Toxicology最新文献

{"title":"Transcriptomics and metabolomics analyses of graphene oxide toxicity on porcine alveolar macrophages","authors":"","doi":"10.1016/j.tox.2024.153953","DOIUrl":"10.1016/j.tox.2024.153953","url":null,"abstract":"<div><p>Graphene oxide (GO) is a type of nanomaterial widely used in tissue engineering, photocatalysis, and biomedicine. GO has been found to produce adverse effects on a broad range of cells and tissues. However, the molecular mechanisms underlying GO toxicity still remain to be explored. In this study, using porcine alveolar macrophages as a study model, we explored the toxic effects of GO and performed genome-wide detection of genes and metabolites associated with GO exposure using RNA-seq and liquid chromatograph mass spectrometer techniques. GO exposure significantly inhibited cell viability and induced apoptosis and oxidative stress in porcine alveolar macrophages. Further, GO exposure promoted cellular inflammation by upregulating the expression of pro-inflammatory cytokines (IL-6, IL-8, and IL-12). Transcriptomic analysis of GO-exposed cells revealed 424 differentially expressed genes. Functional enrichment analysis showed that the differentially expressed genes were significantly enriched in the pathways of Ribosome and oxidative phosphorylation (OXPHOS). In addition, metabolic analysis identified 203 differential metabolites, and these metabolites were significantly enriched in biosynthesis of cofactors, purine metabolism, and nucleotide metabolism. Integrative analyses of transcriptome and metabolome showed that OXPHOS was the most significantly enriched pathway and the involved genes were downregulated. This study revealed the toxic effects of GO on porcine alveolar macrophages and provided global insights to the metabolomic and transcriptomic alterations related to GO exposure. The results contributed to our understanding of the molecular mechanism of GO, and may further promote the detection of biomarkers for the prediction and control of GO toxicity.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142228754","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pleiotrophin modulates acute and long-term LPS-induced neuroinflammatory responses and hippocampal neurogenesis","authors":"","doi":"10.1016/j.tox.2024.153947","DOIUrl":"10.1016/j.tox.2024.153947","url":null,"abstract":"<div><p>The hippocampus is one of the most vulnerable regions affected in disorders characterized by overt neuroinflammation such as neurodegenerative diseases. Pleiotrophin (PTN) is a neurotrophic factor that modulates acute neuroinflammation in different contexts. PTN is found highly upregulated in the brain in different chronic disorders characterized by neuroinflammation, suggesting an important role in the modulation of sustained neuroinflammation. To test this hypothesis, we studied the acute and long-term effects of a single lipopolysaccharide (LPS; 5 mg/kg) administration in <em>Ptn</em>^<em>+</em>/+ and <em>Ptn</em>^-/- mice, and in mice with <em>Ptn</em>-overexpression (<em>Ptn</em>-Tg). Endogenous PTN levels proportionally modulate LPS-induced increase in TNF-α plasma levels one hour after treatment. In the dentate gyrus (DG) of the hippocampus, a lower percentage of DCX+ cells were detected in saline-treated <em>Ptn</em>^-/- mice compared to <em>Ptn</em>^<em>+</em>/+ mice, suggesting a crucial role of PTN in the maintenance of hippocampal neuronal progenitors. The data show that PTN overexpression tends to potentiate acute microglial responses in the DG 16 hours after LPS treatment. Remarkably, a significant increase in the number of neuronal progenitors together with astrogliosis was detected 10 months after a single injection of LPS treatment in wild type mice. However, these LPS-induced long-term effects were prevented in <em>Ptn</em>^-/- and <em>Ptn</em>-Tg mice, suggesting that PTN modulates LPS-induced long-term neurogenesis changes and astrocytic response in the hippocampus. The data presented here suggest that endogenous PTN levels are crucial in the regulation of acute LPS-induced systemic and hippocampal microglial responses in young mice. Furthermore, our findings provide evidence of the key role of PTN in the regulation of long-term LPS effects on astrocytic response and neurogenesis in the hippocampus.