Journal of Biochemical and Molecular Toxicology最新文献

{"title":"SP1-Induced GLS2 Promotes Hypoxia/Reoxygenation-Induced AC16 Cell Injury by Regulating Ferroptosis Via an AMPK/mTOR Signaling Pathway","authors":"Tao Guo,&nbsp;Weiguo Chen,&nbsp;Xiaochun Lei,&nbsp;Penghui He,&nbsp;Xihui Wang,&nbsp;Xia Chen","doi":"10.1002/jbt.70768","DOIUrl":"10.1002/jbt.70768","url":null,"abstract":"<div>\u0000 \u0000 <p>Myocardial ischemia-reperfusion injury (MIRI) is featured by post-ischemic cardiomyocyte death and reperfusion myocardial damage, which is an unresolved fatal complication in acute myocardial infarction (AMI) treatment. Recent literature has indicated that glutaminase 2 (GLS2) is involved in promoting the ferroptosis of cardiomyocytes, but whether it plays a role in MIRI is still unknown. This research aims to explore the role and mechanism of GLS2 in the development of MIRI. Cell viability and apoptosis were analyzed using 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) and flow cytometry. Bcl-2 related X protein (Bax), Cleaved-caspase-3, Specificity protein 1 (SP1), Glutathione Peroxidase 4 (GPX4), GLS2, p-AMPK, AMPK, p-mTOR, and mTOR protein abundances were determined using Western blot. Interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) levels were analyzed using ELISA. The Fe²⁺ level in AC16 cells was assessed using the Iron assay kit. Glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) products were examined using special assay kits. After JASPAR prediction, the binding between SP1 and GLS2 promoter was verified using Chromatin immunoprecipitation (ChIP) and dual-luciferase reporter assays. The effect of GLS2 on myocardial injury was detected using a mouse MI model. Ischemia/Reperfusion treatment repressed AC16 cell proliferation and induced cell apoptosis, inflammatory response, and ferroptosis. Moreover, GLS2 knockdown relieved hypoxia/reoxygenation (H/R)-triggered AC16 cell injury and ferroptosis. In the mechanism, SP1 was a transcription factor of GLS2 and upregulated the transcription of GLS2 via binding to its promoter region. Silencing of SP1 activated the AMPK/mTOR pathway by inhibiting GLS2. Meanwhile, AMPK inhibitor Dorsomorphin overturned the protective effect of GLS2 downregulation on myocardial cells. GLS2 silencing repressed myocardial damage <i>in vivo</i>. SP1-activated GLS2 could aggravate H/R-induced cardiomyocyte injury and ferroptosis by inactivating the AMPK/mTOR pathway, providing a promising therapeutic target for MIRI treatment in the future.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444003","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":"Protective Effects of Gallic Acid in LPS-Induced Lung Injury via Modulation of Oxidative Stress: AKT1/NRF2 and IL-10 Signaling","authors":"Onur Unal,&nbsp;Halil Asci,&nbsp;Esma Selcuk,&nbsp;Adem Milletsever,&nbsp;Muhammet Yusuf Tepebasi,&nbsp;Yaren Asci,&nbsp;Abdurrahman Gulal,&nbsp;Ozlem Ozmen","doi":"10.1002/jbt.70776","DOIUrl":"10.1002/jbt.70776","url":null,"abstract":"<p>This study investigated the protective effects of Gallic acid (GA) on Lipopolysaccharide (LPS)-induced acute lung injury (ALI), focusing on inflammatory cytokines and barrier integrity markers through histopathological, immunohistochemical, and genetic evaluations. Thirty-two adult male Wistar Albino rats were divided into Control, LPS, LPS + GA, and GA groups. LPS (5 mg/kg, intraperitoneal) induced ALI and GA (100 mg/kg, intraperitoneal) was administered to the treatment group. LPS caused hemorrhage, interalveolar septa thickening, inflammatory cell infiltration, and hyperemia. Interleukin (IL)-1β, IL-6, IL-17A, and glycogen synthase kinase-3 beta (GSK3β) increased, while IL-10, aquaporin 2 (AQP2), zonula occludens 1 (ZO-1), claudin 5 (Clau-5), serine/threonine kinase 1 (AKT1), and nuclear factor erythroid 2–related factor 2 (NRF2) decreased. GA reduced tissue damage and pro-inflammatory cytokines while restoring AKT1, NRF2, AQP2, ZO-1, and Clau-5. These findings suggest that GA attenuates LPS-induced lung injury and is associated with modulation of inflammatory and antioxidant-related signaling, including components of the IL-10–AKT1/GSK3β/NRF2 axis.