Journal of Biochemical and Molecular Toxicology最新文献_第3页

Dose-Dependent Hepatotoxicity in Wistar Rat Neonates From Early-Life Arsenic Exposure 早期砷暴露对Wistar大鼠新生儿肝毒性的剂量依赖性

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70254

Navneet Kumar, Astha Mathur, Suresh Kumar Bunker, Placheril J. John

{"title":"Dose-Dependent Hepatotoxicity in Wistar Rat Neonates From Early-Life Arsenic Exposure","authors":"Navneet Kumar, Astha Mathur, Suresh Kumar Bunker, Placheril J. John","doi":"10.1002/jbt.70254","DOIUrl":"https://doi.org/10.1002/jbt.70254","url":null,"abstract":"<div>\u0000 \u0000 <p>Arsenic, a highly toxic heavy metal widely found in the environment, is a known carcinogen and toxin. Our study examined the effects of sodium arsenite on Wistar rat neonates exposed during gestation and weaning periods. The pregnant and weaning rats were given the low dose (LDG), median dose (MDG), and high dose (HDG) daily as 8.2, 12.3, and 16.4 mg/kgbw of NaAsO<sub>2</sub>, respectively. The results revealed that despite not affecting litter size, gestation index, or immediate postnatal observations, prolonged exposure to high doses of sodium arsenite led to increased liver weights, indicating potential liver stress or damage. Arsenic accumulation in liver tissues was significant, and histological examinations revealed liver damage, vascular congestion, and inflammation. Elevated levels of ALT, AST, ALP, and GGT were observed in arsenic-exposed groups during liver function tests, indicating hepatocellular injury and impaired function. Exposure to arsenic led to a dose-dependent decline in the mRNA expression levels and activity of antioxidant enzymes, including GST, GR, GPx, SOD, and CAT, showing that oxidative stress is present. Furthermore, LPx levels were increased. Metallothionein gene expression was upregulated, indicating a protective response against arsenic toxicity. Our findings underscore the risks associated with gestational and weaning exposure to sodium arsenite, providing insight into potential mechanisms behind arsenic-induced health issues and highlighting the importance of understanding these risks during critical developmental stages.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827021","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}

引用次数: 0

Circ_0038632 Acts as a Sponge of miR-4306 to Facilitate Breast Cancer Progression Through Regulating CXCR4 Expression Circ_0038632作为miR-4306的海绵，通过调节CXCR4的表达促进乳腺癌的进展

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70249

Yuesheng Zhao, Haiou Liu, Qi Wang, Zubin Li, Kun Zhao, Huibo Sun, Yanyong Zhang, Na Li, Wenhui Li

{"title":"Circ_0038632 Acts as a Sponge of miR-4306 to Facilitate Breast Cancer Progression Through Regulating CXCR4 Expression","authors":"Yuesheng Zhao, Haiou Liu, Qi Wang, Zubin Li, Kun Zhao, Huibo Sun, Yanyong Zhang, Na Li, Wenhui Li","doi":"10.1002/jbt.70249","DOIUrl":"https://doi.org/10.1002/jbt.70249","url":null,"abstract":"<div>\u0000 \u0000 <p>CircRNA plays an important role in the progression of breast cancer. This study focused on the molecular mechanism of circ_0038632 in regulating breast cancer. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression levels of circ_0038632, microRNA-4306 (miR-4306) and C-X-C chemokine receptor type 4 (CXCR4) mRNA in BC tissues and cells. Western blot was applied to detect the expression of CXCR4 protein and metastasis-related proteins (MMP2 and MMP9). Cell proliferation and apoptosis were observed by colony formation assay and flow cytometry. Scratch and Transwell assays were performed to detect the cell transfer ability. The angiogenesis ability of human vascular endothelial cells (HUVECs) was measured by the tube forming assay. Dual luciferase reporting assay was used to verify the relationship between miR-4306 and circ_0038632 or CXCR4. In vivo assay was used to detect the influence of circ_0038632 on the formation of BC tumors. Circ_0038632 and CXCR4 were highly expressed in BC tissue and cells, while miR-4306 was lowly expressed. Inhibition of circ_0038632 would restrain BC cell colony formation, migration, invasion, enhance cells apoptosis, and decrease HUVECs tube formation. Circ_0038632 acted as a sponge of miR-4306, and miR-4306 inhibitor would reverse the suppression effect of si-circ_0038632 in BC cells. CXCR4 was a target of miR-4306, and the overexpression of CXCR4 turned the growth inhibition of BC cells caused by exogenetic miR-4306. Importantly, circ_0038632 increased CXCR4 expression via sponging miR-4306. Finally, circ_0038632 knockdown inhibited the BC tumor formation. In conclusion, circ_0038632 contributed to the malignant progression of BC via regulating miR-4306/CXCR4 axis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826754","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}

