Toxicological Research最新文献

Hepatocyte-specific RIG-I loss attenuates metabolic dysfunction-associated steatotic liver disease in mice via changes in mitochondrial respiration and metabolite profiles. 肝细胞特异性 RIG-I 的缺失可通过线粒体呼吸和代谢物谱的变化减轻小鼠代谢功能障碍相关的脂肪性肝病。

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-09-23 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00264-x

Jin Kyung Seok, Gabsik Yang, Jung In Jee, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee

{"title":"Hepatocyte-specific RIG-I loss attenuates metabolic dysfunction-associated steatotic liver disease in mice via changes in mitochondrial respiration and metabolite profiles.","authors":"Jin Kyung Seok, Gabsik Yang, Jung In Jee, Han Chang Kang, Yong-Yeon Cho, Hye Suk Lee, Joo Young Lee","doi":"10.1007/s43188-024-00264-x","DOIUrl":"https://doi.org/10.1007/s43188-024-00264-x","url":null,"abstract":"Pattern recognition receptor (PRR)-mediated inflammation is an important determinant of the initiation and progression of metabolic diseases such as metabolic dysfunction-associated steatotic liver disease (MASLD). In this study, we investigated whether RIG-I is involved in hepatic metabolic reprogramming in a high-fat diet (HFD)-induced MASLD model in hepatocyte-specific RIG-I-KO (RIG-I∆hep) mice. Our study revealed that hepatic deficiency of RIG-I improved HFD-induced metabolic imbalances, including glucose impairment and insulin resistance. Hepatic steatosis and liver triglyceride levels were reduced in RIG-I-deficient hepatocytes in HFD-induced MASLD mice, and this was accompanied by the reduced expression of lipogenesis genes, such as PPARγ, Dga2, and Pck1. Hepatic RIG-I deficiency alters whole-body metabolic rates in the HFD-induced MASLD model; there is higher energy consumption in RIG-I∆hep mice. Deletion of RIG-I activated glycolysis and tricarboxylic acid (TCA) cycle-related metabolites in hepatocytes from both HFD-induced MASLD mice and methionine-choline-deficient diet (MCD)-fed mice. RIG-I deficiency enhanced AMPK activation and mitochondrial function in hepatocytes from HFD-induced MASLD mice. These findings indicate that deletion of RIG-I can activate cellular metabolism in hepatocytes by switching on both glycolysis and mitochondrial respiration, resulting in metabolic changes induced by a HFD and stimulation of mitochondrial activity. In summary, RIG-I may be a key regulator of cellular metabolism that influences the development of metabolic diseases such as MASLD.Supplementary information: The online version contains supplementary material available at 10.1007/s43188-024-00264-x.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"683-695"},"PeriodicalIF":1.6,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436585/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354455","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

Correction: Upregulation of YPEL3 expression and induction of human breast cancer cell death by microRNAs. 更正：microRNA 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 : 2024-08-29 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00261-0

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

引用次数: 0

The impact of manganese on vascular endothelium. 锰对血管内皮的影响

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-08-13 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00260-1

Gustavo H Oliveira-Paula, Airton C Martins, Beatriz Ferrer, Alexey A Tinkov, Anatoly V Skalny, Michael Aschner

