Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Synthesis, Structural Characterization, Biological Effects and Molecular Docking Study of New Schiff Base Ligands Containing Sulfonyl Units","authors":"Fatma Hamurcu,&nbsp;Saliha Alyar,&nbsp;Busra Aksoy Erden,&nbsp;Yavuz Erden","doi":"10.1002/jbt.70485","DOIUrl":"https://doi.org/10.1002/jbt.70485","url":null,"abstract":"<div>\u0000 \u0000 <p>Schiff bases containing sulfonyl units are important compounds because of their potential biological properties in the therapeutical field. In this study, three novel ligands (L1, L2, and L3) containing the sulfonyl groups, a derivative of Schiff base, were synthesized, and their molecular structures were characterized by FT-IR, ¹H-NMR, ¹³C NMR, and elemental analysis results. The antiproliferative activities of these Schiff base ligands were evaluated against human colon cancer (HT-29 and Caco-2) and mouse fibroblast (L929) cells by the 3-(4,5-dimethylthiazol-2-yl)−2,5-diphenyltetrazolium bromide (MTT) method. In addition, the antioxidant activities of these ligands were determined. Their potential activities against Peroxiredoxin 2 enzyme were assessed with molecular docking studies. When the spectral evaluation of the novel Schiff Base compounds (L1-3), the characteristic peaks and bands of target compounds were observed from ¹H NMR, ¹³C NMR, and FT-IR results. The elemental analysis results supported the structures of the characterized compounds. All compounds' DPPH radical scavenging effect was similar to rutin at the highest applied concentration. According to molecular docking results, it was determined that hydrogen bond and steric interactions played a role in the interaction of the compounds and Peroxiredoxin 2 protein. It was observed that there was a parallelism between molecular docking results and antioxidant activity results. As a result of in silico and in vitro studies, it was found that L2 compound was the most effective compound with −60.083 MolDock Score and −61.079 total energy data. It was observed that hydrogen bonding and steric interactions played a role in the interaction of the compounds with the protein. Each compound showed cytotoxic effects against human colon cancer cells with increasing doses but not against healthy cells. These results support the hope that these compounds can be used for therapeutic purposes.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145011955","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":"Neurokinin B Inhibition Preserves BBB Integrity in Ischemic Stroke via Suppression of Egr-1-Mediated Claudin-5 Downregulation","authors":"Jijing Fu,&nbsp;Lihua Song,&nbsp;Fumin Ping,&nbsp;Ran Wang,&nbsp;Hui Li,&nbsp;Bo Yang,&nbsp;Suli Dong","doi":"10.1002/jbt.70483","DOIUrl":"https://doi.org/10.1002/jbt.70483","url":null,"abstract":"<div>\u0000 \u0000 <p>Blood-Brain Barrier (BBB) dysfunction acts as a key mediator of ischemic brain injury, contributing to brain edema, inflammatory cell infiltration, and neuronal damage. The integrity of the BBB is largely maintained by tight junction proteins, such as Claudin-5, and its disruption exacerbates neurological deficits. Neurokinin B (NKB), a neuropeptide that belongs to the tachykinin family, has been implicated in various physiological processes, including neuroinflammation and vascular function. However, the precise effects of NKB on BBB integrity during ischemic stroke have not been thoroughly investigated. Herein, we explore the role of NKB and its receptor, NKB receptor 3 (NK3R), in the context of ischemic stroke. Our results show a significant increase in both NKB and NK3R levels in the infarcted hemisphere of middle cerebral artery occlusion (MCAO)-operated mice. When we experimentally reduced NKB levels, we observed a notable decrease in infarct volume, improved neurological function, and better BBB permeability. Additionally, we found that inhibiting NKB restored the expression of Claudin-5, which in turn reduced endothelial permeability in both in vivo and in vitro experiments. We additionally recognized early growth response protein 1 (Egr-1) as a critical downstream target of NKB, which plays a key role in compromising the endothelial barrier. Silencing Egr-1 effectively reversed the increase in endothelial permeability and the decrease in Claudin-5 caused by NKB, highlighting an important regulatory pathway. These findings emphasize the involvement of NKB in the disruption of the BBB during ischemic stroke, primarily through the upregulation of Egr-1, which leads to reduced Claudin-5 expression. Therefore, targeting NKB could be a promising therapeutic strategy for maintaining BBB integrity and reducing neuronal damage after ischemic stroke.