Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Kisspeptin-10 Protects Against TNF-α-Induced Chondrocyte Senescence via the SIRT1/p53/p21 Signaling","authors":"Jinchao Qiu,&nbsp;Guosheng Chen,&nbsp;Guoxuan Peng,&nbsp;Guoxin Qu,&nbsp;Tingguo Ren,&nbsp;Jin Deng","doi":"10.1002/jbt.70298","DOIUrl":"https://doi.org/10.1002/jbt.70298","url":null,"abstract":"<div>\u0000 \u0000 <p>In Osteoarthritis (OA), the senescence of chondrocytes plays a pivotal role, contributing to cartilage degradation and impairing tissue repair mechanisms. (Kp-10), a peptide hormone, exerts diverse biological functions across multiple cell types and tissues via its receptor Gpr54. However, its role in chondrocytes and OA has been understudied. This study investigates the role of Kp-10 in mitigating TNF-α- induced senescence in primary chondrocytes, a hallmark of OA pathogenesis. Gpr54 expression was confirmed in both primary chondrocytes and the ATDC5 chondrogenic cell line, with TNF-α treatment leading to a dose-dependent decrease in Gpr54 expression. Kp-10 treatment at concentrations of 50 and 100 nM effectively ameliorated TNF-α-induced senescence, as evidenced by diminished senescence-associated β-galactosidase staining and enhanced telomerase activity. Moreover, Kisspeptin-10 modulated the expression of key regulators involved in cellular aging, including hTERT and TERF2, and suppressed the activation of the p53/p21 pathway. Notably, Kp-10 restored SIRT1 expression, which was downregulated by TNF-α. Silencing SIRT1 abolished the protective effects of Kp-10, highlighting the essential role of SIRT1 in its anti-senescence action. These findings suggest that Kp-10 may be a promising therapeutic strategy for OA by mitigating chondrocyte senescence and improving cellular function by modulating the SIRT1 and p53/p21 pathways.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108817","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":"Advances in Exosome Research: Multifaceted Roles in Myeloid Leukemia Progression and Therapy","authors":"Jianlan Zheng,&nbsp;Huafang Wang,&nbsp;Lili Ge","doi":"10.1002/jbt.70315","DOIUrl":"https://doi.org/10.1002/jbt.70315","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent advancements in exosome research have revealed their crucial role in myeloid leukemia, encompassing chronic myeloid leukemia (CML) and acute myeloid leukemia (AML). Exosomes, small extracellular vesicles released by various cells, play a significant role in intercellular communication and impact key cellular processes such as growth, proliferation, angiogenesis, survival, and apoptosis. In leukemia, exosomes contribute to disease progression and therapeutic resistance by facilitating immune evasion, enhancing tumor cell proliferation, and promoting angiogenesis. For instance, exosomes derived from CML cells can transfer drug resistance to sensitive cells, and some exosomes derived from AML patients contain cytokines like TGF-β1 that inhibit immune cell activity. Exosomes also influence tumor organotropism by interacting with extracellular matrix molecules and modifying the tumor microenvironment. Despite their high potential, clinical applications of exosomes are limited. Their natural nanoparticle properties—such as adaptability, biodegradability, low toxicity, and the ability to cross biological barriers—make them promising candidates for targeted drug delivery and personalized medicine. Further research is necessary to scale up exosome production and harness their full therapeutic potential. By integrating advancements in exosome biology with innovative therapeutic strategies, there is significant potential for improved management and treatment of leukemia.