Journal of Biochemical and Molecular Toxicology最新文献_第6页

Glycitein Mitigates Doxorubicin-Induced Cardiotoxicity by Mitigating Apoptosis and Inflammatory Responses in Albino Rats 糖苷通过减轻白化大鼠的细胞凋亡和炎症反应减轻阿霉素诱导的心脏毒性

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-12 DOI: 10.1002/jbt.70489

Zhou Jingya, Li Peng

{"title":"Glycitein Mitigates Doxorubicin-Induced Cardiotoxicity by Mitigating Apoptosis and Inflammatory Responses in Albino Rats","authors":"Zhou Jingya, Li Peng","doi":"10.1002/jbt.70489","DOIUrl":"https://doi.org/10.1002/jbt.70489","url":null,"abstract":"<div>\u0000 \u0000 <p>Advancements in immune and targeted therapies have significantly enhanced cancer-specific outcomes for numerous patients. However, a proportion of these therapies is associated with cardiovascular toxicities, which pose challenges in patient management. Doxorubicin, an antineoplastic agent commonly prescribed for treating malignancies, is particularly notable for its efficacy, however, clinical usage is restricted due to its myocardial toxicity. Bioactive compounds possess immense pharmacological properties and supplementation of bioactive compounds had proven to ameliorate drug-induced toxicities. In this study, we aimed to evaluate the ameliorative effect of bioactive compound glycitein against DOX-triggered myocardial toxicity. DOX-treated Wistar rats were subsequently administered with two different doses of glycitein. The change in body weight and arterial pressure was recorded. After 24 h, the last treatment animals were euthanized, blood and cardiac tissue samples were collected. The levels of C-RP, uric acid, total protein, lipid peroxidation, and antioxidants were quantified in the experimental animals to assess the impact of glycitein against DOX-induced oxidative stress. Lipid-lowering effect and ATPase-regulating effect of glycitein in DOX-administered rats were measured. Inflammatory inducers and apoptotic proteins in the DOX-administered animals were quantified to examine the anti-inflammatory and antiapoptotic effect of glycitein. Cardiac histopathological examination was performed to ratify the cardioprotective potency of glycitein against DOX. The results of our research prove glycitein treatment scavenged free radicals induced by DOX and rendered lipid-lowering, anti-inflammatory, antiapoptotic, and cardioprotective effects in the DOX-administered rats. Overall, our research concludes that glycitein is a potent bioactive compound which can be supplemented along with doxorubicin in cancer patients to prevent anticancer drug-induced cardiotoxicity.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038327","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

YY1-Upregulated MTHFD2 Drives Non-Small Cell Lung Cancer Progression Through the Regulation of LRRK2 yy1上调MTHFD2通过调控LRRK2驱动非小细胞肺癌进展

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-12 DOI: 10.1002/jbt.70504

Zichun Wei, Jixian Liu, Xinyu Luan, Chundong Gu

{"title":"YY1-Upregulated MTHFD2 Drives Non-Small Cell Lung Cancer Progression Through the Regulation of LRRK2","authors":"Zichun Wei, Jixian Liu, Xinyu Luan, Chundong Gu","doi":"10.1002/jbt.70504","DOIUrl":"https://doi.org/10.1002/jbt.70504","url":null,"abstract":"<div>\u0000 \u0000 <p>The mitochondrial folate enzyme methylenetetrahydrofolate dehydrogenase/cyclohydrolase 2 (MTHFD2) has been revealed to extensively participate in the development of non-small cell lung cancer (NSCLC). This study further explored molecular mechanisms which enhance MTHFD2 expression and how MTHFD2 contributes to NSCLC development. Cell growth was evaluated by detecting viability and colony formation potential. Cell apoptosis was detected by flow cytometry. Cell migration and invasion were assessed by transwell and wound-healing assays. Expression analysis was performed by a quantitative PCR, immunoblotting, or immunohistochemistry method. The Yin Yang 1 (YY1)/MTHFD2 relationship was confirmed by luciferase and chromatin immunoprecipitation (ChIP) assays. The MTHFD2/leucine-rich repeat kinase 2 (LRRK2) interaction was tested by co-immunoprecipitation (Co-IP) experiments. MTHFD2 expression was increased in human NSCLC tumors and cell lines. MTHFD2 was identified as a candidate driver in malignant phenotypes of A549 and H322 NSCLC cells in vitro. MTHFD2 depletion suppressed the growth of A549 xenografts in vivo. Mechanistically, YY1 enhanced the transcription of MTHFD2. YY1 elevated MTHFD2 expression to modulate the in vitro phenotypes of A549 and H322 NSCLC cells. Furthermore, MTHFD2 interacted with LRRK2 to regulate LRRK2 expression. MTHFD2 targeted LRRK2 to alter NSCLC cell phenotypes in vitro and growth in vivo. Our findings demonstrate for the first time the protumorigenic role of the YY1/MTHFD2/LRRK2 cascade in NSCLC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038177","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