{"title":"The impact of manganese on vascular endothelium.","authors":"Gustavo H Oliveira-Paula, Airton C Martins, Beatriz Ferrer, Alexey A Tinkov, Anatoly V Skalny, Michael Aschner","doi":"10.1007/s43188-024-00260-1","DOIUrl":"https://doi.org/10.1007/s43188-024-00260-1","url":null,"abstract":"Manganese (Mn) is an essential trace element involved in various physiological processes, but excessive exposure may lead to toxicity. The vascular endothelium, a monolayer of endothelial cells within blood vessels, is a primary target of Mn toxicity. This review provides a comprehensive overview of the impact of Mn on vascular endothelium, focusing on both peripheral and brain endothelial cells. In vitro studies have demonstrated that high concentrations of Mn can induce endothelial cell cytotoxicity, increase permeability, and disrupt cell-cell junctions through mechanisms involving oxidative stress, mitochondrial damage, and activation of signaling pathways, such as Smad2/3-Snail. Conversely, low concentrations of Mn may protect endothelial cells from the deleterious effects of high glucose and advanced glycation end-products. In the central nervous system, Mn can cross the blood-brain barrier (BBB) and accumulate in the brain parenchyma, leading to neurotoxicity. Several transport mechanisms, including ZIP8, ZIP14, and SPCA1, have been identified for Mn uptake by brain endothelial cells. Mn exposure can impair BBB integrity by disrupting tight junctions and increasing permeability. In vivo studies have corroborated these findings, highlighting the importance of endothelial barriers in mediating Mn toxicity in the brain and kidneys. Maintaining optimal Mn homeostasis is crucial for preserving endothelial function, and further research is needed to develop targeted therapeutic strategies to prevent or mitigate the adverse effects of Mn overexposure.Graphical abstract: ","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"501-517"},"PeriodicalIF":1.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354458","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

Therapeutic strategies for colorectal cancer: antitumor efficacy of dopamine D2 receptor antagonists. 结直肠癌的治疗策略：多巴胺 D2 受体拮抗剂的抗肿瘤功效。

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-08-07 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00259-8

Sang Hoon Joo, Kyung-Soo Chun

引用次数: 0

Retraction Note: Flavonoid fractions of diosmin and hesperidin mitigate lead acetate-induced biochemical, oxidative stress, and histopathological alterations in Wistar rats. 撤稿说明：黄酮类成分中的薯蓣皂苷和橙皮甙可减轻醋酸铅诱导的 Wistar 大鼠生化、氧化应激和组织病理学改变。

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-07-30 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00257-w

Ibrahim Yusuf Lamidi, Hudu Garba Mikail, Sani Adamu, Isaac Oluwatobi Akefe, Mohammed Bashir Tijjani, Sabo Isa Salihu, Aisha Omobolanle Olatunji, Abdussalam Hassan, Nubwa Daniel, Victoria Aderonke Adegoke

引用次数: 0

Adverse events associated with SARS-CoV-2 neutralizing monoclonal antibodies using the FDA adverse event reporting system database. 使用 FDA 不良事件报告系统数据库，了解与 SARS-CoV-2 中和单克隆抗体相关的不良事件。

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-07-30 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00256-x

Min Joung Choi, Se-Hun Oh, Yun-Kyoung Song, Sung Hwan Ki

{"title":"Adverse events associated with SARS-CoV-2 neutralizing monoclonal antibodies using the FDA adverse event reporting system database.","authors":"Min Joung Choi, Se-Hun Oh, Yun-Kyoung Song, Sung Hwan Ki","doi":"10.1007/s43188-024-00256-x","DOIUrl":"https://doi.org/10.1007/s43188-024-00256-x","url":null,"abstract":"The purpose of this study was to analyze the important medical events (IMEs) of anti-severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) monoclonal antibodies using the reports from the United States Food and Drug Administration (US FDA) adverse event reporting system (FAERS) and to detect safety signals. In this study, data from the FAERS from January 2020 to December 2022 were used to investigate signals associated with five monoclonal antibody products (bamlanivimab, bamlanivimab/etesevimab, bebtelovimab, casirivimab/imdevimab, sotrovimab) in coronavirus disease 2019 (COVID-19) patients and one monoclonal antibody product (tixagevimab/cilgavimab) in patients wherein COVID-19 vaccination was not recommended. Disproportionality analyses were conducted using the reporting odds ratio, and an information component to identify safety signals. There were 17,937,860 drug AE reports associated with all drugs in the FAERS documented during research period. Among them, 42,642 were AE reports associated with anti-SARS-CoV-2 monoclonal antibodies. The SOCs including respiratory, thoracic and mediastinal, and vascular disorders were frequently reported for all the six products. The three most commonly detected IMEs were hypoxia, COVID-19 pneumonia, and anaphylactic reaction due to SARS-CoV-2 neutralizing antibodies. Even though the purposes of use were different, the types of signals between drugs were similar. Careful monitoring of these AEs should be considered for certain COVID-19 patients, at risk, when they are treated with monoclonal antibody products.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"673-682"},"PeriodicalIF":1.6,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436521/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354452","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

