Human & experimental toxicology最新文献_第4页

Establishment and validation of an in vitro liver model based extracellular matrix for hepatotoxicity prediction. 基于细胞外基质的肝模型肝毒性预测的建立与验证。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-07-15 DOI: 10.1177/09603271251350797

Yue Yu, Haodong Zhong, Qianyi Niu, Manman Zhao, Bo Li, Xiaobing Zhou

{"title":"Establishment and validation of an in vitro liver model based extracellular matrix for hepatotoxicity prediction.","authors":"Yue Yu, Haodong Zhong, Qianyi Niu, Manman Zhao, Bo Li, Xiaobing Zhou","doi":"10.1177/09603271251350797","DOIUrl":"https://doi.org/10.1177/09603271251350797","url":null,"abstract":"IntroductionThree-dimension (3D) cell culture presents a promising alternative of drug-induced liver injury (DILI). To advance preclinical toxicology research, we developed an in vitro liver model using HepG2 for toxic evaluation.MethodsThe model was constructed based on the extracellular matrix. We assessed its long-term stability by monitoring the morphological change and anabolic capacity for 2 weeks, with functional analyses including albumin/urea production, lipid accumulation with Nile red staining, bile secretion with CLF signal, and transporter/enzyme expression including PGP, MRP2, BSEP, and CYP3A4.ResultsThe model could be maintained for at least 10 days with enhanced hepatic synthetic functions indicated by albumin and urea nitrogen. Compared with the two-dimensional (2D) cultures, 3D culture exhibited enhanced lipid accumulation and biliary excretion. Key hepatic transporters PGP, MRP2, and BSEP and the metabolic enzyme cytochrome P450 3A4 were expressed between day 5 and 7. Single-exposure induced measurable apoptosis, mitochondrial disfunction and viability assays, while repeated treatment replicated impaired bile acid transport by reduced CLF intensity, and cytotoxicity with elevated AST, ALT, and decreased survival.DiscussionOur 3D model surpasses conventional 2D systems in culture duration and functional complexity. It is suitable for DILI prediction after single- and repeated- treatment, which makes it particularly valuable for preclinical drug screening.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251350797"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144639077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Clinical characteristics and the risk factors analysis in patients with delayed encephalopathy after acute carbon monoxide poisoning. 急性一氧化碳中毒后迟发性脑病的临床特点及危险因素分析。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-04-03 DOI: 10.1177/09603271251332234

Ziang Han, Sumeng Shi, Yan Zhang, Ding Yuan, Zhigao Xu, Yanxia Gao

{"title":"Clinical characteristics and the risk factors analysis in patients with delayed encephalopathy after acute carbon monoxide poisoning.","authors":"Ziang Han, Sumeng Shi, Yan Zhang, Ding Yuan, Zhigao Xu, Yanxia Gao","doi":"10.1177/09603271251332234","DOIUrl":"10.1177/09603271251332234","url":null,"abstract":"IntroductionAcute carbon monoxide poisoning (ACMP) remains a leading cause of morbidity and mortality from fatal inhaled poisoning. Delayed encephalopathy after ACMP (DEACMP) has become one of the most complex and serious complications.MethodsIn this research, an observational study was performed from January 2016 to December 2019 to investigate the potential relevant risk factors of DEACMP with data collected from Level 3 medical facilities located in Northern China. Within the 4-year data collection period, the final study cohort consisted of 240 (117 males, 123 females).ResultsUni-variable analysis identified older age, medical history of cerebrovascular accident, basic disease of diabetes, and longer duration of loss of consciousness as relevant factors for DEACMP; while multivariable logistic regression revealed that the older age (OR, 1.45; 95% CI, 1.25-1.69; P < 0.01), longer duration of loss of consciousness (OR, 1.39; 95% CI, 1.36-1.45; P < 0.01), and cerebrovascular accidents occurring (OR, 1.23; 95% CI, 1.03-1.47; P = 0.04) were independent predictors for DEACMP.DiscussionFurthermore, additional research is needed to testify to the relevance and to elucidate the potential pathogenesis, consequently determining the clinical guideline and approving the best prevention and treatment strategy for DEACMP.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251332234"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143782362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Robinin attenuates cardiac hypertrophy in pulmonary heart disease by modulating SIRT1/NF-κB signaling and inhibiting oxidative stress and the NLRP3 inflammasome. Robinin通过调节SIRT1/NF-κB信号，抑制氧化应激和NLRP3炎性体，减轻肺心病心肌肥厚。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-07-18 DOI: 10.1177/09603271251361892