Protective Effects of Quercetin Against Vincristine-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis in Rats 槲皮素通过调节氧化应激、炎症和细胞凋亡对长春新碱引起的大鼠肾毒性的保护作用

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-12 DOI: 10.1002/jbt.70516

Özge Kandemir, Sefa Küçükler, Selçuk Özdemir, Elif Dalkılıç, Sevda Sağ, Cuneyt Caglayan, Fatih Mehmet Kandemir

{"title":"Protective Effects of Quercetin Against Vincristine-Induced Nephrotoxicity via Modulation of Oxidative Stress, Inflammation, and Apoptosis in Rats","authors":"Özge Kandemir, Sefa Küçükler, Selçuk Özdemir, Elif Dalkılıç, Sevda Sağ, Cuneyt Caglayan, Fatih Mehmet Kandemir","doi":"10.1002/jbt.70516","DOIUrl":"https://doi.org/10.1002/jbt.70516","url":null,"abstract":"<div>\u0000 \u0000 <p>Vincristine is a widely used chemotherapeutic agent in pediatric leukemias and solid tumors, but the use of this chemotherapeutic agent is associated with many organ damages, especially nephrotoxicity. Quercetin, a natural flavonoid, is known for its antioxidant and anti-inflammatory potential. Vincristine was intraperitoneally administered at a dose of 0.1 mg/kg body weight, and quercetin was orally administered at doses of 25 and 50 mg/kg body weight. Both treatments were applied to the rats on days 1–6 and 9–14. Renal function was assessed via serum urea and creatinine levels. Oxidative stress and lipid peroxidation were evaluated by measuring GSH, SOD, CAT, GPx, and MDA. The mRNA levels of apoptotic markers such as p53, Bax, Bcl-2, Jnk and Beclin-1 and inflammatory markers such as TNF-α, IL-1β, COX-2, and PGE-2 were analyzed by RT-qPCR. The HO-1, Nrf2, PGC-1α and SIRT1, NFκB and STAT3 protein levels were determined by ELISA. In addition, the protein levels of PI3K and AKT in survival pathways were analyzed using the Western blot method. The results showed that vincristine significantly impaired renal function by increasing oxidative stress, inflammation, and apoptosis. Quercetin protected renal function by enhancing antioxidant defense, reducing inflammatory signals and reversing apoptosis. The findings reveal that quercetin exhibits protective effects against vincristine-induced nephrotoxicity through antioxidant, anti-inflammatory and antiapoptotic mechanisms.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038021","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

NKX2-1 Restricts the Growth and Metastasis of Lung Squamous Cell Carcinoma Through Transcriptive Suppression of AKR1B10 NKX2-1通过抑制AKR1B10转录抑制肺鳞癌的生长和转移

