Alexander, Jin Suzuki, Toshinari Suzuki, Akiko Inomata","doi":"10.2131/jts.50.33","DOIUrl":"https://doi.org/10.2131/jts.50.33","url":null,"abstract":"In illicit drug markets, the most recently expanding new synthetic opioid subclass is benzimidazoles, also known as nitazenes, which were originally developed as analgesics in the 1950s. The emergence of this classical, potent drug family has attracted extensive research interest in the field of forensic toxicology; however, information on their psychological and physical dependence is very limited. Herein, we evaluated the rewarding effects of four nitazene analogs using a battery of in vivo experiments, with a positive control drug (isotonitazene). The four test materials, metonitazene, etodesnitazene, metodesnitazene, and flunitazene, were administered to male C57BL/6J mice by i.p. administration at 0.5, 2, 20, and 20 mg/kg, respectively. In comprehensive behavioral observation tests, representative opioid-related physiological and behavioral states, including analgesia, stereotypic circling behavior, hyperlocomotion, and Straub tail response, were observed. A set of conditioned place preference tests revealed that all the four analogs induced palatability in mice. Furthermore, measurements of dopamine levels in the nucleus accumbens shell by in vivo microdialysis resulted in significant elevations in all test material-treated groups, suggesting that the nitazenes elicit the rewarding effect through a neural circuit originating from the μ-opioid receptor activation at the ventral tegmental area. Our findings add important data regarding the psychological dependence of nitazenes and highlight the abuse potential of these four materials and other prevailing nitazene analogs.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"33-43"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950773","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

Toxicity of nickel, copper, and selenium in medaka embryos (oryzias latipes): a comparative study. 镍、铜和硒对稻尾草胚毒性的比较研究。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.23

Sylvester Addai-Arhin, Seiya Shino, Masaya Uchida, Hiroshi Ishibashi, Koji Arizono, Nobuaki Tominaga

{"title":"Toxicity of nickel, copper, and selenium in medaka embryos (oryzias latipes): a comparative study.","authors":"Sylvester Addai-Arhin, Seiya Shino, Masaya Uchida, Hiroshi Ishibashi, Koji Arizono, Nobuaki Tominaga","doi":"10.2131/jts.50.23","DOIUrl":"https://doi.org/10.2131/jts.50.23","url":null,"abstract":"The indispensability of biometals nickel, copper, and selenium in pharmaceutical, agricultural, and other industrial applications, coupled with their release from mining processes, has made them potent environmental contaminants, especially when present in aquatic ecosystems at levels above the essential range. The toxicity of these biometals in fish embryogenesis, including their toxicity levels, was studied using medaka embryos. Test solutions (0.001-10 ppm) of the biometals, along with an isotonic solution as a control, were introduced into the embryos using a nanosecond pulsed electric field application. The exposed embryos were cultured at 25 ± 1°C and microscopically observed daily for 14 days in an isotonic solution. Developmental abnormalities and toxicity were observed during the 14-day observation period. All biometals caused some abnormalities in developing embryos at all concentrations. Major abnormalities included delayed development; deformities such as curvature of bones or spines; abnormal formation of the hearts, eyes, and circulatory systems; and mortality. The toxicity of the biometals was significantly different (p < 0.05) from that of the control. Gene expression analysis revealed that 4747, 1961, and 1952 genes were affected by copper, nickel, and selenium, respectively. Copper affected the highest number of genes and caused the highest toxicity. These results indicate that nickel, copper, and selenium can cause toxicity in developing fish embryos at concentrations ranging from 0.01 ppb to 10 ppm. Therefore, there is a need to constantly monitor the levels of these biometals, particularly in aquatic ecosystems, to preserve aquatic life.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"23-32"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950775","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

Benzalkonium chloride initiates proinflammatory responses via NLRP3 inflammasome activation. 苯扎氯铵通过NLRP3炎性体激活引发促炎反应。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.11

Tomohiro Kagi, Maoko Tan, Wakana Suzuki, Kohei Otani, Sara Suzuki, Yusuke Hirata, Takuya Noguchi, Atsushi Matsuzawa

