Journal of Toxicological Sciences最新文献_第3页

Induction of systemic inflammation by welding fume exposure in office workers as well as welders in welding factories. 办公室工作人员和焊接工厂的焊工接触焊接烟雾引起全身炎症。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.215

Mayumi Tsuji, Chihaya Koriyama, Tatsuto Nakane, Susumu Ueno, Yasuhiro Ishihara

{"title":"Induction of systemic inflammation by welding fume exposure in office workers as well as welders in welding factories.","authors":"Mayumi Tsuji, Chihaya Koriyama, Tatsuto Nakane, Susumu Ueno, Yasuhiro Ishihara","doi":"10.2131/jts.50.215","DOIUrl":"https://doi.org/10.2131/jts.50.215","url":null,"abstract":"Welding fumes are metal particles of 1 µm or less generated during welding. Welding fumes generated in welding factories spread throughout the workplace. However, the effects of exposure have been measured primarily in welding workers, and no research has been conducted on the effects of fumes on workplace office workers. In this study, we recruited welding and office workers who worked in the same factories at ten workplaces in Japan, mainly in the Kyushu and Kanto regions, and separated their serum after blood sampling. We also obtained serum from the general subjects of Minami-Kagoshima City, which is located far from the welding factory. Cytokines and chemokines were quantified in the serum samples, and the concentration of interleukin (IL)-1β was significantly increased in office workers and welders compared with general subjects. Importantly, the serum concentrations of IL-12p70, IL-17A, IL-33, tumor necrosis factor α, and C-C motif chemokine ligand 3 in office workers were significantly higher than those in the general subjects, and there was no significant difference in the levels of these inflammatory molecules between welders and general subjects. This study suggests that office workers exposed to high fume concentrations exhibit increased systemic inflammation. Exposure assessments should be conducted not only for welders but also for office workers to reduce exposure risks.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 5","pages":"215-221"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144007435","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

Toxicological effects of Sb(III), Sb(V), and NMG-Sb(V) in human lung, kidney, and liver cells: cytotoxicity and fibrotic factor induction. Sb（III）、Sb(V)和NMG-Sb(V)在人肺、肾和肝细胞中的毒理学效应：细胞毒性和纤维化因子诱导。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.283

Nicole Roldán, Marcelo Verdugo, Noriyuki Suzuki, Natali Zamora, Waldo Quiroz, Alexis Gonzalez, Javier Tognarelli, Yasumitsu Ogra

{"title":"Toxicological effects of Sb(III), Sb(V), and NMG-Sb(V) in human lung, kidney, and liver cells: cytotoxicity and fibrotic factor induction.","authors":"Nicole Roldán, Marcelo Verdugo, Noriyuki Suzuki, Natali Zamora, Waldo Quiroz, Alexis Gonzalez, Javier Tognarelli, Yasumitsu Ogra","doi":"10.2131/jts.50.283","DOIUrl":"https://doi.org/10.2131/jts.50.283","url":null,"abstract":"Antimony ecotoxicity studies are often hindered by the incorrect selection of Sb(III) standards and the application of concentrations that do not reflect real environmental exposure. In this study, we used environmentally relevant concentrations of inorganic Sb in its pentavalent [Sb(V)] and trivalent [Sb(III)] oxidation states, as well as the organic species NMG-Sb(V), which is present in Meglumine Antimoniate, to evaluate the effects of Sb on cell viability in human lung (A549), kidney (HEK293), and liver (HepG2) cell lines. Cell viability was assessed in these cells following treatment with 0.001 to 1 µg/L of Sb(V), 1 to 500 µg/L of Sb(III), and 0 to 1000 mg/L of MA. We also measured ROS production and the expression of the profibrotic markers CTGF, α-SMA, and PAI-1, which are associated with fibrosis activation. No significant changes in cell viability were observed in HepG2 and A549 cells. However, in HEK293 cells, viability decreased by 20-40% at Sb(III) concentrations between 1 µg/L and 1 mg/L. CTGF expression was significantly increased at 17 µg/L of Sb(III), while α-SMA and PAI-1 expression increased at 21 µg/L of Sb(V). These findings suggest that different species of Sb can induce increased expression of mRNA for fibrotic genes in human liver and kidney cell lines at concentrations found in the environment.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 6","pages":"283-292"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199551","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