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-12 DOI: 10.1002/jbt.70507

Dan Yu, Ping Liu, Ruichen Gao, Ting Jiang, Caiwen Shi, Yan Wang, Ming Liu

{"title":"NKX2-1 Restricts the Growth and Metastasis of Lung Squamous Cell Carcinoma Through Transcriptive Suppression of AKR1B10","authors":"Dan Yu, Ping Liu, Ruichen Gao, Ting Jiang, Caiwen Shi, Yan Wang, Ming Liu","doi":"10.1002/jbt.70507","DOIUrl":"https://doi.org/10.1002/jbt.70507","url":null,"abstract":"<p>Lung squamous cell carcinoma (LUSC) is associated with poor prognosis and limited treatment options. In this study, we investigate the role of <i>NKX2-1</i> as a tumor suppressor in LUSC. Our analysis of The Cancer Genome Atlas (TCGA) revealed that <i>NKX2-1</i> expression is significantly lower in LUSC tissues compared to lung adenocarcinoma (LUAD) and normal lung tissues, and patients with low <i>NKX2-1</i> expression have poorer survival rates. The CCK8, colony formation, EdU incorporation, wound healing, and Transwell assays demonstrated that <i>NKX2-1</i> overexpression inhibited the proliferation, migration, and invasion of the LUSC cell lines SK-MES-1 and NCI-H520. Moreover, in a subcutaneous xenograft model, <i>NKX2-1</i> overexpression reduced tumorigenic potential of the injected SK-MES-1 cells. The transcriptomic analysis highlighted the dysregulation of key genes associated with <i>NKX2-1</i> expression levels. <i>AKR1B10</i> was expressed at higher levels in LUSC tissues and negatively correlated with <i>NKX2-1</i>. Dual-luciferase assays verified that <i>NKX2-1</i> suppressed the transcription of <i>AKR1B10</i> by direct binding to its promoter. The tumor-suppressive effects of <i>NKX2-1</i> diminished upon <i>AKR1B10</i> overexpression, which indicated an <i>AKR1B10</i>-dependent mechanism. In sum, our findings indicated that <i>NKX2-1</i> limited tumor growth and metastasis in LUSC by repressing <i>AKR1B10</i> transcription, thereby revealing potential therapeutic targets to improve clinical outcomes in these patients.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70507","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037725","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}

引用次数: 0

NAT10-Mediated N4-Acetylation of SLC7A11 mRNA Promotes Hepatocellular Carcinoma Progression and Metastasis by Repressing Ferroptosis nat10介导的SLC7A11 mRNA的n4乙酰化通过抑制铁下垂促进肝癌的进展和转移

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-12 DOI: 10.1002/jbt.70496

Chen Wang, Jiangwen Liu, Haosheng Chang, Yali Wu, Zhiwei Chai, Ping Jia, Yueyue Yuan, Ling Tan

{"title":"NAT10-Mediated N4-Acetylation of SLC7A11 mRNA Promotes Hepatocellular Carcinoma Progression and Metastasis by Repressing Ferroptosis","authors":"Chen Wang, Jiangwen Liu, Haosheng Chang, Yali Wu, Zhiwei Chai, Ping Jia, Yueyue Yuan, Ling Tan","doi":"10.1002/jbt.70496","DOIUrl":"https://doi.org/10.1002/jbt.70496","url":null,"abstract":"<div>\u0000 \u0000 <p>N-acetyltransferase 10 (NAT10) catalyzes N4-acetylcytidine (ac4C) modification of mRNA, yet its role in hepatocellular carcinoma (HCC) and ferroptosis remains elusive. A retrospective study with 100 HCC patients assessed NAT10 and SLC7A11 expression. Immunohistochemistry evaluated protein levels in HCC tissues. <i>In vitro</i> experiments using HCC cell lines explored NAT10's impact on proliferation, migration, invasion, and apoptosis. In vivo, nude mice with HCC xenografts underwent stable si-NAT10 transfection, monitoring tumor growth and metastasis. Ferrostatin-1 treatment investigated NAT10's role in ferroptosis. RNA immunoprecipitation and acRIP assays examined NAT10's influence on SLC7A11 mRNA stability. Elevated NAT10 expression correlated with poor outcomes and TACE therapy resistance in HCC. NAT10 silencing inhibited HCC cell functions, promoting apoptosis and ferroptosis in vitro; Ferrostatin-1 reversed these effects. In vivo models confirmed NAT10's significance in HCC progression, reducing tumor volume and weight with increased apoptosis. Ferrostatin-1 counteracted these effects, underlining ferroptosis in NAT10-driven tumorigenesis. NAT10 knockdown increased Fe<sup>2+</sup> accumulation and decreased SLC7A11 and GPX4 expression, indicating that NAT10 knockdown enhanced ferroptosis. Mechanistically, NAT10 stabilized SLC7A11 mRNA via ac4C acetylation, suppressing ferroptosis. This epigenetic modification emerged as a regulator of ferroptosis evasion in HCC. Overall, NAT10 promotes HCC progression by inhibiting ferroptosis through ac4C acetylation of SLC7A11 mRNA.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145038326","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