{"title":"Benzalkonium chloride initiates proinflammatory responses via NLRP3 inflammasome activation.","authors":"Tomohiro Kagi, Maoko Tan, Wakana Suzuki, Kohei Otani, Sara Suzuki, Yusuke Hirata, Takuya Noguchi, Atsushi Matsuzawa","doi":"10.2131/jts.50.11","DOIUrl":"https://doi.org/10.2131/jts.50.11","url":null,"abstract":"A representative surfactant, benzalkonium chloride (BAC) is used as a disinfectant, but sometimes causes serious side effects, including lung disorders such as interstitial pneumonia. However, its pathogenic mechanisms remain unexplained. In this study, we identified a novel mechanism by which BAC initiates inflammatory responses that may be responsible for its side effects. We firstly investigated whether BAC initiates inflammation, and found that BAC promotes the secretion of the pro-inflammatory cytokine interleukin-1β (IL-1β) but not tumor necrosis factor-α (TNF-α) in macrophages. Interestingly, the IL-1β secretion triggered by the surfactants was completely blocked by the K-ATP channel blocker glibenclamide or the calcium chelating agent 1,2-bis(2-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid (BAPTA)-AM. Moreover, genetic experiments revealed that BAC-dependent IL-1β secretion is mediated by the NLRP3 inflammasome. These results suggest that derangement of ion fluxes associated with the interfacial effects of BAC triggers NLRP3 inflammasome activation and subsequent inflammation. Thus, the NLRP3-dependent mechanisms triggered by BAC may explain the pathogenesis of surfactant-caused adverse effects.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"11-21"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950772","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

Investigation of additional suitable positive controls in the human Cell Line Activation Test. 人类细胞系激活试验中其他合适阳性对照的研究。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.1

Kanako Nakayama, Shiho Oeda, Hideyuki Mizumachi, Morihiko Hirota, Akiko Tamura, Masaaki Miyazawa

{"title":"Investigation of additional suitable positive controls in the human Cell Line Activation Test.","authors":"Kanako Nakayama, Shiho Oeda, Hideyuki Mizumachi, Morihiko Hirota, Akiko Tamura, Masaaki Miyazawa","doi":"10.2131/jts.50.1","DOIUrl":"https://doi.org/10.2131/jts.50.1","url":null,"abstract":"The human Cell Line Activation Test (h-CLAT) is an in vitro skin sensitization assay adopted by the OECD as Test Guideline 442E. In the h-CLAT, 2,4-dinitrochlorobenzene (DNCB) is used as a positive control; however, DNCB is considered a poisonous substance under the Poisonous and Deleterious Substances Control Act in Japan since 2014 because of its high acute toxicity. Strict control, handling, and storage are required when using DNCB, which is a burden to the users. Although the use of other suitable positive controls with historical data is accepted by the guideline, to our knowledge, there have been no reports of such substances. Therefore, in this study, we investigated suitable positive controls that can be used in addition to DNCB for the h-CLAT. Three candidates that are not considered poisonous substances, imidazolidinyl urea, hydroxycitronellal, and 2,4-dinitrofluorobenzene, were selected. To determine their suitability as positive controls, the h-CLAT was performed repeatedly for each chemical in two laboratories. For imidazolidinyl urea, the results that failed the positive control criteria were observed in both laboratories, indicating that it was inconclusive for the suitability as a positive control at the tested concentration. In contrast, all experiments with hydroxycitronellal and 2,4-dinitrofluorobenzene met the criteria and resulted in relative fluorescence intensity values of CD86/CD54, which were comparable to those for DNCB. Based on these results, hydroxycitronellal and 2,4-dinitrofluorobenzene may be used as positive controls. This study would provide valuable information for users examining other suitable positive controls in the h-CLAT.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 1","pages":"1-9"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142950774","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

Discovery and development of COVID-19 vaccines and therapeutics: nonclinical perspectives. COVID-19 疫苗和疗法的发现与开发：非临床视角。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.79