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12981322/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444053","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":"Entinostat Induces Dual Apoptotic and Autophagic Cell Death in Small-Cell Lung Cancer via Epigenetic Modulation of HDAC1-p53-AMPK/mTOR Axis","authors":"Zhongkai Tong,&nbsp;Xiaoxiao Zhu,&nbsp;Cenli Wang,&nbsp;Mengqing Hu,&nbsp;Xiaofei Liang,&nbsp;Chunli Wu,&nbsp;Zhenyan Li,&nbsp;Lin He,&nbsp;Zhaoxing Dong,&nbsp;Yong Zhou","doi":"10.1002/jbt.70720","DOIUrl":"10.1002/jbt.70720","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Entinostat, a selective HDAC1/3 inhibitor, has shown anti-tumor activity in small cell lung cancer (SCLC), but the precise molecular mechanisms underlying its efficacy remain incompletely understood. This study aimed to investigate the functional role and mechanism of Entinostat in SCLC, with a focus on HDAC1 inhibition and its downstream effects on cell death pathways. The anti-tumor effects of Entinostat were evaluated in SCLC cell lines and a xenograft mouse model using MTT, flow cytometry, immunofluorescence, western blotting, and rescue experiments with HDAC1 overexpression and pathway-specific inhibitors. We found that Entinostat significantly inhibited SCLC cell viability and induced both apoptosis and autophagy. Mechanistically, Entinostat downregulated HDAC1 protein levels, increased p53 acetylation and phosphorylation, activated AMPK, and suppressed mTOR signaling. HDAC1 overexpression reversed these molecular changes and attenuated Entinostat-induced cytotoxicity. In vivo, Entinostat suppressed tumor growth and consistently modulated the HDAC1/p53/AMPK/mTOR pathway. In conclusion, Entinostat exerts potent anti-tumor activity in SCLC by simultaneously inducing apoptosis and autophagy through epigenetic modulation of p53 via HDAC1 inhibition and subsequent regulation of the AMPK/mTOR axis.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147443948","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":"Investigating the Role of MicroRNAs in Mesenchymal Stem Cell Osteogenic Differentiation","authors":"Zhenglin Leng,&nbsp;Shenzhen Pan,&nbsp;Qiang Guo,&nbsp;Limin Liu,&nbsp;Zengshun Wang,&nbsp;Junfeng Ma,&nbsp;Haibin Zhou,&nbsp;Jingyuan Zhou","doi":"10.1002/jbt.70724","DOIUrl":"10.1002/jbt.70724","url":null,"abstract":"<div>\u0000 \u0000 <p>Mesenchymal stem cells (MSCs) are multipotent progenitors that give rise to osteoblasts, which are essential for bone formation, remodeling, and skeletal homeostasis. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as critical post-transcriptional regulators of gene expression that fine-tune MSC commitment, osteoblast proliferation, and matrix mineralization. In this review, we first summarize the physiological mechanisms of bone remodeling and the differentiation of MSCs into osteoblasts, with particular attention to the coordinated roles of osteoblasts, osteoclasts, and osteocytes. We then discuss how specific miRNAs regulate osteoblast growth and maturation by targeting key transcription factors such as Runx2 and osterix, as well as major signaling pathways including BMP and Wnt. Building on this mechanistic framework, we examine the contribution of dysregulated miRNAs to metabolic bone diseases, with a focus on osteoporosis, where alterations in age-related, hormonal, and inflammatory environments reshape miRNA networks and favor bone loss. Current and emerging clinical applications of miRNAs are also reviewed, including their use as minimally invasive circulating biomarkers for fracture risk assessment and treatment monitoring, and as therapeutic targets or tools through miRNA mimics and inhibitory agents. Finally, we highlight future perspectives that involve integrated analysis of miRNAs and other non-coding RNAs, advanced profiling approaches such as single-cell RNA sequencing, and miRNA-guided strategies for bone tissue regeneration. A comprehensive understanding of these regulatory networks is expected to support the development of more precise diagnostic tools and targeted therapies for osteoporosis and related skeletal disorders.