Chao Wang, Lei Qin, Xinrui Zhang, Yubao Liu

{"title":"Robinin attenuates cardiac hypertrophy in pulmonary heart disease by modulating SIRT1/NF-κB signaling and inhibiting oxidative stress and the NLRP3 inflammasome.","authors":"Chao Wang, Lei Qin, Xinrui Zhang, Yubao Liu","doi":"10.1177/09603271251361892","DOIUrl":"https://doi.org/10.1177/09603271251361892","url":null,"abstract":"BackgroundRobinin possesses certain antioxidative and anti-inflammatory properties. However, its mechanisms of action in cardiac hypertrophy (CH) and fibrosis remain inadequately explored.MethodsAn in vitro model of CH was established using angiotensin II-treated rat H9c2 cardiomyocytes treated with escalating concentrations of Robinin. For the in vivo model, pulmonary heart disease-induced CH in rats was induced by chronic hypercapnia and TAC. Myocardial cell markers were evaluated through qRT-PCR, Western blotting, ELISA, cellular immunofluorescence, and HE staining. The role of SIRT1 in Robinin's effects was determined using pharmacological inhibition with SIRT1-IN-1.ResultsIn vitro, Robinin suppressed hypertrophic (ANP, BNP, β-MHC) and fibrotic markers (MyHC, Collagen I, TGF-β1) and reduced NLRP3 components (IL-1β, IL-18, ASC, Caspase-1) and oxidative stress (OS, ↓MDA, ↑SOD/HO-1/Nrf2) in a dose-dependent manner. These effects were mediated by SIRT1 upregulation and NF-κB inactivation. Crucially, SIRT1 inhibition abolished Robinin's protection against hypertrophy and inflammation. In vivo, Robinin attenuated pulmonary heart disease-induced hypertrophy, fibrosis, NLRP3 activation, and OS while restoring SIRT1/NF-κB balance.ConclusionRobinin alleviates CH in pulmonary heart disease by modulating the SIRT1/NF-κB pathway to suppress OS and NLRP3 inflammasome activation, establishing its novel therapeutic potential.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251361892"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144661409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the role of rare earth elements (praseodymium, samarium, lanthanum, and terbium) and oxidative stress in polycystic ovary syndrome: A case-control study. 探讨稀土元素（镨、钐、镧和铽）和氧化应激在多囊卵巢综合征中的作用：一项病例对照研究。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-16 DOI: 10.1177/09603271251342280

Manal Abudawood

{"title":"Exploring the role of rare earth elements (praseodymium, samarium, lanthanum, and terbium) and oxidative stress in polycystic ovary syndrome: A case-control study.","authors":"Manal Abudawood","doi":"10.1177/09603271251342280","DOIUrl":"https://doi.org/10.1177/09603271251342280","url":null,"abstract":"BackgroundPraseodymium (Pr), Samarium (Sm), Lanthanum (La), and Terbium (Tb) are rare earth elements (REEs) that can accumulate in the body and induce oxidative stress (OS), which may contribute to polycystic ovary syndrome (PCOS), a condition affecting 116 million women worldwide. With the increasing use of REEs, understanding their role in PCOS is crucial.DesignThis case-control study included 56 PCOS cases and 50 healthy controls, with confounding factors such as age, BMI, and hormones controlled. Inductively Coupled Plasma Mass Spectrometry (ICP-MS) was used to measure serum levels of Pr, Sm, La, and Tb, and Pearson correlation was performed to explore their relationship with oxidative stress markers such as malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD).ResultA significant increase in serum levels of Pr, Sm, La, and Tb was observed in PCOS cases compared to controls (p < 0.05). The 95% confidence intervals (CIs) for the differences in serum Pr, Sm, La, and Tb levels were [0.0008, 0.0032], [0.0002, 0.0091], [0.0019, 0.0073], and [0.0002, 0.0129], respectively. Additionally, serum levels of MDA were significantly elevated, accompanied by reduction in the antioxidant markers-GSH and SOD (p < 0.001). Elevated REE levels were positively correlated with increased MDA and negatively correlated with GSH and SOD, indicating increased oxidative stress.ConclusionThese findings suggest that oxidative stress-induced metal intoxication may play a critical role in the development of PCOS. Future studies should explore the clinical significance of REE exposure and its potential as a target for preventive strategies in PCOS management.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251342280"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144083033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Integrated gut microbiota and serum metabolomics reveal glyphosate-induced hepatic injury in mice. 综合肠道微生物群和血清代谢组学揭示草甘膦诱导的小鼠肝损伤。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-11 DOI: 10.1177/09603271251326877

Gang Li, Yu Cheng, Xiaolei Yang, Zijun Chai, Zhihui Mu, Hong Chao, Hongjie Li, Yanbo Qi, Lei Qi, Jicheng Liu