Nasir Khan, Jean Sathish, Cynthia M Rohde

{"title":"Discovery and development of COVID-19 vaccines and therapeutics: nonclinical perspectives.","authors":"Nasir Khan, Jean Sathish, Cynthia M Rohde","doi":"10.2131/jts.49.79","DOIUrl":"10.2131/jts.49.79","url":null,"abstract":"The development and regulatory review of BNT162b2, a COVID-19 vaccine, and PaxlovidTM (nirmatrelvir tablets/ritonavir tablets), a COVID-19 therapeutic, are benchmarks for accelerated innovation during a global pandemic. Rapid choice of the SARS-CoV-2 spike protein and main protease (Mpro) as targets for the vaccine and therapeutic, respectively, leveraged the available knowledge of the biology of SARS-CoV-2 and related viruses. The nonclinical immunogenicity and safety of BNT162b2 was rigorously assessed. Likewise, a comprehensive nonclinical safety assessment was conducted for the therapeutic candidates, lufotrelvir (PF-07304814) and nirmatrelvir (PF-07321332). The development and regulatory review of BNT162b2 and Paxlovid was enabled through close collaboration of the pharmaceutical industry with regulatory agencies and public health organizations. This experience highlights approaches that could be adopted for pandemic preparedness including risk-based investment strategies, conduct of activities in parallel that normally are conducted sequentially, quick kill decisions, simultaneous evaluation of multiple candidates, and use of flexible, established vaccine platforms.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 3","pages":"79-94"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140022108","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 the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin. 比较小鼠、大鼠和猪口服α-糖基异槲皮素后的粪便细菌微生物群。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.151

Hong Liu, Ryo Inoue, Mihoko Koyanagi, Shim-Mo Hayashi, Gen Watanabe, Kentaro Nagaoka

{"title":"Comparison of the fecal bacterial microbiota in mice, rats, and pigs after oral administration of alpha-glycosyl isoquercitrin.","authors":"Hong Liu, Ryo Inoue, Mihoko Koyanagi, Shim-Mo Hayashi, Gen Watanabe, Kentaro Nagaoka","doi":"10.2131/jts.49.151","DOIUrl":"10.2131/jts.49.151","url":null,"abstract":"Alpha-glycosyl isoquercitrin (AGIQ) is composed of isoquercitrin and its glucosylated derivatives and has many biological activities, including anti-inflammatory, antioxidant, and anti-cancer properties. However, the effect of AGIQ administered orally on gut microbiota composition remains unclear. The objective of this study was to evaluate the effect of AGIQ on the gut microbiota of animals in different dose groups. Male rats and mice received different doses of AGIQ (1.5%, 3%, or 5% w/v) in diet for carcinogenic or chronic toxicity studies (rasH2 mice: 6 months; Sprague-Dawley rats: 12 months). Male minipigs received 100, 300, or 1000 mg/kg/day for 28 days. Fecal samples were collected from the different animal species and analyzed using 16S-rRNA gene sequencing. No significant changes were observed in alpha and beta diversity of the gut microbiota. Characteristic bacteria that responded to AGIQ were identified in each animal species, and, interestingly, Kineothrix alysoides, a butyrate-producing bacterium, was commonly detected in all three species, suggesting that it may be related to the biological activities of AGIQ. AGIQ selectively modulated the number of beneficial butyrate-producing commensal bacterium beneficial bacteria without changing the diversity of gut microbiota, which further supports the safe use of AGIQ in food products.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 4","pages":"151-161"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331802","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

Integrating mathematical approaches (IMAS): Novel methodology for predicting dermal absorption rates of chemicals under finite dose conditions. 综合数学方法（IMAS）：在有限剂量条件下预测化学品皮肤吸收率的新方法。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.219

