Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Oleuropein Promotes DNA Damage in Prostate Cancer Cells via HIF-1α Downregulation","authors":"Hanping Wei,&nbsp;Haoran Wu,&nbsp;Wei Feng","doi":"10.1002/jbt.70524","DOIUrl":"10.1002/jbt.70524","url":null,"abstract":"<div>\u0000 \u0000 <p>This study aimed to investigate the effects of oleuropein (Ole) on prostate cancer (PCa) cells and its underlying mechanisms, particularly whether it mediates DNA damage through HIF-1α. PCa cells DU145 were treated with different concentrations of Ole (25, 50, 100, 250, and 500 μM) or transfected with HIF-1α overexpression plasmid. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was used to detect the cell viability; flow cytometry was used to detect apoptosis; quantitative reverse transcription polymerase chain reaction and western blot were employed to measure HIF-1α expression levels. Additionally, comet assay and western blot were employed to evaluate DNA damage and the expression of DNA damage-related proteins (γH2AX and p53). Ole significantly inhibited DU145 cell viability in a concentration-dependent manner (<i>p</i> &lt; 0.01). Additionally, apoptosis rates increased significantly with increasing Ole concentrations (<i>p</i> &lt; 0.01). Ole induced DNA damage in DU145 cells. Notably, overexpression of HIF-1α partially reversed the effects of Ole on PCa cells. Ole inhibits DU145 cell viability, promotes apoptosis, and induces DNA damage, possibly through the HIF-1α pathway. HIF-1α plays a potential role in the anticancer effects of Ole, providing new experimental evidence for its application in PCa research.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191778","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":"WTAP Promotes Malignant Progression and Immune Escape of Glioblastoma by Regulating N6-methyladenosine Modification of CENPF","authors":"Feng Li,&nbsp;Bo Cui,&nbsp;Yuan Shao,&nbsp;Ke Gao","doi":"10.1002/jbt.70523","DOIUrl":"10.1002/jbt.70523","url":null,"abstract":"<div>\u0000 \u0000 <p>Glioblastoma (GBM) is a malignant tumor. It has been shown that centromere protein F (CENPF) may serve as a potential prognostic biomarker for glioma patients, while Wilms' tumor 1-associating protein (WTAP) is frequently upregulated across various cancers. However, the specific roles of CENPF and WTAP in GBM remain largely undefined. The differently expressed genes in GBM and expression levels of CENPF and WTAP were analyzed using bioinformatics analysis. The gene expression was examined using quantitative real-time polymerase chain reaction (qRT-PCR) and western blot. The cell counting kit-8 (CCK8), flow cytometry, transwell, and wound healing assays were used to detect cell viability, apoptosis, invasion, and migration, respectively. The volume and weight of xenograft tumors in mice were detected, and Ki-67, Cleaved caspase-3, and CENPF levels were examined by immunohistochemistry (IHC) assays. CD8⁺ T cell proliferation and apoptosis were examined by immunofluorescence (IF) and terminal deoxynucleotidyl transferase dUTP Nick-End Labeling (TUNEL), respectively. RMBase v3.0 website was used to predict the N6-methyladenosine (m6A) methylation modification sites of CENPF. The relationship between WTAP and CENPF was analyzed using the RNA-protein binding sites prediction (RBP) website and RNA immunoprecipitation (RIP) assay. Additionally, the m6A methylation levels of CENPF were detected using methylated RNA immunoprecipitation (Me-RIP). In GBM cells and tissues, CENPF expression was increased. Furthermore, CENPF promoted cell viability, invasion, and migration, and inhibited apoptosis and CD8⁺ T cell immunity in GBM. <i>In vivo</i>, CENPF promoted the growth of mice tumors. Mechanistically, WTAP regulated the expression of CENPF via m6A modification. Moreover, WTAP facilitated GBM progression and immune escape through upregulating CENPF. Together, WTAP promotes cell malignant progression and immune escape in GBM through regulating m6A modification of CENPF. These findings may provide a novel theoretical basis for the treatment of GBM.