Human & Experimental Toxicology最新文献

CircRNA_001373 promotes liver fibrosis by regulating autophagy activation in hepatic stellate cells via the miR-142a-5p/Becn1 axis CircRNA_001373通过miR-142a-5p/Becn1轴调节肝星状细胞的自噬激活，从而促进肝纤维化

IF 2.8 4区医学 Q3 TOXICOLOGY

Human & Experimental Toxicology

Pub Date : 2024-09-18 DOI: 10.1177/09603271241265105

Ying Cao, Huan Yang, Bingying Wang

The purpose of this study was to investigate the regulatory role and underlying mechanisms of circRNA_001373 in the hepatic stellate cell (HSC) activation. Quantitative real-time polymerase chain reaction was used to detect the expression of circRNA_001373, miR-142a-5p and Becn1. The viability of JS-1 cells was measured by Cell Counting Kit-8. The targeting relationship between miR-142a-5p and CircRNA_001373, as well as between miR-142a-5p and Becn1 was predicted using CircInteractome and TargetScan databases, respectively, and validated by dual-luciferase reporter assay. Western blot was utilized to determine the expression levels of proteins related to autophagy and the activation if HSCs in JS-1 cells. After activation by platelet-derived growth factor-BB, an increase was observed in the expression of collagen I and α-smooth muscle actin proteins. The expression of CircRNA_001373 was up-regulated in the activated HSCs. Knockdown of CircRNA_001373 significantly inhibited cell viability and activation of JS-1 cells, as well as autophagy in the activated HSCs. CircRNA_001373 could sponge miR-142a-5p in the activated HSCs, which in turn elevated the Becn1 expression. Concurrent knockdown of both CircRNA_001373 and miR-142a-5p reversed the inhibitory effects of the knockdown of CircRNA_001373 alone on cell viability and autophagy in activated JS-1 cells. CircRNA_ 001373 promotes cell viability and autophagy as well as the activation of JS-1 cells by regulating the miR-142a-5p/Becn1 axis.

本研究旨在探讨circRNA_001373在肝星状细胞（HSC）活化过程中的调控作用及其内在机制。研究采用定量实时聚合酶链反应检测circRNA_001373、miR-142a-5p和Becn1的表达。用细胞计数试剂盒-8测定了JS-1细胞的活力。利用 CircInteractome 和 TargetScan 数据库分别预测了 miR-142a-5p 与 CircRNA_001373 之间以及 miR-142a-5p 与 Becn1 之间的靶向关系，并通过双荧光素酶报告实验进行了验证。利用Western印迹法测定了JS-1细胞中与自噬和造血干细胞活化有关的蛋白质的表达水平。经血小板衍生生长因子-BB激活后，观察到胶原蛋白I和α-平滑肌肌动蛋白的表达增加。在活化的造血干细胞中，CircRNA_001373的表达上调。敲除CircRNA_001373能显著抑制JS-1细胞的活力和活化，并抑制活化的造血干细胞的自噬。CircRNA_001373能在活化的造血干细胞中海绵化miR-142a-5p，进而提高Becn1的表达。同时敲除CircRNA_001373和miR-142a-5p可逆转单独敲除CircRNA_001373对活化的JS-1细胞活力和自噬的抑制作用。CircRNA_001373通过调节miR-142a-5p/Becn1轴促进细胞活力和自噬以及活化JS-1细胞。

{"title":"CircRNA_001373 promotes liver fibrosis by regulating autophagy activation in hepatic stellate cells via the miR-142a-5p/Becn1 axis","authors":"Ying Cao, Huan Yang, Bingying Wang","doi":"10.1177/09603271241265105","DOIUrl":"https://doi.org/10.1177/09603271241265105","url":null,"abstract":"The purpose of this study was to investigate the regulatory role and underlying mechanisms of circRNA_001373 in the hepatic stellate cell (HSC) activation. Quantitative real-time polymerase chain reaction was used to detect the expression of circRNA_001373, miR-142a-5p and Becn1. The viability of JS-1 cells was measured by Cell Counting Kit-8. The targeting relationship between miR-142a-5p and CircRNA_001373, as well as between miR-142a-5p and Becn1 was predicted using CircInteractome and TargetScan databases, respectively, and validated by dual-luciferase reporter assay. Western blot was utilized to determine the expression levels of proteins related to autophagy and the activation if HSCs in JS-1 cells. After activation by platelet-derived growth factor-BB, an increase was observed in the expression of collagen I and α-smooth muscle actin proteins. The expression of CircRNA_001373 was up-regulated in the activated HSCs. Knockdown of CircRNA_001373 significantly inhibited cell viability and activation of JS-1 cells, as well as autophagy in the activated HSCs. CircRNA_001373 could sponge miR-142a-5p in the activated HSCs, which in turn elevated the Becn1 expression. Concurrent knockdown of both CircRNA_001373 and miR-142a-5p reversed the inhibitory effects of the knockdown of CircRNA_001373 alone on cell viability and autophagy in activated JS-1 cells. CircRNA_ 001373 promotes cell viability and autophagy as well as the activation of JS-1 cells by regulating the miR-142a-5p/Becn1 axis.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260002","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

Sulforaphane triggers Sirtuin 3-mediated ferroptosis in colorectal cancer cells via activating the adenosine 5‘-monophosphate (AMP)-activated protein kinase/ mechanistic target of rapamycin signaling pathway 红豆杉通过激活 5'-单磷酸腺苷（AMP）激活的蛋白激酶/雷帕霉素机制靶点信号通路，触发 Sirtuin 3 介导的结直肠癌细胞铁变态反应