Ryoki Kunita, Takafumi Nishijima, Hiroaki Todo, Masaaki Miyazawa

{"title":"Integrating mathematical approaches (IMAS): Novel methodology for predicting dermal absorption rates of chemicals under finite dose conditions.","authors":"Ryoki Kunita, Takafumi Nishijima, Hiroaki Todo, Masaaki Miyazawa","doi":"10.2131/jts.49.219","DOIUrl":"https://doi.org/10.2131/jts.49.219","url":null,"abstract":"Quantitative structure permeation relationship (QSPR) models have gained prominence in recent years owing to their capacity to elucidate the influence of physicochemical properties on the dermal absorption of chemicals. These models facilitate the prediction of permeation coefficient (Kp) values, indicating the skin permeability of a chemical under infinite dose conditions. Conversely, obtaining dermal absorption rates (DAs) under finite dose conditions, which are crucial for skin product safety evaluation, remains a challenge when relying solely on Kp predictions from QSPR models. One proposed resolution involves using Kroes' methodology, categorizing DAs based on Kp values; however, refinement becomes necessary owing to discreteness in the obtained values. We previously developed a mathematical model using Kp values obtained from in vitro dermal absorption tests to predict DAs. The present study introduces a new methodology, Integrating Mathematical Approaches (IMAS), which combines QSPR models and our mathematical model to predict DAs for risk assessments without conducting in vitro dermal absorption tests. Regarding 40 chemicals (76.1 ≤ MW ≤ 220; -1.4 ≤ Log Ko/w ≤ 3.1), IMAS showed that 65.0% (26/40) predictions of DA values were accurate to within twofold of the observed values in finite dose experiments. Compared to Kroes' methodology, IMAS notably mitigated overestimation, particularly for hydrophilic chemicals with water solubility exceeding 57.0 mg/cm3. These findings highlight the value of IMAS as a tool for skin product risk assessments, particularly for hydrophilic compounds.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 5","pages":"219-230"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140858801","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

Lung carcinogenicity by whole body inhalation exposure to Anatase-type Nano-titanium Dioxide in rats. 大鼠全身吸入 Anatase 型纳米二氧化钛对肺部的致癌性。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.359

Tatsuya Kasai, Shigeyuki Hirai, Yuske Furukawa, Kyouhei Misumi, Tomoki Takeda, Yuko Goto, Kenji Takanobu, Kengo Yoneyama, Shotaro Yamano, Hideki Senoh, Yumi Umeda

{"title":"Lung carcinogenicity by whole body inhalation exposure to Anatase-type Nano-titanium Dioxide in rats.","authors":"Tatsuya Kasai, Shigeyuki Hirai, Yuske Furukawa, Kyouhei Misumi, Tomoki Takeda, Yuko Goto, Kenji Takanobu, Kengo Yoneyama, Shotaro Yamano, Hideki Senoh, Yumi Umeda","doi":"10.2131/jts.49.359","DOIUrl":"https://doi.org/10.2131/jts.49.359","url":null,"abstract":"To investigate the carcinogenicity of anatase-type nano-titanium dioxide (aNTiO2), F344/DuCrlCrlj rats were exposed to aNTiO2 aerosol at concentrations of 0, 0.5, 2, and 8 mg/m3. The rats were divided into 2 groups: carcinogenicity study groups were exposed for two years, and satellite study groups were exposed for one year followed by recovery for 1 day, 26 weeks, and 52 weeks after the end of exposure. In the carcinogenicity groups, bronchiolo-alveolar carcinomas were observed in two 8 mg/m3-exposed males, showing an increasing trend by Peto's test. However, this incidence was at the upper limit of JBRC's historical control data. Bronchiolo-alveolar adenomas were observed in 1, 2, 3, and 4 rats of the 0, 0.5, 2, and 8 mg/m3-exposed females and were not statistically significant. However, the incidence in the 8 mg/m3-exposed females exceeded JBRC's historical control data. Therefore, we conclude there is equivocal evidence for the carcinogenicity of aNTiO2 in rats. No lung tumors were observed in the satellite groups. Particle-induced non-neoplastic lesions (alveolar epithelial hyperplasia and focal fibrosis) were observed in exposed males and females in both the carcinogenicity and satellite groups. Increased lung weight and neutrophils of bronchoalveolar lavage fluid were observed in the 8 mg/m3-exposed carcinogenicity groups. The aNTiO2 deposited in the lungs of the satellite group rats was decreased at 26 weeks after the end of exposure compared to 1 day after the end of exposure. At 52 weeks after the end of exposure, the decreased level was the same at 26 weeks after the end of exposure.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 8","pages":"359-383"},"PeriodicalIF":1.8,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141889657","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

Investigation of normalization procedures for transcriptome profiles of compounds oriented toward practical study design. 以实用研究设计为导向的化合物转录组图谱归一化程序研究。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.249