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24002282/pdfft?md5=bf8375a734d360887ae399a3ea167971&pid=1-s2.0-S0300483X24002282-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142164825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Using microfluidic and conventional platforms to evaluate the effects of lanthanides on spheroid formation","authors":"","doi":"10.1016/j.tox.2024.153931","DOIUrl":"10.1016/j.tox.2024.153931","url":null,"abstract":"<div><p>Metastasis contributes to the increased mortality rate of cancer, but the intricate mechanisms remain unclear. Cancer cells from a primary tumor invade nearby tissues and access the lymphatic or circulatory system. If these cells manage to survive and extravasate from the vasculature into distant tissues and ultimately adapt to survive, they will proliferate and facilitate malignant tumor formation. Traditional two-dimensional (2D) cell cultures offer a rapid and convenient method for validating the efficacy of anticancer drugs within a reasonable cost range, but their utility is limited because of tumors’ high heterogeneity <em>in vivo</em> and spatial complexities. Three-dimensional (3D) cell cultures that mimic the physiological conditions of cancer cells <em>in vivo</em> have gained considerable interest. In these cultures, cells assemble into spheroids through gravity, magnetic forces, or their low-adhesion to the plates. Although these approaches address some of the limitations of 2D cultures, they often require a considerable amount of time and cost. Therefore, this study aims to enhance the effectiveness of 3D culture techniques by using microfluidic systems to provide a high-throughput and sensitive pipeline for drug screening. Using these systems, we studied the effects of lanthanide elements, which have garnered interest in cancer treatment, on spheroid formation and cell spreading. Our findings suggest that these elements alter the compactness of cell spheroids and decrease cell mobility.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142120687","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"There is no need for overnight fasting of rats in regulatory toxicology studies","authors":"","doi":"10.1016/j.tox.2024.153937","DOIUrl":"10.1016/j.tox.2024.153937","url":null,"abstract":"<div><div>For many years overnight fasting of rats before the collection of clinical pathology blood samples and necropsy has been a common procedure in toxicological studies for regulatory purposes. The fasting was thought to minimize the intragroup variability for clinical pathology and organ weights. However, depriving rats of food overnight will impact animal welfare by interfering with the general metabolism and may result in physiological and behavioural changes. The effects of overnight fasting in comparison to rats that were not fasted prior to necropsy was investigated in lactating rats based on an evaluation of organ weights, haematological, and clinical biochemical parameters. The results of 92 OECD 422 studies were analysed (i.e., Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test) of which approximately half of the studies incorporated fasting prior to necropsy and the other half did not. Terminal body and organ weights from all 92 studies were evaluated. Clinical pathology was included in 78 of these 92 studies. Decreased glucose levels following fasting had been reported in the literature but were not observed when comparing 39 studies with fasted conditions versus 39 studies with non-fasted conditions. Both literature and the analysed database exhibited a reduction in liver weight, alanine aminotransferase, and alkaline phosphatase levels in overnight fasted groups. These differences between fasted and non-fasted states are considered of little account as study results are always interpreted based on the differences in parameter values between treated animals compared to control animals within a study. Contrarily to previously suggested, intragroup variability was lower in the majority of parameters in non-fasted animals. According to laboratory historical data, clinical pathology and organ weight parameters are found to be very similar in male and female rats, indicating that the results of this study may be extrapolatable to non-lactating female and male rats. Based on these comparisons, it is recommended not to fast rats prior to necropsy but to continue feeding all rats <em>ad libitum</em>, to minimize physiological changes in these animals, to reduce variability, improve animal welfare and thereby improve the scientific value of study results.