Potential of connexin 32 as a predictive marker for drug-induced cholestatic liver injury in a collagen vitrigel-culture model of HepG2-NIAS cells, a new subline of HepG2 cells, with bile canaliculus-like structures. 连接蛋白32在HepG2- nias细胞（一种具有胆管样结构的HepG2细胞亚系）胶原培养模型中作为药物性胆汁淤积性肝损伤预测标志物的潜力

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.135

Miaki Uzu, Toshiaki Takezawa

{"title":"Potential of connexin 32 as a predictive marker for drug-induced cholestatic liver injury in a collagen vitrigel-culture model of HepG2-NIAS cells, a new subline of HepG2 cells, with bile canaliculus-like structures.","authors":"Miaki Uzu, Toshiaki Takezawa","doi":"10.2131/jts.50.135","DOIUrl":"10.2131/jts.50.135","url":null,"abstract":"Cholestatic drug-induced liver injury (DILI) is caused by the aberrant excretion of bile acids (BAs) from hepatocytes via bile canaliculus-like structures (BCLSs) into the bile ducts. The precise in vitro evaluation method for cholestatic DILI has not been established due to a lack of specific markers and cell resources. We previously reported that HepG2-NIAS cells cultured on a collagen vitrigel (CV) membrane formed BCLSs with high protein expression of transporters involved in the excretion of BAs, including bile salt export pump (BSEP). In this study, the potential of connexin (Cx) 32, a component of gap junction, as a predictive marker for cholestatic DILI was investigated using a CV-culture model of HepG2-NIAS cells. The cells were treated with 7 drugs with different DILI-risk levels, and cell toxicity and Cx32 expression were evaluated. Cell toxicity was significantly increased not only by high DILI-risk drugs (troglitazone and cyclosporine A) but also by chlorpromazine with low DILI-risk. Furthermore, cell toxicity of troglitazone was not enhanced by a co-treatment with taurocholate, suggesting the low involvement of inhibition of BA excretion via BSEP in cholestatic DILI. In contrast, the total protein expression of Cx32 and co-localization of Cx32 and F-actin, which is composed of BCLSs, were significantly increased only by high DILI-risk drugs. Treatment with high DILI-risk drugs also induced the increased protein expression of zonula occludens (ZO)-1, which supports BCLSs concerted with Cx32. These results suggest that Cx32 expression in the CV-culture model of HepG2-NIAS cells may be a prominent predictive marker for cholestatic DILI.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"135-145"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537434","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

Perfluorooctane sulfonate induces hepatotoxicity through promoting inflammation, cell death and autophagy in a rat model. 在大鼠模型中，全氟辛烷磺酸通过促进炎症、细胞死亡和自噬诱导肝毒性。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.45

Leilei Tang, Jianjun Zhu, Sheng Zhuge, Jiawen Yu, Guojun Jiang

{"title":"Perfluorooctane sulfonate induces hepatotoxicity through promoting inflammation, cell death and autophagy in a rat model.","authors":"Leilei Tang, Jianjun Zhu, Sheng Zhuge, Jiawen Yu, Guojun Jiang","doi":"10.2131/jts.50.45","DOIUrl":"10.2131/jts.50.45","url":null,"abstract":"Perfluorooctane sulfonate (PFOS) is reported to cause hepatotoxicity in animals and humans. However, the underlying mechanism by which it affects organelle toxicity in the liver are not well elucidated yet. This study aimed to investigate the mechanisms underlying PFOS-induced hepatic toxicity, focusing on inflammation, cell death, and autophagy. We established a PFOS-exposed Sprague-Dawley (SD) rat liver injury model by intraperitoneal injection of PFOS (1 mg/kg and 10 mg/kg body weight) every alternate day for 15 days. Our findings indicated that PFOS increased liver weight, caused lipid disorder and hepatic steatosis in rats. Meanwhile, PFOS disrupted the structure of mitochondria, increased accumulation of reactive oxygen species (ROS), repressed superoxide dismutase (SOD) and glutathione peroxidase (GSH-PX) levels, and elevated malondialdehyde (MDA) and nitric oxide synthase (NOS) amounts. We found PFOS induced inflammation as evidenced by activation of NOD-like receptor protein 3 (NLRP3), Cleaved cysteine-aspartic acid protease (caspase)1, tumor necrosis factor (TNF)α and interleukin (IL)-1β levels. Moreover, PFOS exposure significantly decreased B-cell lymphoma2 (Bcl2)/Bcl2 associated X (Bax) ratio and increased the protein expression of Cleaved caspase-3. Compared with the control group, PFOS upregulated the protein expression of necroptotic markers and autophagy-related proteins. In conclusion, PFOS induced inflammation, cell death, and autophagy through oxidative stress by ROS overload, thereby providing a mechanistic explanation for PFOS-induced hepatotoxicity.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 2","pages":"45-55"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143080637","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