{"title":"Integrated gut microbiota and serum metabolomics reveal glyphosate-induced hepatic injury in mice.","authors":"Gang Li, Yu Cheng, Xiaolei Yang, Zijun Chai, Zhihui Mu, Hong Chao, Hongjie Li, Yanbo Qi, Lei Qi, Jicheng Liu","doi":"10.1177/09603271251326877","DOIUrl":"10.1177/09603271251326877","url":null,"abstract":"IntroductionGlyphosate (GLP) is one of the most widely used herbicides in the world. However, its underlying effects on the liver remain unclear. This study aims to investigate the toxic effects and the gut microbiome- and serum metabolite-related mechanisms of GLP on the liver in mice.Methods16S rDNA sequencing and UPLC-Q-TOF-MS/MS were used to investigate the mechanisms of GLP toxicity in mice administered with 0, 50, 250 and 500 mg/kg/day GLP for 30 days.ResultsGLP induced hepatocyte edema and ballooning as well as inflammatory cell infiltration. Exposure to GLP resulted in increased levels of serum ALT, TBIL, DBIL, and GLU. Microbiota analysis at the phylum level demonstrated that the proportions of Patescibacteria decreased in the GLP-treated group. The genus-level analysis identified 11 different genera, with eight decreased and three increased in the GLP-exposed group. Metabolomics analysis of serum showed 42 differential metabolites between the GLP and control groups. The metabolic pathway enrichment analysis revealed that the pentose phosphate pathway (PPP) and pyrimidine metabolism were significantly activated. Spearman analysis showed that the changes in the differential metabolites of the PPP and pyrimidine metabolism and gut microbiota were strongly associated with the biochemical index.DiscussionIn conclusion, GLP exposure induces hepatic injury through alterations in the gut microbiome and metabolic pathways, particularly by activating the pentose phosphate pathway and pyrimidine metabolism.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251326877"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Thanks to Reviewers. 感谢评论者。

Human & experimental toxicology Pub Date : 2025-01-01 DOI: 10.1177/09603271251315241

引用次数: 0

High-dose vitamin C potently induces apoptosis in acute lymphoblastic leukemia by activating ER stress response. 高剂量维生素C可通过激活内质网应激反应诱导急性淋巴细胞白血病细胞凋亡。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-29 DOI: 10.1177/09603271251345656

Hui Meng Sun, Yanan Jiang, Kaiping Luo, Dong Hui Xing, Yixin Zhai, Xiang He, Wenqi Wu, Zhigang Zhao

{"title":"High-dose vitamin C potently induces apoptosis in acute lymphoblastic leukemia by activating ER stress response.","authors":"Hui Meng Sun, Yanan Jiang, Kaiping Luo, Dong Hui Xing, Yixin Zhai, Xiang He, Wenqi Wu, Zhigang Zhao","doi":"10.1177/09603271251345656","DOIUrl":"https://doi.org/10.1177/09603271251345656","url":null,"abstract":"IntroductionHigh-dose Vitamin C has shown significant anti-tumor effects in various cancers, including hematological malignancies. However, its therapeutic efficacy against acute lymphoblastic leukemia (ALL) remains underexplored.MethodsALL cell lines and normal bone marrow mononuclear cells were treated with Vitamin C to assess cell viability, apoptosis, proliferation, and cell cycle progression. Colony formation assays evaluated long-term growth. Additionally, transgenic mouse models were employed to evaluate the in vivo antitumor activity of high-dose Vitamin C in ALL. Western blotting, ROS detection 2',7'-Dichlorofluorescin diacetate (DCFH-DA), and RNA sequencing with GSEA were conducted to explore Vitamin C's mechanism of action.ResultsOur results demonstrated that high-dose Vitamin C exhibited potent cytotoxicity toward ALL cells at relatively low concentrations (200 μM) while sparing normal human bone marrow mononuclear cells even at concentrations as high as 1 mM. Vitamin C effectively inhibited ALL cell line proliferation, induced apoptosis, and disrupted cell cycle progression. We further identified that the increased expression of Solute Carrier Family 23 Member 1 (SLC23A1) in ALL cells enhanced their sensitivity to Vitamin C. In SLC23A1 knockout cells, treatment with 200 μM Vitamin C significantly restored cell viability and reduced apoptosis compared to controls. Mechanistically, high-dose Vitamin C induced apoptosis in ALL cells by activating the ER stress response through the PERK/CHOP pathway.ConclusionTaken together, our findings suggest that high-dose Vitamin C demonstrated significant anti-leukemic effects in ALL, showing cytotoxicity at 200 μM. Furthermore, SLC23A1 may serve as a potential biomarker for predicting the therapeutic response to Vitamin C treatment in ALL patients.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251345656"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183114","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retraction: Association of miR-9-5p and NFIC in the progression of gastric cancer. 撤回：miR-9-5p和NFIC在胃癌进展中的关联。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-05-08 DOI: 10.1177/09603271251336600