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012857","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":"Methyltransferase-Like 3-Mediated m6A Modification of Heat Shock Protein Family A Member 4-Like Facilitates Interleukin-1β-Induced Chondrocyte Injury to Promote Osteoarthritis Progression","authors":"Chen Chen,&nbsp;Pingbo Chen,&nbsp;Zunyu Du,&nbsp;Jinniu Zhang,&nbsp;Yun Zhou","doi":"10.1002/jbt.70492","DOIUrl":"https://doi.org/10.1002/jbt.70492","url":null,"abstract":"<div>\u0000 \u0000 <p>Heat shock protein family A member 4-like (HSPA4L) has been shown to be overexpressed in osteoarthritis (OA) patients, but its role in OA process still unknown. Chondrocytes were stimulated with interleukin-1β (IL-1β) to mimic OA cell model in vitro, and rat was injected with monosodium iodoacetate (MIA) to construct OA rat model in vivo. The expression of HSPA4L, methyltransferase-like 3 (METTL3) and extracellular matrix (ECM)-related markers was examined by qRT-PCR or western blot. Cell proliferation and apoptosis were determined by CCK8 assay, EdU assay, TUNEL staining and flow cytometry. The levels of TNF-α and ROS were determined to assess cell inflammation and oxidative stress. The interaction between HSPA4L and METTL3 was confirmed by MeRIP assay and dual-luciferase reporter assay. Saffron-O and fast green staining was performed to evaluate cartilage degeneration in rats. HSPA4L expression was higher in OA patients and IL-1β-induced chondrocytes. Silencing of HSPA4L enhanced proliferation, while suppressed IL-1β-induced chondrocyte apoptosis, ECM degradation, inflammation and oxidative stress. METTL3 was upregulated in OA patients and IL-1β-induced chondrocytes, and it could increase HSPA4L expression by m6A modification. METTL3 knockdown inhibited IL-1β-induced chondrocyte injury, as well as alleviated cartilage degeneration in OA rat models, while these effects were reversed by HSPA4L overexpression. METTL3-mediated HSPA4L accelerated OA progression through m6A modification, providing a novel insight for OA treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012625","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":"A Low Concentration of Butyrate has a Protective Action Against the Deleterious Effects of Clostridioides difficile Toxins on Enteric Glia","authors":"Arkila P. R. Sousa,&nbsp;Andrea V. Loureiro,&nbsp;Renata F. C. Leitão,&nbsp;Cirle A. Warren,&nbsp;Gerly A. C. Brito,&nbsp;Deiziane V. S. Costa","doi":"10.1002/jbt.70475","DOIUrl":"https://doi.org/10.1002/jbt.70475","url":null,"abstract":"<div>\u0000 \u0000 <p>Microbiota, which plays a vital role in susceptibility to <i>Clostridioides difficile</i> infection (CDI), synthesizes butyrate. Enteric glia is a component of the enteric nervous system (ENS) and is affected by <i>C. difficile</i> toxins A (TcdA) and B (TcdB). Here, we evaluated whether butyrate modulates the response of enteric glia to <i>C. difficile</i> toxins. In vitro, rat enteric glia were incubated with TcdA or TcdB alone, or in combination with butyrate 1 h before the toxin challenge. After 18 h incubation, enteric glia were collected to analyze cell death and expression of <i>Bcl2</i> (an antiapoptotic factor), <i>S100B</i>, and <i>IL-6</i> by qPCR. <i>C. difficile</i> toxins induced enteric glia death, increased levels of caspase 3/7, downregulated <i>Bcl2</i>, and upregulated the expression of pro-inflammatory mediators (<i>S100B</i> and <i>IL-6</i>). In high concentration, butyrate (200 µM) potentialized the effects of <i>C. difficile</i> toxins in promoting enteric glia death and caspase 3/7 activity. In contrast, a low butyrate concentration (0.2 µM) decreased enteric glia death and caspase 3/7 activity induced by <i>C. difficile</i> toxins. In addition, a low concentration of butyrate (0.2 µM) upregulated <i>Bcl2</i> expression compared to control cells and decreased the downregulation of <i>Bcl2</i> and upregulation of <i>IL-6</i> induced by TcdB. Further, a low butyrate concentration (0.2 µM) also diminished <i>S100B</i> upregulation induced by TcdA. Our findings suggest that low and high concentrations of butyrate can differentially affect the susceptibility of enteric glia to <i>C. difficile</i> toxins. These findings bring new perspectives on how microbiota-derived products may modulate the response of enteric glia to <i>C. difficile</i> toxins.