Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Methotrexate Alters Nrf2/HO-1 Protein Expression and Intrinsic Apoptosis-Associated Protein Responses in OVCAR-3 Ovarian Cancer Cells: Differential Modulation by Antioxidant Compounds","authors":"Oya Korkmaz","doi":"10.1002/jbt.71073","DOIUrl":"10.1002/jbt.71073","url":null,"abstract":"<p>Methotrexate (MTX) exerts cytotoxic effects primarily through folate pathway inhibition; however, increasing evidence suggests that MTX-induced oxidative stress and mitochondrial apoptosis significantly contribute to cellular injury. The present study aimed to investigate MTX-induced redox imbalance and intrinsic apoptotic activation in OVCAR-3 ovarian cancer cells and to evaluate whether sodium selenite, fucoidan, caffeic acid, and resveratrol differentially modulate redox and mitochondrial signaling pathways. OVCAR-3 cells were exposed for 24 h to MTX (10 µM) alone or in combination with sodium selenite (SS), fucoidan (FUC), caffeic acid (CA), or resveratrol (RSV). Oxidative stress parameters, including total antioxidant capacity (TAC), total oxidant capacity (TOC), oxidative stress index (OSI), and malondialdehyde (MDA) were measured. Redox signaling proteins (Nrf2 and HO-1) and intrinsic apoptotic markers (Bax, Bcl-2, cytochrome-c, cleaved caspase-9, and cleaved caspase-3) were quantified by ELISA. MTX significantly decreased TAC while increasing TOC, OSI, and MDA levels, indicating marked oxidative imbalance. Concurrently, Nrf2 and HO-1 protein expression levels were significantly reduced. MTX also increased the Bax/Bcl-2 ratio, increased cytochrome-c protein levels, and elevated cleaved caspase-9 and caspase-3 levels, consistent with activation of intrinsic mitochondrial apoptotic signaling. Antioxidant co-treatment partially restored redox balance and attenuated alterations in intrinsic apoptosis-associated protein markers. Among the concentrations examined, resveratrol produced the largest modulatory effect. MTX induces redox-dependent coordinated alterations in intrinsic apoptosis-associated proteins in OVCAR-3 cells. Integrated evaluation of Nrf2 and HO-1 protein expression together with cytochrome-c–caspase signaling provides supportive evidence regarding MTX-induced cellular stress responses. Selected antioxidants partially modulate this pathway, suggesting a regulatory role in redox-associated chemotherapeutic stress.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71073","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720872","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":"Sinapic Acid Attenuates LPS-Induced Acute Kidney Injury in Rats: Changes in Autophagy-Related, Apoptotic, Inflammatory, and Oxidative Stress Markers","authors":"Serdar Doğan,&nbsp;Hamza Malik Okuyan,&nbsp;Ayça Coşkun,&nbsp;Şeyda Öznur Ayçiçek Özen,&nbsp;Mehmet Doğan,&nbsp;İhsan Karaboğa,&nbsp;Sibel Kulaksızoğlu","doi":"10.1002/jbt.71075","DOIUrl":"10.1002/jbt.71075","url":null,"abstract":"<p>Lipopolysaccharide (LPS)-induced acute kidney injury (AKI) is associated with high morbidity and mortality. The molecular mechanisms underlying sepsis-associated renal injury remain incompletely understood. Sinapic acid (SA), a bioactive phenolic compound, exhibits antioxidant, anti-inflammatory, and cytoprotective properties, but its nephroprotective role in LPS-induced AKI has not been clarified. We evaluated the protective effects of SA in an LPS-induced AKI rat model and examined its associations with autophagy-related, apoptotic, inflammatory, and oxidative stress markers. AKI was induced by a single intraperitoneal injection of LPS (5 mg/kg) following 7 days of oral SA pretreatment (40 mg/kg/day). LPS administration caused marked renal tubular injury and significantly increased serum BUN, CREA, and UA levels. SA pretreatment significantly attenuated these alterations. Moreover, LPS increased renal BECN1 immunoreactivity and circulating SQSTM1/p62 levels, indicating alterations in autophagy-related markers, together with increased renal TNF-α and Caspase-3 immunoreactivity. SA pretreatment significantly attenuated the LPS-induced increases in these markers. LPS also increased renal MDA levels and serum total oxidant status. SA pretreatment significantly reduced renal MDA without significantly altering SOD, GPx, or total antioxidant status, indicating attenuation of lipid peroxidation rather than a generalized enhancement of antioxidant defenses. Furthermore, SA attenuated the LPS-induced reductions in serum albumin and total protein and the increase in LDH. Collectively, these findings suggest that SA pretreatment attenuates LPS-induced AKI and that this protective effect is accompanied by changes in autophagy-related markers, reduced renal TNF-α and Caspase-3 immunoreactivity, and decreased renal lipid peroxidation.