Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Biological Evaluation, Molecular Docking, MD Simulation Study and Synthesis of (Z)-N’-(3-phenoxybenzylidene)-2-(substituted-amino aryl) Acetohydrazid","authors":"Navin B. Patel,&nbsp;Deepti S. Ghaisas,&nbsp;Vatsal M. Patel,&nbsp;Faiyazalam M. Shaiikh,&nbsp;Mohit Agrawal,&nbsp;Mohd Imran,&nbsp;Gildardo Rivera,&nbsp;Hetal I. Soni","doi":"10.1002/jbt.71114","DOIUrl":"10.1002/jbt.71114","url":null,"abstract":"<p>In order to investigate their possible biological activity, a number of new Schiff base compounds based on diaryl ether, specifically 2-(substituted-arylamino)-N′-(3-phenoxybenzylidene) acetohydrazides, were created. IR, ¹H NMR, and ¹³C NMR spectrum studies were used to characterize all substances. A structure–activity link influenced by the kind of substituents on the aryl moiety was suggested by the evaluation of the synthesized derivatives’ in vitro biological activity, which showed significant activity patterns among substituted analogs. Molecular docking studies demonstrated favorable binding interactions of the most active compounds with the selected biological target, supported by key hydrogen bonding and hydrophobic interactions within the active site. Furthermore, molecular dynamics simulations confirmed the stability of the ligand–protein complexes, indicating their potential as promising lead molecules. The novelty of this study lies in the design of hybrid diaryl ether–Schiff base derivatives and their combined experimental and computational evaluation, providing insights into their biological potential and guiding future optimization.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13600652/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149030498","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":"Eupatilin Alleviates Acute Myocardial Ischemia-Reperfusion Injury in Rats via the Akt/GSK-3β Pathway by Targeting COXs","authors":"Min Guo,&nbsp;Qianqian Li,&nbsp;Lili Ji","doi":"10.1002/jbt.71111","DOIUrl":"10.1002/jbt.71111","url":null,"abstract":"<p>Eupatilin confers cardioprotection against myocardial ischemia-reperfusion injury (MIRI). Cyclooxygenases (COXs) serve as key rate-limiting enzymes for prostaglandin biosynthesis. This study investigated the effects of eupatilin on COXs.</p><p>H9c2 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R) were treated with graded doses of eupatilin, with aspirin serving as the positive control. Cellular reactive oxygen species (ROS), cell viability, and COX1/COX2 protein expression were subsequently detected. In-vivo acute MIRI was established in rats by 30-min ligation of the left anterior descending coronary artery followed by reperfusion. MIRI-modeled rats received eupatilin or aspirin treatment. Cardiac function was evaluated by echocardiography. Levels of prostaglandin E2 (PGE2), thromboxane A2 (TXA2), and cardiac troponin I (cTnI) were quantified by ELISA. Myocardial infarct size was assessed by TTC staining, and collagen deposition was determined by Masson staining. Immunohistochemistry was performed to detect myocardial COX1 and COX2 expression.</p><p>In OGD/R-injured H9c2 cells, eupatilin dose-dependently restored cell viability and suppressed cellular ROS overproduction. It suppressed OGD/R-induced upregulation of COX1 and COX2 and increased phosphorylation of Akt1 (S473) and GSK-3β (S9). Molecular docking revealed favorable binding affinity between eupatilin and COXs. In MIRI-model rats, deteriorated cardiac function was accompanied by increased PGE2, TXA2 and cTnI, as well as aggravated myocardial infarction and collagen deposition. Eupatilin administration alleviated myocardial injury by counteracting these pathological alterations. Moreover, eupatilin suppressed MIRI-driven COX1/COX2 overexpression and enhanced Akt1-GSK-3β phosphorylation.</p><p>Eupatilin alleviate acute MIRI via COXs inhibition and activation of the Akt/GSK-3β pathway, providing a theoretical basis for its application against MIRI.