引用次数: 0

miR-126-3p Serves as a Biomarker for Hepatitis B Virus-Associated Chronic Acute Liver Failure and Regulates Inflammation by Regulating ERRFI1 miR-126-3p作为乙型肝炎病毒相关慢性急性肝衰竭的生物标志物，通过调节ERRFI1调节炎症

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70252

Yiping Luo, Qiuping Ren, Jun He, Menghang Wu

{"title":"miR-126-3p Serves as a Biomarker for Hepatitis B Virus-Associated Chronic Acute Liver Failure and Regulates Inflammation by Regulating ERRFI1","authors":"Yiping Luo, Qiuping Ren, Jun He, Menghang Wu","doi":"10.1002/jbt.70252","DOIUrl":"https://doi.org/10.1002/jbt.70252","url":null,"abstract":"<div>\u0000 \u0000 <p>Hepatitis B virus-associated chronic acute liver failure (HBV-ACLF) is the leading cause of ACLF, affecting approximately 90% of patients with ACLF. The objective of this study was to investigate the clinical relevance of miR-126-3p on HBV-ACLF as well as the regulatory impact of ERRFI1 and miR-126-3p on the inflammatory response caused by ACLF via in vitro experimental methodologies. RT-qPCR was utilized to quantify the expression levels of miR-126-3p, ERRFI1, NLRP3, caspase 1, and IL-1β. The clinical function of miR-126-3p was assessed using ROC analysis or Kaplan-Meier curve. Cell proliferation was quantified via the CCK-8 assay, while the dual-luciferase reporter assay was employed to confirm the specific binding interaction between miR-126-3p and ERRFI1. In patients with HBV-ACLF, a significant downregulation of miR-126-3p expression was observed; The level of miR-126-3p served as a prognostic indicator for the progression of HBV-ACLF, with reduced expression being associated with an unfavorable clinical outcome. In addition, miR-126-3p was found to modulate LPS-induced cell proliferation, and inflammation in THLE-2 cells through the regulation of ERRFI1 expression. Therefore, miR-126-3p might serve as a biomarker for HBV-ACLF.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143827020","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}

引用次数: 0

USP30 Aggravating the Malignant Progression of Breast Cancer and Its Resistance to Tamoxifen by Inhibiting the Ubiquitination of TOMM40 USP30通过抑制TOMM40泛素化加速乳腺癌恶性进展及其对他莫昔芬的耐药性

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70258

Xinran Gao, Junbiao Liu, Baoqing Jia, Jiaxin Guo

{"title":"USP30 Aggravating the Malignant Progression of Breast Cancer and Its Resistance to Tamoxifen by Inhibiting the Ubiquitination of TOMM40","authors":"Xinran Gao, Junbiao Liu, Baoqing Jia, Jiaxin Guo","doi":"10.1002/jbt.70258","DOIUrl":"https://doi.org/10.1002/jbt.70258","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Breast cancer (BC) is the most common malignancy among women, with high incidence and mortality rates globally. Translocase of outer mitochondrial membrane 40 (TOMM40) has also been identified as an important prognostic biomarker for BC. Meanwhile, the ubiquitin-specific protease 30 (USP30) has also been shown to promote BC progression. However, the specific mechanisms underlying the role of USP30/TOMM40 in BC development remain unclear. Therefore, this study aims to delve into the potential mechanisms of USP30/TOMM40 in the progression of BC. The expression of TOMM40 and USP30 in BC tumors and cells was verified by bioinformatics analysis and western blot (WB). The effects of USP30/TOMM40 on BC cell proliferation, angiogenesis, glycolysis, and ferroptosis were determined by colony formation, tube formation assays and commercial kits. The co-immunoprecipitation (Co-IP) experiment was applied to verify the interaction between USP30 and TOMM40. The ubiquitination level of TOMM40 was detected by ubiquitinated antibodies. The effect of tamoxifen (TAM) on BC cell viability was measured by MTT assay. TOMM40 and USP30 were highly expressed in BC tumors and cells. Silencing TOMM40 blocked the proliferation, angiogenesis, glycolytic, and induced ferroptosis of BC cells. USP30 bound to TOMM40 and reduced its ubiquitination level. TOMM40 overexpressed abolished the tumor suppressive effect of USP30 knockdown and enhanced the resistance of BC to TAM. In conclusion, USP30 deubiquitinating TOMM40 promoted BC development and TAM resistance.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826752","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}