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71075","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720939","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":"Elucidating the Mechanisms of Trichloroethylene-Induced Kidney Cancer: Network Toxicology, Molecular Docking, and In Vitro Validation","authors":"Weijie Ma,&nbsp;Hui Cai","doi":"10.1002/jbt.71071","DOIUrl":"10.1002/jbt.71071","url":null,"abstract":"<p>Trichloroethylene (TCE), a pervasive environmental contaminant, is epidemiologically linked to kidney, but the precise molecular mechanisms underlying this association remain insufficiently elucidated. To decipher the toxicological network, an integrated approach combining network toxicology, molecular docking, and in vitro validation was employed, resulting in the identification of TP53, ACTB, and CASP3 as pivotal hubs from 599 intersecting targets. Functional enrichment analyses implicated these targets in the dysregulation of cellular proliferation and apoptosis, predominantly mediated by the PI3K-Akt signaling cascade, while clinical correlation analysis revealed that their significant overexpression in tumor tissues was associated with advanced pathological staging, unfavorable prognosis, and heightened infiltration of immunosuppressive cell populations, including Tr1 cells, macrophages, and exhausted T cells. Furthermore, potential binding interactions between TCE and these proteins were predicted by molecular docking and subsequently validated by in vitro experiments, wherein TCE exposure dose-dependently upregulated TP53 and ACTB expression while concomitantly reducing cleaved CASP3 levels. Collectively, this study establishes a mechanistic framework demonstrating that TCE promotes kidney carcinogenesis by directly dysregulating TP53, ACTB, and CASP3, offering critical insights into environ-mental oncogenesis and potential therapeutic interventions.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":""},"PeriodicalIF":3.6,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.71071","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723108","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":"Sevoflurane Alleviates Myocardial Ischemia-Reperfusion Injury via the HMGB1/ACSL4 Pathway to Suppress Ferroptosis.","authors":"Yuliu Mei, Yunfei Cao, Cheng Sheng, Ge Sun, Manhua Zhu","doi":"10.1002/jbt.71062","DOIUrl":"10.1002/jbt.71062","url":null,"abstract":"<p><p>Sevoflurane (sevo) exhibits cardioprotective effects against myocardial ischemia/reperfusion injury (MIRI); however, its precise molecular mechanism of action remains elusive and warrants further in-depth investigation. A rat model of MIRI and a hypoxia/reoxygenation (H/R) model in the H9c2 cardiomyocytes were established separately, followed by sevo treatment. Hematoxylin-eosin staining, Perls staining, transmission electron microscope, FerroOrange staining, and Liperfluo staining were used to assess myocardial pathological damage, iron deposition, and oxidative stress. The contents of malondialdehyde, glutathione, Fe²⁺, and NADP + /NADPH were examined via relevant kits. Western blot, co-immunoprecipitation, and immunofluorescence staining assays were employed to verify the interaction between high mobility group box 1 (HMGB1) and acyl-CoA synthetase long chain family member 4 (ACSL4). In the rat MIRI model, sevo treatment mitigated myocardial tissue damage, attenuated oxidative stress, suppressed Fe²⁺ accumulation, and downregulated the expression of HMGB1 and ACSL4. In the H9c2 cardiomyocyte H/R injury model, sevo treatment enhanced cell viability, reduced intracellular Fe²⁺ levels, and alleviated lipid peroxidation. HMGB1 interacted with ACSL4 to stabilize ACSL4 protein expression. Furthermore, HMGB1 overexpression promoted H/R-induced injury and ferroptosis in cardiomyocytes, whereas sevo abrogated these effects. Sevo alleviates MIRI and H/R injury by suppressing the HMGB1/ACSL4 pathway to mitigate ferroptosis, providing a new theoretical basis for myocardial protection approaches.