Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Correction to “YY1-Upregulated MTHFD2 Drives Non-Small Cell Lung Cancer Progression Through the Regulation of Lrrk2”","authors":"","doi":"10.1002/jbt.71107","DOIUrl":"10.1002/jbt.71107","url":null,"abstract":"<p>Z. Wei, J. Liu, X. Luan, and C. Gu, “ YY1-Upregulated MTHFD2 Drives Non-Small Cell Lung Cancer Progression Through the Regulation of LRRK2,” <i>Journal of Biochemical and Molecular Toxicology</i> 39 (2025): e70504, https://doi.org/10.1002/jbt.70504.</p><p>In the above published article, the wrong hospital (The First Affiliated Hospital of Dalian Medical University) was associated with the ethics approval number of 2025395 within text sections 2.2 Human Specimens, 2.6 Subcutaneous Xenograft Models and Immunohistochemistry, and within the Ethics Statement section at the end of the article. The correct hospital is Peking University Shenzhen Hospital.</p><p>We apologize for this error.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13536932/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874312","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":"Medicarpin Mediates the Protective Effect of Cell Pyroptosis Against Sepsis-Induced Liver Injury by NLRP3/GSDMD/Caspase-1 Axis","authors":"Pengfei Chen,&nbsp;Weifeng Jiang","doi":"10.1002/jbt.71098","DOIUrl":"10.1002/jbt.71098","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>The liver is a decisive organ that is damaged by sepsis. Medicarpin (Med) is a principal wing-type final product of 5-deoxyisoflavone sub-branch in <i>M. truncatula</i>, and exerts anti-tumor and anti-inflammatory effects in diverse diseases. This research aimed to elucidate the Med function and the prospective mechanism in sepsis-induced liver injury. After treating THLE-2 cells with diverse Med concentrations (0, 5, 10, 20, 40, 80, 160 μM), Med toxic effect on THLE-2 cells was checked through a Cell Counting Kit-8 (CCK-8) experiment. Based on a sepsis-induced liver injury model using lipopolysaccharide (LPS) and THLE-2 cells, Med function in sepsis-induced liver injury was verified via CCK-8 assay, Western blot, immunofluorescence, and ELISA. Also, Med mechanism in sepsis-induced liver injury was examined via Western blot, CCK-8 assay, and ELISA. Furthermore, Med role in sepsis-induced liver injury in vivo model was elucidated through animal experiments, hematoxylin-eosin staining, ELISA, Western blot, and immunofluorescence. Med possessed no obvious impact on THLE-2 cell viability when Med concentration was lower than 160 μM. Med alleviated repression of LPS-induced THLE-2 cell viability, and also reduced THLE-2 cell pyroptosis induced by LPS. From a mechanistic perspective, our data further illustrated that LPS induced a decrease in THLE-2 cell viability, and Med enhanced cell viability, while this impact was partially reversed after NLRP3 overexpression, indicating that Med partially counteracted the effects of NLRP3 overexpression on cell viability. Meanwhile, in vivo experimental data further demonstrated that Med alleviated liver injury and pyroptosis in sepsis mice, mainly through reduction of ALT and AST levels, a decrease in liver injury score of mice, a reduction in IL-1β and IL-18 levels, as well as a decrease in NLRP3, ASC, cleaved caspase-1, and GSDMD-N protein levels. In conclusion, Med exerted its protective effect on sepsis-induced liver injury through NLRP3/GSDMD/caspase-1-mediated cell pyroptosis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539280/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880586","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":"Nanoplastic Particle Exposure Induces Toxicity and Amplifies Cellular Stress in THP-1 Macrophages: Insights on Molecular Pathways and Circulating Proteome Interaction.","authors":"Balamurali Mahalakshmi, Gobichettipalayam Balasubramaniam Maadurshni, Thittumpuram Manikandan Anjana, Jeganathan Manivannan","doi":"10.1002/jbt.71103","DOIUrl":"10.1002/jbt.71103","url":null,"abstract":"<p><p>The widespread accumulation of polystyrene nanoplastic particles (NPPs) in the environment has raised significant human health concerns, specifically on immune function. However, the underlying molecular mechanisms behind NPP induced immune cell (monocyte/macrophage) toxicity and their