引用次数: 0

MYCN/MNX1 Axis Drives NSCLC Progression by Inducing Macrophage M2 Polarization and CD8+ T Cell Apoptosis via the Wnt/β-Catenin Pathway MYCN/MNX1轴通过Wnt/β-Catenin通路诱导巨噬细胞M2极化和CD8+ T细胞凋亡驱动NSCLC进展

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70251

Chengzhang Cao, Haiyin Lai, Yuzhen Shi

{"title":"MYCN/MNX1 Axis Drives NSCLC Progression by Inducing Macrophage M2 Polarization and CD8+ T Cell Apoptosis via the Wnt/β-Catenin Pathway","authors":"Chengzhang Cao, Haiyin Lai, Yuzhen Shi","doi":"10.1002/jbt.70251","DOIUrl":"https://doi.org/10.1002/jbt.70251","url":null,"abstract":"<div>\u0000 \u0000 <p>Enhanced macrophage M2 polarization and CD8<sup>+</sup> T cell dysfunction contribute to the pathophysiology of non-small cell lung cancer (NSCLC). Motor neuron and pancreatic homeobox 1 (MNX1) has emerged as a potential tumor-promoting player. Here, we clarified the activity of MNX1 in NSCLC. PMA-induced THP-1 M0-like macrophages or CD8<sup>+</sup> T cells were co-cultured with NSCLC cells. Cell colony formation, migration, proliferation, apoptosis, and invasiveness were assessed by colony formation, wound healing, CCK-8, flow cytometry, and transwell assays, respectively. The ratio of CD206<sup>+</sup> macrophages was analyzed by flow cytometry. Ki-67 expression was tested by immunofluorescence. ChIP and luciferase assays were used to evaluate the relationship between MYCN and MNX1. MNX1 was highly expressed in NSCLC, and its loss-of-function suppressed cell growth, motility, and invasiveness in NSCLC cells. MNX1 depletion also diminished macrophage M2 polarization and CD8<sup>+</sup> T cell apoptosis. Mechanistically, MYCN increased MNX1 expression at the transcriptional level. MNX1 increase reversed the impact of MYCN depletion on NSCLC cell malignant behaviors, macrophage M2 polarization, and CD8<sup>+</sup> T cell viability. MYCN depletion diminished the in vivo growth of A549 subcutaneous xenografts. Additionally, MNX1 increase counteracted the impact of MYCN depletion on the Wnt/β-catenin pathway. Our findings elucidate the oncogenic role of the MYCN/MNX1/Wnt/β-catenin pathway in NSCLC by driving macrophage M2 polarization and diminishing CD8<sup>+</sup> T cell viability. Our study thus uncovers a novel mechanism underlying NSCLC development and highlights potential targets for combating NSCLC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826750","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}

引用次数: 0

Modulation of VEGF/eNOS/TGF-β Axis by Piracetam as a New Avenue to Ameliorate Valproic Acid-Induced Placental Toxicity and Teratogenicity in Rats 吡拉西坦对血管内皮生长因子/eNOS/TGF-β轴的调节是改善丙戊酸诱导的大鼠胎盘毒性和致畸性的新途径