</div></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142112245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel “cells-on-particles” cytotoxicity testing platform in vitro: design, characterization, and validation against engineered nanoparticle aerosol","authors":"","doi":"10.1016/j.tox.2024.153936","DOIUrl":"10.1016/j.tox.2024.153936","url":null,"abstract":"<div><p>The presented research introduces the \"Cells-on-Particles\" integrated aerosol sampling and cytotoxicity testing in vitro platform, which allows for the direct assessment of the biological effects of captured aerosol particles on a selected cell type without the need for extraction or resuspension steps. By utilizing particles with unaltered chemical and physical properties, the method enables simple and fast screening of biological effects on specific cell types, making it a promising tool for assessing the cytotoxicity of particulate matter in ambient and occupational air. Platforms fabricated from cellulose acetate (CA) and poly[ε]caprolactone (PCL) were proven to be biocompatible and promoted the attachment and growth of the human bronchial epithelial cell line BEAS-2B. The PCL platforms were exposed to simulated occupational aerosols of silver, copper, and graphene oxide nanoparticles. Each nanoparticle type exhibited different and dose-dependent cytotoxic effects on cells, evidenced by reduced cell viability and distinct, particle type-dependent gene expression patterns. Notably, copper nanoparticles were identified as the most cytotoxic, and graphene oxide the least. Comparing the “Cells-on-Particles\" and submerged exposure (“Particles-on-Cells\") testing strategies, BEAS-2B cells responded to selected nanoparticles in a comparable manner, suggesting the developed testing system could be proposed for further evaluation with more complex environmental aerosols. Despite limitations, including particle agglomeration and the need for more replicates to address variability, the “Cells-on-Particles” platform enables effective detection of toxicity induced by relatively low levels of nanoparticles, demonstrating good sensitivity and a relatively simpler procedure compared to standard 2D cell exposure methods.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142095132","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Perinatal exposure to Aroclor 1254 disrupts thyrotropin-releasing hormone mRNA expression in the paraventricular nucleus of male and female rats","authors":"","doi":"10.1016/j.tox.2024.153935","DOIUrl":"10.1016/j.tox.2024.153935","url":null,"abstract":"<div><p>Polychlorinated biphenyls (PCBs) are industrial pollutants that act as endocrine disruptors and alter thyroid function. However, it is still unclear whether PCBs can affect hypothalamic thyrotropin releasing hormone (Trh) mRNA expression through TH signaling disruption. As salt-loading dehydration induces tertiary hypothyroidism in the hypothalamic parvocellular paraventricular nuclei (paPVN), and perinatal exposure to Aroclor 1254 (A1254) disrupts the hydric balance in rats, we hypothesized that TRH synthesis could be altered during dehydration in TRH neurons that control the hypothalamic–pituitary–thyroid (HPT) axis activity in rats perinatally exposed to A1254. We examined Trh mRNA expression in the paPVN and the response to salt-loading dehydration (hyperosmotic (hyper) stress) in the progeny of Wistar pregnant rats receiving 0 mg/kg BW (control) or 30 mg/kg BW A1254 daily from gestational days 10–19. Three-month-old offspring were subjected to normosmotic or hyper conditions and Trh mRNA, glucocorticoid receptor (GR) mRNA expression were measured in the PVN by RT-PCR. TRH mRNA and TRH+ neurons were measured in the paPVN by fluorescent <em>in situ</em> hybridization (FISH). As expected, Trh mRNA levels were decreased in the paPVN of male and female rats in the hyper group. Basal Trh mRNA expression and serum TSH were decreased in male rats in the A1254 group. Notably, Trh mRNA levels were further decreased in the paPVN of male and female A1254 + hyper rats, in which the GR mRNA expression was significantly decreased. These results support the hypothesis that perinatal exposure to A1254 results in inadequate adaptive response of the HPT axis in adulthood and contributes to dysregulation of the HPT axis response to salt-loading dehydration.