Environmental Toxicology最新文献

{"title":"CAB39 modulates epithelial–mesenchymal transition through NF-κB signaling activation, enhancing invasion, and metastasis in bladder cancer","authors":"Jianbiao Huang,&nbsp;Huanhuan Deng,&nbsp;Shuaiyun Xiao,&nbsp;Yuanzhen Lin,&nbsp;Zhaojun Yu,&nbsp;Xiangda Xu,&nbsp;Lifen Peng,&nbsp;Haichao Chao,&nbsp;Tao Zeng","doi":"10.1002/tox.24333","DOIUrl":"10.1002/tox.24333","url":null,"abstract":"<p>Bladder cancer (BC), the predominant urological malignancy in men, exhibits complex molecular underpinnings contributing to its progression. This investigation aims to elucidate the expression dynamics of calcium-binding protein 39 (CAB39) in both healthy and cancerous tissues and to explore its functional role in the epithelial–mesenchymal transition (EMT) within human bladder cancer contexts. Utilizing immunohistochemistry and quantitative reverse transcription analyses, we assessed CAB39 expression across BC specimens and cell lines. Further, we implemented wound healing, cell invasion, and CCK-8 proliferation assays in CAB39-knockdown cell lines, alongside a nude mouse xenograft model, to gauge the impact of diminished CAB39 expression on the invasive, migratory, and proliferative capacities of BC cells. Our gene set enrichment analysis probed into the repertoire of genes augmented by increased CAB39 expression in BC cells, with subsequent validation via western blotting. Our findings reveal a pronounced overexpression of CAB39 in both BC tissues and cellular models, inversely correlated with disease prognosis. Remarkably, the oncogenic trajectory of bladder cancer was mitigated upon the establishment of shRNA-mediated CAB39 knockdown in vitro and in vivo, effectively reversing the cancer's invasive and metastatic behaviors and curbing tumorigenesis in xenograft models. Hence, CAB39 emerges as a critical biomarker for bladder cancer progression, significantly implicated in facilitating EMT via the upregulation of neural cadherin (N-cadherin) and the suppression of epithelial cadherin through NF-κB signaling pathways. CU-T12-9 effectively overturned the downregulation of p65-NF-kB and N-cadherin, key elements involved in EMT and cell motility, induced by CAB39 knockdown. This study underscores CAB39's pivotal role in bladder cancer pathophysiology and its potential as a therapeutic target.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 10","pages":"4791-4802"},"PeriodicalIF":4.4,"publicationDate":"2024-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142016773","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":"Machine learning analysis of oxidative stress-related phenotypes for specific gene screening in ovarian cancer","authors":"Chenxiang Pan,&nbsp;Chunyu Pan,&nbsp;Lili Chen,&nbsp;Aidi Lin","doi":"10.1002/tox.24321","DOIUrl":"10.1002/tox.24321","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Oxidative stress serves a crucial role in tumor development. However, the relationship between ovarian cancer and oxidative stress remains unknown. We aimed to create an oxidative stress-related prognostic signature to enhance the prognosis prediction of CC patients using bioinformatics.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>The genes differentially expressed and associated with oxidative stress were extracted with the help of “limma” packages. The model for prognosis was created using Multivariate Cox regression analysis to determine the risk related to the genes related to oxidative stress. Patients were categorized as low-risk or high-risk based on the median score. The receiver operation characteristic (ROC) and survival curves were used to evaluate the predictive effect of the prognostic signature. We utilized quantitative real-time PCR to assess the expression levels of key genes associated with oxidative stress in ovarian cancer cell lines (SKOV3, OVCAR3, and HeyA8) and normal ovarian epithelial cells (HOSEpiC).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>A signature comprising seven genes associated with oxidative stress was developed to prognosticate patients with ovarian cancer. Overall survival (OS) of the patient having CC was determined using Kaplan–Meier analysis. It was found that patient with a higher risk score had lower OS than the low-risk score. The signature of genes associated with oxidative stress was found to be independently prognostic for 1, 2, and 3 years. Further research found that the expression levels of nine hub genes had a strong association with patient outcomes. Our analysis revealed a higher expression of CX3CR1 in ovarian cancer cell lines compared with normal cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>To deploy a novel oxidative stress-related prognostic signature as an independent biomarker in cervical cancer, we developed and validated it.