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13595355/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149016873","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":"Estradiol Promotes Tumor Progression in ERα-Low Endometrial Cancer via the GPER/SphK1 Pathway","authors":"Xiuwen Wang,&nbsp;Haofei Sun,&nbsp;Xin Wen,&nbsp;Weiwei Xin,&nbsp;Zhandong Hu,&nbsp;Zhongwei Zhao,&nbsp;Lizhi Zhang","doi":"10.1002/jbt.71112","DOIUrl":"10.1002/jbt.71112","url":null,"abstract":"<p>Endometrial cancer (EC) is the most common gynecological malignancy in postmenopausal women. Patients with low estrogen receptor alpha (ERα) expression frequently develop aggressive pathological subtypes and have poor prognosis. The role of estradiol (E2) in ERα-low EC remains poorly understood. This study investigated the tumor-promoting effects of E2 using clinical data, in vitro functional assays, and a mouse xenograft model. We found that serum E2 levels were elevated in ERα-low patients, of whom 67.7% showed high tumor expression of G protein-coupled estrogen receptor (GPER). High GPER expression correlated with increased E2 levels, enhanced sphingosine kinase 1 (SphK1) activity, and higher Ki67 proliferation index. In vitro, E2 promoted proliferation, migration, and invasion of HEC-1A cells (low ERα, high GPER). These effects were suppressed by pharmacological inhibition or siRNA knockdown of GPER or SphK1. Mechanistically, E2 activated the ERK1/2 pathway via the GPER/SphK1 axis, leading to upregulation of Cyclin D1, Cyclin E1, and MMP-9. In vivo, E2 stimulated xenograft tumor growth, an effect mitigated by inhibitors of GPER, SphK1, and ERK. Our findings demonstrate that E2 drives progression of ERα-low endometrial cancer through the GPER/SphK1 signaling pathway, revealing potential therapeutic targets for this high-risk subgroup.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13590039/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149012397","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":"Novel Pyrazole-4-Carbaldehyde Derivatives Having Potent COX-2 Inhibition and Anti-Tubercular Activity: Microwave-Assisted Green Synthesis and Molecular Docking","authors":"Megha Kokane,&nbsp;Dnyandev Bhosale,&nbsp;Dattatraya Raut,&nbsp;Pushpa Hadimani,&nbsp;Ashwini Narale,&nbsp;Prafulla Choudhari,&nbsp;Anjana Lawand","doi":"10.1002/jbt.71113","DOIUrl":"https://doi.org/10.1002/jbt.71113","url":null,"abstract":"<p>A series of 1-(4-Chorophenyl)-3Aryl-1-<i>H</i>-pyrazole-4-carbaldehyde derivatives were synthesized under the microwave irradiation (MW) technique. IR, ¹H-NMR, ¹³C-NMR, and mass spectroscopic techniques were used to confirm the structure of the synthesized compounds. The newly synthesized Pyrazole aldehydes were evaluated for their in vitro anti-inflammatory and anti-tubercular activity. Among them, the compounds <b>4c</b> and <b>4e</b> exhibited significant reduction of LPS-induced COX-2 protein levels across all tested concentrations. Whereas compounds <b>4f</b> and <b>4j</b> exhibited sensitivity to tuberculosis at the lowest concentration of 6.25 µg/mL, which was comparable to that of the standard drug pyrazinamide. Molecular docking against the Crystal structure of diclofenac bound to the cyclooxygenase active site of COX-2 (PDB ID: 5KIR) also supports the experimental results. The molecular docking studies have demonstrated their better-fit potential as anti-inflammatory agents.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 10","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71113","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148981473","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 NHE1 Overcomes Temozolomide-Resistance in Glioblastoma via ROS-AKT/ERK Axis-Mediated Autophagy Suppression","authors":"Dan Li,&nbsp;Yuhui Li,&nbsp;Xuan Zheng,&nbsp;Zhuo Wang,&nbsp;Yang Wang,&nbsp;Jun Zhang,&nbsp;Jianxiong Guo,&nbsp;Lei Wang,&nbsp;Jingwu Li,&nbsp;Yongliang Liu,&nbsp;Yufeng Li","doi":"10.1002/jbt.71110","DOIUrl":"10.1002/jbt.71110","url":null,"abstract":"<p>Glioblastoma (GBM) is the most aggressive primary brain tumor in adults, with temozolomide (TMZ) resistance being a major barrier to improved clinical outcomes. Dysregulated autophagy is closely associated with TMZ resistance in GBM, but the role of sodium/hydrogen exchanger 1 (NHE1)—a key regulator of intracellular pH homeostasis—in this process remains uncharacterized. We established a TMZ-resistant GBM cell line (U251TR) and