The Journal of Toxicological Sciences and Fundamental Toxicological Sciences to become open access journals. 《毒理学科学杂志》和《基础毒理学科学》成为开放获取期刊。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.R1

Toshiyuki Kaji, Akira Naganuma

{"title":"The Journal of Toxicological Sciences and Fundamental Toxicological Sciences to become open access journals.","authors":"Toshiyuki Kaji, Akira Naganuma","doi":"10.2131/jts.50.R1","DOIUrl":"https://doi.org/10.2131/jts.50.R1","url":null,"abstract":"We would like to express our gratitude for your contributions to our official scientific journals, The Journal of Toxicological Sciences and Fundamental Toxicological Sciences.We have decided to make both journals open access in order to internationalize them and expand their reach to a broader audience. Articles will be published under the Creative Commons license with the highest degree of freedom, CC BY (4.0). As a result of this change, article copyright will belong to the authors, and secondary use, including copying, distribution, display, storage, modification, and commercial use, can be carried out without the relevant society's permission.The new Instructions for Authors will be published on the journal websites in advance. These new submission guidelines \u2028will apply to papers submitted on or after June 1, 2025 (Japan time). Please note that the previous Instructions for Authors will apply to papers submitted until May 31, 2025 (Japan time).We hope that this change will encourage you to submit more of your excellent papers to The Journal of Toxicological Sciences and Fundamental Toxicological Sciences.Toshiyuki Kaji, Ph.D.Editor-in-ChiefThe Journal of Toxicological SciencesAkira Naganuma, Ph.D.Editor-in-ChiefFundamental Toxicological Sciences.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 5","pages":"R1"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143971045","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

miRNA-214-3p targets BNIP3 to affect autophagy and thus drive gastric cancer progression. miRNA-214-3p通过靶向BNIP3影响自噬从而驱动胃癌进展。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.235

Changjiang Chen, Shen Guan, Yong Zhuang, Mingming Xie, Qingxia Huang, Xiaoling Li, Chunkang Yang, Jinliang Jian

{"title":"miRNA-214-3p targets BNIP3 to affect autophagy and thus drive gastric cancer progression.","authors":"Changjiang Chen, Shen Guan, Yong Zhuang, Mingming Xie, Qingxia Huang, Xiaoling Li, Chunkang Yang, Jinliang Jian","doi":"10.2131/jts.50.235","DOIUrl":"https://doi.org/10.2131/jts.50.235","url":null,"abstract":"With a fourth-place death rate among all malignancies, gastric cancer (GC) is one of the most prevalent tumors globally. As a primary malignant characteristic of GC, metastasis contributes substantially to a high death rate and unfavorable prognosis. miRNA-214-3p can influence cell apoptosis since it is an autophagy-regulating molecule. Its significance in GC malignant development has not, however, been investigated in terms of mechanism. qRT-PCR was utilized to confirm expression of miRNA-214-3p in GC tissues and cells. Bioinformatics analysis was then implemented to examine BNIP3 expression in GC as well as binding interaction between BNIP3 and miRNA-214-3p. The targeting capability of miRNA-214-3p on BNIP3 was confirmed using the dual-luciferase assay. Capacities of cells to proliferate, migrate, and invade were assayed using Transwell assays and colony formation. In order to determine if GC cells were capable of autophagy, immunofluorescence and western blot were employed. In GC, miRNA-214-3p was substantially expressed in GC tissues and cells, but BNIP3 was downregulated, as shown by bioinformatics analysis and verified by cell tests. MiRNA-214-3p targeted BNIP3, as shown by further bioinformatics analysis, and dual-luciferase experiment verified this binding connection. MicroRNA-214-3p facilitated cell invasion, migration, and proliferation, as shown by Transwell tests and colony formation. MiRNA-214-3p accelerated malignant development of GC by targeting BNIP3 to impact autophagy, as demonstrated by immunofluorescence and western blot analyses. By targeting BNIP3 to affect autophagy, miRNA-214-3p aided in the malignant growth of GC. This suggested that miRNA-214-3p may function as a likely therapeutic target or biomarker for the disease, with significant implications for early diagnosis and treatment of patients.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 5","pages":"235-244"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000714","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