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 10","pages":"4763-4775"},"PeriodicalIF":4.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003914","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":"Identifying and validating necroptosis-associated features to predict clinical outcome and immunotherapy response in patients with glioblastoma","authors":"Qinghua Yuan,&nbsp;Weida Gao,&nbsp;Mian Guo,&nbsp;Bo Liu","doi":"10.1002/tox.24309","DOIUrl":"10.1002/tox.24309","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Necroptosis is a type of programmed cell death involved in the pathogenesis of cancers. This work developed a prognostic glioblastoma (GBM) model based on necroptosis-related genes.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>RNA-Seq data were collected from the TCGA database. The “WGCNA” method was used to identify co-expression modules, based on which GO and KEGG analyses were conducted. A protein–protein interaction (PPI) network was compiled. The number of key prognostic genes was reduced applying COX regression and least absolute shrinkage and selection operator (LASSO) analysis to build a RiskScore model. Differences in immune microenvironments were assessed using CIBERSORT, ESTIMATE, MCP-count, and TIMER databases. The potential impact of key prognostic genes on GBM was validated by cellular experiments.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>GBM patients in the higher necroptosis score group had higher immune scores and worse survival. The Brown module, which was closely related to the necroptosis score, was considered as a key gene module. Three key genes (GZMB, PLAUR, SOCS3) were obtained by performing regression analysis on the five clusters. The RiskScore model was significantly, positively, correlated with necroptosis score. Low-risk patients could benefit from immunotherapy, while high-risk patients may be more suitable to take multiple chemotherapy drugs. The nomogram showed strong performance in survival prediction. GZMB, PLAUR, and SOCS3 played key roles in GBM development. Among them, high-expressed GZMB was related to the invasive and migratory abilities of GBM cells.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>A genetic signature associated with necroptosis was developed, and we constructed a RiskScore model to provide reference for predicting clinical outcomes and immunotherapy responses of patients with GBM.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 10","pages":"4729-4743"},"PeriodicalIF":4.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003913","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":"Shared molecular signatures between systemic lupus erythematosus and osteoporosis","authors":"Xin Yuan,&nbsp;Ze-mao Zheng,&nbsp;Weinan Lai","doi":"10.1002/tox.24313","DOIUrl":"10.1002/tox.24313","url":null,"abstract":"<p>This study explores the molecular interplay between systemic lupus erythematosus (SLE) and osteoporosis (OP), aiming to uncover shared gene signatures and pathways for better treatment approaches. Leveraging microarray data from the Gene Expression Omnibus (GEO) database, we employed weighted gene coexpression network analysis to identify coexpression modules in SLE and OP, with subsequent protein–protein interaction analysis clarifying the connections among shared genes. Key genes were pinpointed using CytoHubba and random forest algorithms, validated across independent GEO datasets, and further analyzed through gene set enrichment analysis (GSEA) and immune infiltration studies. We discovered two highly correlated modules in SLE and OP, isolating 30 shared genes and identifying GBP1, SOCS1, IFI16, and XAF1 as central to both conditions. Notably, XAF1 and GBP1 mRNA levels were significantly elevated in the peripheral blood of SLE patients compared with healthy and RA counterparts, underscoring their potential as biomarkers. GSEA and immune infiltration analyses indicated pronounced immune and inflammatory responses, especially in interferon signaling pathways, implicating these core-shared gene networks in the diseases' pathogenesis. The findings highlight the involvement of GBP1, SOCS1, IFI16, and XAF1 in SLE with concurrent OP and suggest that targeting immune and inflammatory responses, particularly through interferon pathways, may offer therapeutic promise for these intertwined conditions.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 10","pages":"4744-4753"},"PeriodicalIF":4.