observed that U251TR cells displayed higher autophagic activity, increased reactive oxygen species (ROS) levels, and reduced apoptotic rates compared to parental U251 cells. Treatment with the NHE1-specific inhibitor HOE-642 dose-dependently suppressed cell viability, inhibited NHE1 activity, reduced intracellular ROS production, and promoted apoptosis in U251TR cells, with a positive feedback loop identified between NHE1 and ROS. Mechanistically, HOE-642 blocked autophagic initiation and flux primarily via the ROS-AKT/ERK signaling axis, in which reduced ROS downregulated p-AKT and p-ERK1/2, where ERK exerted pro-autophagic effects and AKT exerted anti-autophagic effects. In vivo, combined HOE-642 and TMZ treatment significantly reduced xenograft tumor volume and weight, inhibited autophagy, and activated apoptosis compared to TMZ monotherapy, without causing evident systemic toxicity. Our findings identify a novel NHE1-ROS-AKT/ERK-autophagy regulatory axis in TMZ-resistant GBM, validating NHE1 as a potential therapeutic target to enhance TMZ sensitivity by disrupting the autophagy-apoptosis balance, and providing a new strategy for GBM treatment.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575469/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968316","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":"Exploring the Differential Impact of Melatonin Timing Administration (Day vs. Night) on Mitigating Cerebellar Damage Caused by Monosodium Glutamate in Rats","authors":"Alaa Gamal Ahmad,&nbsp;Noha M. Abd El-Fadeal,&nbsp;Horeya Erfan Korayem Arafat,&nbsp;Dalia Ibrahim Ahmed,&nbsp;Rasha Atta","doi":"10.1002/jbt.71108","DOIUrl":"10.1002/jbt.71108","url":null,"abstract":"<p>In tune with the light/dark cycle of the environment, melatonin is secreted on a circadian rhythm. After the lights go out, circulating melatonin levels gradually rise and peak in the middle of the dark phase. Herein, we studied the possible protective timing of melatonin administration on monosodium glutamate-induced cerebellar ataxia in rat models. Thirty-two adult albino male were randomly categorized into four groups: control group, MSG group (4 g/kg/day), day-time melatonin group (MSG + melatonin, 10 mg/kg/day at 9.00 a.m.), and night-time melatonin group (MSG + melatonin, 10 mg/kg/day at 9.00 p.m.). After 10 days of injections, behavioral assessments and serum melatonin were measured. Then rats were sacrificed, cerebellar immunohistopathology, oxidative stress (GPX, GR, NO, iNOS), gene expression of pro-inflammatory genes (PI3K, TNF-α, IL-6) and antioxidant genes (NRF2/HO-1) were assessed. Administration of MSG significantly caused motor deficits, increased levels of NO, INOS, PI3K, TNF-α, and IL-6 levels (<i>p</i> &lt; 0.05), while significantly decreased GPX, GR, NRF2/HO-1, and serum melatonin level (<i>p</i> &lt; 0.05). Histological analysis revealed that MSG exerted degenerative effects, including the presence of pyknotic Purkinje cells, with strong positive reactions for COX2. However, melatonin administration improved these parameters in both treated groups with the superiority of the night melatonin in improving motor behaviors, histological parameters, decreasing COX2 levels, INOS, PI3K, and increasing the expression of NRF2 levels, and increasing the serum melatonin levels. Night-time melatonin administration was more effective in protection against motor incoordination and cerebellar damage than day-melatonin administration.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13575435/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148968236","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":"Rhapontigenin Alleviates Sepsis-Associated Acute Kidney Injury and Is Accompanied by Modulation of Ferroptosis, Inflammation, and NF-κB Signaling","authors":"Jing Kuang,&nbsp;Xiaoyun Zhu,&nbsp;Jun Fang,&nbsp;Shuli Hu,&nbsp;Wei Dai,&nbsp;Xuepeng Fan","doi":"10.1002/jbt.71096","DOIUrl":"10.1002/jbt.71096","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Sepsis-associated acute kidney injury (SA-AKI) is a common complication in critically ill patients and is associated with high mortality. Evidence suggests that ferroptosis-related lipid peroxidation and inflammatory