relationship with existing pathological conditions remain largely unexplored. The current study explored the interaction of NPPs with serum proteins and composition of protein corona through proteomic analysis (LC-HRMS/MS). Further, we investigated the immunotoxic effects on THP-1 macrophage cells via various cellular and molecular assays, including cytotoxicity, oxidative stress, mitochondrial function, intracellular calcium homeostasis, apoptosis and stress signaling pathway assessment. This study further assessed the amplification potential of NPPs on inflammatory (TNF α and lipopolysaccharide), atherogenic (ox-LDL) and environmental (polycyclic aromatic hydrocarbons (PAH)) stress conditions. The findings demonstrated that NPPs triggered cytotoxicity in a dose dependent manner along with excessive ROS generation, mitochondrial impairment, elevated intracellular calcium levels and apoptosis by altering BAX and BCL2 expression. We also found that NPPs activated stress signaling pathways through modulating HSP27, SAPK/JNK, p38 MAPK and c-Jun phosphorylation. Interestingly, pathway inhibition studies confirmed the involvement of p38 MAPK, ERK and mitochondrial ROS signaling in NPP-associated toxicity. In addition, NPPs exposure augmented inflammatory response, promoted atherogenesis (foam cell formation), amplified PAH induced toxicity. Together, these observations revealed precise adverse outcome pathways (AoP) and stress amplification effects of NPPs on macrophages and consequent toxic effects on the immune system.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":"e71103"},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13531021/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865023","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":"Sclareol Inhibit Cell Growth and Induces Apoptosis via Activation of p53/p21 Signaling Pathways in Human Oral Squamous Cell Carcinoma Cells.","authors":"Anandhi Nallu, Suresh Kathiresan, Theerthu Azhamuthu, Hemavardhani Ramadoss, Nihal Ahamed Abulkalam Asath, Pugazhendhi Ravichandran, Rajeswari Vasu","doi":"10.1002/jbt.71106","DOIUrl":"10.1002/jbt.71106","url":null,"abstract":"<p><p>One of the most common prevalent forms of cancer in the world is oral squamous cell carcinoma (OSCC). In the present study, we explore the chemotherapeutic effect of Sclareol on human oral carcinoma KB cells in scientifically found that cellular and molecular alterations. The human oral carcinoma KB cell and African green monkey kidney normal cell line (Vero) were evaluated for a several types of investigations following they had been various concentrations of Sclareol (5-50 µM) and cisplatin (0-10 µM) for 24 h. Additionally, we exhibited that sclareol induces cytotoxicity effect by MTT assay, Reactive oxidative stress (ROS) was measured by DCFH-DA staining assay, loss of mitochondrial membrane potential (Δψm) was assessed by Rho123 staining method, nuclear condensation, and apoptotic morphological changes was investigated by DAPI and AO/EtBr staining in KB cells. Sclareol promoted oxidative stress via an imbalance in redox status and increased DNA damage in human oral carcinoma KB cells. Besides, Sclareol induces apoptosis by activating dependent p21^waf1/cip1, thereby down-regulating the expression levels of phosphorylation of Rb (ser 780), cyclin D1, and cyclin-E. Furthermore, it is associated with mitochondrial-mediated apoptotic and proapoptotic markers, as evidenced by the downregulated Bcl-2 protein and the upregulation of (Bax, Cytochrome C, Cleaved PARP, Cleaved Caspase and Caspase-9 &-3) induced apoptosis signaling through p53 independent pathways. Therefore, our present study findings suggest that Sclareol could be the productive new chemotherapeutic agent for against oral squamous cell carcinoma.