Journal of Biochemical and Molecular Toxicology最新文献

{"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,&nbsp;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}

{"title":"Network Toxicology and Molecular Docking Strategy for Analyzing the Toxicity and Mechanisms of Bisphenol A in Alzheimer's Disease","authors":"Sumei Xu,&nbsp;Liping Jiang,&nbsp;Zhuo Zhang,&nbsp;Xin Luo,&nbsp;Huilan Wu,&nbsp;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}

{"title":"Kisspeptin 10 Inhibited the Proliferation, Migration, and Stemness of Esophageal Cancer Cells via Regulating the SIX1/Wnt/β-Catetin Signaling","authors":"Chenfan Guo,&nbsp;Gun Wu,&nbsp;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}

{"title":"Bone Marrow Mesenchymal Stem Cell-Derived Exosomal USP10 Alleviates Cerebral Ischemia-Reperfusion Injury via Stabilizing SLC7A11 by Deubiquitination","authors":"Nannuan Liu,&nbsp;Yue Xu,&nbsp;Genshan Gao,&nbsp;Yao Liu,&nbsp;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. Fe²⁺, 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}

{"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,&nbsp;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}

{"title":"Synthesis, Cytotoxic Activity, Antiquorum Sensing Effect, Docking and Md Simulation of Novel 1,3-Disubstituted 2-Mercapto-1H-Benzo[D]Imidazolium Chlorides","authors":"Mohammad Mavvaji,&nbsp;Muhammed Tilahun Muhammed,&nbsp;Ebru Onem,&nbsp;Halime Güzin Aslan,&nbsp;Sadeq K. Alhag,&nbsp;Senem Akkoc","doi":"10.1002/jbt.70248","DOIUrl":"https://doi.org/10.1002/jbt.70248","url":null,"abstract":"<p>A series of benzimidazolium chlorides (<b>2a-c</b>) and their corresponding 2-mercapto derivatives (<b>3a-c</b>) were proficiently synthesized and analyzed by NMR and LC-MS spectra. The in vitro cytotoxic assay demonstrated that some synthesized compounds were active on the cancer cell lines. The binding potential of the most active three compounds to topoisomerase II alpha (topo2α) was explored to unveil the possible mode of action for the cytotoxic activity. The binding potential was examined through molecular docking. The stability of compound-enzyme complexes from docking was investigated through molecular dynamics (MD) simulation. The docking study revealed that the three compounds (<b>3a-c</b>) showed the ability to bind to the enzyme. However, the binding strength of compounds was weaker than that of the standard drug, doxorubicin. The MD simulation analysis demonstrated that compounds <b>3a</b> and <b>3b</b> gave relatively stable complexes with the enzyme and thus they would remain inside the binding pocket during the simulation period. Furthermore, the pharmacokinetic properties of the relatively active compounds were computed <i>in silico</i>. The computation disclosed that all of compounds exhibited drug-like properties. It is worth mentioning that all of them were found to be nontoxic. In furtherance, the inhibitory effect of compounds (<b>3a-c</b>) on the quorum sensing system was inspected using the biomonitor strains <i>Chromobacterium violaceum</i> 026, <i>Chromobacterium. violaceum</i> VIR07 and <i>Pseudomonas aeruginosa</i> PAO1. In this regard, we focused on the appraisal of the virulence factors, including pyocyanin, elastase, and biofilm formation that are created by <i>P. aeruginosa</i> PAO1 as the source of infectious diseases. As a result, it was determined that all examined compounds displayed statistically significant inhibition effects, and the highest activity was observed on elastase production with an inhibition rate of 84–86%.</p>","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":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70248","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143787327","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":"Polyphyllin VII Enhances the Antitumor Activity of Cisplatin in Non-Small Cell Lung Cancer Cells by Inducing Ferroptosis and Enhancing Apoptosis","authors":"Yuanzhou Wu,&nbsp;Liang Yang,&nbsp;Zizhao Li,&nbsp;Qunqing Chen,&nbsp;Jia Hu","doi":"10.1002/jbt.70186","DOIUrl":"https://doi.org/10.1002/jbt.70186","url":null,"abstract":"<div>\u0000 \u0000 <p>Cisplatin (DDP) resistance in non-small cell lung cancer (NSCLC) is