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003915","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":"Value of hepatic artery digital subtraction angiography in the detection of small hepatocellular carcinoma lesions","authors":"Tao Bai,&nbsp;Shaolong Lu,&nbsp;Jie Chen,&nbsp;Jiazhou Ye,&nbsp;Xiaobo Wang,&nbsp;Zhihong Tang,&nbsp;Hongyuan Fu,&nbsp;Lequn Li,&nbsp;Feixiang Wu","doi":"10.1002/tox.24316","DOIUrl":"10.1002/tox.24316","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To compare the detection rates of hepatic artery digital subtraction angiography (HA-DSA) and magnetic resonance imaging (MRI) gadolinium diethylenetriaminepentaacetic acid (MRI-Gd-DTPA) and MRI gadolinium diethylenetriaminepentaacetic acid (MRI-Gd-EOB-DTPA) for small (diameter ≤2 cm) hepatocellular carcinoma (HCC) lesions.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>A prospective analysis of patients admitted to the Tumor Hospital of Guangxi Medical University between January 1, 2015, and December 30, 2016, was conducted. The detection rates of the three methods were analyzed. The diameter of small HCC lesions detected using HA-DSA and MRI-Gd-EOB-DTPA were evaluated. The diagnostic value of HCC Barcelona staging for HA-DSA was analyzed.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>For 107 small lesions detected in 57 patients, the detection rates of HA-DSA and MRI-Gd-DTPA were 86.0% (92/107) and 71.0% (76/107), respectively (<i>p</i> &lt; .05). Of 77 small lesions detected in 42 patients using MRI-Gd-EOB-DTPA and HA-DSA, 67 were detected using HA-DSA, all of which had a rich blood supply, and 72 were detected using MRI-Gd-EOB-DTPA. The minimum diameter of lesions detected using MRI-Gd-EOB-DTPA was approximately 0.4 cm, whereas that of lesions detected using HA-DSA was approximately 0.5 cm. After HA-DSA, a change in the Barcelona staging occurred in 33.3% (62/186) of cases but not after MRI-Gd-DTPA; HA-DSA was significantly better than MRI-Gd-DTPA for staging (<i>p</i> = .03).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>HA-DSA and MRI-Gd-EOB-DTPA have high diagnostic values for the detection of small HCC lesions, which is helpful for accurate staging of HCC and provides the most valuable information for patient treatment and prognosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 10","pages":"4754-4762"},"PeriodicalIF":4.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003916","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":"Deciphering the role of lipid metabolism and acetylation in osteosarcoma: A comprehensive molecular analysis","authors":"Yong Wen,&nbsp;Xijiang Zhang,&nbsp;Jin Zhang,&nbsp;Zhisheng Lu","doi":"10.1002/tox.24325","DOIUrl":"10.1002/tox.24325","url":null,"abstract":"<p>Osteosarcoma, known for its rapid progression and high metastatic potential, poses significant challenges in adolescent oncology. This study delves into the roles of lipid metabolism and acetylation genes in the disease's pathogenesis. Utilizing gene set variation analysis, we examined 14 lipid metabolism-related pathways in osteosarcoma patients, identifying significant variances in three pathways between metastatic and primary cases. Additionally, differences in four acetylation genes between these groups were observed. A comprehensive analysis pinpointed 62 lipid metabolism-related genes, with 39 exhibiting significant correlations with acetylation genes, termed lipid metabolism acetylation (LMA) genes. Employing machine learning techniques like Lasso+RSF and GBM, we developed a predictive model for overall survival based on LMA genes. This model, with an average c-index of 0.771, focuses on three key genes: CYP2C8, PAFAH2, and ACOX3, whose prognostic value was confirmed through survival and receiver operating characteristic curve analyses. Quantitative RT-PCR results indicated higher expression levels of ACOX3 and PAFAH2 in OS cells (143B, HOS, MG63) than in osteoblasts (hFOB1.19), while CYP2C8 was lower in OS cells. Furthermore, drug sensitivity analysis through the pRRophetic algorithm suggested potential targeted therapies, revealing drugs with differential sensitivity based on LMA scores and varied treatment responses related to the expression of core genes. This study not only highlights the crucial role of lipid metabolism and acetylation in osteosarcoma but also offers a foundation for personalized treatment strategies, marking a notable advancement in combating this severe form of adolescent cancer.