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145012624","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":"Folic Acid-Chitosan-PLGA Nano Delivery System Against Liver Cancer Cells: In Vitro Studies","authors":"Arianaz Hosseini,&nbsp;Javad Mohammadnejad,&nbsp;Asghar Narmani,&nbsp;Hanieh Jafari","doi":"10.1002/jbt.70478","DOIUrl":"https://doi.org/10.1002/jbt.70478","url":null,"abstract":"<div>\u0000 \u0000 <p>Among cancers, liver cancer is the fourth leading cause of mortality worldwide and drawbacks of conventional approaches could not inhibit this cancer. Thus, an efficient folic acid (FA)-functionalized chitosan (CS)-poly lactic-co-glycolic acid (PLGA) nanocarrier was fabricated for delivery of sodium butyrate (NB) therapeutics to HepG2 liver cancer cells. The fabricated CS-NB-PLGA-FA nanocarrier was characterized by FT-IR, DLS, TEM, and TGA. A size range of 45 nm to 80 nm, surface charge of 4.2 mV, and drug encapsulation of 15.17% were measured for nanocarrier. Controlled (about fivefolds within 2 h) and pH-sensitive drug release manner observed in PBS as well. The MTT assay indicated that CS-NB-PLGA-FA resulted in about 13% cell viability after 24 h of treatment with 400 nM concentrations (IC₅₀: 300 nM). The qRT-PCR technique revealed nearly a 7.9- and 5.8-fold increase for Caspase9 and Bax genes while a decrease of about fivefold for the Bcl2 gene after treatment with CS-NB-PLGA-FA. Additionally, about 60% apoptosis was observed for the cells treated with nanocarrier. Remarkable enhancement did indicate for ROS (increase in the catalase and SOD units). These data have demonstrated that CS-NB-PLGA-FA could be a promising candidate against liver cancer.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144998806","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":"VIPR1 induces cuproptosis and inhibits the HIF-1α pathway in colon cancer","authors":"Xue Liu,&nbsp;Ye Lin,&nbsp;Jingzhi Zhang","doi":"10.1002/jbt.70472","DOIUrl":"https://doi.org/10.1002/jbt.70472","url":null,"abstract":"<div>\u0000 \u0000 <p>Cuproptosis, a recently characterized form of programmed cell death, has been implicated in tumor progression; however, its specific role in colon cancer remains poorly understood. This study aims to elucidate the potential involvement of cuproptosis-related genes in the development and progression of colon cancer. Differentially expressed genes (DEGs) associated with cuproptosis in colon cancer were identified through bioinformatics analysis of the GSE4183 and GSE74602 datasets. Gain-of-function experiments were performed in HT29 and HCT116 colon cancer cell lines to evaluate their effects on cellular proliferation, migration, and invasion. Functional assays, including JC-1 staining, copper (Cu²⁺) quantification, and lactate/pyruvate measurements, were employed to assess mitochondrial membrane potential and metabolic reprogramming. The involvement of hypoxia-inducible factor-1 alpha (HIF-1α) was further explored through overexpression and rescue assays. To confirm the dependency of the observed effects on cuproptosis, tetrathiomolybdate (TTM) was used as a copper chelator. Additionally, vasoactive intestinal peptide receptor 1 (<i>VIPR1</i>) signaling was activated using its agonist, vasoactive intestinal peptide (VIP). Five downregulated cuproptosis-related hub genes (<i>VIPR1</i>, <i>PYY</i>, <i>NPY</i>, <i>VIP</i>, and <i>SST</i>) were identified as potential diagnostic biomarkers for colon cancer. Among them, <i>VIPR1</i> overexpression significantly suppressed the proliferation, migration, and invasion of colon cancer cells, accompanied by upregulation of cuproptosis-associated proteins FDX1 and DLST. These effects were markedly attenuated by <i>HIF1A</i> overexpression. The application of the copper chelator TTM abolished the antitumor effects mediated by <i>VIPR1</i>, confirming cuproptosis dependency. Furthermore, treatment with the VIPR1 agonist VIP enhanced <i>VIPR1</i> signaling, further inhibited malignant cellular behaviors, and downregulated HIF-1α activity. Dual-luciferase reporter assays showed that HIF-1α overexpression reduced the transcriptional activity of wild-type FDX1 and DLST promoters. <i>VIPR1</i> acts as a tumor suppressor in colon cancer by promoting cuproptosis and disrupting cellular metabolic fitness through inhibition of HIF-1α signaling, thereby representing a promising target for therapeutic intervention.