IF 2.8 4区医学 Q3 TOXICOLOGY

Human & Experimental Toxicology

Pub Date : 2024-09-18 DOI: 10.1177/09603271241266106

Bo Hu, Ping Cao, Jing-hui Wang, Wei Feng, Yang Zhang, Hui Yang

ObjectiveThis study aimed to explore the expression and biological functions of SIRT3 in colorectal cancer cells (HCT-116), the impacts of sulforaphane on the ferroptosis of HCT-116 cells and the involvement of the SIRT3/AMPK/mTOR axis in those effects.MethodsSIRT3-overexpressing (OE) and SIRT3-knockout (KO) cell lines were treated with different concentrations of sulforaphane, RSL-3, and IKE. Cell viability, intracellular ROS, MDA, iron levels, as well as mRNA and protein expressions of target genes were measured.ResultsSIRT3 expression in HCT-116 cells was increased by ferroptosis inducers and decreased by ferroptosis inhibitors. SIRT3 overexpression reduced cell viability and increased intracellular levels of ROS, MDA, and iron, whereas SIRT3 knockdown achieved the opposite effects. SIRT3 overexpression suppressed SLC7A11 expression and promoted the activation of AMPK/mTOR pathway. Restoration of SLC7A11 expression blocked the effects of SIRT3 on ferroptosis induction and cell viability inhibition. SIRT3 effects on cell viability and ferroptosis were antagonized by inhibitors of AMPK or mTOR. Moreover, sulforaphane triggered the ferroptosis of HCT-116 cells by activating the SIRT3/AMPK/mTOR axis.ConclusionsSIRT3 triggered SLC7A11-mediated ferroptosis in HCT-116 cells, reducing cell viability by activating the AMPK/mTOR pathway, and sulforaphane targets it to inhibit colorectal cancer.

目的本研究旨在探讨SIRT3在结直肠癌细胞（HCT-116）中的表达和生物学功能、红景天对HCT-116细胞铁变态反应的影响以及SIRT3/AMPK/mTOR轴在这些影响中的参与作用。方法用不同浓度的红景天、RSL-3和IKE处理SIRT3高表达（OE）和SIRT3基因敲除（KO）细胞系。结果SIRT3在HCT-116细胞中的表达在铁色素沉着诱导剂的作用下增加，在铁色素沉着抑制剂的作用下减少。SIRT3 的过表达降低了细胞活力，增加了细胞内 ROS、MDA 和铁的水平，而 SIRT3 的敲除则产生了相反的效果。SIRT3 的过表达抑制了 SLC7A11 的表达，促进了 AMPK/mTOR 通路的激活。恢复 SLC7A11 的表达阻断了 SIRT3 诱导铁变态反应和抑制细胞活力的作用。AMPK 或 mTOR 抑制剂可拮抗 SIRT3 对细胞活力和铁突变的影响。结论SIRT3通过激活AMPK/mTOR通路触发了SLC7A11介导的HCT-116细胞铁蛋白沉降，降低了细胞活力，而莱菔硫烷则以其为靶点抑制结直肠癌。

{"title":"Sulforaphane triggers Sirtuin 3-mediated ferroptosis in colorectal cancer cells via activating the adenosine 5‘-monophosphate (AMP)-activated protein kinase/ mechanistic target of rapamycin signaling pathway","authors":"Bo Hu, Ping Cao, Jing-hui Wang, Wei Feng, Yang Zhang, Hui Yang","doi":"10.1177/09603271241266106","DOIUrl":"https://doi.org/10.1177/09603271241266106","url":null,"abstract":"ObjectiveThis study aimed to explore the expression and biological functions of SIRT3 in colorectal cancer cells (HCT-116), the impacts of sulforaphane on the ferroptosis of HCT-116 cells and the involvement of the SIRT3/AMPK/mTOR axis in those effects.MethodsSIRT3-overexpressing (OE) and SIRT3-knockout (KO) cell lines were treated with different concentrations of sulforaphane, RSL-3, and IKE. Cell viability, intracellular ROS, MDA, iron levels, as well as mRNA and protein expressions of target genes were measured.ResultsSIRT3 expression in HCT-116 cells was increased by ferroptosis inducers and decreased by ferroptosis inhibitors. SIRT3 overexpression reduced cell viability and increased intracellular levels of ROS, MDA, and iron, whereas SIRT3 knockdown achieved the opposite effects. SIRT3 overexpression suppressed SLC7A11 expression and promoted the activation of AMPK/mTOR pathway. Restoration of SLC7A11 expression blocked the effects of SIRT3 on ferroptosis induction and cell viability inhibition. SIRT3 effects on cell viability and ferroptosis were antagonized by inhibitors of AMPK or mTOR. Moreover, sulforaphane triggered the ferroptosis of HCT-116 cells by activating the SIRT3/AMPK/mTOR axis.ConclusionsSIRT3 triggered SLC7A11-mediated ferroptosis in HCT-116 cells, reducing cell viability by activating the AMPK/mTOR pathway, and sulforaphane targets it to inhibit colorectal cancer.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260004","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

Ergot alkaloid consumption alters serotonin receptor-induced vasoactivity in ovine umbilical vasculature 食用麦角生物碱会改变血清素受体诱导的绵羊脐血管活性

IF 2.8 4区医学 Q3 TOXICOLOGY

Human & Experimental Toxicology

Pub Date : 2024-09-14 DOI: 10.1177/09603271241269027

James L Klotz, Jessica L Britt, Maslyn A Greene, Coral Kent-Dennis, Susan K Duckett