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108818","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":"β-Sitosterol Ameliorates Ulcerative Colitis Through Modulation of the AMPK/MLCK Anti-Inflammatory Pathway","authors":"Yuansen Zhang,&nbsp;Xiaosheng Jin,&nbsp;Huanhuan Xia,&nbsp;Xiaoqiu Wu,&nbsp;Wenjun Chen,&nbsp;Mengxiao Zhuang,&nbsp;Sensen Tang","doi":"10.1002/jbt.70287","DOIUrl":"https://doi.org/10.1002/jbt.70287","url":null,"abstract":"<div>\u0000 \u0000 <p>Ulcerative colitis (UC), a common inflammatory bowel disease, has become increasingly prevalent worldwide, posing significant health challenges. This study explored the anti-inflammatory effects of β-sitosterol on UC and its underlying molecular mechanisms. Using a dextran sulfate sodium (DSS)-induced colitis model in male C57BL/6 mice, the therapeutic potential of β-sitosterol at low (2 mg/kg) and high (6 mg/kg) doses was compared with sulfasalazine (300 mg/kg) as a positive control. Disease progression was assessed through Disease Activity Index (DAI) scores, histological analysis, and inflammatory marker expression. β-sitosterol significantly ameliorated colonic inflammation, demonstrated by lower DAI scores, improved histological architecture, and reduced levels of inflammatory mediators, including NO, MPO, IL-6, and iNOS, while upregulating the anti-inflammatory cytokine IL-10. Mechanistically, β-sitosterol promoted AMP-activated protein kinase (AMPK) expression and suppressed myosin light chain kinase (MLCK) expression. These findings were validated in vitro using LPS-stimulated Caco-2 cells, where β-sitosterol decreased inflammatory marker levels and modulated AMPK/MLCK signaling. Notably, the use of Compound C, an AMPK inhibitor, reversed these effects by suppressing AMPK activity and restoring MLCK expression, confirming that the anti-inflammatory actions of β-sitosterol are AMPK-dependent. In conclusion, this study highlights the therapeutic potential of β-sitosterol in UC through modulation of the AMPK/MLCK signaling pathway. These findings not only deepen our understanding of β-sitosterol's anti-inflammatory properties but also suggest its potential in developing novel AMPK-targeted therapies for inflammatory bowel disease management.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108816","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 Methylindoline Derivative in Ameliorating Cadmium-Induced Nephritis Experimented in Zebrafish Model","authors":"S. P. Ramya Ranjan Nayak,&nbsp;Aveeda Herold,&nbsp;Marapatla Shiny,&nbsp;Girija Sastry Vedula,&nbsp;Ilavenil Soundharrajan,&nbsp;Bader O. Almutairi,&nbsp;S. Karthick Raja Namasivayam,&nbsp;Kathiravan Muthu Kumaradoss,&nbsp;Jesu Arockiaraj","doi":"10.1002/jbt.70312","DOIUrl":"https://doi.org/10.1002/jbt.70312","url":null,"abstract":"<div>\u0000 \u0000 <p>Since kidney diseases are a major global concern, their impact on public health makes them an important area of study. The kidneys, as the primary organs responsible for excreting waste, are particularly vulnerable to heavy metal poisoning. Cadmium (Cd), a naturally occurring heavy metal found in contaminated food and water, poses a serious risk to renal health. Due to their remarkable biological properties, methylindoline derivatives are being investigated for a variety of medicinal applications. The primary objective of this study is to screen and assess the anti-inflammatory and anti-nephritic qualities of methylindoline derivatives (IA, IB, IC, ID, IE). Through network pharmacology and molecular docking analyzes, the derivative IC ((E)-3-(2-(4-methoxyphenyl)-2-oxoethylidene)-5-methylindolin-2-one) was identified for further study. In In Vitro screening, IC showed strong antioxidant and anti-inflammatory properties in a dose-dependent manner. It effectively reduced oxidative stress, lipid peroxidation, and apoptosis induced by cadmium in zebrafish. In renal tissues, IC treatment decreased levels of lactate dehydrogenase (LDH) and malondialdehyde (MDA) while restoring the activity of antioxidant enzymes such as catalase (CAT) and superoxide dismutase (SOD). The expression of pro-inflammatory cytokine genes, including TNF-α, IL-1β, IL-6, and NF-κB, was also significantly downregulated by IC. Histopathological analysis of zebrafish kidneys demonstrated the restoration of renal tissue architecture, validating the protective effects of IC. These results highlight IC's therapeutic potential in treating cadmium-induced nephritis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108980","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":"1-Aryl-3-Ethyl-3-Methyl- and 1-Aryl-3-Methylsuccinimides as Drug Candidates for Cancer: Toxicity Prediction, Molecular Docking, and