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24002166/pdfft?md5=6d0ea01b6891714a31062ba7ba6c2174&pid=1-s2.0-S0300483X24002166-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating combined effects of chronic, low-dose exposures of cadmium (CLEC) and hyperglycemia on insulin signaling dysfunction in a hepatocellular model","authors":"","doi":"10.1016/j.tox.2024.153929","DOIUrl":"10.1016/j.tox.2024.153929","url":null,"abstract":"<div><p>The pathophysiological effects of chronic heavy metal exposures on human health remains uncertain. In this study, we developed a novel chronic, low-dose exposure of Cadmium (CLEC) model using the hepatocellular cell lines, HepG2 and HUH7. We modulated cell culture conditions to mimic human normoglycemic (5.6 mM) and hyperglycemic (15 mM) states with concomitant cadmium (Cd) exposures for 24 weeks. CLEC cells undergo non-trivial alterations in glucose signaling and metabolic characteristics within our model. We observe elevated baseline reactive oxygen species (ROS) production and decreased 2-NBDG uptake indicative of glucose metabolic dysfunction. Additionally, induction of metallothionein (MT) expression, increased activation of Akt signaling (via phosphorylation) and reduced IRS-2 protein expression are observed in CLEC cells. Cell line specific changes are observed with HepG2 showing a much higher MT gene induction compared to HUH7 cell line which impacts glucose metabolic dysfunction. Hyperglycemic culture conditions (representing type II diabetes) significantly modulate CLEC effects on cells. In conclusion, pathophysiologically relevant models of chronic heavy metal exposures are urgently needed to gain an in-depth, mechanistic understanding of the long-term impacts of toxic metals (e.g., Cd) on human metabolic health.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142081622","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Artificial intelligence-based data extraction for next generation risk assessment: Is fine-tuning of a large language model worth the effort?","authors":"","doi":"10.1016/j.tox.2024.153933","DOIUrl":"10.1016/j.tox.2024.153933","url":null,"abstract":"<div><p>To underpin scientific evaluations of chemical risks, agencies such as the European Food Safety Authority (EFSA) heavily rely on the outcome of systematic reviews, which currently require extensive manual effort. One specific challenge constitutes the meaningful use of vast amounts of valuable data from new approach methodologies (NAMs) which are mostly reported in an unstructured way in the scientific literature. In the EFSA-initiated project ‘AI4NAMS’, the potential of large language models (LLMs) was explored. Models from the GPT family, where GPT refers to Generative Pre-trained Transformer, were used for searching, extracting, and integrating data from scientific publications for NAM-based risk assessment. A case study on bisphenol A (BPA), a substance of very high concern due to its adverse effects on human health, focused on the structured extraction of information on test systems measuring biologic activities of BPA. Fine-tuning of a GPT-3 model (<em>Curie</em> base model) for extraction tasks was tested and the performance of the fine-tuned model was compared to the performance of a ready-to-use model (<em>text-davinci-002</em>). To update findings from the AI4NAMS project and to check for technical progress, the fine-tuning exercise was repeated and a newer ready-to-use model (<em>text-davinci-003)</em> served as comparison. In both cases, the fine-tuned <em>Curie</em> model was found to be superior to the ready-to-use model. Performance improvement was also obvious between <em>text-davinci-002</em> and the newer <em>text-davinci-003</em>. Our findings demonstrate how fine-tuning and the swift general technical development improve model performance and contribute to the growing number of investigations on the use of AI in scientific and regulatory tasks.