Journal of Biochemical and Molecular Toxicology最新文献

{"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}

{"title":"Synergistic Anticancer Effects of Silibinin and Sulforaphane: Targeting Gastric Cancer via PI3K/AKT and ERK1/2 MAPK Pathway Inhibition and Molecular Docking Insights","authors":"Yanfeng Liu,&nbsp;Ming Zhang","doi":"10.1002/jbt.70237","DOIUrl":"https://doi.org/10.1002/jbt.70237","url":null,"abstract":"<div>\u0000 \u0000 <p>In the current period of pharmaceutical discovery, herbal remedies have shown to be an unmatched supply of anticancer medications. By changing the tumor microenvironment and several signaling pathways, plants and their byproducts through analogs have an important part in the therapy for carcinoma. The current investigation assessed the effectiveness of inhibiting the development of gastric cancer cells in HGC-27 cells by attenuating the PI3K/AKT and ERK 1/2 MAPK signaling pathways using the natural medicines silibinin (SIL) and sulforaphane (SFN) complemented by molecular docking analysis. After being exposed to various doses of SIL and SFN (SIL+SFN) for 24 h (0–50 µM), the cells were evaluated for multiple studies. The MTT assay was used to examine the combo that SIL+SFN induced cytotoxicity. ROS was assessed by DCFH-DA staining. Apoptotic changes were investigated, and MMP levels in HGC-27 cells were investigated utilizing the proper fluorescent staining techniques. Flow cytometry and western blot analysis were used to evaluate the protein profiles of cell survival, cell cycle, proliferation, and apoptosis. The molecular docking was conducted with Autodock Vina (v1.5.6). The docking results were analyzed using BIOVIA Discovery Studio Visualizer to identify key interactions. The relative cytotoxicity of SIL and SFN was found to be approximately 24.96 and 28.79 μM, correspondingly, according to the findings. After a 24-h incubation period, the combination of SIL and SFN generates significant cytotoxicity in HGC-27 cells, with an IC₅₀ of 15.43 μM. Furthermore, HGC-27 cells administered SIL and SFN simultaneously exhibited elevated apoptotic signals and significant ROS production. Molecular docking demonstrated strong binding affinities between the compounds and the target proteins, supporting their potential mechanisms of action. Therefore, the combination usage of SIL + SFN has been viewed as a chemotherapeutic drug since it prevents the synthesis of PI3K/AKT and ERK 1/2 MAPK mediated control of cell growth and cell cycle-regulating proteins. To utilize them commercially conducting more in vivo research in the near future will be necessary to ascertain how well the co-treatment triggers apoptosis.</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":"143717029","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":"Apelin-13 Protects Against Myocardial Hypoxia/Reoxygenation (H/R) Injury by Inhibiting Ferroptosis Via Nrf2 Activation","authors":"Fan Liang,&nbsp;Chen Li,&nbsp;Yumiao Liu,&nbsp;Yanbo Sui","doi":"10.1002/jbt.70223","DOIUrl":"https://doi.org/10.1002/jbt.70223","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemia-reperfusion (IR)-induced myocardial damage represents <i>a major</i> pathological event in coronary artery disease (CAD). Effective therapeutic strategies are urgently needed to improve clinical outcomes for CAD patients. Apelin-13, primarily produced by magnocellular neurons, exhibits diverse biological functions across various cell types and tissues. However, its role in myocardial IR injury remains unexplored. In this study, we utilized an in vitro model of myocardial IR injury using H9c2 cardiomyocytes to investigate the potential protective effects of Apelin-13. Our findings reveal that Apelin-13 protects against hypoxia/reoxygenation (H/R)-induced oxidative stress in H9c2 cells by reducing mitochondrial reactive oxygen species (ROS) and malondialdehyde (MDA) levels, while enhancing superoxide dismutase (SOD) activity. Additionally, Apelin-13 alleviates H/R-induced mitochondrial dysfunction, as evidenced by increased mitochondrial membrane potential (MMP) and adenosine triphosphate (ATP) production. Crucially, Apelin-13 mitigates H/R-induced cardiomyocyte injury, as shown by reduced levels of creatine kinase-myocardial band (CK-MB), cardiac troponin I (cTnI), and lactate dehydrogenase (LDH). Remarkably, Apelin-13 also counteracts ferroptosis during H/R by decreasing ferrous iron (Fe²⁺) concentrations, increasing glutathione (GSH) levels, and suppressing glutathione peroxidase 4 (GPX4) and ferritin heavy chain 1 (FTH1) expression. These protective actions were negated by the ferroptosis inducer Erastin. Further investigation revealed that Apelin-13 activates the transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) through enhanced nuclear translocation and upregulation of heme oxygenase-1 (HO-1). Conversely, Nrf2 knockdown nullified the protective effects of Apelin-13 against ferroptosis and cardiomyocyte injury, underscoring the critical involvement of Nrf2 in mediating these benefits. Collectively, our results highlight the promising therapeutic potential of Apelin-13 in managing CAD.</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":"143717030","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":"Sevoflurane Mediates LINC00339/miR-671-5p/PSMB2 Axis to Improve Cardiomyocytes Against Hypoxia/Reoxygenation Injury","authors":"Juan Li,&nbsp;Chuan Mou,&nbsp;Yawei Yuan,&nbsp;Long Wang,&nbsp;Caihong Wu","doi":"10.1002/jbt.70234","DOIUrl":"https://doi.org/10.1002/jbt.70234","url":null,"abstract":"<div>\u0000 \u0000 <p>Ischemia/reperfusion (I/R) causes a deterioration in heart function, leading to myocardial infarction. It is aimed at investigating the protective mechanism of sevoflurane (Sevo) on cardiomyocytes by constructing a cellular model of hypoxic/reoxygenation (H/R) in this study.