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390103","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":"Design and Characterization of Schiff Base Polymer-Ag-Nanocomposites: Advancing Antioxidant With Computational Studies","authors":"Afroz Jahan,&nbsp;Paramjit Singh,&nbsp; Roshani,&nbsp;Mohd. Fahim,&nbsp;Shazia Anjum,&nbsp;Rabiya Mehandi,&nbsp;Nahid Nishat","doi":"10.1002/jbt.70770","DOIUrl":"10.1002/jbt.70770","url":null,"abstract":"<div>\u0000 \u0000 <p>For a very long time, Schiff base polymers (SBP) derived from p-phenylenediamine and salicylaldehyde have attracted considerable interest due to their bioactive and coordination properties. Here, we report the synthesis, characterization, computational, and antioxidant activities of Schiff base polymer-Ag-nanocomposites (SBP-AgNC) by combining p-phenylenediamine and salicylaldehyde Schiff bases with silver nanocomposites (AgNC). The reaction of Ag nanoparticles with SBP results in synergistic enhancement of antioxidant activity. The docking results with three different proteins, primarily <i>dihydrofolate reductase</i> of <i>Staphylococcus aureus</i> (3FRB), <i>Sortase C</i> of <i>Streptococcus pneumoniae</i> (3G69), and <i>Glutaredoxin</i> 2 of <i>Escherichia coli</i> (7DKP), shows a binding affinity of −11.6 Kcal/mol toward the <i>dihydrofolate reductase</i> (PDB: 3FRB), −9.0 Kcal/mol with <i>Sortase C</i> (PDB:3G69), and −8.6 Kcal/mol <i>Glutaredoxin</i> 2 (PDB:7DKP). Moreover, hydrogen bonding and π−π stacking interactions play a significant role in the antibacterial activity of SBP; thus, SBP-AgNC1 shows excellent antioxidant activity (IC₅₀ mM [DPPH] = 0.0719 ± 0.04) and good thermal stability up to 350°C. Lastly, this study explored innovative antioxidant materials that are suitable for applications in packaging, food preservation, and biomedicine.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390121","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":"Hesperidin Attenuates H₂O₂-Induced Neurotoxicity via Modulation of Inflammatory Pathways and MMP Activity in Differentiated SH-SY5Y Cells: In Vitro and In Silico Models","authors":"Hamiyet Eciroglu-Sarban,&nbsp;Fatma Yildiz,&nbsp;Fatma Gonca Kocanci,&nbsp;Pinar Altin-Celik,&nbsp;Muazzez Derya-Andeden","doi":"10.1002/jbt.70774","DOIUrl":"10.1002/jbt.70774","url":null,"abstract":"<p>Chronic inflammation, often aggravated by oxidative stress, is a key contributor to the pathogenesis of neurodegenerative diseases. Molecular mediators such as NF-κB, COX-2, pro-inflammatory cytokines, and matrix metalloproteinases (MMP-2/MMP-9) disrupt blood-brain barrier (BBB) integrity and promote neuronal damage. Hesperidin, a natural citrus flavonoid with low cytotoxicity and high antioxidant capacity, has shown promise as a neuroprotective agent. This study aimed to evaluate its anti-inflammatory and neuroprotective effects in differentiated SH-SY5Y neuroblastoma cells exposed to hydrogen peroxide (H₂O₂), a well-established inducer of oxidative neurotoxicity. The protective effects of Hesperidin (75 and 100 µM for 48 h), administered as both pre- and post-treatment, were evaluated through cell viability assays, assessment of oxidative stress parameters, and expression analysis of inflammatory mediators (TNF-α, IL-1β, IL-6, NF-κB, COX-2), and MMP-2/MMP-9, using ELISA and RT-qPCR. In silico molecular docking analyses were also conducted using CB-Dock2 Tools to support the experimental findings. In our results, Hesperidin significantly increased cell viability (<i>p</i> &lt; 0.001) and reduced morphological damage. It also downregulated TNF-α, IL-1β, and IL-6 at both mRNA and protein levels (<i>p</i> &lt; 0.05–0.005), while markedly suppressing NF-κB, COX-2, MMP-2, and MMP-9 expression (<i>p</i> &lt; 0.01–0.005) and decreasing oxidative stress (<i>p</i> &lt; 0.005). Molecular docking revealed strong binding affinities of Hesperidin to key inflammatory targets, particularly COX-2 (–12.2 kcal/mol) and TNF-α (–11.6 kcal/mol). These findings indicate that Hesperidin exerts potent neuroprotective effects against H₂O₂-induced oxidative stress and neuroinflammation by modulating pro-inflammatory signaling pathways, matrix metalloproteinase activity, and redox homeostasis. These results highlight Hesperidin's potential as a therapeutic candidate for neurodegenerative disorders.