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":"e71106"},"PeriodicalIF":3.6,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548068/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900569","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":"Inhibition of Tropomyosin Receptor Kinase B Signaling Alters Hepatic Mitochondrial Enzyme Activity and Oxidative Stress in Mice With Sucrose-Induced Insulin Resistance","authors":"Akın Bodur,&nbsp;Hüseyin Çınar Zihni,&nbsp;Katip Korkmaz,&nbsp;Solmaz Bodur,&nbsp;Ahmet Alver","doi":"10.1002/jbt.71104","DOIUrl":"10.1002/jbt.71104","url":null,"abstract":"<p>BDNF and its receptor, TrkB, are essential regulators of energy homeostasis in both central and peripheral tissues, including the liver. This study aimed to investigate the effects of ANA-12, a selective TrkB antagonist, on hepatic mitochondrial enzyme activities and biochemical parameters in a mouse model of sucrose-induced insulin resistance. Male C57BL/6J mice were divided into four groups: Control, Sucrose (35% solution), Sucrose+DMSO, and Sucrose+ANA-12 (0.5 mg/kg). Following a 16-week dietary intervention, ANA-12 was administered via intraperitoneal injection during the final 21 days. Hepatic activities of cytochrome c oxidase, superoxide dismutase (SOD), and catalase (CAT), along with malondialdehyde (MDA) levels, were analyzed to evaluate mitochondrial enzyme activity and oxidative stress-related biochemical changes. Chronic sucrose consumption significantly increased body weight, serum insulin levels, HOMA-IR scores, and cholesterol levels. While ANA-12 treatment showed a numerical tendency to attenuate weight gain and HOMA-IR scores, these changes did not reach statistical significance. However, the ANA-12 group exhibited significantly lower serum leptin and ceramide levels compared to the Sucrose+DMSO group. In the liver, sucrose consumption triggered oxidative stress, as evidenced by increased MDA levels. Conversely, TrkB inhibition was associated with increased cytochrome c oxidase activity, altered SOD activity, and reduced hepatic MDA concentrations compared with the Sucrose+DMSO group, suggesting partial modulation of oxidative stress-related biochemical alterations. Furthermore, chronic sucrose consumption was associated with reduced hepatic BDNF levels. Overall, these findings indicate that TrkB inhibition may influence selected hepatic mitochondrial enzyme activities and redox-related markers under sucrose-induced metabolic stress. However, these results should be interpreted cautiously because systemic insulin resistance markers were not significantly improved, and additional control groups are required to clarify ANA-12-specific and vehicle-related effects.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865030","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":"Protective Effects of Luteolin Against Cisplatin-Induced Hepatic and Renal Toxicity: Biochemical and Cellular Evidence","authors":"Özge Temiz,&nbsp;Suna Kizilyildirim,&nbsp;Tuba Ozdemir-Sanci,&nbsp;Emine Terzi,&nbsp;Beyza Ecem Oz-Bedir,&nbsp;Mehmet Akyuz,&nbsp;Hikmet Y. Cogun,&nbsp;Ferit Kargin,&nbsp;Tuba Aydin,&nbsp;Ahmet Cakir","doi":"10.1002/jbt.71100","DOIUrl":"10.1002/jbt.71100","url":null,"abstract":"<p>Cisplatin is a widely used chemotherapeutic agent; however, its clinical utility is frequently limited by dose-dependent adverse effects, particularly hepatotoxicity and nephrotoxicity. Luteolin, a naturally occurring flavonoid abundant in various medicinal plants, exhibits well-documented antioxidant and anticancer activities. This study investigated whether Luteolin isolated from <i>Pistacia terebinthus</i> fruits could attenuate Cisplatin-induced organ toxicity while enhancing its antiproliferative effects. For the in vivo experiments, 48 male Swiss albino mice (9–10 weeks old, 26–30 g) were randomly assigned to eight groups (<i>n</i> = 6/group): control, Cisplatin, Luteolin (25, 50, or 100 mg/kg), and Cisplatin plus Luteolin (25, 50, or 100 mg/kg). Cisplatin (10 mg/kg/day, intraperitoneally) and/or Luteolin (25–100 mg/kg/day, orally) were administered for 14 consecutive days. Serum biochemical parameters, oxidative stress markers, antioxidant enzyme activities, and tissue injury-related biomarkers were evaluated in liver and kidney tissues. Cisplatin administration significantly increased serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), bilirubin, and glucose levels, whereas co-treatment with Luteolin markedly attenuated these alterations in a dose-dependent manner. In addition, Luteolin restored Cisplatin-induced disturbances in oxidative stress and antioxidant defense markers, including malondialdehyde (MDA), 8-hydroxy-2′-deoxyguanosine (8-OHdG), HSP70 levels, superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPx), glutathione reductase (GR), and glutathione S-transferase (GST) activities in liver and kidney tissues. To support the in vivo findings, in vitro antiproliferative assays were performed using Saos-2 osteosarcoma, HTB-9 bladder cancer, A549 lung cancer, and BEAS-2B normal epithelial cell lines. Cells were treated with Luteolin (5–200 µM) alone or in combination with Cisplatin IC50 concentrations for 24–48 h, and cell viability was assessed using the WST-1 assay. Co-treatment with Luteolin significantly enhanced Cisplatin-induced growth inhibition in cancer cells while exerting limited cytotoxicity in normal cells. Luteolin alone also demonstrated concentration-dependent antiproliferative activity. In conclusion, Luteolin exerted marked hepatorenal protective effects and enhanced the antiproliferative activity of Cisplatin in experimental models. These findings suggest that Luteolin may represent a promising adjunctive candidate for reducing Cisplatin-associated toxicity while improving therapeutic responsiveness.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528490/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864991","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":"Fibulin-1 Improves Caerulein-Induced Acute Pancreatitis In Vitro by Inhibiting Ferroptosis","authors":"Xiaowei Mai,&nbsp;ShuLiu He,&nbsp;YangYang Li,&nbsp;Lei Zhang,&nbsp;QiZhong Xu,&nbsp;YinSheng Wen","doi":"10.1002/jbt.71099","DOIUrl":"10.1002/jbt.71099","url":null,"abstract":"<p>Acute pancreatitis is an inflammatory disease of the pancreas that is often accompanied by various complications, which seriously impair patient health. Fibulin-1 (FBLN1) is an extracellular matrix (ECM) protein that plays a crucial role in several cellular processes. Previous quantitative analyses of plasma protein profiles of severe acute pancreatitis patients and healthy volunteers have shown that the expression of FBLN1 is decreased in severe acute pancreatitis patients. However, the regulatory roles of FBLN1 in patients with acute pancreatitis have not been fully investigated. In this study, FBLN1 was found to be expressed at lower levels in acute pancreatitis. Moreover, FBLN1 inhibited Caerulein-triggered inflammatory injury in AR42J cells. It was also found that FBLN1 suppressed Caerulein-triggered ferroptosis in AR42J cells, and that FBLN1 could activate the NRF2/HO-1 pathway. In conclusion, FBLN1 may relieve Caerulein-induced acute pancreatitis in AR42J cells by inhibiting ferroptosis, providing insights on the use of FBLN1 in acute pancreatitis treatment.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865047","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":"Therapeutic Potential of Nanocurcumin in Mitigating Duloxetine-Induced Hepatic Damage: Biochemical and Histopathological Insights","authors":"Hassanali Abedi,&nbsp;Maryam Jalali Jahromi,&nbsp;Zahra Mohammadzade,&nbsp;Bahareh Ebrahimi,&nbsp;Pegah Abdollahzadeh,&nbsp;Arash Hassannezhad,&nbsp;Farhad Sheikhnia,&nbsp;Hossein Kargar Jahromi","doi":"10.1002/jbt.71102","DOIUrl":"10.1002/jbt.71102","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Duloxetine, a serotonin-norepinephrine reuptake inhibitor, commonly prescribed for depression and chronic pain, has been implicated in hepatotoxicity, primarily driven by oxidative stress and inflammatory responses. This has led to growing interest in naturally derived antioxidant compounds as potential protective strategies. The aim of this study was to evaluate the hepatoprotective potential of nanocurcumin against duloxetine-induced liver injury in a controlled animal model. Male Wistar rats were divided into eight experimental groups, control, Solvent, curcumin 200 mg/kg, nanocurcumin 200 mg/kg, duloxetine 60 mg/kg, and treatment groups that simultaneously received duloxetine and nanocurcumin. Biochemical assays measured liver function enzymes (ALT, AST), oxidative stress markers (MDA, TOS), and antioxidant enzymes (SOD, GPx). Proinflammatory cytokine levels, TNF-α were also measured and liver tissue was evaluated histologically. Duloxetine administration significantly increased liver enzymes, oxidative stress markers, and TNF-α levels, along with histopathological evidence of liver injury. Concomitant treatment with nanocurcumin reduced these effects and attenuated these changes, as evidenced by normalization of biochemical indices, enhanced antioxidant defense, suppression of proinflammatory cytokines, and preservation of liver structure. Nanocurcumin exhibits potent hepatoprotective effects against duloxetine-induced liver injury, likely through enhancement of antioxidant capacity and modulation of inflammatory responses. These findings support its potential as an adjunctive therapy to duloxetine to mitigate hepatic side effects.