Consumption of ergot alkaloids during the second half of gestation has been shown to decrease umbilical artery vasoactivity resulting in decreased birth weights. Negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors in other tissues. Vasoactivity of serotonin (5-HT) receptors 5-HT2A and 5-HT1B/1D in umbilical artery and vein from ewes receiving endophyte-infected seed (E + 1.77 mg ergovaline/hd/d) or a control total mixed ration (CON; 0 mg ergovaline/hd/d) tall fescue seed at d-110 and d-133 of gestation was evaluated. Gravid reproduction tracts were collected from ewes. Two-mm sections of umbilical artery and vein were exposed to increasing concentrations of a 5-HT1B/1D agonist and 5-HT2A agonist. The 5-HT1B/1D agonist did not stimulate a contractile response in artery or vein or either gestation time point. 5-HT2A agonist caused large responses in artery with greatest occurring at d-110 and decreasing in magnitude as days of gestation increased ( p < 0.05). On d-110 and 133 of gestation, arteries from CON ewes had greater contractile response than arteries collected from E+ ewes ( p < 0.05). Veins responded to increasing concentrations of the 5-HT2A agonist. Maximal d-110 vein response was greater than d-133 when exposed to 5-HT2A agonist ( p < 0.05). Unlike the artery, veins from E+ ewes had greater d-133 contractile response than CON ( p < 0.05). Vascular contractions of umbilical artery and vein are induced by 5-HT2A receptor activity and not 5-HT1B/1D. Umbilical artery 5-HT2A receptor activity was more sensitive to seed treatment and could be responsible for ergot alkaloid-induced intra-uterine growth restriction.

研究表明，在妊娠后半期服用麦角生物碱会降低脐动脉血管活性，导致出生体重下降。麦角生物碱对血管的负面影响主要是通过其他组织中的血清素能和肾上腺素能受体介导的。在妊娠 d-110 和 d-133 天时，对接受内生菌感染种子（E + 1.77 mg 麦角碱/hd/d）或总混合饲料对照（CON；0 mg 麦角碱/hd/d）高羊茅种子的母羊的脐动脉和静脉中血清素（5-HT）受体 5-HT2A 和 5-HT1B/1D 的血管活性进行了评估。从母羊身上采集妊娠生殖道。将两毫米的脐动脉和静脉切片暴露于浓度不断增加的 5-HT1B/1D 激动剂和 5-HT2A 激动剂中。5-HT1B/1D 激动剂不会刺激动脉或静脉或任何一个妊娠时间点的收缩反应。5-HT2A 激动剂在动脉中引起了较大的反应，最大的反应发生在妊娠第 110 天，随着妊娠天数的增加，反应幅度逐渐减小（p <0.05）。在妊娠第 110 天和第 133 天，来自 CON 母羊的动脉比来自 E+ 母羊的动脉有更大的收缩反应（p < 0.05）。静脉对浓度不断增加的 5-HT2A 激动剂有反应。当暴露于 5-HT2A 激动剂时，d-110 静脉的最大反应大于 d-133（p < 0.05）。与动脉不同，E+母羊静脉的 d-133 收缩反应大于 CON（p < 0.05）。脐动脉和静脉的血管收缩是由 5-HT2A 受体活性而非 5-HT1B/1D 引起的。脐动脉 5-HT2A 受体活性对种子处理更敏感，可能是麦角生物碱诱导宫内生长受限的原因。

{"title":"Ergot alkaloid consumption alters serotonin receptor-induced vasoactivity in ovine umbilical vasculature","authors":"James L Klotz, Jessica L Britt, Maslyn A Greene, Coral Kent-Dennis, Susan K Duckett","doi":"10.1177/09603271241269027","DOIUrl":"https://doi.org/10.1177/09603271241269027","url":null,"abstract":"Consumption of ergot alkaloids during the second half of gestation has been shown to decrease umbilical artery vasoactivity resulting in decreased birth weights. Negative vascular effects of ergot alkaloids are mediated predominantly through serotonergic and adrenergic receptors in other tissues. Vasoactivity of serotonin (5-HT) receptors 5-HT2A and 5-HT1B/1D in umbilical artery and vein from ewes receiving endophyte-infected seed (E + 1.77 mg ergovaline/hd/d) or a control total mixed ration (CON; 0 mg ergovaline/hd/d) tall fescue seed at d-110 and d-133 of gestation was evaluated. Gravid reproduction tracts were collected from ewes. Two-mm sections of umbilical artery and vein were exposed to increasing concentrations of a 5-HT1B/1D agonist and 5-HT2A agonist. The 5-HT1B/1D agonist did not stimulate a contractile response in artery or vein or either gestation time point. 5-HT2A agonist caused large responses in artery with greatest occurring at d-110 and decreasing in magnitude as days of gestation increased ( p < 0.05). On d-110 and 133 of gestation, arteries from CON ewes had greater contractile response than arteries collected from E+ ewes ( p < 0.05). Veins responded to increasing concentrations of the 5-HT2A agonist. Maximal d-110 vein response was greater than d-133 when exposed to 5-HT2A agonist ( p < 0.05). Unlike the artery, veins from E+ ewes had greater d-133 contractile response than CON ( p < 0.05). Vascular contractions of umbilical artery and vein are induced by 5-HT2A receptor activity and not 5-HT1B/1D. Umbilical artery 5-HT2A receptor activity was more sensitive to seed treatment and could be responsible for ergot alkaloid-induced intra-uterine growth restriction.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142260005","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