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191701","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":"Cucurbitacin-E-Glucoside Augments Tamoxifen's Anticancer Efficacy by Targeting PPARγ and NF-kB: In Vivo and In Silico Studies","authors":"Yasmin Sabry,&nbsp;Mohammed A. Hussein,&nbsp;Mohamed F. Elshal","doi":"10.1002/jbt.70540","DOIUrl":"10.1002/jbt.70540","url":null,"abstract":"&lt;div&gt;\u0000 \u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Background&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Cucurbitacin-E-glucoside (CEG), a natural compound from the Cucurbitaceae family, has shown anti-proliferative effects on various human cancer cell lines and is believed to inhibit the peroxisome proliferative activated receptor gamma (PPARγ) signaling pathway. We aimed to investigate the anti-cancer effects of CEG in a mouse model of Ehrlich ascites carcinoma (EAC) and its capacity to improve the efficacy of tamoxifen (TAM) treatment. By examining the in vivo and in silico interactions between CEG and tamoxifen with PPARγ, this study presents a novel approach to cancer management.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Methods&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;CEG (50 mg/k.g.b.w.) and TAM (20 mg/k.g.b.w.) were administered individually and/or in combination with the EAC-bearing mice. After 4 weeks of treatment, tumor weight and volume were measured. Additionally, inflammation and oxidative stress biomarkers, as well as apoptotic and antiapoptotic genes, were evaluated using ELISA and qRT-PCR. DNA cell cycle analysis of cancer cells was also performed using flow cytometry. To elucidate the molecular mechanism of CEG, PPARγ and NF-κB, the key transcription factor, were studied using Western blot and molecular docking studies.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Results&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Oral administration of CEG and tamoxifen individually and/or in combination led to significant decreases in tumor volume and weight. Additionally, the drug combination led to significant decreases in the proliferation index S phase and G2 phase. Moreover, treatment of CEG induces the expression of apoptotic PPARα and PPARγ as well as inhibits the expression of antiapoptotic Bcl-2 and HIF-1Α genes. Meanwhile, combining CEG with TAM showed a significant increase in liver GSH, CAT, SOD, NP-SH, and protein as well as significant decreases in levels of the plasma inflammatory markers IL-2, IL-6, TGF- β1, and the angiogenesis marker VEGF-C. Western blot analyses showed that CEG alone induced 2.8-fold PPARγ upregulation and 1.9-fold NF-κB suppression (&lt;i&gt;p&lt;/i&gt; &lt; 0.01) compared to the EAC group. Molecular docking analyses of CEG within the ligand-binding domains of the PPARγ and the inflammation transcription factor NF-KB proteins demonstrated comparable binding affinities to the PPARγ agonist Rosiglitazone and the NF-KB inhibitor MG-132, corroborating results obtained in vivo.&lt;/p&gt;\u0000 &lt;/section&gt;\u0000 \u0000 &lt;section&gt;\u0000 \u0000 &lt;h3&gt; Conclusion&lt;/h3&gt;\u0000 \u0000 &lt;p&gt;Our findings show that CEG therapy activates apoptotic PPARα and PPARγ genes and suppresses anti-apoptotic Bcl-2 and HIF-1Α genes, while reducing the oxidative stress and inflammation in EAC cells through a mechanism involving inhibition of NF","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191720","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":"Genistein and Gastrointestinal Cancers: A Comprehensive Review of Recent Studies and Future Outlook","authors":"Rohit Yennawar,&nbsp;Nosheen Abjani,&nbsp;Neel Parekh,&nbsp;Roja Rani Budha,&nbsp;Ginpreet Kaur,&nbsp;Hemant Joshi,&nbsp;Seema Ramniwas,&nbsp;Harvinder Popli,&nbsp;Shafiul Haque,&nbsp;Darin Mansor Mathkor,&nbsp;Hardeep Singh Tuli","doi":"10.1002/jbt.70533","DOIUrl":"10.1002/jbt.70533","url":null,"abstract":"<div>\u0000 \u0000 <p>Cancer is a global disease that causes millions of deaths annually, with gastrointestinal cancers becoming more prevalent than lung and breast cancers. Lifestyle factors like smoking and unhealthy eating habits increase the risk of cancer. Precision medicine approaches are needed to improve patient outcomes and cancer survival rates. Genistein, a natural isoflavonoid, acts as an anticancer medication by inducing apoptosis, preventing metastasis, and triggering cell death. It relies on various signaling pathways, including JAK1/2-STAT3, AKT/MDM2, EGFR, MEK/ERK, Shh-Gli1, MMP-2, FLT4, STAT3, PLK-1, and others. Elevated serum concentrations of isoflavones like genistein and daidzein have been linked to a decreased incidence of stomach cancer. Consumption of genistein through diet has been linked to potential health benefits, such as heart disease prevention, gastrointestinal, prostate, and breast cancer prevention through chemotherapy, and alleviation of postmenopausal symptoms. Genistein is a potent anticancer medication that works against various cancer types. This review examines the pharmacokinetics, chemistry, and possible applications of genistein in the treatment of pancreatic, esophageal, gastric, liver, and colorectal malignancies. The utilization of nanotechnology in conjunction with genistein is also discussed.