responses contribute to renal injury. The potential effects of rhapontigenin (Rha), a natural compound with antioxidant and anti-inflammatory properties, have not been directly examined in SA-AKI. HK-2 cells were pretreated with Rha for 3 h, followed by stimulation with 10 ng/mL LPS for 24 h to establish an in vitro sepsis-associated injury model. Cell viability was assessed by CCK-8. Ferroptosis-related changes were evaluated by measuring GPX4 and xCT expression, intracellular Fe2+, ROS, MDA, and BODIPY-C11-detected lipid ROS. Erastin and ferrostatin-1 (Fer-1) were used for pharmacological intervention. Inflammatory cytokines (IL-1β, IL-6, and TNF-α) were quantified by ELISA. NF-κB activation was assessed by the p-NF-κB/NF-κB and p-IκBα/IκBα ratios and p65 nuclear localization, with RANKL used as an NF-κB activator. In vivo, male C57BL/6J mice underwent cecal ligation and puncture (CLP) to induce SA-AKI. The effects of Rha on kidney histology, renal injury markers, ferroptosis-related indices, inflammatory cytokines, and NF-κB signaling were evaluated. The IC50 of Rha was not reached within the tested concentration range of 0–80 μM. Rha at 5–40 μM did not significantly affect basal HK-2 cell viability, whereas 80 μM caused a slight decrease. Rha treatment at 20 and 40 μM increased cell viability, decreased intracellular Fe2+, ROS, MDA, and lipid ROS levels, and increased GPX4 and xCT expression in LPS-treated HK-2 cells. Rha also reduced erastin-induced Fe2+ accumulation, while Fer-1 decreased Fe2+ and ROS levels and increased GPX4 and xCT expression in LPS-treated cells. In addition, Rha lowered IL-1β, IL-6, and TNF-α levels and reduced NF-κB phosphorylation and p65 nuclear localization. RANKL partially reversed the effects of Rha on p65 nuclear localization, cell viability, Fe2+ accumulation, ROS production, and inflammatory cytokine levels. In CLP mice, Rha at 25 and 50 mg/kg reduced serum NGAL, KIM-1, Scr, and BUN levels and decreased renal Fe2+, MDA, and inflammatory cytokine levels. The kidney injury score was significantly reduced at 50 mg/kg. Rha alleviated experimental SA-AKI, accompanied by reductions in ferroptosis-related changes, inflammatory responses, and NF-κB activation.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13548073/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900590","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":"Mechanistic Insights Into Cholinergic, Neurotrophic, and Glutamatergic Pathways in Fluoride Neurotoxicity","authors":"Ashiru Dahiru,&nbsp;Ismat Nawaz,&nbsp;Syeda Kiran Riaz,&nbsp;Nazneen Bangash,&nbsp;Muhammad Tayyab,&nbsp;Summaya Sohail Chaudry,&nbsp;Muhammad Jadoon Khan,&nbsp;Qingyu Huang,&nbsp;Syed Ali Musstjab Akber Shah Eqani","doi":"10.1002/jbt.71095","DOIUrl":"10.1002/jbt.71095","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigated the molecular and histopathological mechanism(s) contributing to fluoride induced neurotoxicity in male and female rats, focusing on dysregulation of cholinergic, neurotrophic, glutamatergic pathways and the accompanying structural alterations in the brain tissue. Forty male and female rats were administered sodium fluoride in water at concentrations (ppm) of 0.5 (control), 50 (low), 150 (medium), and 300 (high dose) for 90 days. The mRNA expression levels of cholinergic markers (acetylcholinesterase-<i>AChE</i>, butyrylcholinesterase-<i>BChE</i>), the brain derived neurotrophic factor (<i>BDNF</i>) and the metabotropic glutamate receptor 5 (<i>mGluR5</i>) were quantified using RT-qPCR, and histopathological alterations of different regions of brain was assessed by hematoxylin and eosin (H&amp;E) staining. Chronic NaF exposure resulted dose-dependent neurodegenerative changes in the hippocampal CA1, CA3, and dentate gyrus (DG) regions, characterized by neuronal shrinkage, pyknosis, vacuolization, and spongiosis. The histopathological lesions were more pronounced in male rats than in females. Chronic fluoride exposure also resulted in a dose-dependent decrease of blood AChE (1.09−0.604 mU/mL) and BChE (0.575−0.311 mU/mL) activities in both genders. Furthermore, chronic NaF exposure significantly down-regulated the expression of <i>AChE</i>, <i>BDNF</i>, and <i>mGluR5</i> in fluoride-treated groups compared to controls. These findings demonstrate that prolonged NaF exposure disrupts cholinergic, neurotrophic, and glutamatergic signaling pathways, thereby contributing to neurotoxicity and potential neurodegeneration. Collectively, this mechanistic evidence underlines the importance of public health to monitor environmental fluoride exposure and highlight the potential for therapeutic strategies targeting cholinergic, neurotrophic and glutamatergic pathways to mitigate fluoride-induced neuronal injury.