Expression of PVT-1 and miR-29a/29b as reliable biomarkers for liver cirrhosis and their correlation with the inflammatory biomarkers profile. PVT-1和miR-29a/29b的表达作为肝硬化的可靠生物标志物及其与炎症生物标志物谱的相关性。

IF 2.8 4区医学 Q2 Environmental Science

Human & Experimental Toxicology

Pub Date : 2024-04-30 DOI: 10.1177/09603271241251451

Shaza E. Khalaf, Shima N. Abdelfattah, Amal K. Khaliefa, Sahar A. Daoud, Enas Yahia, Nabil A. Hasona

Background & AimsThe liver is a vital organ responsible for numerous metabolic processes, which can be significantly impacted by long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). These ribonucleic acid (RNA) molecules have been shown to play a crucial role in regulating gene expression, and their dysregulation has been implicated in numerous liver disorders. Our study aimed to investigate the diagnostic accuracy of plasmacytoma variant translocation-1 (PVT-1), microRNA-29a/29b (miR-29a/miR-29b), and inflammatory biomarkers [ interleukine-6 (IL-6), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), and insulin growth factor-1 (IGF-1)] as diagnostic and prognostic biomarkers for liver cirrhosis. Therefore, understanding the mechanisms by which lncRNAs and miRNAs influence liver metabolism is of paramount importance in developing effective treatments for liver-related diseases.MethodsSerum samples were collected from 164 participants, comprising 114 cirrhotic patients with varying grades (35 grade I, 35 grade II, and 44 grade III) and 50 healthy controls. PVT-1 and miR-29a/miR-29b expression was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-PCR), while the serum levels of inflammatory biomarkers were assessed using enzyme-linked immunosorbent assay (ELISA).ResultsThe study participants exhibited notable differences in PVT-1 and miR-29a/miR-29b expression. ROC analysis revealed excellent discriminative power for PVT-1 and miR-29a/miR-29b in distinguishing cirrhotic patients from healthy controls.ConclusionThis study demonstrates the promising potential of PVT-1 and miR-29a/miR-29b as early diagnostic biomarkers for liver cirrhosis detection, requiring further validation in larger cohorts. Our findings also reinforce the diagnostic value of circulating inflammatory biomarkers (IL-6, TNF-α, TGF-β, and IGF-1) levels for liver cirrhosis screening.

背景& 目的肝脏是负责众多新陈代谢过程的重要器官，长非编码RNA（lncRNA）和microRNA（miRNA）可对这些过程产生重大影响。这些核糖核酸（RNA）分子已被证明在调节基因表达方面起着至关重要的作用，它们的失调与许多肝脏疾病有关。我们的研究旨在探讨浆细胞瘤变异易位-1（PVT-1）、microRNA-29a/29b（miR-29a/miR-29b）和炎症生物标志物[白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、转化生长因子-β（TGF-β）和胰岛素生长因子-1（IGF-1）]作为肝硬化诊断和预后生物标志物的诊断准确性。因此，了解 lncRNAs 和 miRNAs 影响肝脏代谢的机制对于开发有效治疗肝脏相关疾病的方法至关重要。方法收集了 164 名参与者的血清样本，其中包括 114 名不同等级的肝硬化患者（35 名 I 级、35 名 II 级和 44 名 III 级）和 50 名健康对照者。通过反转录-定量聚合酶链反应（RT-PCR）分析了PVT-1和miR-29a/miR-29b的表达，同时使用酶联免疫吸附测定法（ELISA）评估了血清中炎症生物标志物的水平。ROC分析表明，PVT-1和miR-29a/miR-29b在区分肝硬化患者和健康对照组方面具有很好的鉴别力。我们的研究结果还加强了循环炎症生物标志物（IL-6、TNF-α、TGF-β 和 IGF-1）水平在肝硬化筛查中的诊断价值。

{"title":"Expression of PVT-1 and miR-29a/29b as reliable biomarkers for liver cirrhosis and their correlation with the inflammatory biomarkers profile.","authors":"Shaza E. Khalaf, Shima N. Abdelfattah, Amal K. Khaliefa, Sahar A. Daoud, Enas Yahia, Nabil A. Hasona","doi":"10.1177/09603271241251451","DOIUrl":"https://doi.org/10.1177/09603271241251451","url":null,"abstract":"Background & AimsThe liver is a vital organ responsible for numerous metabolic processes, which can be significantly impacted by long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). These ribonucleic acid (RNA) molecules have been shown to play a crucial role in regulating gene expression, and their dysregulation has been implicated in numerous liver disorders. Our study aimed to investigate the diagnostic accuracy of plasmacytoma variant translocation-1 (PVT-1), microRNA-29a/29b (miR-29a/miR-29b), and inflammatory biomarkers [ interleukine-6 (IL-6), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-β), and insulin growth factor-1 (IGF-1)] as diagnostic and prognostic biomarkers for liver cirrhosis. Therefore, understanding the mechanisms by which lncRNAs and miRNAs influence liver metabolism is of paramount importance in developing effective treatments for liver-related diseases.MethodsSerum samples were collected from 164 participants, comprising 114 cirrhotic patients with varying grades (35 grade I, 35 grade II, and 44 grade III) and 50 healthy controls. PVT-1 and miR-29a/miR-29b expression was analyzed by reverse transcription-quantitative polymerase chain reaction (RT-PCR), while the serum levels of inflammatory biomarkers were assessed using enzyme-linked immunosorbent assay (ELISA).ResultsThe study participants exhibited notable differences in PVT-1 and miR-29a/miR-29b expression. ROC analysis revealed excellent discriminative power for PVT-1 and miR-29a/miR-29b in distinguishing cirrhotic patients from healthy controls.ConclusionThis study demonstrates the promising potential of PVT-1 and miR-29a/miR-29b as early diagnostic biomarkers for liver cirrhosis detection, requiring further validation in larger cohorts. Our findings also reinforce the diagnostic value of circulating inflammatory biomarkers (IL-6, TNF-α, TGF-β, and IGF-1) levels for liver cirrhosis screening.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140831933","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