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0300483X24002142/pdfft?md5=06ab65bd995796906967d17e831bbbda&pid=1-s2.0-S0300483X24002142-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the protective potential of NRF2 overexpressed neural extracellular vesicles against cisplatin-induced neurotoxicity via NRF2/ARE pathway","authors":"","doi":"10.1016/j.tox.2024.153934","DOIUrl":"10.1016/j.tox.2024.153934","url":null,"abstract":"<div><p>Neurotoxicity is characterized by the accumulation of harmful chemicals such as heavy metals and drugs in neural tissue, resulting in subsequent neuronal death. Among chemicals platinum-based cancer drugs are frequently used due to their antineoplastic effects, but this drug is also known to cause a wide range of toxicities, such as neurotoxicity. The nuclear-factor-erythroid 2-related factor-2 (NRF2) is crucial in combating oxidative stress and maintaining cellular homeostasis. This study thoroughly explores the protective effects of extracellular vesicles derived from NRF2 gene overexpressed neural progenitor cells (NEVs) on cisplatin-induced neurotoxicity. Therefore, extracellular vesicles derived from neural progenitor cells were isolated and characterized. The Cisplatin neurotoxicity dose was 75 µM in mature, post-mitotic neurons. 1.25 µM of tert-butyl hydroquinone that induces NRF2/ARE pathway was used as the positive control. The effects of extracellular vesicles (EVs) were investigated using functional and molecular assays such as PCR and protein-based assays. Here, we observed that NEVs dose-dependently protected post-mitotic neuron cells in response to cisplatin. The study also examined whether the effect was EV-induced by limiting EV biogenesis. The molecular basis of preventive treatment was established. When pre-administered, 1×10⁸ particles/ml of NEVs maintained antioxidant and detoxifying gene and protein expression levels similar to control cell levels. Furthermore, NEVs reduced both cellular and mitochondrial ROS levels and preserved mitochondrial membrane potential. In addition, Catalase and SOD levels were found higher in NEV-treated cells compared to cisplatin control. The findings in NRF2-based protection of cisplatin-induced neurotoxicity may provide further evidence for the relationship between EVs and inhibition of neuronal stress through the NRF2/ARE pathway, increasing the understanding of neuroprotective responses and the development of gene-engineered EV therapy options for peripheral neuropathy or other neurodegenerative diseases. This is the first study in the literature to investigate the neutralizing potency of NRF2 overexpressed neural EVs against cisplatin-induced neurotoxicity.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142056557","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mutual regulation between histone methyltransferase Suv39h1 and the Wnt/β-catenin signaling pathway promoted cell proliferation and inhibited apoptosis in bone marrow mesenchymal stem cells exposed to hydroquinone","authors":"","doi":"10.1016/j.tox.2024.153932","DOIUrl":"10.1016/j.tox.2024.153932","url":null,"abstract":"<div><p>Hydroquinone (HQ), a metabolite of benzene, is frequently utilized as a surrogate for benzene in in vitro studies and is associated with the development of acute myeloid leukemia (AML). In the hemotoxicity caused by benzene and HQ, cell apoptosis plays a key role. However, the molecular mechanisms underlying HQ are unknown. Studies have indicated that Suv39h1 is involved in regulating cell division and proliferation by regulating histone H3K9me3. Meanwhile, the Wnt/β-catenin signaling pathway also plays a significant role in cell proliferation and apoptosis. Therefore, this study was aimed at exploring the regulatory role of Suv39h1 and the Wnt/β-catenin signaling pathway in the effects of HQ on bone marrow mesenchymal stem cells (BMSCs), as well as its influence on cell proliferation and apoptosis. The results demonstrated that HQ elevated the levels of Suv39h1 and H3K9me3 and activated the Wnt/β-catenin signaling pathway by upregulating β-catenin, Wnt2b, C-myc, and Cyclin D1 and downregulating Wnt5a, resulting in an increase in cell growth and a decrease in apoptosis. Suv39h1 knockdown inhibited the Wnt/β-catenin signaling pathway. Meanwhile, inhibition of the Wnt/β-catenin signaling pathway resulted in the down-regulation of Suv39h1 and H3K9me3 in BMSCs. They both promoted cell proliferation and inhibited apoptosis in the effects of HQ on BMSCs by downregulating the expression of Cyt-C, Bax, Caspase 3, and Caspase 9 and upregulating the expression of Bcl-xl. Therefore, we concluded that Suv39h1 and the Wnt/β-catenin signaling pathway may mutually regulate each other in the effects of HQ on BMSCs in order to ameliorate the altered function of BMSCs.</p></div>","PeriodicalId":23159,"journal":{"name":"Toxicology","volume":null,"pages":null},"PeriodicalIF":4.8,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142047250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}