Mechanisms of Propofol in Alleviating Neuropathic Pain by Inhibiting Microglial Pyroptosis in Spinal Cord Through the KDM3A/WNT5A Axis 异丙酚通过KDM3A/WNT5A轴抑制脊髓小胶质细胞焦亡减轻神经性疼痛的机制

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-12 DOI: 10.1002/jbt.70498

Sun-hui Xia, Di Zhou, Yuqiu Zhang, Jing Jiao, Changhong Miao

{"title":"Mechanisms of Propofol in Alleviating Neuropathic Pain by Inhibiting Microglial Pyroptosis in Spinal Cord Through the KDM3A/WNT5A Axis","authors":"Sun-hui Xia, Di Zhou, Yuqiu Zhang, Jing Jiao, Changhong Miao","doi":"10.1002/jbt.70498","DOIUrl":"https://doi.org/10.1002/jbt.70498","url":null,"abstract":"<div>\u0000 \u0000 <p>Propofol is a short-acting intravenous anesthetic commonly used for induction and maintenance of general anesthesia and sedation during medical procedures. This study aimed to explore the mechanism of propofol on microglial pyroptosis in spinal cord in neuropathic pain (NP). A chronic constriction injury (CCI) model of NP was established in rats. The paw withdrawal mechanical threshold (PWMT) and paw withdrawal thermal latency (PWTL) were measured in rats. The tissue pathology was observed. The expression of NLR family pyrin domain containing 3 (NLRP3) and Iba1 was measured. Microglial cells (BV2) were cultured and treated with lipopolysaccharide (LPS). The cell model was treated with propofol. The levels of lysine demethylase 3A (KDM3A)/H3 dimethylation at lysine 9 (H3K9me2)/Wnt family member 5A (WNT5A) in the tissue and cells were measured. The enrichment of KDM3A and H3K9me2 in the WNT5A promoter region was analyzed. KDM3A and WNT5A were upregulated in CCI. Propofol treatment reduced KDM3A and WNT5A expression, increased PWMT and PWTL, alleviated inflammation, and inhibited microglial pyroptosis in spinal cord. KDM3A promoted WNT5A expression by inhibiting H3K9me2. Overexpression of KDM3A or WNT5A partially reversed the inhibitory effect of propofol on pyroptosis. In conclusion, propofol inhibits microglial pyroptosis in spinal cord and alleviates NP through the KDM3A/WNT5A pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145037726","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

Rutin Alleviates Breast Cancer Resistance to Tamoxifen By Downregulating ABC Transporters, Inducing ROS Generation and Resetting Redox Status 芦丁通过下调ABC转运蛋白、诱导ROS生成和重置氧化还原状态减轻乳腺癌对他莫昔芬的耐药

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-08 DOI: 10.1002/jbt.70490

Heba Effat, Aliaa M. Radwan, Marwa Sharaky, Hamed A. Abosharaf

{"title":"Rutin Alleviates Breast Cancer Resistance to Tamoxifen By Downregulating ABC Transporters, Inducing ROS Generation and Resetting Redox Status","authors":"Heba Effat, Aliaa M. Radwan, Marwa Sharaky, Hamed A. Abosharaf","doi":"10.1002/jbt.70490","DOIUrl":"https://doi.org/10.1002/jbt.70490","url":null,"abstract":"<div>\u0000 \u0000 <p>Breast cancer is one of the most lethal cancers in women worldwide. Tamoxifen (TAM), a nonsteroidal antiestrogen, is a highly successful treatment for breast cancer. However, developed resistance to TAM can substantially impair chemotherapy efficacy, resulting in poor prognosis and cancer recurrence. Rutin (RUT) is a dietary flavonoid with potent anticancer activities, however its fundamental mechanisms in the treatment of TAM-resistant breast cancer remain obscure. We used cell viability assay, qPCR, flow cytometric analysis combined with immunoblotting and molecular docking studies to assess the effects of RUT on chemoresistance, ATP-binding cassette transporters (ABC), and redox status resetting in TAM resistant breast cancer cells. Our results revealed that the treatment of resistant LCC2 cells with a combination of TAM and RUT effectively inhibited cell growth and proliferation. RUT reverses the resistance of LCC2 cells to TAM by downregulating the expression of <i>ABCB1, ABCC1, ABCC2</i>, and <i>ABCG2</i> multidrug resistance genes and inducing the production of reactive oxygen species. Further, western blot results exhibited that TAM combined with RUT reduced the expression levels of Nrf2, GCL, GLS, and SLCA711 proteins in LCC2 cells, which was corroborated by molecular docking. TAM and RUT combination may provide a promising treatment pathway to conquer TAM resistance and hence extend the life expectancy in breast cancer patients.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012414","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