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12972607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147390084","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":"Ubiquitin-Specific Peptidase 16 Alleviates Chondrocyte Damage in Osteoarthritis Through Deubiquitinating and Stabilizing POU Class 2 Homeobox 1","authors":"Wei Lu,&nbsp;Yi Lu,&nbsp;Sixie Xu,&nbsp;Zebu Xiao,&nbsp;Tianxiang Cheng,&nbsp;Yanru Hu,&nbsp;Yuanxiang Xiong,&nbsp;Yuan Lin","doi":"10.1002/jbt.70773","DOIUrl":"10.1002/jbt.70773","url":null,"abstract":"<div>\u0000 \u0000 <p>Osteoarthritis (OA), marked by articular cartilage degeneration, severely impairs joint function. Ubiquitin-specific peptidase 16 (USP16) is crucial for regulating cellular protein stability and signaling pathways. This study seeks to elucidate USP16's impact and mechanism on chondrocyte injury in OA. The expression of USP16 in OA was analyzed using the Gene Expression Omnibus (GEO) database. An in vitro model using IL-1β to induce OA-like conditions. Real-time quantitative PCR (RT-qPCR) and western blot were used to detect gene expression in tissues and cells. The cellular oxidative stress levels were assessed using cell metabolism kits specifically targeted at reactive oxygen species (ROS), malondialdehyde (MDA), and superoxide dismutase (SOD). Enzyme-linked immunosorbent (ELISA) assays were conducted to detect the levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in cell culture supernatants and serum, thereby evaluating the inflammatory response state. The apoptotic status of the cells was detected by flow cytometry. The Ubibrowser website was used to predict proteins that interact with USP16. Co-immunoprecipitation (CoIP) and GST pull-down experiments were conducted to validate the interaction between USP16 and POU class 2 homeobox 1 (POU2F1). The cycloheximide (CHX) chase assay was utilized to determine the half-life of proteins. Mouse models of OA were established for in vivo validation, and the degree of cartilage degeneration was assessed through hematoxylin–eosin (HE) staining. USP16 expression was found to be reduced in OA patients and in HACCs induced by IL-1β. The induction of IL-1β led to an increase in oxidative stress levels in human articular chondrocyte cells (HACCs), accelerated the inflammatory response and the rate of apoptosis within HACCs, and inhibited the normal expression of chondrogenesis-related proteins in HACCs. However, overexpressing USP16 was able to alleviate these adverse effects. Furthermore, USP16 interacted with POU2F1 and stabilized its expression by means of deubiquitination. Notably, when POU2F1 was knocked down, the protective effect of overexpressing USP16 on IL-1β-induced HACCs was significantly weakened. In vivo experiments demonstrated that overexpressing USP16 effectively inhibited the degenerative process of mouse cartilage, significantly lowered the Osteoarthritis Research Society International (OARSI) and Mankin scores in mice, decreased oxidative stress levels, and suppressed inflammatory responses. USP16 regulates chondrocyte damage in OA by exerting its deubiquitination role to stabilize the POU2F1 protein, providing a potential target and theoretical foundation for OA treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377317","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":"Short-Chain Fatty Acids Modulate Iron Metabolism and Induce Oxidative Stress and Ferroptosis in Breast Cancer Cells","authors":"Bilal Rah,&nbsp;Jasmin Shafarin,&nbsp;Aisha Saleh Janeeh,&nbsp;Rumaisa Rafiq,&nbsp;Tayma Mohamed Subhi Kurabi,&nbsp;Jibran Sualeh Muhammad,&nbsp;Eyad Elkord,&nbsp;Mawieh Hamad","doi":"10.1002/jbt.70771","DOIUrl":"10.1002/jbt.70771","url":null,"abstract":"<div>\u0000 \u0000 <p>Short-chain fatty acids (SCFAs), produced through the fermentation of dietary fibers by gut microbiota, play a crucial role in regulating gut microbiota composition, immune function, and overall health. Emerging evidence suggests that SCFAs exhibit antiproliferative effects in various cancers, though the underlying molecular mechanisms remain unclear, particularly in breast cancer (BC). This study aimed to explore the impact of SCFAs, including sodium acetate, propionate, butyrate, and pentanoate, on iron metabolism and ferroptosis in BC cells. The effects of SCFAs were examined in MCF-7 and MDA-MB-231 BC cell lines. Cell viability, intracellular