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13527748/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865148","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":"Post-Transcriptional Regulators of Inflammation: The Role of microRNAs in Acne Inversa Pathogenesis","authors":"Emad Bahashwan","doi":"10.1002/jbt.71072","DOIUrl":"10.1002/jbt.71072","url":null,"abstract":"<div>\u0000 \u0000 <p>Acne inversa (AI) or Hidradenitis suppurativa is a chronic, inflammatory disorder characterized by painful nodules, abscesses, and scarring, primarily affecting apocrine gland-rich areas. Despite advances in understanding its clinical features, the molecular mechanisms driving AI remain incompletely defined. Emerging evidence highlights the critical role of microRNAs (miRNAs), small non-coding RNAs that regulate gene expression post-transcriptionally, in modulating inflammatory and immune pathways implicated in AI pathogenesis. Specific miRNAs are dysregulated in AI lesional skin and systemic circulation, influencing cytokine production, immune cell recruitment, and keratinocyte activation. These findings position miRNAs as promising non-invasive biomarkers for early diagnosis and disease monitoring. Furthermore, targeting miRNA expression offers a novel therapeutic strategy to restore immune homeostasis and prevent disease progression. This review synthesizes current knowledge on miRNA involvement in AI, underscoring their potential to revolutionize personalized diagnosis and treatment approaches for this complex inflammatory disease.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865061","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":"Fisetin Attenuates Uterine Leiomyoma in Rats: Potential Crosstalk Between HMGB1, SphK1/S1P, and TGF-β Signaling","authors":"Nashwa Maghraby,&nbsp;Esraa Khalaf,&nbsp;Marwa T. Hussien,&nbsp;Ahmed M. A. Sobh,&nbsp;Nagla T. Elmelegy","doi":"10.1002/jbt.71105","DOIUrl":"10.1002/jbt.71105","url":null,"abstract":"<p>Uterine leiomyomas (UL) represent one of the most prevalent gynecological benign tumors with a considerable global medical and economic burden. Effective therapeutic strategies that preserve the uterus and maintain fertility are still lacking. Fisetin (FIS), a naturally occurring dietary flavonoid, exhibits antitumor, anti-inflammatory, and antifibrotic properties, yet its therapeutic potential in UL remains incompletely defined. This study investigated the therapeutic effects of fisetin on UL and the possible underlying mechanisms. UL was experimentally induced in adult female rats by monosodium glutamate (MSG), and animals were assigned to Control, FIS, UL, and UL + FIS groups. Blood and tissue samples were subjected to hormonal, biochemical, histopathological, and immunohistochemical assessments. Serum estradiol, progesterone, and S1P levels were measured using ELISA, while qPCR quantified the expression of key signaling molecules, including SphK1, TGF-β1, HMGB1, TNF-α, and IL-1β. Immunohistochemistry assessed TGF-β1 and α-SMA expressions, and histopathology (H&amp;E and Masson's Trichrome stains) evaluated tissue architecture and fibrosis. The results showed that fisetin administration significantly reduced the elevated sex hormones, inhibited S1P signaling, and suppressed proinflammatory mediators (HMGB1, TNF-α, IL-1β) and profibrotic mediators (TGF-β1, α-SMA). Histopathological evaluation confirmed decreased fibrotic remodeling and improved tissue architecture. Overall, these results suggest that fisetin's effect may involve coordinated modulation of the S1P/SphK1, TGF-β, and HMGB1 axes, highlighting its potential as a novel uterus-preserving therapeutic agent for UL.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13528568/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148864988","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}