Brucine Inhibits Gastric Cancer via Activation of Ferroptosis Through Regulating the NF-κB Signaling Pathway 马钱子碱通过调节NF-κB信号通路激活铁下垂抑制胃癌

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-08 DOI: 10.1002/jbt.70479

Bo Zhang, Changwei Yu, Sisi Zhang, Min Zhang

{"title":"Brucine Inhibits Gastric Cancer via Activation of Ferroptosis Through Regulating the NF-κB Signaling Pathway","authors":"Bo Zhang, Changwei Yu, Sisi Zhang, Min Zhang","doi":"10.1002/jbt.70479","DOIUrl":"https://doi.org/10.1002/jbt.70479","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastric cancer (GC) is the third leading cause of cancer mortality globally, often presenting with insidious symptoms that lead to late-stage diagnoses, underscoring the critical need for innovative diagnostic and therapeutic strategies. One such avenue is the exploration of ferroptosis, a regulated form of cell death implicated in various pathological conditions and malignancies. In this study, we demonstrate that brucine, an alkaloid derived from <i>Strychnos nux-vomica</i>, exerts significant antitumor effects on GC cells both in vitro and in vivo. Brucine treatment dose-dependently inhibits proliferation, migration, and invasion, and induces apoptosis and ferroptosis. Specifically, brucine treatment diminished cell viability, DNA synthesis, and colony formation, increased the expression of proapoptotic markers such as Bax, and decreased the expression of antiapoptotic Bcl-2. Additionally, brucine inhibited migration and invasion by modulating epithelial-mesenchymal transition markers. In ferroptosis assays, brucine potentiated the effects of the ferroptosis inducer Erastin, elevating levels of intracellular iron, malondialdehyde, and reactive oxygen species, while reducing glutathione levels. In vivo experiments showed that brucine markedly reduced tumor growth and modified the expression of key biomarkers in a xenograft model. Furthermore, our findings suggest that brucine's effects on cancer cell behavior and ferroptosis are associated with suppression of the NF-κB signaling pathway, suggesting an indirect modulation of this pathway. In conclusion, this study elucidates the comprehensive antitumor properties of brucine against GC, highlighting its ability to inhibit cellular proliferation, migration, and invasion, while promoting apoptotic and ferroptotic pathways. These effects are potentially mediated through indirect modulation of the NF-κB signaling pathway.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012859","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

Eugenol Promotes Immune Function and Survival Rate in Cecal Ligation Puncture Induced Sepsis Rat Model by Targeting A2A Receptor to Regulate Oxidative Stress Pathway 丁香酚通过A2A受体调控氧化应激通路，提高盲肠结扎穿刺脓毒症大鼠模型的免疫功能和存活率

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-08 DOI: 10.1002/jbt.70481

Alka, Alok Shiomurti Tripathi, Rahul Kumar Maurya, Mohammad Yasir, Magdi E. A. Zaki, Saurabh Srivastava, Safia Obaidur Rab, Tabinda Hasan, Hailah M. Almohaimeed, Ahmed M. Basri, Ammar A. Basabrain, Amany I. Almars, Deepak Mishra, Lucy Mohapatra, Prabhjot Singh, Vipin Kumar Mishra

