Toxicological Research最新文献_第5页

Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs. 微小RNA上调YPEL3的表达并诱导人类乳腺癌细胞死亡。

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-06-21 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00251-2

Boyoung Lee, Yeo-Jung Kwon, Sangyun Shin, Tae-Uk Kwon, Hyemin Park, Hyein Lee, Ji-Heung Kwak, Young-Jin Chun

{"title":"Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs.","authors":"Boyoung Lee, Yeo-Jung Kwon, Sangyun Shin, Tae-Uk Kwon, Hyemin Park, Hyein Lee, Ji-Heung Kwak, Young-Jin Chun","doi":"10.1007/s43188-024-00251-2","DOIUrl":"https://doi.org/10.1007/s43188-024-00251-2","url":null,"abstract":"MicroRNAs (miRNAs), molecules comprising 18-22 nucleotides, regulate expression of genes post-transcriptionally at the 3' untranslated region of target mRNAs. However, the biological roles and mechanisms of action of miRNAs in breast cancer remain unelucidated. Thus, in this study, we aimed to investigate the functions and possible mechanisms of action of miRNAs in breast cancer to suppress carcinogenesis. Using miRNA databases, we selected miR-34a and miR-605-5p to downregulate MDM4 and MDM2, respectively, because these ubiquitin E3 ligases degrade p53 and promote carcinogenesis. Results showed that miR-34a and miR-605-5p suppressed MDM4 and MDM2 expression, respectively. Moreover, they reduced the expression of yes‑associated protein 1 (YAP1), a well-known oncogene involved in Hippo signaling, but upregulated the mRNA and protein expression of yippee-like 3 (YPEL3). To elucidate whether these miRNAs promote cellular senescence and death through YPEL3 upregulation, we examined their effects on cellular proliferation, SA-β-gal activity, and mitochondrial activity in human breast cancer MCF-7 cells. Given their upregulating effect on YPEL3 expression, miR-34a and miR-605-5p increased the number of β-galactosidase-positive cells and depolarized live cells (by 10%-12%). These data suggest that miR-34a and miR-605-5p promote cellular senescence and cell death. Thus, they may act as tumor suppressors by inducing Hippo signaling and may serve as novel therapeutic agents in breast cancer treatment.Supplementary information: The online version contains supplementary material available at 10.1007/s43188-024-00251-2.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"599-611"},"PeriodicalIF":1.6,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436705/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354460","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

Neuroprotective effects of cerebroprotein hydrolysate and its combination with antioxidants against oxidative stress-induced HT22 cell death. 脑蛋白水解物及其与抗氧化剂的结合对氧化应激诱导的 HT22 细胞死亡的神经保护作用

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-05-31 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00248-x

Eun-Ju Yang, Jae Cheon Kim, Dong Hee Na

{"title":"Neuroprotective effects of cerebroprotein hydrolysate and its combination with antioxidants against oxidative stress-induced HT22 cell death.","authors":"Eun-Ju Yang, Jae Cheon Kim, Dong Hee Na","doi":"10.1007/s43188-024-00248-x","DOIUrl":"10.1007/s43188-024-00248-x","url":null,"abstract":"This study aimed to investigate the neuroprotective effects of cerebroprotein hydrolysate (CPH) against oxidative stress-induced HT22 cell death. Additionally, the effect of antioxidants such as quercetin (QC) and N-acetyl-L-cysteine (NAC) on the neuroprotective activity of CPH was evaluated. The mouse-derived hippocampal neuronal cell line HT22 was pretreated with CPH or a mixture of CPH and QC or NAC. HT22 cell death was induced by either 10 mM glutamate, 2.5 μM amyloid-β (Aβ)25-35, and 300 μM cobalt chloride (CoCl2). As results, CPH effectively alleviated HT22 cell death induced by glutamate, Aβ25-35, and CoCl2. In addition, CPH combination with QC augmented cell viability in both glutamate- and Aβ25-35-stressed conditions but had no synergic effect on the CoCl2-stressed condition. The synergic effect of CPH and NAC combination was observed under all cell death conditions. The neuroprotective actions of CPH and its combinations with QC or NAC against various oxidative stress-induced HT22 cell deaths were demonstrated, providing a promising strategy for developing CPH preparations for the prevention and/or treatment of neurodegenerative diseases such as Alzheimer's disease.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"541-550"},"PeriodicalIF":1.6,"publicationDate":"2024-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436692/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354456","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

Methylmercury exposure at dosage conditions that do not affect growth can impair memory in adolescent mice. 在不影响生长的剂量条件下接触甲基汞会损害青春期小鼠的记忆力。

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-04-27 eCollection Date: 2024-07-01 DOI: 10.1007/s43188-024-00239-y

Ryota Yamagata, Ai Saito, Ryoko Fukushima, Osamu Nakagawasai, Naoya Yamashita, Koichi Tan-No, Gi-Wook Hwang