Baicalein exerts beneficial effects in lipopolysaccharide-induced pulmonary inflammation by modulating macrophage polarization and inhibiting pyroptosis 黄芩苷通过调节巨噬细胞极化和抑制脓毒症，对脂多糖诱导的肺部炎症产生有益影响

IF 2.8 4区医学 Q2 Environmental Science

Human & Experimental Toxicology

Pub Date : 2024-04-26 DOI: 10.1177/09603271241249990

Yile Kou, Lu Zhang, Zhaoling Shi, Guocheng Zhang, Jing Chang, Qian Bai, Na Gao, Hui Ding

The disruption of the immune system by viral attack is a major influencing factor in the lethality of COVID-19. Baicalein is one of the key effective compounds against COVID-19. The molecular mechanisms regarding the anti-inflammatory properties of Baicalein are still unclear. In this study, we established LPS-induced mice to elucidate the role of Baicalein in the treatment of acute lung injury (ALI) and its potential molecular mechanisms. In vivo experiments showed that Baicalein could significantly ameliorate LPS-induced acute lung injury and reduce proteinous edema in lung tissue. In addition, Baicalein inhibited M1 macrophage polarization, promote M2 macrophage polarization, and regulate inflammatory responses. Furthermore, Baicalein could inhibit the expression of protein molecules associated with pyroptosis and mitigate the lung tissue injury. In summary, we revealed the therapeutic effects of Baicalein in acute lung injury, providing the theoretical basis for its clinical application.

病毒攻击对免疫系统的破坏是 COVID-19 致死的主要影响因素。黄芩素是对抗 COVID-19 的主要有效化合物之一。有关黄芩苷抗炎特性的分子机制尚不清楚。在本研究中，我们建立了 LPS 诱导的小鼠，以阐明黄芩苷在治疗急性肺损伤（ALI）中的作用及其潜在的分子机制。体内实验表明，Baicalein能明显改善LPS诱导的急性肺损伤，减轻肺组织蛋白性水肿。此外，黄芩苷还能抑制 M1 巨噬细胞极化，促进 M2 巨噬细胞极化，调节炎症反应。此外，黄芩苷还能抑制与脓毒症相关的蛋白分子的表达，减轻肺组织损伤。综上所述，我们揭示了黄芩苷对急性肺损伤的治疗作用，为其临床应用提供了理论依据。

引用次数: 0

Reassessing clinical presentations of emamectin benzoate poisoning: A comprehensive study 重新评估苯甲酸阿维菌素中毒的临床表现：一项综合研究

IF 2.8 4区医学 Q2 Environmental Science

Human & Experimental Toxicology

Pub Date : 2024-04-25 DOI: 10.1177/09603271241249965

Chi-Syuan Pan, Chi-Chan Lee, Jiun-Hao Yu, Han-Wei Mu, Dong-Zong Hung, Chun-Hung Chen

BackgroundThe mechanism of emamectin benzoate (EMB—a macrocyclic lactone insecticide like abamectin) action involves the disruption of glutamate-gated chloride channels and GABA receptors in insects, leading to paralysis and death. EMB overdose can breach the blood–brain barrier, resulting in severe poisoning and altered consciousness.AimReview EMB poisoning presentations in patients and reevaluate clinical manifestations.Materials and MethodsThis retrospective study reviewed (August 31, 2008–August 31, 2023) medical university hospital records. We analyzed symptoms, patient characteristics, vital signs, Glasgow Coma Scale scores, laboratory findings, and outcomes.ResultsTen patients (males: 6, females: 4, median age = 64.5 years) experienced EMB poisoning. Common symptoms included sore throat, gastrointestinal distress, dyspnea, and altered consciousness; two patients showed laryngeal corrosive injuries. Management involved activated charcoal administration, gastric lavage, and intensive care unit admission.DiscussionSore throat and corrosive injuries were distinctive presentations of EMB poisoning, warranting vigilance. Potential mechanisms of corrosive injury include skin and eye irritation effects of EMB, the solvents of which might exert corrosive action.ConclusionEMB poisoning manifests as diverse symptoms, including sore throat, gastrointestinal symptoms, central nervous system depression, and potential aspiration pneumonia. Recognizing and promptly managing EMB poisoning are crucial for enhancing patient outcomes and minimizing complications.