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e71062"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455096/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700410","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":"Industrial Hydrocarbons Exposure Deteriorates Sperm Integrity and Reproductive Function.","authors":"Madhan Kumar Pichandi, Babujanarthanam Ranganathanan, Doraiah Abilash","doi":"10.1002/jbt.71052","DOIUrl":"10.1002/jbt.71052","url":null,"abstract":"<p><p>Occupational exposure to polycyclic aromatic hydrocarbons (PAHs) or metal fumes in the workplace may be detrimental to male fertility. The present study compared sperm concentration, total motility, strict morphology and oxidative stress and SDF levels between 81 men, controls (n = 17) and workers from plastic industry workers (n = 18), steel EAF process (n = 15), waste incineration plants (n = 16) or aluminium factories smelting in the same plant for all workplaces involved in this cross-sectional research. In all treated groups, the sperm concentration, motility, normal morphology, acrosome integrity and membrane function dropped significantly compared with those in controls (p < 0.001). Elevated ROS, MDA and low SOD and CAT activities confirmed the presence of severe oxidoreductive imbalance, particularly in Aluminium and incineration workers. DNA breaks assayed by SCD and comet showed a clear positive exposure-response relationship with the highest OTM in aluminium workers. Network pharmacologic work showed that 67 shared targets were regulated by PAH exposure and male infertility. The hub gene analysis pointed at EGFR, ESR1, RELA, PTGS2, MMP2 and MMP9 as the core hub genes while KEGG enrichment suggested that the HIF-1 and TNF-related inflammatory pathway, along with the endocrine disruption side of stress activating signalling, was involved. Inflammatory signal activation and endocrine disturbance together seemed to end up with really severe damage to sperm DNA, and it also turned on a bunch of mechanisms through which these chemical carcinogens can exert effect. ROS and MDA were negatively correlated with motility as well as sperm concentration significantly (p < 0.05), whereas antioxidant enzymes showed a positive correlation. These findings show how PAH-related industrial poisoning disrupts important reproductive output through ROS-mediated genetic instability and suggest the relevance of protection measures in high-risk industries.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e71052"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669560","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 Mechanistic Review of Environmental Stressor to Decode Their Effect on Congenital Malformations: A Developmental Toxicity.","authors":"Adarsh Kumar Shukla, Rashmi Mahajan, Anuj Kumar Tyagi, Kamendra Swaroop","doi":"10.1002/jbt.71067","DOIUrl":"10.1002/jbt.71067","url":null,"abstract":"<p><p>Environmental toxicants (ENVOTOX) have emerged as critical risk factors for congenital malformations (CMFs) in the modern industrial era. Although epidemiological evidence underscores their adverse impact on pregnancy outcomes, the underlying molecular mechanisms remain insufficiently defined. This review consolidates current insights into exposome toxicity profiling, developmental pathway disruptions, and molecular mapping to identify potential biomarkers and mechanistic links between ENVOTOX and CMFs. Protein-protein interaction (PPI) network analysis identified 35 CMF-associated proteins, with ten fibroblast growth factors (FGFs: FGF4, FGF5, FGF8, FGF9, FGF10, FGF16, FGF17, FGF18, FGF20, and FGF22) prioritized as hub nodes. Molecular docking analysis showed high binding affinity of FGF9 and FGF4 toward dioxin-associated toxicants, with dibenzo-p-dioxin (DBPDO) exhibiting the strongest interaction (binding energy: -7.2 kcal/mol), followed by polychlorinated dibenzofurans (PCDBFs) (-6.7 kcal/mol) with FGF9. Notably, FGF9 exhibited mutagenic binding potential at ASN146, mediated through π-donor hydrogen bonding with DBPDO. Comparative toxicity data further highlighted the acute risks, as DBPDO demonstrated a lower LD₅₀ (2.26 mol/kg) relative to PCDBFs (4.134 mol/kg). Collectively, this review emphasizes the central role of FGFs in mediating ENVOTOX-induced teratogenicity and offers molecular-level perspectives to guide biomarker discovery and intervention strategies for mitigating CMF risk.