a common cause of treatment failure and a significant contributor to increased mortality. To tackle this issue, the integration of traditional Chinese medicine with chemotherapy has been proposed as a promising approach. The potential synergistic effect of combining polyphyllin VII (PPVII) and DDP in overcoming DDP resistance in NSCLC cells has not been thoroughly investigated yet. In this study, H1299 cells were exposed to gradient concentrations of PPVII and DDP to determine their 50% inhibitory concentration values, and the most effective concentration was applied in subsequent experiments. The combination of PPVII and DDP was evaluated for its effects on H1299 cell proliferation, apoptosis, viability, and the expression of proteins linked to apoptosis and ferroptosis. To further elucidate the underlying mechanisms, the impact of the combination on DNA damage in H1299 cells was also examined. Our results demonstrated that PPVII significantly potentiated the antitumor effects of DDP in H1299 cells in a dose-dependent manner (<i>p</i> &lt; 0.05). Furthermore, PPVII was observed to work synergistically with DDP to suppress proliferation and promote apoptosis in H1299 cells (<i>p</i> &lt; 0.05). Western blotting analysis proved that the combination treatment upregulated proapoptotic proteins (B-cell lymphoma 2-associated X protein, cleaved-caspase 3 and cleaved-PARP), downregulated antiapoptotic protein (Bcl-2), and promoted ferroptosis-associated proteins (long-chain acyl-coenzyme A synthase 4 and NADPH oxidase 4) as well as DNA damage-associated protein (γH2AX) (<i>p</i> &lt; 0.05). Overall, the combination of PPVII and DDP significantly enhanced antitumor activity in H1299 cells through the modulation of DNA damage and ferroptosis, suggesting its potential as an effective therapeutic approach against DDP-resistant NSCLC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741482","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":"M2 Macrophage-Extracellular Vesicle-Derived lncRNA-NEAT1 Regulates miR-204-5p/RRS1-mediated Cell Cycle to Promote the Occurrence and Development of Colorectal Cancer","authors":"Guorui Ma,&nbsp;Xinlin Wu,&nbsp; Agudamu,&nbsp;Junjie Shen,&nbsp;Zhe Bao,&nbsp;Zhiwen Yang","doi":"10.1002/jbt.70168","DOIUrl":"https://doi.org/10.1002/jbt.70168","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is a prevalent malignancy of the digestive system. Here, we explored the role of M2 macrophage-derived extracellular vesicles (EVs) carrying long non-coding RNA-nuclear paraspeckle assembly transcript 1 (lncRNA-NEAT1) in promoting CRC progression via regulation of the miR-204-5p/regulator of ribosome synthesis 1 (RRS1) axis and cell cycle dynamics. Firstly, we differentiated WTHP-1 cells into M0 and M2 macrophages and transfected M2 macrophages with sh-NEAT1 lentivirus plasmids. EVs were isolated from M2 macrophages and administered to SW480 cells along with miR-204-5p inhibitors or si-RRS1 for 24 h. M2-EVs-derived lncRNA-NEAT1 enhanced CRC cell proliferation, migration, invasion, and viability while reducing apoptosis. This was accompanied by increased expression of RRS1, WEE1 G2 checkpoint kinase (WEE1), cyclin-dependent kinase 1 (CDK1), and CyclinB1, reduced miR-204-5p levels, and a lower proportion of cells in the G2/M phase. Knockdown of lncRNA-NEAT1 in M2 macrophages reversed these effects. Mechanistically, M2-EVs-derived lncRNA-NEAT1 functioned as a competing endogenous RNA (ceRNA), sponging miR-204-5p to upregulate RRS1 expression. In summary, M2 macrophage-derived EVs carrying lncRNA-NEAT1 promote CRC development by modulating the miR-204-5p/RRS1 axis, influencing the cell cycle and apoptosis. These findings provide insights into the tumor-promoting mechanisms of macrophage-derived EVs in CRC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741483","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":"Tumor-Derived Exosomal circ_0020095 Promotes Colon Cancer Cell Proliferation and Metastasis by Inhibiting M1 Macrophage Polarization","authors":"Yue Han,&nbsp;Zhe Zhou,&nbsp;Rudong Li,&nbsp;Hong Wang","doi":"10.1002/jbt.70225","DOIUrl":"https://doi.org/10.1002/jbt.70225","url":null,"abstract":"<div>\u0000 \u0000 <p>Tumor-associated