Acetate attenuates lead-induced dysregulation of testicular steroidogenesis and spermatogenesis by targeting oxidative stress, inflammatory cytokines, and apoptosis. 醋酸盐通过靶向氧化应激、炎症细胞因子和细胞凋亡，减轻铅诱导的睾丸类固醇生成和精子生成失调。

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-06-28 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00250-3

Elizabeth Enohnyket Besong, Tunmise Maryanne Akhigbe, Precious Adeoye Oyedokun, Moses Agbomhere Hamed, Roland Eghoghosoa Akhigbe

{"title":"Acetate attenuates lead-induced dysregulation of testicular steroidogenesis and spermatogenesis by targeting oxidative stress, inflammatory cytokines, and apoptosis.","authors":"Elizabeth Enohnyket Besong, Tunmise Maryanne Akhigbe, Precious Adeoye Oyedokun, Moses Agbomhere Hamed, Roland Eghoghosoa Akhigbe","doi":"10.1007/s43188-024-00250-3","DOIUrl":"https://doi.org/10.1007/s43188-024-00250-3","url":null,"abstract":"Lead exposure has been implicated in the aetiopathogenesis of male infertility via an oxidative stress-sensitive pathway. Conversely, acetate has been shown to confer cellular protection by improving the antioxidant defense mechanism. Yet, the effect of acetate on lead-induced testicular toxicity, viz., dysregulation of testicular steroidogenesis and spermatogenesis, has not been reported. The present study probed the influence of acetate on lead-induced dysregulation of testicular steroidogenesis and spermatogenesis. In our study, a reduction in body weight gain and testicular weight was identified in lead-exposed rats. While histopathological results established distortion of testicular histoarchitecture, reduced germ cell count, and suppressed spermatogenesis, biochemical studies confirmed that lead-deregulated testicular steroidogenesis was associated with reduced circulating gonadotropin-releasing hormone and gonadotropins, as well as down-regulated testicular 3β-HSD and 17β-HSD activities. These findings were accompanied by increased testicular malondialdehyde, TNF-α, IL-1β, and IL-6, and reduced glutathione, thiol and non-thiol protein levels, total antioxidant capacity, superoxide dismutase, and catalase activities. In addition, lead exposure increased NFkB and Bax levels, as well as caspase 3 activity, but reduced Bcl-2 levels. However, co-administration of acetate ameliorated lead-induced alterations. Collectively, acetate attenuated lead-induced dysregulation of testicular steroidogenesis and spermatogenesis by targeting oxidative stress, NFkB-mediated inflammation, and caspase 3-driven apoptosis.Supplementary information: The online version contains supplementary material available at 10.1007/s43188-024-00250-3.","PeriodicalId":23181,"journal":{"name":"Toxicological Research","volume":"40 4","pages":"613-626"},"PeriodicalIF":1.6,"publicationDate":"2024-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11436558/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142354451","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

Correction to: Determination of ethanol in blood samples using partial least square regression applied to surface enhanced Raman spectroscopy. 更正：利用表面增强拉曼光谱的部分最小平方回归法测定血液样本中的乙醇含量。

IF 1.6 4区医学

Toxicological Research Pub Date : 2024-06-26 eCollection Date: 2024-10-01 DOI: 10.1007/s43188-024-00245-0

Güneş Açikgöz, Berna Hamamci, Abdulkadir Yildiz

引用次数: 0

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":"https://doi.org/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