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-14 DOI: 10.1002/jbt.70266

Alzahraa A. Elhemiely, Wessam H. Elesawy

{"title":"Modulation of VEGF/eNOS/TGF-β Axis by Piracetam as a New Avenue to Ameliorate Valproic Acid-Induced Placental Toxicity and Teratogenicity in Rats","authors":"Alzahraa A. Elhemiely, Wessam H. Elesawy","doi":"10.1002/jbt.70266","DOIUrl":"https://doi.org/10.1002/jbt.70266","url":null,"abstract":"<div>\u0000 \u0000 <p>Valproic acid (VPA) is a very effective therapy used to treat generalized epilepsy, but it must be avoided during pregnancy as it leads to a high risk of teratogenesis. Its teratogenic effect is believed to be due to its placental toxic effect, altering angiogenesis and inducing oxidative stress. Piracetam (PIRA) is a derivative of the neurotransmitter γ-aminobutyric acid (GABA) and has anti-oxidative and pro-angiogenic features. However, its effects against Valproic acid-evoked placental toxicity and abnormal fetal development have not been mechanistically examined. Herein, the present study targets angiogenesis and oxidative stress by Piracetam to investigate the potential modulation of Valproic acid-induced placental toxicity and abnormal fetal development in rats. After administration of Valproic acid (500 mg/kg/day, orally) and/or piracetam (500 mg/kg/day, orally) from the 6th to 15th of gestation, fetuses and placenta were obtained for analysis. The present findings revealed that Piracetam improved the histopathological lesions in the placenta and restored the labyrinth zone area percent. Moreover, it improved the intra-uterine growth retardation (IUGR) via restoring fetal body weight and length and also ameliorated all external malformations (subcutaneous hemorrhage, fore limb, and hind limb anomalies) and additionally amended the skeletal lack of ossification. These favorable effects of Piracetam were mediated by the enhancement of placental angiogenesis via the VEGF/eNOS/TGF-β pathway and attenuating placental oxidative stress, which appeared as decreased MDA content and increased GSH and TAC levels. In conclusion, activation of placental angiogenesis via the VEGF/eNOS/TGF-β axis alongside inhibition of oxidative stress by Piracetam can ameliorate Valproic acid-evoked placental toxicity and, subsequently, fetal malformations in rats.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143826755","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}

引用次数: 0

Network Toxicology and Molecular Docking Strategy for Analyzing the Toxicity and Mechanisms of Bisphenol A in Alzheimer's Disease 网络毒理学和分子对接策略分析双酚A对阿尔茨海默病的毒性和机制

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-07 DOI: 10.1002/jbt.70247

Sumei Xu, Liping Jiang, Zhuo Zhang, Xin Luo, Huilan Wu, Zhirong Tan

{"title":"Network Toxicology and Molecular Docking Strategy for Analyzing the Toxicity and Mechanisms of Bisphenol A in Alzheimer's Disease","authors":"Sumei Xu, Liping Jiang, Zhuo Zhang, Xin Luo, Huilan Wu, Zhirong Tan","doi":"10.1002/jbt.70247","DOIUrl":"https://doi.org/10.1002/jbt.70247","url":null,"abstract":"<div>\u0000 \u0000 <p>Alzheimer's disease (AD) is a chronic and progressive neurodegenerative disorder marked by memory deterioration and cognitive impairment. Bisphenol A (BPA), a common environmental pollutant, has been linked to neurotoxicity and may contribute to AD development. This study aims to uncover potential toxicological targets and molecular mechanisms of BPA-induced AD. BPA's potential neurotoxic effects were predicted using ProTox and ADMETlab. Target prediction for BPA was conducted through the STITCH and Swiss Target Prediction platforms, while AD-related targets were compiled from GeneCards, OMIM, and the Therapeutic Target Database (TTD). Protein-protein interaction (PPI) networks were constructed using STRING and visualized in Cytoscape, and gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed. Molecular docking was employed to evaluate the binding interactions between BPA and the identified core targets. Through systematic bioinformatics analyses, 137 candidate targets for BPA-elicited AD were identified. Screening via PPI network analysis highlighted five key targets: STAT3, AKT1, INS, EGFR, and PTEN. GO and KEGG pathway enrichment revealed significant involvement in oxidative stress, neuronal apoptosis, neurodegenerative processes, and pathways such as PI3K/AKT, MAPK, lipid and atherosclerosis, and AD signaling. Molecular docking simulations confirmed strong binding affinities between BPA and these core targets. This study sheds light on the molecular mechanisms underlying BPA's neurotoxic effects in the context of AD and provides a foundation for further research into preventive and therapeutic strategies. The integration of network toxicology and molecular docking offers a robust framework for unraveling toxic pathways of uncharacterized environmental and chemical agents.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787326","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}