macrophages (TAM) have been shown to regulate colon cancer (CC) progression. However, it is not clear whether tumor-derived exosomal circular RNA (circRNA) regulates TAM to influence CC progression. The expression levels of circ_0020095, M1 macrophage markers, M2 macrophage markers, and interleukin-1 receptor-associated kinase 1 (IRAK1) were determined by qRT-PCR. Cell proliferation, migration and invasion were examined by EdU assay, wound healing assay and transwell assay. Exosomes derived from CC cells were used to treat M0 macrophages. M1 macrophage surface marker CD86 was detected by flow cytometry, and protein expression was examined by western blot. Then, the medium of exosome-treated M0 macrophages was used to culture CC cells to determine CC cell functions. RNA pull-down assay, RIP assay and dual-luciferase reporter assay were performed to validate interaction. Circ_0020095 had elevated expression in CC tissues and cells, and its knockdown repressed CC cell proliferation and metastasis. M0 macrophages could take by CC cell-derived exosomes to regulate circ_0020095 expression. Exosomal circ_0020095 restrained M1 macrophage polarization and increased M2 macrophage polarization to enhance CC cell progression. Besides, IRAK1 silencing could promote CC cell proliferation and metastasis by inhibiting M1 macrophage polarization, and its overexpression also abolished the effect of exosomal circ_0020095. Mechanistically, circ_0020095 could competitively bind to IGF2BP1 and then reduced the binding ability of IGF2BP1 and IRAK1 3'UTR. Tumor-derived exosomal circ_0020095 promoted CC cell progression via inhibiting M1 macrophage polarization through IGF2BP1/IRAK1 axis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143741484","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":"Silencing of PODXL2 Modulates Cell Viability and Tumor Immune Microenvironment of Prostate Cancer and Involves PI3K/AKT Pathway Inactivation","authors":"Yaowu Su,&nbsp;Liang Zhou,&nbsp;Qin Yu,&nbsp;Weihua Liu,&nbsp;Wei Liu","doi":"10.1002/jbt.70210","DOIUrl":"https://doi.org/10.1002/jbt.70210","url":null,"abstract":"<div>\u0000 \u0000 <p>Prostate cancer (PCa) is one of the malignant tumors affecting men and is an important reason for the increase in male mortality worldwide. The pathogenesis of PCa is not fully understood. Thus, there is an urgent need to discover novel therapeutic targets to facilitate the development of effective anti-PCa strategies. Quantitative real-time PCR and Western blot were applied to detect the PODXL2 expressions in PCa tissues and cells. Progression-free survival of PCa patients was assessed using Kaplan–Meier survival analysis. The relevance between PODXL2 expressions and PCa clinical index was assessed with a Chi-square test. Cell infection, cell coculture system, Cell Counting Kit-8 assay, TUNEL staining, Transwell, analysis of PCa cell epithelial-mesenchymal transition (EMT) morphological changes, flow cytometry, and enzyme-linked immunosorbent assay were used for the analysis of PODXL2 functions in PCa. Meanwhile, the PODXL2 mechanism in PCa was dissected via Western blot, immunofluorescence analysis, Cell Counting Kit-8 assay, Transwell, and flow cytometry. Furthermore, PODXL2 impacts in PCa growth were examined in vivo using TUNEL staining, immunohistochemistry, and Western blot. PODXL2 expressions were raised in PCa tissues and cells, and PCa patients with high PODXL2 expressions owned poorer progression-free survival, and PODXL2 was interrelated to the TNM stage and distant metastasis of PCa. Interference with PODXL2 weakened PCa cell proliferation, invasion, EMT, and immune escape, while promoting PCa cell apoptosis. Furthermore, silencing PODXL2 reduced PCa cell proliferation, invasion, EMT, immune escape, and boosted cell apoptosis, which involved PI3K/AKT pathway inactivation. Meanwhile, PODXL2 knockdown reduced the tumor weight of PCa and promoted apoptosis in vivo. Interference with PODXL2 inhibited PCa cell proliferation, invasion, EMT, immune escape, enhanced cell apoptosis, and involved PI3K/AKT pathway inactivation.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143717031","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}