[Human hybrid] epithelioid cells (AC16) were induced by H/R to establish a model of myocardial I/R injury and Sevo postconditioning. The expression of long intergenic non-protein coding RNA 339 (LINC00339), microRNA-671-5p (miR-671-5p) and proteasome 20S subunit beta 2 (PSMB2) was detected by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Viability and apoptosis of AC16 cells were detected by cell counting kit-8 (CCK-8) assay and flow cytometry, respectively. The levels of interleukin-6 (IL-6), IL-10, tumor necrosis factor-a (TNF-a), reactive oxygen species (ROS), malondialdehyde (MDA), glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD), were detected. LINC00339 expression was upregulated in H/R cardiomyocytes relative to the Control group, whereas Sevo decreased LINC00339 expression in H/R cardiomyocytes. The viability of AC16 cells were increased, and apoptosis, oxidative stress, and inflammatory responses decreased in the Sevo postconditioning group relative to the H/R group, but the protective effect of Sevo on H/R cardiomyocytes was partially reversed by LINC00339 overexpression. LINC00339 negatively regulated miR-671-5p, and miR-671-5p upregulation could alleviate the damage of LINC00339 on H/R cardiomyocytes. PSMB2, a downstream target gene of miR-671-5p, could inhibit the protective effect of Sevo on H/R cardiomyocytes. Sevo postconditioning exerts a protective effect in H/R-induced cardiomyocyte injury, which may be achieved by interfering with LINC00339/miR-671-5p/PSMB2 expression.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707450","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":"Investigating the Role and Regulatory Mechanisms of the Histone Deacetylase 4 Gene in Chondrocyte Differentiation Impairments Associated With Kashin–Beck Disease","authors":"Lei Yang,&nbsp;Chaowei Wang,&nbsp;Jie Zhou,&nbsp;Feihong Chen,&nbsp;Lian Liu,&nbsp;Lulu Bai,&nbsp;Xi Wang,&nbsp;Xiong Guo,&nbsp;Shuangqiang Yi","doi":"10.1002/jbt.70231","DOIUrl":"https://doi.org/10.1002/jbt.70231","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to investigate the role of the HDAC4 gene in the pathogenesis of Kashin–Beck disease (KBD) cartilage injury and chondrocyte differentiation induced by T-2 toxin. Immunohistochemistry was used to compare HDAC4 and PTHrP protein expression levels in cartilage from children and adults who have KBD and from respective controls, as well as in cartilage from a rat model exposed to T-2 toxin and selenium deficiency. A KBD cell model was established by exposure to T-2 toxin, and RNA interference was employed to silence HDAC4. Expression levels of mRNA and protein expression levels were subsequently measured before and after HDAC4 gene silencing for genes related to the PTHrP–HDAC4 signaling pathway and cartilage differentiation by real-time quantitative reverse transcription PCR and western blotting. We found that HDAC4 expression levels were not consistent between adult and child chondrocytes. Silencing of HDAC4 resulted in a significant increase in the mRNA expression of Runx2 and PTHrP, and elevated the levels of both the mRNA and protein of MMP13, and increased both the mRNA and protein levels of MEF2C. Notably, following the addition of T-2 toxin, there was a significant increase in Runx2 expression, whereas the levels of MEF2C and MMP13 were markedly decreased in comparison to pre-silencing conditions. These findings indicate that T-2 toxin may influence HDAC4 expression, and the role and regulatory mechanisms of this gene in impairing the differentiation of KBD chondrocytes were explored, thereby offering novel insights into the pathogenesis of KBD.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707623","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":"Promotion of Autophagy and Apoptosis in Colorectal Cancer Exposed to Imatinib and Thymoquinone","authors":"Dalia El-Khouly,&nbsp;Nadia A. Thabet,&nbsp;Mohamed Sayed-Ahmed,&nbsp;Mervat M. Omran","doi":"10.1002/jbt.70238","DOIUrl":"https://doi.org/10.1002/jbt.70238","url":null,"abstract":"<p>Cancer cells possess high proliferative ability and usually override apoptosis and metastasize to distant lesions. Autophagy in cancer cells is a double-edged weapon where a cross-regulation postulation between apoptosis and autophagy exists. The aim of the present study was to investigate the effect of adding Thymoquinone (TQ) to Imatinib (IM) in HCT₁₁₆ human colorectal cancer cell line model on various apoptotic and autophagy markers. The combination doses of IM and TQ were selected according to our previous study concerned with cytotoxicity and uptake/efflux genes modulation. In the current study, the combination induced autophagy in HCT₁₁₆ cell line which in turn enhanced apoptosis. Moreover, early apoptosis was evidenced. The induction of both autophagy and apoptosis resulted in programmed cell death. The assessment of AMPK, Par-4, apoptosis markers, colony formation assays, flow cytometry and autophagy detection by acridine orange proved this rapport.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 4","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70238","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707449","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}