引用次数: 0

Kisspeptin 10 Inhibited the Proliferation, Migration, and Stemness of Esophageal Cancer Cells via Regulating the SIX1/Wnt/β-Catetin Signaling Kisspeptin 10通过调节SIX1/Wnt/β-Catetin信号传导抑制食管癌细胞的增殖、迁移和干性

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-07 DOI: 10.1002/jbt.70244

Chenfan Guo, Gun Wu, Tao Liu

{"title":"Kisspeptin 10 Inhibited the Proliferation, Migration, and Stemness of Esophageal Cancer Cells via Regulating the SIX1/Wnt/β-Catetin Signaling","authors":"Chenfan Guo, Gun Wu, Tao Liu","doi":"10.1002/jbt.70244","DOIUrl":"https://doi.org/10.1002/jbt.70244","url":null,"abstract":"<div>\u0000 \u0000 <p>Esophageal cancer (EC) treatment remains challenging due to the disease's aggressive nature, frequent late-stage diagnosis, and the need for effective multimodal therapies with minimal side effects. Kisspeptin-10, a naturally occurring neuropeptide and known GPR54 agonist, has been shown to significantly influence tumor growth and progression. However, its specific role in EC remains poorly understood. To address this knowledge gap, we designed this study to investigate the role of Kisspeptin-10 (KP-10) and its receptor GPR54 in EC. We first assessed KP-10 expression in esophageal carcinoma tissues and cell lines using immunohistochemistry, real-time PCR, and western blot analysis. Through lentivirus transduction, we manipulated KP-10 expression and evaluated its effects on cell viability, apoptosis, migration, stemness, epithelial-mesenchymal transition (EMT), and the SIX1/Wnt/β-catenin signaling pathway. These evaluations were performed using CCK-8 assay, TUNEL assay, Transwell assay, mammosphere formation assay, and western blot analysis. Our results demonstrated significantly reduced expression of both KP-10 and GPR54 in EC samples and cell lines compared to healthy tissues. Following KP-10 overexpression in KYSE150 EC cells, we observed inhibited cell growth, promoted apoptosis, decreased cell migration, reduced cancer stem cell properties, and suppressed EMT. Furthermore, KP-10 overexpression inhibited the Wnt/β-catenin signaling pathway, an effect that was reversed by SIX1 overexpression, suggesting that KP-10's impact on this pathway is mediated through SIX1. These findings indicate that KP-10 plays a crucial role in suppressing EC progression and represents a promising therapeutic target for clinical treatment. However, more comprehensive studies are needed to fully elucidate the underlying mechanisms and explore the clinical potential of KP-10 in EC therapy.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787328","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}

引用次数: 0

Bone Marrow Mesenchymal Stem Cell-Derived Exosomal USP10 Alleviates Cerebral Ischemia-Reperfusion Injury via Stabilizing SLC7A11 by Deubiquitination 骨髓间充质干细胞来源的外泌体USP10通过去泛素化稳定SLC7A11减轻脑缺血再灌注损伤