{"title":"Methylmercury exposure at dosage conditions that do not affect growth can impair memory in adolescent mice.","authors":"Ryota Yamagata, Ai Saito, Ryoko Fukushima, Osamu Nakagawasai, Naoya Yamashita, Koichi Tan-No, Gi-Wook Hwang","doi":"10.1007/s43188-024-00239-y","DOIUrl":"10.1007/s43188-024-00239-y","url":null,"abstract":"Methylmercury is an environmental pollutant that can induce serious central nervous system damage. Its ubiquitous presence in the environment in trace amounts has raised concerns about potential adverse effects on human health. Although many studies have evaluated the effects of methylmercury on neural development in fetal and neonatal mice, there has been less focus on studies using adolescent mice. Therefore, in this study, the effects of methylmercury on brain neurodevelopment and maturation were evaluated by various neurobehavioral trials using adolescent mice exposed to 30 ppm methylmercuric chloride (approximately 24 ppm methylmercury) for up to 8 weeks. Under these administration conditions, weight gain in adolescent mice was unaffected by methylmercury exposure. Furthermore, methylmercury exposure in adolescent mice had no effect on sociability as assessed by the social interaction test, impulsivity as assessed by the cliff avoidance reaction test, depressive behavior as assessed by the tail-suspension test, or locomotor activity as assessed using the Supermex system. In contrast, short-term memory assessed by the Y-maze test, as well as long-term memory assessed by novel object recognition and passive avoidance tests, revealed impairments induced by methylmercury exposure in adolescent mice. These results suggest that long-term exposure to methylmercury during adolescence potentially impairs memory function, and the nervous pathway of brain areas involved in learning and memory are particularly vulnerable to the adverse effects of methylmercury.Supplementary information: The online version contains supplementary material available at 10.1007/s43188-024-00239-y.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 3","pages":"441-448"},"PeriodicalIF":1.6,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141443374","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

n-Acetylcysteine protects against diazinon-induced histopathological damage and apoptosis in renal tissue of rats. 正乙酰半胱氨酸可防止重氮酮诱导的大鼠肾组织病理损伤和细胞凋亡。

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-03-07 eCollection Date: 2024-04-01 DOI: 10.1007/s43188-024-00226-3

Gaiqin Dong, Qingfeng Li, Chun Yu, Qing Wang, Danhua Zuo, Xiaozhong Li

{"title":"n-Acetylcysteine protects against diazinon-induced histopathological damage and apoptosis in renal tissue of rats.","authors":"Gaiqin Dong, Qingfeng Li, Chun Yu, Qing Wang, Danhua Zuo, Xiaozhong Li","doi":"10.1007/s43188-024-00226-3","DOIUrl":"10.1007/s43188-024-00226-3","url":null,"abstract":"Diazinon (DZN) is a member of organophosphorus insecticides that has cytotoxic effects on different organs. n-Acetyl cysteine (NAC) is a widely used antioxidant in clinical, in vivo and in vitro studies. We evaluated the protective role of NAC against DZN-induced toxicity in kidney tissue of Wistar rats. 30 male Wistar rats were divided into 5 groups of control, single dose of DZN, continuous dose of DZN, single doses of DZN + NAC and continuous doses of DZN + NAC. Kidney function test (blood urea nitrogen, creatinine and uric acid) was provided. Levels of malondialdehyde (MDA), total antioxidant capacity (TAC) and total sulfhydryl (T-SH) were determined in renal tissues. Renal cells apoptosis was detected using TUNEL assay. The mRNA expressions of apoptosis, oxidative stress and inflammatory mediators, including B-cell lymphoma-2 (Bcl2), Bcl-2-associated X protein (Bax), superoxide dismutase (SOD), catalase (CAT), Interleukin 10 (IL-10), Tumor necrosis factor-α (TNF-α), Caspase-3 and Caspase-8 were analyzed in kidney tissues using Real Time PCR method. Chronic exposure to DZN was associated with severe morphological changes in the kidney, as well as impairment of its function and decreased kidney weights. Continues treatment with DZN significantly decreased the percentage of renal apoptotic cells as compared to rats treated with continuous dose of DZN alone (17.69 ± 3.67% vs. 39.46% ± 2.44%; p < 0.001). Continuous exposure to DZN significantly decreased TAC and T-SH contents, as well as SOD and CAT expression, but increased MDA contents in the kidney tissues (p < 0.001). A significant increase was observed in mRNA expression of Bax, Caspase-3, Caspase-8, as well as TNF-α following exposure to DZN, but the expression of IL-10 and Bcl2 was significantly decreased. NAC can protect kidney tissue against DZN-induced toxicity by elevating antioxidants capacity, mitigating oxidative stress, inflammation and apoptosis.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 2","pages":"285-295"},"PeriodicalIF":1.6,"publicationDate":"2024-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10959863/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140207673","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

Pathological changes in various organs in HLA-B*57:01 transgenic mice with abacavir-induced skin eruption 阿巴卡韦诱发皮肤糜烂的 HLA-B*57:01 转基因小鼠各器官的病理变化

IF 2.3 4区医学

Toxicological Research Pub Date : 2024-01-06 DOI: 10.1007/s43188-023-00220-1

Akira Kazaoka, Kazuyoshi Kumagai, Junya Matsushita, Tetsuo Aida, Saki Kuwahara, Shigeki Aoki, Kousei Ito