{"title":"Eugenol Promotes Immune Function and Survival Rate in Cecal Ligation Puncture Induced Sepsis Rat Model by Targeting A2A Receptor to Regulate Oxidative Stress Pathway","authors":"Alka, Alok Shiomurti Tripathi, Rahul Kumar Maurya, Mohammad Yasir, Magdi E. A. Zaki, Saurabh Srivastava, Safia Obaidur Rab, Tabinda Hasan, Hailah M. Almohaimeed, Ahmed M. Basri, Ammar A. Basabrain, Amany I. Almars, Deepak Mishra, Lucy Mohapatra, Prabhjot Singh, Vipin Kumar Mishra","doi":"10.1002/jbt.70481","DOIUrl":"https://doi.org/10.1002/jbt.70481","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates the potential protective effects of eugenol on cecal ligation puncture (CLP) induced sepsis rat model. CLP was used to induce sepsis in rats and then treated with eugenol at doses of 25 and 50 mg/kg, i.p. for a duration of 7 days. Effects of eugenol was observed on survival rates, markers of oxidative stress, inflammatory cells, and markers in rats. Further network pharmacology study was performed to assess the possible targets for eugenol in the management of sepsis. An interaction study of selected proteins, that is, ADORA2A and HDAC8, with eugenol was observed with a docking study. The eugenol-treated group showed an improvement in the survival rate in the sepsis group of rats. Treatment with eugenol ameliorates oxidative stress, inflammatory mediators, and cells in sepsis rats. Histopathological changes (spleen and lung tissue) were observed to be ameliorates in group of rats treated with eugenol versus the sepsis group. Network pharmacology suggest the 14 common target of interaction between eugenol and sepsis, which was further observed for immunomodulation molecular pathway of sepsis with STRING pathway and gene ontology study. Docking study shows binding strength of ADORA2A-eugenol and HDAC8-eugenol complex was observed to be −6.5 and −5.6 kcal/mol, respectively. Data of investigation concludes that eugenol enhances survival rate in sepsis in rats by reducing inflammation and oxidative stress, as it promotes the immune cell function and neutrophil trapping to xenobiotics and is digested by enhancing oxidative stress in immune cells.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011954","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

Sevoflurane Attenuates Acute Lung Injury Following Intestinal Ischemia-Reperfusion via Targeting NLRP3 Inflammasome 七氟醚通过靶向NLRP3炎性体减轻肠缺血再灌注后的急性肺损伤

IF 2.8 3区医学

Journal of Biochemical and Molecular Toxicology Pub Date : 2025-09-08 DOI: 10.1002/jbt.70491

Xin Liu, Shan Jiang, Yinghui Wu, Liang Zhong, Xiaohua Zeng, Shixiang Fu

{"title":"Sevoflurane Attenuates Acute Lung Injury Following Intestinal Ischemia-Reperfusion via Targeting NLRP3 Inflammasome","authors":"Xin Liu, Shan Jiang, Yinghui Wu, Liang Zhong, Xiaohua Zeng, Shixiang Fu","doi":"10.1002/jbt.70491","DOIUrl":"https://doi.org/10.1002/jbt.70491","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute lung injury (ALI) is a major contributor to the high morbidity and mortality associated with intestinal ischemia-reperfusion (II/R). Despite its severity, current clinical management of ALI remains limited to supportive care without addressing the cause of the disease, underscoring the urgent need to investigate the underlying mechanism and develop targeted therapies. In this study, we employed both in vitro and in vivo models to explore ALI in the setting of II/R. Our findings demonstrated that II/R-induced systemic inflammation activates nucleotide-binding oligomerization (NOD)-like receptor family pyrin domain containing 3 (NLRP3) inflammasome in lung endothelium, leading to the release of pro-inflammatory cytokine interleukin-1β (IL-1β) and pyroptotic cell death. This cascade ultimately damages lung vasculature and exacerbates ALI. Importantly, we revealed that sevoflurane, a commonly used anesthetic, can inhibit NLRP3 inflammation under II/R condition and provide protection against ALI. Mechanistically, sevoflurane downregulates NLRP3 expression via deactivating inhibitor of nuclear factor kappa-B kinase (IKK)/nuclear factor kappa-B kinase (NF-κB) signaling pathway, and simultaneously inhibits NLRP3 activation through protein kinase A (PKA)-mediated mechanism. These findings offered novel insights into the pathogenesis of II/R-induced ALI and highlighted the therapeutic potential of sevoflurane. Given sevoflurane's established clinical use, our results could have immediate implications for patient care in II/R situations.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012858","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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