In silico model to predict dermal absorption of chemicals in finite dose conditions. 在有限剂量条件下预测皮肤吸收化学物质的硅模型。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.171

Ibuki Narita, Hiroaki Todo, Chihiro Fujiwara, Hiroyuki Teramae, Takeshi Oshizaka, Shoko Itakura, Syuuhei Komatsu, Kozo Takayama, Kenji Sugibayashi

{"title":"In silico model to predict dermal absorption of chemicals in finite dose conditions.","authors":"Ibuki Narita, Hiroaki Todo, Chihiro Fujiwara, Hiroyuki Teramae, Takeshi Oshizaka, Shoko Itakura, Syuuhei Komatsu, Kozo Takayama, Kenji Sugibayashi","doi":"10.2131/jts.50.171","DOIUrl":"10.2131/jts.50.171","url":null,"abstract":"The development of in silico approaches that can estimate the dermal absorption of chemicals exposed in practical conditions is highly anticipated. In the present study, an in silico model to estimate both the dermal absorption rate and dermal permeation profile was developed for the application of chemicals in finite dose conditions. Forty-three chemicals with molecular weights in the range 116-362 and logKo/w in the range 1.1-4.5 were used to develop an in silico model. A gradient boosting tree approach was applied to estimate permeation parameters for diffusion and partition coefficients of the chemicals in skin using physicochemical parameters of the chemicals such as molecular weight, lipophilicity, and the highest and lowest occupied molecular orbitals as the descriptor. In addition, 11 chemicals with different molecular weights and lipophilicities were applied on excised human skin in a finite dose condition, and dermal absorption profiles were obtained. Consideration of donor-solvent evaporation time, saturated concentrations of the chemicals, and donor-solvent coverage area on the skin surface, in addition to estimated skin permeation parameters of the chemicals, showed comparatively good dermal absorption profiles, although some cases of underestimation of dermal absorption were identified. It will be necessary to verify the accuracy of this model through experiments using more chemicals. However, the obtained results suggested that the established model may be valid to estimate the dermal absorption of chemicals in practical conditions.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 4","pages":"171-186"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143772434","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

Differential effects of different time windows of postnatal perfluorooctane sulfonate exposure on cognitive development in mouse hippocampus. 出生后全氟辛烷磺酸暴露不同时间窗对小鼠海马认知发育的差异影响。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.223

Ayane Ninomiya, Asahi Haijima, Yuki Fujiwara, Reika Kawabata-Iwakawa, Izuki Amano, Noriyuki Koibuchi