引用次数: 0

Protective effects of dexmedetomidine against propofol-induced memory impairment in developing rat involved Src and RARα. 右美托咪定对异丙酚诱导的大鼠Src和RARα记忆损伤的保护作用。

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-04-29 DOI: 10.1177/09603271251336467

Xiaoyan Xu, Jianmei Yang, Qiang Jia, Qianqian Hu, Huiling Liu

{"title":"Protective effects of dexmedetomidine against propofol-induced memory impairment in developing rat involved Src and RARα.","authors":"Xiaoyan Xu, Jianmei Yang, Qiang Jia, Qianqian Hu, Huiling Liu","doi":"10.1177/09603271251336467","DOIUrl":"https://doi.org/10.1177/09603271251336467","url":null,"abstract":"BackgroundDexmedetomidine (DEX) can offer protection to the nervous, urinary and circulatory systems. It can alleviate local oxidative stress, reduce inflammatory responses, inhibite cellular autophagy and decrease apoptosis.AimTo explore the potential protection and possible mechanisms of DEX against propofol (PPF)-induced memory impairment in developing rats.Material and methodsThe effects of DEX on spatial learning and passive avoidance abilities of rats were evaluated using eight-arm mirror maze and passive avoidance experiments. mRNA levels were detected using RT-qPCR analysis while protein levels were determined using western blot. A network pharmacology approach was used to predict potential targets of DEX against PPF-induced memory impairment. The cell autophagy and apoptosis were detected using commercial kits.ResultsDEX improved the impairment of developing rats on spatial learning and passive avoidance caused by PPF exposure. DEX regulates autophagic activity to inhibit neuronal apoptosis. RARα and Src were potential targets for DEX against memory impairment caused by PPF exposure. DEX upregulated the expression levels of Bdnf, p-CREB/CREB, p-Akt/Akt, and p-TrkB/TrkB proteins.ConclusionDEX may regulate Bdnf/TrkB and activate the activity of the PI3K/Akt signaling pathway by targeting RARα and Src, thereby inhibiting excessive autophagy and alleviating memory impairment.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251336467"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144045608","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of grape seed extract on doxorubicin-induced testicular and epididymal damage in rats. 葡萄籽提取物对多柔比星诱发的大鼠睾丸和附睾损伤的影响

Human & experimental toxicology Pub Date : 2025-01-01 Epub Date: 2025-03-14 DOI: 10.1177/09603271251319787

Emine Sarman, Halit Bugra Koca

{"title":"Effect of grape seed extract on doxorubicin-induced testicular and epididymal damage in rats.","authors":"Emine Sarman, Halit Bugra Koca","doi":"10.1177/09603271251319787","DOIUrl":"10.1177/09603271251319787","url":null,"abstract":"IntroductionDoxorubicin (DXR), a chemotherapeutic antibiotic, is widely used as an anticancer drug in clinics. Grape seed extract is known for its potent antioxidant properties. The aim of this study is to investigate the effect of high-antioxidant content Vitis vinifera L. seed extract against DXR-induced testicular and epididymal damage.Methods30 male rats were randomly divided into five groups with six animals in each group: Control, Sham, DXR (a single i.p. dose of 15 mg/kg), DXR + VIT (120 mg/kg VIT seed extract via gavage for 14 days and a single i.p. dose of DXR (15 mg/kg) on day 5, VIT (120 mg/kg VIT seed extract via gavage for 14 days). Animals were sacrificed under anesthesia 24 hours after the last drug administration, and blood, testis, and epididymis tissues were collected.ResultsTissues from the DXR group exhibited atrophic seminiferous tubules, Leydig cell degeneration, tunica albuginea and basal membrane thinning, immature spermatogenic cells, vascular congestion, epididymal atrophy, epithelial cell deletion, decreased sperm count, increased connective tissue, and absence of sperm in the lumen. Serum levels of interleukin 6 (IL-6), interleukin 1β (IL-1β), Tumor Necrosis Factor α (TNF-α), Total Oxidant Status (TOS), Total Antioxidant Status (TAS), and testosterone were increased in the DXR group, while interleukin 10 (IL-10) levels were decreased. The DXR + VIT group showed a near-recovery similar to the control.ConclusionDXR increased oxidative stress, apoptosis, and inflammation in the testis and epididymis, whereas VIT exhibited protective effects against these damages.","PeriodicalId":94029,"journal":{"name":"Human & experimental toxicology","volume":"44 ","pages":"9603271251319787"},"PeriodicalIF":0.0,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143631134","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0