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-07 DOI: 10.1002/jbt.70246

Nannuan Liu, Yue Xu, Genshan Gao, Yao Liu, Wenli Hu

{"title":"Bone Marrow Mesenchymal Stem Cell-Derived Exosomal USP10 Alleviates Cerebral Ischemia-Reperfusion Injury via Stabilizing SLC7A11 by Deubiquitination","authors":"Nannuan Liu, Yue Xu, Genshan Gao, Yao Liu, Wenli Hu","doi":"10.1002/jbt.70246","DOIUrl":"https://doi.org/10.1002/jbt.70246","url":null,"abstract":"<div>\u0000 \u0000 <p>Ubiquitination is a widespread posttranslational modification that plays an important biological regulatory role in cells. Research has reported that bone marrow mesenchymal stem cells (BMSCs) can inhibit cerebral ischemia-reperfusion injury. This study aims to explore the effect of deubiquitinating enzymes ubiquitin-specific peptidase 10 (USP10) modified BMSCs exosomes on cerebral ischemia-reperfusion injury and the underlying mechanism. PC12 cells were stimulated with oxygen–glucose deprivation/reoxygenation (OGD/R). The gene expression was detected by qRT-PCR and western blots. CCK8, EdU, and flow cytometry assays were conducted to assess cell viability, proliferation, and apoptosis, respectively. Fe<sup>2+</sup>, ROS, and GSH levels were detected to evaluate ferroptosis. Moreover, BMSCs were identified by flow cytometry, and exosomes were identified by transmission electron microscopy. The relationship between USP10 and solute carrier family 7 member 11 (SLC7A11) was confirmed by immunoprecipitation assay. In addition, the rat cerebral infarction model was conducted to explore the role of USP10-modified BMSCs exosomes in vivo. Overexpression of USP10 alleviated OGD/R-induced PC12 cell injury and ferroptosis. BMSCs exosomes could transport USP10, and USP10-modified BMSCs exosomes mitigated OGD/R-induced injury in PC12 cells. Besides, USP10 regulated SLC7A11 protein expression by mediating its deubiquitination. SLC7A11 knockdown restored the effects of USP10-modified BMSCs exosomes on OGD/R-induced PC12 cells. Moreover, USP10-modified BMSCs exosomes repressed cerebral infarction and ferroptosis in vivo. USP10-modified BMSCs exosomes protected against cerebral ischemia-reperfusion injury via mediating the deubiquitination of SLC7A11.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787329","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}

引用次数: 0

Amelioration of Isoproterenol-Induced Myocardial Infarction by the Phytochemical Koenigicine via Modulation of NF-κB/HO-1/NQO-1 Pathways: An In Vivo Analysis 异丙肾上腺素通过调节NF-κB/HO-1/NQO-1通路改善异丙肾上腺素诱导心肌梗死的体内研究

IF 3.2 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-04-07 DOI: 10.1002/jbt.70224

Tianming Hu, Lan Liu

{"title":"Amelioration of Isoproterenol-Induced Myocardial Infarction by the Phytochemical Koenigicine via Modulation of NF-κB/HO-1/NQO-1 Pathways: An In Vivo Analysis","authors":"Tianming Hu, Lan Liu","doi":"10.1002/jbt.70224","DOIUrl":"https://doi.org/10.1002/jbt.70224","url":null,"abstract":"<div>\u0000 \u0000 <p>Phytochemicals exhibit diverse cardioprotective properties that contribute to the prevention and management of myocardial infarction (MI). In our study, we examined the potency of the phytochemical Koenigicine, which belongs to the carbazole alkaloid, in alleviating MI in an animal model. The animals were supplemented with Koenigicine before MI induction using isoproterenol, with supplementation continuing during the MI induction period. The impact of Koenigicine on mitigating the onset of MI was evaluated by quantifying lipid levels and arterial blood pressure. Its ameliorative potential against isoproterenol-induced cardiac damage was assessed by measuring antioxidant levels and critical biomarkers of MI in the experimental animals. Protein, C-reactive protein (CRP), and uric acid levels were assessed to determine the effect of Koenigicine on immune function and inflammation. Additionally, the impact of Koenigicine on cardiac muscle function and its role in healing ischemic-induced cardiac tissues were examined in MI-induced rats. The effect of Koenigicine treatment on post-ischemic injury was analyzed by quantifying NF-κB, HO-1, and NQO-1 levels, and the findings were confirmed through cardiac histopathological analysis. Koenigicine administration effectively mitigated MI induction by regulating lipid levels and arterial blood pressure. It enhanced the antioxidant defense system, attenuated inflammatory signaling, and thereby prevented MI-induced cardiac tissue damage. The results of MI biomarker analysis confirmed the ameliorative potential of Koenigicine against isoproterenol-induced cardiac inflammation. Furthermore, it demonstrated a positive effect on cardiac function and facilitated the healing process following MI induction. Overall, our findings suggest that Koenigicine provides preventive, suppressive, and ameliorative effects at all stages of MI, addressing gaps in the efficacy of currently available treatments.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143786641","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}

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