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e71067"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13455100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701487","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":"Dexpanthenol Attenuates Methotrexate-Induced Nephrotoxicity Through Modulation of NF-κB-Mediated Inflammation and SIRT1/PGC-1α-NRF2/HO-1-Associated Oxidative Stress Pathways.","authors":"Atila Altuntas, Halil Asci, Esma Selcuk, Huzeyfe Karaosman, Osman Aydin, Ilter Ilhan, Sefa Alperen Ozturk, Ozlem Ozmen","doi":"10.1002/jbt.71055","DOIUrl":"10.1002/jbt.71055","url":null,"abstract":"<p><p>Methotrexate (MTX)-induced nephrotoxicity remains a clinically relevant limitation associated with oxidative stress, inflammation, and apoptosis. Dexpanthenol (DEX), a pantothenic acid derivative, has demonstrated cytoprotective properties; however, its effects on MTX-induced renal injury and related molecular pathways are not fully elucidated. This study investigated the potential renoprotective effects of DEX with a focus on inflammation- and redox-associated signaling. Thirty-two male Wistar rats were allocated into four groups: Control, MTX, MTX + DEX, and DEX. Renal injury was assessed by histopathology, immunohistochemical analysis of caspase-3, NF-κB, and TNF-α, biochemical parameters (urea and creatinine), and RT-qPCR analysis of SIRT1, PGC-1α, NRF2, and HO-1 gene expression. MTX administration resulted in marked renal damage characterized by tubular degeneration, hyperemia, and inflammatory infiltration, accompanied by increased caspase-3, NF-κB, and TNF-α expression (p < 0.001). MTX also significantly suppressed SIRT1, PGC-1α, NRF2, and HO-1 gene expression (p < 0.001). DEX co-treatment attenuated histopathological injury and significantly reduced pro-inflammatory and apoptotic markers while restoring SIRT1, PGC-1α, and HO-1 expression (p < 0.01-0.001), with a non-significant upward trend in NRF2 levels. Biochemically, DEX reduced MTX-induced urea and creatinine elevation. DEX confers significant protection against MTX-induced renal injury, likely through modulation of inflammatory and oxidative stress-related regulatory pathways and attenuation of apoptosis. These findings support the potential of DEX as a pharmacological candidate for mitigating drug-induced nephrotoxicity; however, further studies at the protein and functional levels are warranted.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e71055"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432788/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148669446","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":"miR-766-5p Attenuates Cigarette Smoke-Induced COPD by Targeting MAPK1.","authors":"Chang'an Lv, Jin Xu, Xiaojuan Hu, Zaiyuan Wang, Zhongxia Zhou, Tianxi Chen, Xudong Zhao, Yang Yang, Wei Ding, Xiaoqiao Chen","doi":"10.1002/jbt.71043","DOIUrl":"10.1002/jbt.71043","url":null,"abstract":"<p><p>Chronic obstructive pulmonary disease (COPD) represents a significant health burden in older individuals, and early diagnosis remains a challenge. miR-766-5p is dysregulated in COPD. However, its specific role and underlying mechanisms remain unclear. Exploring the diagnostic value of miR-766-5p in COPD and its protective mechanism through targeting MAPK1 holds significant clinical importance for the identification of novel biomarkers and therapeutic targets. Serum samples were obtained from elderly COPD patients and healthy controls to measure miR-766-5p expression and analyze its clinical significance. In vitro, a cigarette smoke extract (CSE)-induced injury model was established using BEAS-2B cells. Transfection was employed to alter the expression of miR-766-5p and MAPK1, followed by assessments of cell viability, inflammatory responses, oxidative stress, and epithelial-mesenchymal transition (EMT). The direct targeting relationship was confirmed by a dual-luciferase reporter assay. Serum miR-766-5p expression was significantly downregulated in COPD patients compared to healthy controls. Its level showed a positive correlation with pulmonary function and demonstrated diagnostic value for COPD. In cellular experiments, overexpression of miR-766-5p alleviated CSE-induced reductions in cell viability, the release of inflammatory factors (IL-6, IL-1β, TGF-β1), oxidative stress (increased MDA and decreased SOD), and EMT. Mechanistically, MAPK1 was identified as a direct target of miR-766-5p. Furthermore, overexpression of MAPK1 reversed the protective effects of miR-766-5p against CSE-induced cellular injury. miR-766-5p is markedly reduced in COPD and holds potential as a diagnostic biomarker. It exerts a protective role against airway epithelial cell injury by targeting and inhibiting MAPK1.