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145199460","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":"Anti-Inflammatory, Anti-Colitis, and Antioxidant Effects of Salidroside against Dextran Sodium Sulfate Induced Ulcerative Colitis in Rats via Inhibition of NF-κB-INOS-No and TLR4-NF-κB Signaling Pathways","authors":"Song Li,&nbsp;Bishi Wang","doi":"10.1002/jbt.70520","DOIUrl":"10.1002/jbt.70520","url":null,"abstract":"<div>\u0000 \u0000 <p>Ulcerative colitis is a persistent inflammatory bowel disorder that predominantly impacts the mucosal lining of the rectum and colon. Targeting inflammatory reactions serves a preventative function in the management of ulcerative colitis. Salidroside has already exhibited an anti-inflammatory effect against various diseases. The current investigation demonstrated the protective effect of salidroside against dextran sodium sulfate (DSS)-induced UC in rats. 3% DSS was dissolved in the drinking water and administered to the rats for induction of UC in rats and rats were orally administered the salidroside and sulfasalazine for 7 days. The body weight, macroscopic study, organ weight, water intake, food intake, antioxidant, apoptosis, cytokines and inflammatory parameters were estimated. The disease activity index was measured in all groups. The level of VCAM-1, ICAM-1, HO-1 and Nrf₂ were estimated. The mRNA expressions were estimated in the colon tissue. Histopathological study of the colon tissue was also performed. Salidroside treatment remarkably improved the body weight and altered the organ weight. Salidroside treatment significantly (<i>p</i> &lt; 0.001) suppressed the DAI score along with alteration of oxidative stress (MDA, SOD, CAT, GSH), cytokines (TNF-α, IL-1, 1β, 6, 10, 18), inflammatory parameters (TGF-β, PGE₂, COX-2, NF-κB, iNOS), apoptosis (Bcl-2, Bcl-2:Bax ratio, Bax, caspase-3) parameters. Salidroside treatment suppressed the level of VCAM-1, NO, ICAM-1, MPO and upgraded the level of Nrf₂ and HO-1. Salidroside treatment altered the mRNA expression of Ocln, ASC, TNF-α, MCP-1, ZO-1, IFN-γ, IL-1β, IL-6, iNOS, COX-2, TGF-β and TLR4. The results clearly demonstrated that salidroside may exert Anti-inflammatory, anti-colitis, and antioxidant effects by altering the expression of key genes involved in the NF-κB-iNOS-NO and TLR4-NF-κB signaling pathways.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191744","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":"P-Glycoprotein Mitigates Paraquat-Induced Apoptosis in A549 Cells via the P38 MAPK-Regulated Mitochondrial Apoptotic Pathway","authors":"Yucheng Xu,&nbsp;Gang Chen,&nbsp;Shuqing Cui,&nbsp;Yuzhen Han,&nbsp;Zhiqiang Zhang","doi":"10.1002/jbt.70531","DOIUrl":"10.1002/jbt.70531","url":null,"abstract":"<div>\u0000 \u0000 <p>The main pathological change in paraquat (PQ)-induced poisoning is acute lung injury, which can result in respiratory failure and possibly death, and there is currently no effective treatment. P-glycoprotein (P-gp) plays a crucial role in the distribution and regulation of diverse chemical agents and toxins, as well as in the resistance of cancer cells to multiple drugs. This study assessed the involvement of P-gp in the development of acute lung injury caused by PQ and investigated the underlying molecular mechanisms. An ABCB1 overexpression lentiviral plasmid was constructed, and a stable P-gp-overexpressing cell line was obtained by infecting A549 cells with lentiviral particles produced by 293 T cells. A549 cells overexpressing P-gp were treated with or without PQ for 24 h. Apoptotic mechanisms involving mitochondrial membrane potential, caspase activity, and the P38 MAPK signaling pathway were also analyzed. The results showed that P-gp could alleviate proliferation toxicity and cell apoptosis induced by PQ, improve mitochondrial membrane potential, reduce caspase-3 activity, and mitigate oxidative stress imbalance and lipid peroxidation. PQ exposure increased P38 MAPK activity in A549 cells, which was attenuated by P-gp and the antioxidant NAC, leading to decreased ROS generation and suppressing P38 MAPK activity. Suppression of P38 MAPK activity using SB203580 mitigated cell damage and apoptosis, but had no inhibitory effect on oxidative stress. These findings suggest that P38 MAPK signaling participates in the development of PQ-caused acute lung injury. Additionally, the results suggest that P-gp alleviates PQ-induced acute lung injury by impairing the mitochondrial apoptotic pathway that is regulated by ROS/P38 MAPK.