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148900210","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":"Obeticholic Acid and Edaravone Protect Against Cisplatin-Induced Hepatotoxicity Through Modulation of Keap1/Nrf2/ARE, TNF-α/NF-κB, and AKT/GSK-3β Pathways","authors":"Fares E. M. Ali,&nbsp;Adel G. Bakr,&nbsp;Abdel-Gawad S. Shalkami,&nbsp;Ehab A. M. El-Shoura,&nbsp;Lamiaa Khalaf Ahmed,&nbsp;Ali F. Abd-Elsalam,&nbsp;Ahmed A. N. Ahmed,&nbsp;Emad H. M. Hassanein","doi":"10.1002/jbt.71101","DOIUrl":"10.1002/jbt.71101","url":null,"abstract":"<p>Hepatotoxicity is one of the most crucial side effects of chemotherapy administration. Obeticholic acid (OCA) is a semisynthetic bile acid and farnesoid X receptor (FXR) agonist derived from chenodeoxycholic acid, with reported antioxidant and anti-inflammatory effects in liver disorders. This study investigated the hepatoprotective effect of OCA against commonly used chemotherapy cisplatin (CP)-induced hepatotoxicity in rats, as well as the modulatory effects of edaravone (EDA), a potent free radical scavenger, on its effects. Rats were divided into five groups: control (received vehicle), CP (7.5 mg/kg), EDA (30 mg/kg) + CP, OCA (30 mg/kg) + CP, and EDA + OCA + CP. The results of the present study demonstrated that both OCA and EDA significantly mitigated liver damage caused by CP, as evidenced by restoring liver enzymes and histological structure, reestablishment of oxidant/antioxidant status, suppression of inflammation, and attenuation of pro-death signaling. The study highlights the role of key molecular pathways, including Keap1/Nrf2/HO-1,HO-1, TNF-α/NF-κB, and AKT/GSK-3β, in the hepatoprotective mechanisms of OCA. Collectively, these findings suggest that OCA and EDA, particularly in combination, attenuate CP-induced hepatotoxicity and are associated with coordinated modulation of oxidative stress, inflammatory signaling, and AKT/GSK-3β-associated pro-survival/pro-death pathways.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 9","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13539285/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880578","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":"A tsRNA Suppresses Lung Adenocarcinoma Progression Through Targeting Glucose-6-Phosphate Dehydrogenase","authors":"Suo Sha,&nbsp;Meilin Zhang,&nbsp;Qinsong Tao,&nbsp;Yang Liu,&nbsp;Junjun Bao,&nbsp;Ping Guo,&nbsp;Aiting Yan,&nbsp;Cuizhu Wang","doi":"10.1002/jbt.71077","DOIUrl":"10.1002/jbt.71077","url":null,"abstract":"<p>Elucidating the molecular distinctions between invasive and non-invasive forms of lung adenocarcinoma is essential for the development of personalized therapeutic approaches and the optimization of patient outcomes. Transfer RNA-derived small RNAs (tsRNAs) have been recognized as pivotal regulators in oncogenic processes. In this study, we identified a specific tsRNA associated with non-invasive lung adenocarcinoma and demonstrated its suppressive effects on cellular proliferation and metastatic potential. At the molecular level, this tsRNA exerts its regulatory function by targeting and repressing G6PD mRNA, thereby perturbing the equilibrium between NADPH and reactive oxygen species (ROS) production. This discovery positions the identified tsRNA as a promising candidate for therapeutic intervention in non-invasive lung adenocarcinoma. Further investigation into the role of tsRNAs in lung adenocarcinoma is imperative to fully harness their potential in clinical management.</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/PMC13535736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148874307","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}