iron levels, and expression of iron regulatory proteins transferrin (TfR1), ferroportin (FPN), hepcidin, and ferritin (FTH1) were analyzed. Additionally, oxidative stress markers such as reactive oxygen species (ROS), lipid peroxidation, glutathione peroxidase 4 (GPX4), and mitochondrial membrane potential were assessed. Adenosine triphosphate (ATP) production was also measured to determine ferroptosis involvement. SCFAs exhibited a dose-dependent reduction in BC cell proliferation. They increased intracellular iron content, altered iron metabolism-related protein expression, and elevated oxidative stress. This was evidenced by increased ROS levels, lipid peroxidation, GPX4 downregulation, mitochondrial membrane depolarization, and ATP depletion. SCFAs modulate iron metabolism in BC cells, triggering oxidative stress and ferroptosis-induced cell death. These findings highlight SCFAs' potential as therapeutic agents in BC treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377756","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":"Multifaceted Exploration of a New Schiff Base and Its Complexes: Thermal Properties and Biomedical Potential","authors":"Priteshkumar M. Thakor,&nbsp;Jatin D. Patel,&nbsp;Rajesh J. Patel,&nbsp;Sunil H. Chaki,&nbsp;Ankurkumar J. Khimani,&nbsp;Yati H. Vaidya,&nbsp;Gopalkumar G. Raol,&nbsp;Parth Thakor,&nbsp;Anjali B. Thakkar","doi":"10.1002/jbt.70766","DOIUrl":"10.1002/jbt.70766","url":null,"abstract":"<div>\u0000 \u0000 <p>This study presents the thermal and biomedical evaluation of a newly synthesized imine ligand and its six metal complexes. The synthesis and spectral data are detailed in Part 1 of this work. Here, advanced analyses such as LC-MS, SEM, and XRD were used for physicochemical characterization. Thermal stability was assessed using TGA, DTA, and DTG under inert conditions, with kinetic parameters calculated via the Kissinger−Akahira−Sunose method. Biological evaluations included molecular docking, which showed notable α-amylase inhibition, and MTT assays, which confirmed strong anticancer activity against A549 lung cancer cells. Additionally, the ligand and its complexes demonstrated anti-Alzheimer's and stress-resistance effects in <i>Caenorhabditis elegans</i>.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377766","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":"Curcumin Modulates 5-fluorouracil Sensitivity in Colorectal Cancer Cells Through the circ-NRIP1/miR-195-5p/SMURF1/AKT Signaling Axis","authors":"You Chen,&nbsp;Yueli Zhang,&nbsp;Rui Zhang,&nbsp;Jia Liu,&nbsp;Ruijia Li","doi":"10.1002/jbt.70775","DOIUrl":"10.1002/jbt.70775","url":null,"abstract":"<div>\u0000 \u0000 <p>Curcumin has demonstrated antitumor efficacy, and its therapeutic and adjunct potential is increasingly supported by evidence. However, the anticancer mechanisms of curcumin in combination with chemotherapy remain complex and heterogeneous, warranting further investigation. Although 5-fluorouracil (5-FU)-based chemotherapy remains a cornerstone of colorectal cancer (CRC) management, the emergence of chemoresistance significantly limits its clinical application. Therefore, the present work focused on elucidating the role of curcumin in modulating 5-FU sensitivity and exploring the underlying molecular mechanism. Initially, we validated the antitumor effects of curcumin both in vivo and in vitro, and demonstrated its synergistic efficacy when combined with 5-FU. We further identified circ-NRIP1 as a target of curcumin and confirmed that curcumin enhances 5-FU sensitivity in CRC cells by downregulating circ-NRIP1 level. Mechanistic studies revealed that circ-NRIP1 suppresses SMURF1 expression by competitively binding to miR-195-5p, leading to AKT pathway activation, inhibition of apoptosis, and ultimately reduced 5-FU sensitivity in CRC cells. Collectively, our findings verify that curcumin modulates 5-FU sensitivity in CRC to through the circ-NRIP1/miR-195-5p/SMURF1/AKT regulatory axis, providing a novel strategic approach for clinical CRC treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"40 3","pages":""},"PeriodicalIF":2.8,"publicationDate":"2026-03-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377732","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}