{"title":"Differential effects of different time windows of postnatal perfluorooctane sulfonate exposure on cognitive development in mouse hippocampus.","authors":"Ayane Ninomiya, Asahi Haijima, Yuki Fujiwara, Reika Kawabata-Iwakawa, Izuki Amano, Noriyuki Koibuchi","doi":"10.2131/jts.50.223","DOIUrl":"https://doi.org/10.2131/jts.50.223","url":null,"abstract":"Perinatal perfluorooctane sulfonate (PFOS) exposure of the next generation through placenta and breast milk has been of high concern. Epidemiological and animal studies have reported that perinatal PFOS exposure is associated with neurodevelopmental disorders such as learning and autism spectrum disorders in children. However, the sensitive time window of perinatal PFOS exposure for neurodevelopment has yet to be elucidated. Here we examined differential effects of different time windows of postnatal PFOS exposure (postnatal day (PD) 1-7 or 8-14) on cognitive development and gene expression profiles in the hippocampus. Pups were exposed to PFOS from PD 1 to 7 (PD 1-7 group) or from PD 8-14 (PD 8-14 group) through breastfeeding by dams who received a daily gavage of 1 mg/kg body weight PFOS per day during each period. An object location test and an object recognition test revealed the impairment in spatial memory in PD 1-7 group at PD 70. Learning ability was also retarded in a visual discrimination test. According to RNA-seq analysis and real-time PCR, Serpina3g and Tmem91 were significantly downregulated in the hippocampus of PD 1-7 group at PD 21. These results suggest that the first 7 days after birth are critically vulnerable to PFOS exposure and consequent neurodevelopmental deficits rather than the late phase of postpartum. Our work puts a strong emphasis on the importance of monitoring PFOS concentration in pregnant women and potential impact on retardation of neurodevelopment in children.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 5","pages":"223-233"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143999748","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

Long-term exposure to urban particulate matter exacerbates mortality after ischemic stroke in mice. 长期暴露于城市颗粒物会加剧小鼠缺血性中风后的死亡率。

IF 1.8 4区医学

Journal of Toxicological Sciences Pub Date : 2025-01-01 DOI: 10.2131/jts.50.147

Nami Ishihara, Miki Tanaka, Kaede Namba, Shinji Kawano, Sakuno Nishimura, Naoyuki Nezu, Tatsuto Nakane, Ami Oguro, Tomoaki Okuda, Kouichi Itoh, Yu Nabetani, Yasuhiro Ishihara

{"title":"Long-term exposure to urban particulate matter exacerbates mortality after ischemic stroke in mice.","authors":"Nami Ishihara, Miki Tanaka, Kaede Namba, Shinji Kawano, Sakuno Nishimura, Naoyuki Nezu, Tatsuto Nakane, Ami Oguro, Tomoaki Okuda, Kouichi Itoh, Yu Nabetani, Yasuhiro Ishihara","doi":"10.2131/jts.50.147","DOIUrl":"10.2131/jts.50.147","url":null,"abstract":"Exposure to fine particulate matter (PM2.5) has been epidemiologically reported to worsen the prognosis of ischemic stroke; however, the details have not been investigated. One of the major toxic mechanisms of PM2.5 inhalation is oxidative stress, which is mediated by reactive oxygen species generated by PM2.5 components such as metals and polycyclic aromatic hydrocarbons. In this study, we examined the effects of long-term exposure to urban particulate matter, focusing on oxidative stress, on prognosis after ischemic stroke in mice. When mice were intranasally exposed for 28 days to an urban aerosol collected in Beijing, China (CRM28), microglial activation was observed in the cerebral cortex, indicating that CRM28 induced neuroinflammation. CRM28 exposure resulted in increased serum levels of brain natriuretic peptide and troponin I, suggesting that cardiac injury was elicited by CRM28. Lung inflammation was also observed following CRM28 exposure; however, systemic inflammation was not detected. Mice exposed to CRM28 showed an exacerbation of mortality after ischemic stroke induction compared with vehicle mice. A vitamin E-rich diet suppressed CRM28-induced lipid peroxidation in the heart and lungs but not in the brain. A vitamin E-rich diet also attenuated cardiac injury and lung inflammation induced by CRM28 exposure, whereas neuroinflammation was not affected. Mortality after ischemic stroke improved with the administration of a vitamin E-rich diet. Considering that systemic inflammation did not occur, cardiac injury induced by oxidative stress under exposure to urban particulate matter may be involved in increased mortality after ischemic stroke. Antioxidation under air pollution is fundamental for protection against ischemic stroke.","PeriodicalId":17654,"journal":{"name":"Journal of Toxicological Sciences","volume":"50 3","pages":"147-159"},"PeriodicalIF":1.8,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537431","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