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e71043"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443494/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678731","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":"ATF4/SCO2 Inhibits Ferroptosis in Lung Cancer Through Activating the MAPK Signaling Pathway.","authors":"Liang Yu, Sheng Zhang, Jinxi He, Bo Ma, Xuyang Song, Rui Qiu, Bo Yu","doi":"10.1002/jbt.71054","DOIUrl":"10.1002/jbt.71054","url":null,"abstract":"<p><p>Ferroptosis is a specific cell death form resulting from the iron-dependent lipid peroxidation, exhibiting an essential role in cancer progression. The purpose of this study was to explore the underlying mechanism of ferroptosis in lung cancer. The mRNA and protein expression levels were examined via real-time quantitative PCR and Western blotting. Cell malignant behaviors were assessed using cell counting kit-8 (CCK-8) assay, transwell assay, and flow cytometry. Ferroptosis was determined using the indicators lipid reactive oxygen species (ROS), glutathione (GSH), and Fe²⁺. Dual-luciferase reporter assay and chromatin immunoprecipitation assay were performed for binding analysis between activating transcription factor 4 (ATF4) and synthesis of cytochrome c oxidase 2 (SCO2). Associated proteins in mitogen-activated protein kinases (MAPK) signaling pathway were measured by Western blotting. A mouse model was established by implanting lung cancer cells for in vivo research. Lung cancer samples and cells exhibited high expression of SCO2. SCO2 downregulation restrained lung cancer cell growth by inducing ferroptosis. ATF4 was an up-regulated gene in lung cancer, and it elevated SCO2 expression by binding to the promoter of SCO2. ATF4 knockdown repressed cell proliferation and migration while facilitating apoptosis and ferroptosis by down-regulating SCO2. Inhibition of ATF4/SCO2 inactivated the MAPK signaling pathway. ATF4-mediated SCO2 promoted lung tumorigenesis in vivo. This study manifested that ATF4 controlled SCO2 to suppress ferroptosis by activating the MAPK pathway, thus contributing to lung cancer development.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e71054"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443488/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148678809","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":"Phenylsulfonylethyl-Substituted Benzimidazolium Salts: Synthesis, Characterization, Crystal Structure, Molecular Docking, and Inhibitory Properties Against Various Enzymes.","authors":"Yetkin Gök, Ali Kazancı, Yeliz Demir, Zaroon Sajid, Merve İzmirli, Muhammad Haroon, Muhittin Aygün, Aydın Aktaş, İlhami Gülçin","doi":"10.1002/jbt.70893","DOIUrl":"10.1002/jbt.70893","url":null,"abstract":"<p><p>N-heterocyclic carbenes (NHCs) are chemical structures called heterocyclic structures that contain one or more nitrogen atoms. N-heterocyclic compounds are the basic building blocks of many drugs and biologically active molecules. One of these compounds is benzimidazolium salts. Herein, we present the synthesis of a series of phenylsulfonylethyl-substituted benzimidazolium salts. These compounds were characterized using NMR (¹H- and ¹³C-) and FTIR spectroscopic techniques. Compound 1b exhibits a U-shaped benzimidazolium cation paired with a chloride anion. A hierarchical supramolecular architecture arises from C-H⋯Cl chains, C-H⋯π layers, and π⋯π stacking, demonstrating cooperative non-covalent stabilization of the crystal structure. The synthesized benzimidazolium derivatives exhibited notable inhibitory effect against human carbonic anhydrases (hCA I, hCA II)and acetylcholinesterase (AChE), with several compounds showing markedly lower K_i values than the clinical standards. Molecular docking of the NHCs with different receptors showed excellent binding capability with the active site of the target receptors. Moreover, the physicochemical and ADME analysis of the compounds were performed with SwissADME software. Overall examined compounds were found with very good oral bioavailability determined by Lipinski and Verber's rule. The compounds showed Pgp susceptibility with reasonable blood brain barrier permeability.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 8","pages":"e70893"},"PeriodicalIF":3.6,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591711","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}