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191773","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":"Adverse Effects of Furan on Fetal Development, Growth Plate Integrity, and Placental Functioning in Wistar Rats","authors":"Entsar R. Abd-Allah,&nbsp;Haidy A. Abdelaziz,&nbsp;Taha M. A. Eldebss,&nbsp;Heba Ali Abd El-Rahman","doi":"10.1002/jbt.70526","DOIUrl":"10.1002/jbt.70526","url":null,"abstract":"<div>\u0000 \u0000 <p>This study examined the adverse impacts of furan, a pervasive environmental toxin, on fetal development in Wistar rats. Twenty-eight pregnant rats (seven animals per group) were orally administered different doses of furan (18 and 28 mg/kg), distilled water, or corn oil as vehicles from gestation days 6–12, and their progeny at gestation day 20 were assessed for developmental anomalies, oxidative stress, apoptosis, and placental impairment. The findings indicated substantial decreases in fetal weight, length, and survival rates after furan exposure. Histopathological analyses revealed damage to the placenta and fetal liver, marked by necrosis and cellular degeneration. Additionally, the growth plates of fetal tibiae exhibited histopathological alterations. Exposure to furan also impaired oxidative homeostasis, as demonstrated by increased oxidative stress indicators and decreased antioxidant enzyme activity in placental and fetal tissues. Apoptosis was markedly increased in the placenta, as evidenced by increased caspase-3 and Bax levels and reduced expression of Bcl-2. Moreover, furan exposure modified the expression of placental growth factors, potentially affecting fetal development. The comet assay validated furan's genotoxic properties, causing DNA damage in fetal liver tissue. These findings underscore the risks associated with fetal exposure to furan during gestation and emphasize the need for further research to better understand its adverse effects on embryonic development. This knowledge is crucial for developing effective prevention and mitigation strategies to protect maternal and fetal health.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145191763","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":"From Molecular Mechanisms of the Pathogenesis of Sepsis to the Novel Healing Biomolecules: Recent Progressions in Dealing With Sepsis","authors":"Deepak Mishra,&nbsp;Lucy Mohapatra,&nbsp;Dharmanka Bandyopadhyay,&nbsp;Sambit Kumar Parida,&nbsp;Narhari N. Palei","doi":"10.1002/jbt.70522","DOIUrl":"https://doi.org/10.1002/jbt.70522","url":null,"abstract":"<div>\u0000 \u0000 <p>Sepsis is a serious pathological health condition that poses a threat to life on a global scale. It frequently affects people with pre-existing immunodeficiency and is more prevalent in geriatrics. In its most extreme condition, sepsis can cause persistent critical illness. This state is characterized by severe immunological and metabolic dysfunctions, ultimately leading to multiple organ failure. The underlying pathophysiological mechanisms of sepsis are still unclear, despite extensive basic and clinical studies. Existing therapy still principally consists of basic causative and supportive measures, but adjuvant treatments, such as blood clotting or personalized immunotherapy, are yet to be demonstrated to be very beneficial. This review has discussed the major etiopathogenesis involved in the progression of sepsis and its complications including microcirculation, cytokine storm, oxidative stress, mitochondrial dysfunction, and apoptosis. Further, this article aims to highlight novel biomolecules as effective options available for the treatment of the immunological processes that greatly contribute to sepsis, septic shock and propose a paradigm shift from the pathogen to the host response as a potentially more effective strategy of treating and managing sepsis. We strongly believe that the briefing of these two major fields as recent hallmarks of sepsis research i.e understanding the pathogenesis of sepsis and novel approaches to manage the same in this article, will foster research engagement by clinicians and inventors in this dynamic area and will attract further consideration and sustenance from pharma industry and research laboratories.