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935221","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 Vitamin D in Enhancing Duloxetine and Fluoxetine Efficacy: Mechanistic Insights Into NRF2 Activation, Oxidative Stress, and Neurochemical Modulation","authors":"Naveed Khan,&nbsp;Shakir Ullah,&nbsp;Muhammad Ilyas,&nbsp;Muhammad Waseem Khan","doi":"10.1002/jbt.70473","DOIUrl":"https://doi.org/10.1002/jbt.70473","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Depression is a major psychiatric disorder with limited treatment efficacy. Oxidative stress plays a key role in its pathogenesis, and emerging evidence suggests that vitamin D may reduce oxidative damage in neurological conditions. However, its role in modulating antioxidant enzymes and Nrf2 expression in depression remains unclear. This study investigates the effects of vitamin D in a cortisol-induced depression model, focusing on its impact on the antioxidant defense system and Nrf2 activation. Depression was induced in male Wistar rats via intraperitoneal cortisol injection (20 mg/kg). Animals were divided into six groups (<i>n</i> = 5/group), including control, cortisol-only, vitamin D (5 µg/kg) with cortisol, and standard antidepressant (fluoxetine or duloxetine) with or without vitamin D. Depression-like behaviors were assessed using the forced swim and sucrose consumption tests. Nrf2 binding interactions with vitamin D and fluoxetine were analyzed in silico using Pyrex, Drug Studio, and LigPlus. Post-treatment, hippocampal tissues were collected for analysis of antioxidant enzymes, monoamine neurotransmitters (via HPLC), and Nrf2 mRNA expression. Vitamin D showed a better binding energy (−9.3 kcal/mol) compared to fluoxetine (−6.6 kcal/mol). Similarly, vitamin D significantly (<i>p</i> &lt; 0.0001) enhanced the level of enzymatic antidefense markers (catalase, superoxide dismutase, glutathione) and decreased the level of malondialdehyde. The Nrf2 mRNA level was elevated (<i>p</i> &lt; 0.0001) in vitamin D-treated groups compared to positive control groups. Moreover, the mRNA level of the Nrf2 gene was the same as that of the standard groups. Vitamin D also increases the levels of serotonin and norepinephrine in depression. Vitamin D displayed a significant (<i>p</i> &lt; 0.0001) antidepressant effect, as evidenced by behavioral studies during co-therapy with duloxetine and fluoxetine. Altogether, this study reveals that vitamin D helps in ameliorating depression by mediating the antioxidant enzymatic system and increasing the Nrf2 expression during co-therapy with duloxetine and fluoxetine. Moreover, vitamin D also increased the serotonin and norepinephrine levels.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935218","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":"“Modulating Cadmium Chloride-Induced Hepatorenal Damage: Interplay of Trans-Resveratrol and Gamma Irradiation on Wnt/β-Catenin/NOTCH and NF-κB Signaling Axes”","authors":"Rokaya E. Maarouf,&nbsp;Hoda. A. Mansour,&nbsp;Fatma Abdel-Fattah M. Salem,&nbsp;Marwa A. Esmat","doi":"10.1002/jbt.70468","DOIUrl":"https://doi.org/10.1002/jbt.70468","url":null,"abstract":"<div>\u0000 \u0000 <p>Cadmium chloride (CdCl₂) is a powerful environmental toxin that has been documented to induce severe hepatic and renal damage through oxidative stress mechanisms. This study evaluated the protective impact of combined low dose of gamma irradiation (LDR) and trans-resveratrol (Trans-Res) on CdCl₂-induced hepato-renal toxicity in rats. Five groups of 50 male albino rats had been classified as; control, CdCl₂ (2 mg/kg), CdCl₂+LDR (0.75 Gray), CdCl₂+Trans-Res (20 mg/kg/b.wt.), and CdCl₂+Trans-Res+LDR for 6 weeks. CdCl₂ significantly increased the enzymes of liver (alanine aminotransferase [ALT], aspartate aminotransferase [AST], alkaline phosphatase [ALP]) and kidney markers (creatinine, urea), raised oxidative stress levels (hydrogen peroxide [H₂O₂], inducible nitric oxide synthase [iNOS]), lowered antioxidant activity superoxide dismutase (SOD), and increased fat breakdown products malondialdehyde (MDA) while causing inflammation (interleukin-6 [IL-6], nuclear factor kappa B [NF-κB]). Molecular analysis revealed that CdCl₂ downregulated Notch receptor 1 (Notch1) and Beta-catenin (β-catenin) genes with Wingless-related integration site (Wnt) protein and upregulated Axis inhibition protein 2 (Axin2), Cellular myelocytomatosis oncogene (c-myc), and Cyclin D genes with glycogen synthase kinase-3 beta (GSK-3β) and Hairy and enhancer of split 1 (HES1) proteins. Combined Trans-Res+LDR treatment significantly reduced these biochemical alterations, controlled gene expression levels, and enhanced histopathological alterations in the kidney and liver tissues. In conclusion, our findings evidently indicate that trans-resveratrol combined with low-dose of gamma irradiation provides powerful protective effects against CdCl₂-induced hepato-renal injuries through redox homeostasis recovery, suppression of inflammatory mediators, and modulation of apoptotic signaling pathways, which suggest a new therapeutic approach against the toxicity of CdCl₂ heavy metal.