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 10","pages":"4776-4790"},"PeriodicalIF":4.4,"publicationDate":"2024-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142003912","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":"Increased UBD Is a Potential Diagnostic and Prognostic Biomarker in Glioma","authors":"Tao Wu,&nbsp;Mengyu Du,&nbsp;Lin Zeng,&nbsp;Haiyang Wang,&nbsp;Xinfang Li","doi":"10.1002/tox.24398","DOIUrl":"10.1002/tox.24398","url":null,"abstract":"<div>\u0000 \u0000 <p>Various studies have demonstrated that ubiquitin D (UBD) is overexpressed in different cancer types and may serve as a potential prognostic factor. However, additional research is necessary to establish the prognostic significance and possible role of UBD in glioma. Transcriptomic expression data from The Cancer Genome Atlas database (TCGA) and Chinese Glioma Genome Atlas (CGGA) were analyzed to identify UBD expression differences in tumor and normal tissues. The relative levels of UBD in glioma and normal tissues were determined using qRT-PCR and WB. Logistic regression analysis was performed to investigate the association between UBD expression and clinicopathological characteristics of glioma patients. To evaluate the diagnostic and prognostic predictive values of UBD, we used Kaplan–Meier survival curves, Cox regression analysis, diagnostic receiver operating characteristic (ROC) curves, and nomogram model. We also conducted wound healing assays, transwell assays, EdU assays, and colony formation assays to verify the UBD function. Gene ontology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, as well as gene set enrichment analysis (GSEA), were employed to determine the functions of UBD. Finally, we performed the western blot assays to assess changes in EMT markers as well as p-PI3K, p-AKT, and p-mTOR expressions. Our study revealed a remarkable increase of UBD expression in glioma samples. Cox regression analysis demonstrated that high expression of UBD mRNA was an independent prognostic factor for overall survival (OS) in TCGA. ROC curve analysis showed that UBD expression levels could differentiate glioma from adjacent normal tissues accurately. Additionally, knockdown of UBD reduced the migration, invasion, and proliferation ability of glioma cells while UBD overexpression had the opposite effect. GSEA showed that the expression of UBD involved with various pathways including epithelial–mesenchymal transition (EMT), PI3K-AKT-mTOR signaling, P53 pathway, angiogenesis, inflammatory response, KRAS signaling, hypoxia, as well as TGF-β signaling. Furthermore, our findings suggest that UBD accelerates the activation of EMT and PI3K/AKT/mTOR pathway.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5250-5263"},"PeriodicalIF":4.4,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141999621","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":"Integrin αV Inhibition by GMI, a Ganoderma Microsporum Immunomodulatory Protein, Abolish Stemness and Migration in EGFR-Mutated Lung Cancer Cells Resistant to Osimertinib","authors":"Yu-Ting Kang,&nbsp;Hui-Yi Chang,&nbsp;Ya-Chu Hsieh,&nbsp;Chia-Hsuan Chou,&nbsp;I-Lun Hsin,&nbsp;Jiunn-Liang Ko","doi":"10.1002/tox.24399","DOIUrl":"10.1002/tox.24399","url":null,"abstract":"<div>\u0000 \u0000 <p>Integrins, the receptors of the extracellular matrix, are critical in the proliferation and metastasis of cancer cells. GMI, a Ganoderma microsporum immunomodulatory protein, possesses anticancer and antivirus abilities. The object of this study is to investigate the role of GMI in the integrins signaling pathway in lung cancer cells that harbor the EGFR L858R/T790M double mutation and osimertinib-resistance. Liquid chromatography-mass spectrometry and western blot assay were used to investigate the effect of GMI on inhibiting the protein expressions of integrins in H1975 cells. The migration ability and xenograft tumor growth of H1975 were suppressed by GMI. To elucidate the role of the integrin family in lung cancer resistant to osimertinib (AZD-9291, Tagrisso), H1975 cells were used to establish the osimertinib-resistant cells, named H1975/TR cells. The expressions of Integrin αV and stemness markers were much higher in H1975/TR cells than in H1975 cells. GMI suppressed cell viability, tumor spheroid growth, and the expressions of integrin αV and β1 in H1975/TR cells. Furthermore, GMI suppressed the expressions of stemness markers and formation of tumor spheres via blocking integrin αV signaling cascade. This is the first study to reveal the novel function of GMI in constraining cancer stem cells and migration by abolishing the integrin αV-related signaling pathway in EGFR-mutated and osimertinib-resistant lung cancer cells.