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146779","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":"Evaluation of Genetic Marker Polymorphisms (MTHFRC677T and ABCC2 C) for Predicting Methotrexate Toxicity in Psoriasis Patients in Egypt: A Case-Control Study","authors":"Asmaa Mohammad Sayed Ahmed,&nbsp;Mervat Hamdy Abdel Salam,&nbsp;Eman A. F. Zohairy,&nbsp;Mohamed H. M. EL-Komy,&nbsp;Marwa Abdelgwad,&nbsp;Hussein A. Nasr,&nbsp;Abrar Roshdy Abouelkheir","doi":"10.1002/jbt.70537","DOIUrl":"https://doi.org/10.1002/jbt.70537","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Methotrexate is an antineoplastic agent prescribed in various treatment protocols, particularly for psoriasis. Studies on toxicogenomic and clinical data suggest that polymorphism in genes involved in folate metabolism are linked to varying individual responses to methotrexate (MTX). This study aimed to investigate the single nucleotide polymorphisms (SNPs) of two genetic DNA markers (MTHFR 677 C and ABCC2 C), their correlation to protein expression, and laboratory investigations as potential predictors of susceptibility to MTX toxicity among patients. This is a case-control study involving 90 patients treated with methotrexate at the Kasr Al-Ainy psoriasis unit (KAPU), Department of Dermatology. Upon assessing genetic marker polymorphisms, the MTHFR 677 C allele was the most common among all patients (69%). There were more patients with the mutant homozygous (TT) allele in the case group compared to the control group (30% vs. 7%). The ABCC2 C allele was the most prevalent (75%), with the T allele present in 25% of patients. The case group exhibited a lower expression of the CT allele compared to the control group (30% vs. 53%), with a significant difference between the two groups. MTX levels were higher in the case group, while homocysteine levels did not differ significantly between the groups. The C allele of the ABCC2 gene, with a methotrexate cutoff greater than 4.5081 ng/ml, and the MTHFR T polymorphism are strongly associated with toxicity. The risk of toxicity in individuals receiving methotrexate can be predicted with a threshold value of 4.5081 ng/ml for methotrexate levels; however, there was no significant variation in homocysteine levels across the groups.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145146780","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":"Puerarin Enhances the Sensitivity of Colorectal Cancer to 5-Fluorouracil and Oxaliplatin by Inhibiting the PTEN/PI3K/AKT Signaling Pathway","authors":"Xiaowei Wang,&nbsp;Xiaorui Yang,&nbsp;Jiang Wang,&nbsp;Yueli Zhang,&nbsp;Yanrui Zhang","doi":"10.1002/jbt.70517","DOIUrl":"10.1002/jbt.70517","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) represents the most prevalent malignancy within the gastrointestinal system, with metastatic cases comprising approximately 50% of all CRC diagnoses. While chemotherapy remains the cornerstone treatment for metastatic CRC, the emergence of chemoresistance has significantly limited the clinical efficacy of 5-fluorouracil (5-FU) and oxaliplatin-based regimens. In this study, we systematically investigated the therapeutic potential of puerarin in CRC management, focusing on its antitumor properties and chemosensitization effects. Our findings demonstrate that puerarin exhibits significant antitumor activity both in vitro and in vivo, while also potentiating the therapeutic effects of 5-FU and oxaliplatin through synergistic interactions. Mechanistically, we identified PTEN as a critical molecular target of puerarin, evidenced by the reversal of puerarin-mediated effects upon PTEN knockdown. Further molecular characterization revealed that puerarin exerts its antitumor effects through PTEN-mediated suppression of AKT activation and subsequent induction of apoptotic pathways. Importantly, we established that puerarin enhances CRC cell sensitivity to 5-FU and oxaliplatin via modulation of the PTEN/PI3K/AKT signaling axis. These findings not only elucidate a novel molecular mechanism underlying puerarin's anti-CRC activity but also provide a promising therapeutic strategy for overcoming chemoresistance in CRC treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145137645","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}