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935222","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":"Therapeutic Potential of CAPE in Targeting Hallmarks of Cancer in TPC-1 Thyroid Cancer Cells Through Modulation of Mitochondrial Membrane Potential","authors":"Yasin Tülüce,&nbsp;Hümeyra Bucak,&nbsp;Sedat Köstekci","doi":"10.1002/jbt.70487","DOIUrl":"https://doi.org/10.1002/jbt.70487","url":null,"abstract":"<div>\u0000 \u0000 <p>The objective of this study was to examine the chemotherapeutic effect of CAPE, via the mitochondrial membrane potential (MMP, Δψm) pathway in TPC-1 human papillary thyroid cancer cells. The cytotoxic effect of CAPE was evaluated using MTT and crystal violet assays, while its apoptotic activity was measured using Bax, Bcl-2, Caspase-3,-8,-9 and Apaf-1 assays. Effects on mitochondria were performed by analyzing JC-1 fluorescent probe-MMP, ROMO1 and mitochondrial ATP-synthase. The analysis of ROS and 8-OHdG was undertaken to assess the degree of oxidative stress and DNA damage, while LDH analysis was used as a marker of both cytotoxicity and cellular membrane damage. To determine antimetastatic activity, cell migration and colony formation assays were performed. Finally, Giemsa staining was chosen for cytomorphological analysis. CAPE treatment in TPC-1 cells was selected as the effective dose (IC₅₀: 25 µM/48 h) for further experiments, and it was found that this reduced Bcl-2 levels and increased the activation of key components Bax, Caspase-3,-8,-9 and Apaf-1, indicating that CAPE-induced cell death was apoptosis-dependent. The study revealed that CAPE induced mitochondrial depolarization, leading to a substantial decrease in mitochondrial ATP-synthase, along with a notable increase in intracellular ROS, ROMO1 levels, and 8-OHdG DNA damage and extracellular LDH. Furthermore, CAPE exhibited a significant inhibitory effect on cell migration and colony formation, accompanied by cytomorphological changes. In conclusion, this study demonstrates that CAPE, which shows bioactivity by modulating MMP, can target several hallmarks of cancer in TPC-1 cells and therefore has an important potential for future in vivo research.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144935220","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":"EXPRESSION OF CONCERN: Prophylactic Role of D-Saccharic Acid-1,4-Lactone in Tertiary Butyl Hydroperoxide Induced Cytotoxicity and Cell Death of Murine Hepatocytes via Mitochondria-Dependent Pathways","authors":"","doi":"10.1002/jbt.70457","DOIUrl":"https://doi.org/10.1002/jbt.70457","url":null,"abstract":"<p><b>EXPRESSION OF CONCERN</b>: S. Bhattacharya, S. Chatterjee, P. Manna, J. Das, J. Ghosh, R. Gachhui and Parames C. Sil, “Prophylactic Role of D-Saccharic Acid-1,4-Lactone in Tertiary Butyl Hydroperoxide Induced Cytotoxicity and Cell Death of Murine Hepatocytes via Mitochondria-Dependent Pathways,” <i>Journal of Biochemical and Molecular Toxicology</i> 25, no. 6 (2011): 341-354, https://doi.org/10.1002/jbt.20393.</p><p>This Expression of Concern is for the above article, published online on 27 April 2011 in Wiley Online Library (wileyonlinelibrary.com), and has been issued by agreement between the journal Editor-in-Chief, Hari K. Bhat; and Wiley Periodicals, LLC. The Expression of Concern has been agreed upon due to the identification of an overlap between the TBHP image presented in Figure 2e, Panel A, and an image published earlier in the same year by the same authors in a different article. The overlapping image was used to represent a different scientific context. The authors cooperated with the investigation and explained that since the two studies were conducted simultaneously, the figure was inadvertently mismanaged. However, due to the time that has elapsed since the study was conducted, the authors were unable to provide the original image. Since the results shown in Figure 2e are also supported by other figures included in the study, the editors are satisfied that the conclusions remain valid. The journal has therefore decided to issue an Expression of Concern and alert readers to the overlap.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70457","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144929703","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}