背景苯甲酸阿维菌素（EMB--一种类似阿维菌素的大环内酯类杀虫剂）的作用机制是破坏昆虫体内谷氨酸门控氯离子通道和GABA受体，导致麻痹和死亡。本研究回顾了（2008 年 8 月 31 日至 2023 年 8 月 31 日）医科大学医院的病历。我们分析了症状、患者特征、生命体征、格拉斯哥昏迷量表评分、实验室检查结果和预后。结果10例患者（男：6例，女：4例，中位年龄=64.5岁）出现EMB中毒。常见症状包括咽喉疼痛、胃肠道不适、呼吸困难和意识改变；两名患者出现喉部腐蚀性损伤。咽喉疼痛和腐蚀性损伤是 EMB 中毒的独特表现，值得警惕。腐蚀性损伤的潜在机制包括 EMB 对皮肤和眼睛的刺激作用，其中的溶剂可能具有腐蚀作用。识别和及时处理 EMB 中毒对提高患者的治疗效果和减少并发症至关重要。

{"title":"Reassessing clinical presentations of emamectin benzoate poisoning: A comprehensive study","authors":"Chi-Syuan Pan, Chi-Chan Lee, Jiun-Hao Yu, Han-Wei Mu, Dong-Zong Hung, Chun-Hung Chen","doi":"10.1177/09603271241249965","DOIUrl":"https://doi.org/10.1177/09603271241249965","url":null,"abstract":"BackgroundThe mechanism of emamectin benzoate (EMB—a macrocyclic lactone insecticide like abamectin) action involves the disruption of glutamate-gated chloride channels and GABA receptors in insects, leading to paralysis and death. EMB overdose can breach the blood–brain barrier, resulting in severe poisoning and altered consciousness.AimReview EMB poisoning presentations in patients and reevaluate clinical manifestations.Materials and MethodsThis retrospective study reviewed (August 31, 2008–August 31, 2023) medical university hospital records. We analyzed symptoms, patient characteristics, vital signs, Glasgow Coma Scale scores, laboratory findings, and outcomes.ResultsTen patients (males: 6, females: 4, median age = 64.5 years) experienced EMB poisoning. Common symptoms included sore throat, gastrointestinal distress, dyspnea, and altered consciousness; two patients showed laryngeal corrosive injuries. Management involved activated charcoal administration, gastric lavage, and intensive care unit admission.DiscussionSore throat and corrosive injuries were distinctive presentations of EMB poisoning, warranting vigilance. Potential mechanisms of corrosive injury include skin and eye irritation effects of EMB, the solvents of which might exert corrosive action.ConclusionEMB poisoning manifests as diverse symptoms, including sore throat, gastrointestinal symptoms, central nervous system depression, and potential aspiration pneumonia. Recognizing and promptly managing EMB poisoning are crucial for enhancing patient outcomes and minimizing complications.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797800","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

Subchronic inhalation of a novel electronic nicotine delivery system formulation and its corresponding base formulation 亚慢性吸入新型电子尼古丁释放系统配方及其相应的基础配方

IF 2.8 4区医学 Q2 Environmental Science

Human & Experimental Toxicology

Pub Date : 2024-04-22 DOI: 10.1177/09603271241248631

Guy Lalonde, Nikos Tsolakos, Tessa R Moir-Savitz, Alex M Easley, Charles L Gaworski, Michael J Oldham

BackgroundFresh Menthol 3% Nicotine (FM3) is a novel JUUL e-liquid formulation. Its potential toxicity and that of the corresponding base formulation relative to a filtered air (FA) control was studied in a subchronic inhalation study conducted in general accordance with OECD 413.MethodsAerosols generated with an intense puffing regime were administered to rats in a nose-only fashion at 1400 µg aerosol collected mass/L on a 6 hour/day basis for 90 days with a 42-day recovery. Exposure atmospheres met target criteria. Systemic exposure was confirmed by plasma measurement of nicotine.ResultsNo test article-related mortality, clinical signs (other than reversible lower body weight gains in males), clinical pathology or gross findings were noted during this study. No microscopic lesions related to base formulation exposure were identified. Minimal microscopic lesions were observed in the FM3 6-hour exposure group. Microscopic lesions observed in the FM3 6-hour exposure group comprised only minimal laryngeal squamous metaplasia in one male and one female animal. No microscopic lesions related to FM3 exposure remained after the recovery period.ConclusionExposure atmosphere characterization indicated that conditions were achieved to permit thorough assessment of test articles and results indicate a low order of toxicity for the FM3 Electronic nicotine delivery systems (ENDS) formulation and its base formulation.

背景清新薄荷 3% 尼古丁（FM3）是一种新型的 JUUL 电子液体配方。在一项亚慢性吸入研究中，按照 OECD 413 标准对其潜在毒性以及相对于过滤空气（FA）对照的相应基本配方的潜在毒性进行了研究。方法对大鼠进行纯鼻吸入研究，以 1400 微克气溶胶收集质量/升的浓度，每天 6 小时，持续 90 天，42 天后恢复。暴露气氛符合目标标准。结果在这项研究中，没有发现与试验品有关的死亡率、临床症状（雄性动物体重增加较慢的情况除外）、临床病理学或大体检查结果。未发现与接触基础制剂有关的显微病变。在 FM3 6 小时暴露组中观察到的微观病变极少。在接触FM3 6小时组中观察到的显微病变仅包括一只雄性动物和一只雌性动物喉部的轻微鳞状化生。结论暴露环境的特征表明，所达到的条件允许对测试物品进行彻底评估，结果表明 FM3 电子尼古丁释放系统（ENDS）配方及其基本配方的毒性较低。