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 12","pages":"5238-5249"},"PeriodicalIF":4.4,"publicationDate":"2024-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141994555","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":"Cadmium Exposure in Male Rats Results in Ovarian Granulosa Cell Apoptosis in Female Offspring and Paternal Genetic Effects","authors":"Qingyu Li,&nbsp;Yuchen Li,&nbsp;Jianlin Zhu,&nbsp;Zhangpin Liu,&nbsp;Yi Sun,&nbsp;Yake Lv,&nbsp;Jingwen Li,&nbsp;Lingfeng Luo,&nbsp;Chenyun Zhang,&nbsp;Wenchang Zhang","doi":"10.1002/tox.24375","DOIUrl":"10.1002/tox.24375","url":null,"abstract":"<div>\u0000 \u0000 <p>The aim of this study was to investigate whether the damage to male offspring induced by cadmium (Cd) exposure during embryonic period leads to the apoptosis of ovarian granulosa cells (OGCs) in the next generation of female offspring, and whether this apoptosis in the offspring was due to paternal genetic effects. Pregnant Sprague–Dawley (SD) rats were exposed to CdCl₂ (0, 0.5, 2.0, or 8.0 mg/kg) by gavage daily for 20 days to produce the filial 1 (F1) generation. F1 males were mated with newly purchased females to produce the F2 generation, and the F3 generation was generated in the same way. No apoptotic bodies were observed in the OGCs of either the F2 or F3 generation as shown by electron microscopy, and a reduced OGC apoptosis rate (detected by flow cytometry) was observed in F2 OGCs from the Cd-exposed group. Moreover, the mRNA (qRT-PCR) levels of Bax and Bcl-2 and the protein (western blotting) level of pro-caspase-8 increased in the F2 generation (<i>p</i> &lt; 0.05). The expression of apoptosis-related miRNAs (qRT-PCR) and methylation of apoptosis-related genes (determined via bisulfite-sequencing PCR) in OGCs were further determined. Compared with those of the controls, the expression patterns of microRNAs (miRNAs) in the F2 offspring were different in the Cd-exposed group. The miR-92a-2-5p expression levels were decreased in both the F2 and F3 generations (<i>p</i> &lt; 0.05), while the average methylation level of apoptosis-related genes did not change significantly (except for individual loci). In summary, this study showed that the paternal genetic intergenerational effect of male Cd exposure during embryonic period induced apoptosis of OGCs in the offspring was weakened, and the transgenerational effect disappeared; nevertheless, intergenerational and transgenerational changes in apoptosis-related genes, epigenetic modifications, DNA methylation, and miRNAs were observed, and may be important for understanding the homeostatic mechanisms of the body to alleviate the intergenerational transmission of Cd-induced damage.</p>\u0000 </div>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":"39 11","pages":"5187-5198"},"PeriodicalIF":4.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906242","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":"Protective Effect of Hibifolin on Lipopolysaccharide-Induced Acute Lung Injury Through Akt Phosphorylation and NFκB Pathway.","authors":"Yan-Yan Ng, Yung-Chuan Ho, Chi-Hua Yen, Shiuan-Shinn Lee, Ching-Chi Tseng, Sheng-Wen Wu, Yu-Hsiang Kuan","doi":"10.1002/tox.24383","DOIUrl":"https://doi.org/10.1002/tox.24383","url":null,"abstract":"<p><p>Acute lung injury (ALI) is a difficult condition to manage, especially when it is complicated by bacterial sepsis. Hibifolin, a flavonoid glycoside, has anti-inflammatory properties that make it a potential treatment for ALI. However, more research is needed to determine its effectiveness in LPS-induced ALI. In this study, male ICR mice were treated with hibifolin before LPS-induced ALI. Protein content and neutrophil count in bronchoalveolar lavage (BAL) fluid were measured by BCA assay and Giemsa staining method, respectively. The levels of proinflammatory cytokines and adhesive molecules were detected by ELISA assay. The expression of NFκB p65 phosphorylation, IκB degradation, and Akt phosphorylation was assessed by western blot assay. Hibifolin pre-treatment significantly reduced pulmonary vascular barrier dysfunction and neutrophil infiltration into the BAL fluid in LPS-induced ALI mice. In addition, LPS-induced expression of proinflammatory cytokines (IL-1β, IL-6, TNF-α) and adhesive molecules (ICAM-1, VCAM-1) within the BAL fluid were markedly reduced by hibifolin in LPS-induced ALI mice. More, hibifolin inhibited LPS-induced phosphorylation of NFκB p65, degradation of IκB, and phosphorylation of Akt in lungs with ALI mice. In conclusion, hibifolin shows promise in improving the pathophysiological features and proinflammatory responses of LPS-induced ALI in mice through the NFκB pathway and its upstream factor, Akt phosphorylation.</p>","PeriodicalId":11756,"journal":{"name":"Environmental Toxicology","volume":" ","pages":""},"PeriodicalIF":4.4,"publicationDate":"2024-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141906243","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}