Tadahaya Mizuno, Hiroyuki Kusuhara

{"title":"Investigation of normalization procedures for transcriptome profiles of compounds oriented toward practical study design.","authors":"Tadahaya Mizuno, Hiroyuki Kusuhara","doi":"10.2131/jts.49.249","DOIUrl":"https://doi.org/10.2131/jts.49.249","url":null,"abstract":"The transcriptome profile is a representative phenotype-based descriptor of compounds, widely acknowledged for its ability to effectively capture compound effects. However, the presence of batch differences is inevitable. Despite the existence of sophisticated statistical methods, many of them presume a substantial sample size. How should we design a transcriptome analysis to obtain robust compound profiles, particularly in the context of small datasets frequently encountered in practical scenarios? This study addresses this question by investigating the normalization procedures for transcriptome profiles, focusing on the baseline distribution employed in deriving biological responses as profiles. Firstly, we investigated two large GeneChip datasets, comparing the impact of different normalization procedures. Through an evaluation of the similarity between response profiles of biological replicates within each dataset and the similarity between response profiles of the same compound across datasets, we revealed that the baseline distribution defined by all samples within each batch under batch-corrected condition is a good choice for large datasets. Subsequently, we conducted a simulation to explore the influence of the number of control samples on the robustness of response profiles across datasets. The results offer insights into determining the suitable quantity of control samples for diminutive datasets. It is crucial to acknowledge that these conclusions stem from constrained datasets. Nevertheless, we believe that this study enhances our understanding of how to effectively leverage transcriptome profiles of compounds and promotes the accumulation of essential knowledge for the practical application of such profiles.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 6","pages":"249-259"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141199704","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

Transcriptome analysis of cultured human vascular endothelial cells after γ-ray irradiation and correlation analysis with ATP, ADP, and adenosine as secondary soluble factors. γ射线照射后培养的人血管内皮细胞的转录组分析，以及与作为次要可溶性因子的ATP、ADP和腺苷的相关性分析。

IF 2 4区医学

Journal of Toxicological Sciences Pub Date : 2024-01-01 DOI: 10.2131/jts.49.193

Tomoya Fujie, Miyabi Kobayashi, Lihito Ikeuchi, Tsuyoshi Nakano, Kazuki Kitabatake, Yo Shinoda, Yasuyuki Fujiwara, Chika Yamamoto, Mitsutoshi Tsukimoto, Toshiyuki Kaji

{"title":"Transcriptome analysis of cultured human vascular endothelial cells after γ-ray irradiation and correlation analysis with ATP, ADP, and adenosine as secondary soluble factors.","authors":"Tomoya Fujie, Miyabi Kobayashi, Lihito Ikeuchi, Tsuyoshi Nakano, Kazuki Kitabatake, Yo Shinoda, Yasuyuki Fujiwara, Chika Yamamoto, Mitsutoshi Tsukimoto, Toshiyuki Kaji","doi":"10.2131/jts.49.193","DOIUrl":"10.2131/jts.49.193","url":null,"abstract":"Vascular endothelial cells serve as barriers between blood components and subendothelial tissue and regulate the blood coagulation-fibrinolytic system. Ionizing radiation is a common physical stimulant that induces a bystander effect whereby irradiated cells influence neighboring cells through signalings, including purinergic receptor signaling, activated by adenosine 5'-triphosphate (ATP), adenosine 5'-diphosphate (ADP), and adenosine as secondary soluble factors. Human vascular endothelial EA.hy926 cells were cultured and irradiated with γ-rays or treated with ATP, ADP, or adenosine under non-toxic conditions. RNA-seq, gene ontology, and hierarchical clustering analyses were performed. The transcriptome analysis of differentially expressed genes in vascular endothelial cells after γ-ray irradiations suggests that the change of gene expression by γ-irradiation is mediated by ATP and ADP. In addition, the expression and activity of the proteins related to blood coagulation and fibrinolysis systems appear to be secondarily regulated by ATP and ADP in vascular endothelial cells after exposure to γ-irradiation. Although it is unclear whether the changes of the gene expression related to blood coagulation and fibrinolysis systems by γ-irradiation affected the increased hemorrhagic tendency through the exposure to γ-irradiation or the negative feedback to the activated blood coagulation system, the present data indicate that toxicity associated with γ-irradiation involves the dysfunction of vascular endothelial cells related to the blood coagulation-fibrinolytic system, which is mediated by the signalings, including purinergic receptor signaling, activated by ATP and ADP.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"49 4","pages":"193-208"},"PeriodicalIF":2.0,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140331866","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