{"title":"Subchronic inhalation of a novel electronic nicotine delivery system formulation and its corresponding base formulation","authors":"Guy Lalonde, Nikos Tsolakos, Tessa R Moir-Savitz, Alex M Easley, Charles L Gaworski, Michael J Oldham","doi":"10.1177/09603271241248631","DOIUrl":"https://doi.org/10.1177/09603271241248631","url":null,"abstract":"BackgroundFresh Menthol 3% Nicotine (FM3) is a novel JUUL e-liquid formulation. Its potential toxicity and that of the corresponding base formulation relative to a filtered air (FA) control was studied in a subchronic inhalation study conducted in general accordance with OECD 413.MethodsAerosols generated with an intense puffing regime were administered to rats in a nose-only fashion at 1400 µg aerosol collected mass/L on a 6 hour/day basis for 90 days with a 42-day recovery. Exposure atmospheres met target criteria. Systemic exposure was confirmed by plasma measurement of nicotine.ResultsNo test article-related mortality, clinical signs (other than reversible lower body weight gains in males), clinical pathology or gross findings were noted during this study. No microscopic lesions related to base formulation exposure were identified. Minimal microscopic lesions were observed in the FM3 6-hour exposure group. Microscopic lesions observed in the FM3 6-hour exposure group comprised only minimal laryngeal squamous metaplasia in one male and one female animal. No microscopic lesions related to FM3 exposure remained after the recovery period.ConclusionExposure atmosphere characterization indicated that conditions were achieved to permit thorough assessment of test articles and results indicate a low order of toxicity for the FM3 Electronic nicotine delivery systems (ENDS) formulation and its base formulation.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2024-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797885","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

Anti-oxidative properties of nanocrocin in Zearalenone induced toxicity on Hek293 cell; The novel formulation and cellular assessment. 纳米红素对玉米赤霉烯酮致Hek293细胞毒性的抗氧化作用新制剂及细胞评价。

IF 2.8 4区医学 Q2 Environmental Science

Human & Experimental Toxicology

Pub Date : 2023-01-01 DOI: 10.1177/09603271231169911

Fatemeh Ghafari, Zohre Sadeghian, Akram Oftadeh Harsin, Sodabe Khodabandelo, Akram Ranjbar

Background: Zearalenone (ZEA) is a mycotoxin produced by fungi and induces cytotoxicity by the generation of reactive oxygen species. The aim of this study was to evaluate and compare the nephroprotective effects of crocin and nano-crocin against ZEA-induced toxicity in HEK293 cell line via modulation of oxidative stress and special formulation to make nano-crocin.

Method: Nano-crocin physicochemical properties, such as size, load, appearance, and drug release profile were determined. Also, the viability of intoxicated HEK293 cells was evaluated by MTT assay. Furthermore, lactate dehydrogenase lipid Peroxidation (LPO), and oxidative stress biomarkers were measured.

Result: The best nano-crocin formulation with superior entrapment effectiveness (54.66 ± 6.02), more significant drug loading (1.89 ± 0.01), better zeta potential (-23.4 ± 2.844), and smaller particle size (140.3 ± 18.0 nm) was chosen. This study showed that treatment with crocin and nano-crocin in ZEA-induced cells, significantly decreased LDH and LPO levels and increased superoxide dismutase (SOD), catalase (CAT) activities, and total antioxidant capacity (TAC) levels compared to the control group. Moreover, nano-crocin had a more curative effect against oxidative stress than crocin.

Conclusion: Niosomal structure of crocin, when administered with the special formulation, may be more beneficial in reducing ZEA-induced in vitro toxicity than conventional crocin.

背景:玉米赤霉烯酮(ZEA)是一种由真菌产生的真菌毒素，通过产生活性氧诱导细胞毒性。本研究旨在评价和比较藏红花素和纳米藏红花素通过调节氧化应激和特殊配方制备纳米藏红花素对zea诱导HEK293细胞株的肾保护作用。方法:测定纳米藏红花素的大小、负载、外观、释放等理化性质。MTT法检测转染后HEK293细胞的活力。此外，测定乳酸脱氢酶脂质过氧化(LPO)和氧化应激生物标志物。结果:优选出包封效率(54.66±6.02)、载药量(1.89±0.01)、zeta电位(-23.4±2.844)、粒径(140.3±18.0 nm)较小的纳米藏红花素最佳处方。本研究表明，与对照组相比，藏红花素和纳米藏红花素可显著降低zea诱导细胞的LDH和LPO水平，提高超氧化物歧化酶(SOD)、过氧化氢酶(CAT)活性和总抗氧化能力(TAC)水平。此外，纳米藏红花素对氧化应激的治疗效果优于藏红花素。结论:藏红花素的乳质体结构与特殊配方相比，可能更有利于降低zea诱导的体外毒性。

{"title":"Anti-oxidative properties of nanocrocin in Zearalenone induced toxicity on Hek293 cell; The novel formulation and cellular assessment.","authors":"Fatemeh Ghafari, Zohre Sadeghian, Akram Oftadeh Harsin, Sodabe Khodabandelo, Akram Ranjbar","doi":"10.1177/09603271231169911","DOIUrl":"https://doi.org/10.1177/09603271231169911","url":null,"abstract":"Background: Zearalenone (ZEA) is a mycotoxin produced by fungi and induces cytotoxicity by the generation of reactive oxygen species. The aim of this study was to evaluate and compare the nephroprotective effects of crocin and nano-crocin against ZEA-induced toxicity in HEK293 cell line via modulation of oxidative stress and special formulation to make nano-crocin.Method: Nano-crocin physicochemical properties, such as size, load, appearance, and drug release profile were determined. Also, the viability of intoxicated HEK293 cells was evaluated by MTT assay. Furthermore, lactate dehydrogenase lipid Peroxidation (LPO), and oxidative stress biomarkers were measured.Result: The best nano-crocin formulation with superior entrapment effectiveness (54.66 ± 6.02), more significant drug loading (1.89 ± 0.01), better zeta potential (-23.4 ± 2.844), and smaller particle size (140.3 ± 18.0 nm) was chosen. This study showed that treatment with crocin and nano-crocin in ZEA-induced cells, significantly decreased LDH and LPO levels and increased superoxide dismutase (SOD), catalase (CAT) activities, and total antioxidant capacity (TAC) levels compared to the control group. Moreover, nano-crocin had a more curative effect against oxidative stress than crocin.Conclusion: Niosomal structure of crocin, when administered with the special formulation, may be more beneficial in reducing ZEA-induced in vitro toxicity than conventional crocin.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9319789","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

Expression of concern: "Sesamol induces cytotoxicity via mitochondrial apoptosis in SCC-25 cells". 关注的表达:“芝麻醇通过SCC-25细胞的线粒体凋亡诱导细胞毒性”。

IF 2.8 4区医学 Q2 Environmental Science

Human & Experimental Toxicology

Pub Date : 2023-01-01 DOI: 10.1177/09603271231176139

引用次数: 0

Identification and characterization of differentially expressed circRNA in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate. 2,3,7,8-四氯二苯并-对二恶英所致腭裂中circRNA差异表达的鉴定与表征

IF 2.8 4区医学 Q2 Environmental Science

Human & Experimental Toxicology

Pub Date : 2023-01-01 DOI: 10.1177/09603271231183359

Liyun Gao, Jingwen Tan, Chunhua Han, Junfei Fan, Jiayin He, Ting Luo, Shiqun Yu, Xiangxin Che, Lin Zhang, Xin Wang

Various circular RNAs (circRNAs) are novel class of non-coding RNAs, which are pervasively transcribed in the genome. CircRNAs play important roles in human, animals and plants. Up to now, there was no report regarding circRNAs of cleft palate by 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) induce. The present study screened identification and characterization of differential expressed-circRNAs in TCDD-induced cleft palate. 6903 circRNAs candidates came from cleft palates. Among them, 3525 circRNAs are up-regulation, and 3378 circRNAs are down-regulation by TCDD induce. The cluster and GO analysis found that circRNAs involved in biological process, cellular component, and molecular function. Through the analysis of KEGG Pathway, circRNAs made functions via classical signaling pathway in cleft palate, such as TGF-beta signaling pathway, BMP signal pathway, MAPK signaling pathway. In addition, we found down-regulated circRNA224, circRNA3302 and up-regulated circRNA5021 targeted tgfbr3, but up-regulated circRNA4451 targeted tgfbr2. circRNA4451 may make functions through TGF-beta signaling pathway. These results suggested that many different circRNAs may make important role in TCDD-induced cleft palate, which provided a theoretical basis for further research.

各种环状rna (circRNAs)是一类新型的非编码rna，广泛存在于基因组中。circrna在人类、动物和植物中发挥着重要作用。到目前为止，还没有关于2,3,7,8-四氯二苯并二恶英(TCDD)诱发腭裂的环状rna的报道。本研究筛选了tcdd诱导腭裂中差异表达的环状rna的鉴定和表征。6903个环状rna候选基因来自腭裂。其中，3525个circrna被TCDD诱导上调，3378个circrna被TCDD诱导下调。聚类和氧化石墨烯分析发现，环状rna参与生物过程、细胞成分和分子功能。通过对KEGG通路的分析，circrna在腭裂中通过经典的信号通路发挥作用，如tgf - β信号通路、BMP信号通路、MAPK信号通路。此外，我们发现下调的circRNA224、circRNA3302和上调的circRNA5021靶向tgfbr3，而上调的circRNA4451靶向tgfbr2。circRNA4451可能通过tgf - β信号通路发挥作用。这些结果提示，许多不同的circrna可能在tcdd诱导的腭裂中发挥重要作用，为进一步的研究提供了理论基础。

{"title":"Identification and characterization of differentially expressed circRNA in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced cleft palate.","authors":"Liyun Gao, Jingwen Tan, Chunhua Han, Junfei Fan, Jiayin He, Ting Luo, Shiqun Yu, Xiangxin Che, Lin Zhang, Xin Wang","doi":"10.1177/09603271231183359","DOIUrl":"https://doi.org/10.1177/09603271231183359","url":null,"abstract":"Various circular RNAs (circRNAs) are novel class of non-coding RNAs, which are pervasively transcribed in the genome. CircRNAs play important roles in human, animals and plants. Up to now, there was no report regarding circRNAs of cleft palate by 2,3,7,8-tetrachlorodibenzo-pdioxin (TCDD) induce. The present study screened identification and characterization of differential expressed-circRNAs in TCDD-induced cleft palate. 6903 circRNAs candidates came from cleft palates. Among them, 3525 circRNAs are up-regulation, and 3378 circRNAs are down-regulation by TCDD induce. The cluster and GO analysis found that circRNAs involved in biological process, cellular component, and molecular function. Through the analysis of KEGG Pathway, circRNAs made functions via classical signaling pathway in cleft palate, such as TGF-beta signaling pathway, BMP signal pathway, MAPK signaling pathway. In addition, we found down-regulated circRNA224, circRNA3302 and up-regulated circRNA5021 targeted tgfbr3, but up-regulated circRNA4451 targeted tgfbr2. circRNA4451 may make functions through TGF-beta signaling pathway. These results suggested that many different circRNAs may make important role in TCDD-induced cleft palate, which provided a theoretical basis for further research.","PeriodicalId":13181,"journal":{"name":"Human & Experimental Toxicology","volume":null,"pages":null},"PeriodicalIF":2.8,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9622710","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