In Vitro Assessment","authors":"Damir Pinter,&nbsp;Nataša Milošević,&nbsp;Maja Milanović,&nbsp;Dunja Vidović,&nbsp;Jelena Kvrgić,&nbsp;Vesna Kojić,&nbsp;Dimitar Jakimov,&nbsp;Jovana Drljača Lero,&nbsp;Nataša Milić,&nbsp;Bojan Božić,&nbsp;Nebojša Banjac","doi":"10.1002/jbt.70313","DOIUrl":"https://doi.org/10.1002/jbt.70313","url":null,"abstract":"<div>\u0000 \u0000 <p>Twenty-four succinimide derivatives were tested for their antiproliferative effect toward steroid hormone-responsive carcinoma cell lines: estrogen positive human breast carcinoma (MCF-7), lung carcinoma (A549), colon carcinoma (HT-29), and cervix carcinoma (HeLa). In addition, their antiproliferative effect was analyzed against late-stage estrogen and progesterone negative breast carcinoma (MDA-MB-231) and for safety were also investigated against normal fetal lung (MRC-5) cell lines. Molecular docking studies were conducted to observe their binding affinity for steroid hormone receptors and BCRP/ABCG2 transporter. All analyzed succinimides exhibited antiproliferative effects on at least one carcinoma cell line and were safe toward normal fetal lung cells. Their safety was confirmed based on in silico predictions. The succinimides were binding through the same π−stock interactions for the same Phe-778 of the progesterone receptor as the proven ligand and the same Phe-439 of the BCRP as the proven substrate and inhibitor. In addition, interactions with crucial amino acid residues for ligand antagonistic effects on estrogen receptors were observed. The QSAR analysis revealed that the succinimides' binding affinity for sex hormone receptors was governed by their flatness, polarity, size, and polarizability, while the affinity to bind for BCRP was lipophilicity dependent. The succinimides antiproliferative effect on A549 cell line given as IC₅₀ was statistically significant associated with their molar refractivity (<i>p</i> = 0.033), and lipophilicity (XlogP3, <i>p</i> = 0.043), respectively. Finally, the most promising drug candidate with the most pronounced anticancer activity was compound D11 against lung carcinoma (A549) cell lines with an IC₅₀ comparable to doxorubicin.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144108981","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":"DNA Methylation-Induced BNIP3P1 Expression Promotes Pre-Eclampsia Progression via the miR-128-3p/BNIP3 Axis","authors":"Qiqi Zhang,&nbsp;Haoyu Zheng,&nbsp;Muling Zhang","doi":"10.1002/jbt.70307","DOIUrl":"https://doi.org/10.1002/jbt.70307","url":null,"abstract":"<div>\u0000 \u0000 <p>Pre-eclampsia (PE) is a severe, pregnancy-specific disorder characterized by abnormal trophoblast function, leading to impaired placental development and adverse maternal and fetal outcomes. Despite extensive research, the precise molecular mechanisms underlying PE pathogenesis remain incompletely understood. Emerging evidence suggests that long noncoding RNAs (lncRNAs), particularly pseudogenes, play critical roles in regulating trophoblast function, contributing to PE development. This study aims to investigate the role of the lncRNA pseudogene BNIP3P1 in the development of PE, focusing on its regulatory interactions with the miR-128-3p/BNIP3 axis and the involvement of DNA methylation in BNIP3P1 expression. Placental tissues from PE patients (<i>n</i> = 30) and healthy controls (<i>n</i> = 15) were analyzed for BNIP3P1 and BNIP3 expression using qRT-PCR, western blot, and immunohistochemistry (IHC). In Vitro functional assays utilizing HTR-8/SVneo and JAR trophoblast cell lines were employed to assess the effects of BNIP3P1 overexpression and miR-128-3p/BNIP3 interaction on cell proliferation, invasion, migration, and apoptosis. The DNA methylation status of the BNIP3P1 promoter was analyzed using methylation-specific PCR (MSP) and demethylation treatment with 5-Azacytidine. Additionally, a PE mouse model induced by SFLT-1 recombinant protein was used to evaluate the role of BNIP3P1 In Vivo. BNIP3P1 and BNIP3 were significantly upregulated in PE placental tissues and were positively correlated with clinical indicators such as blood pressure, albumin-to-creatinine ratio (ACR), and serum uric acid levels. In Vitro, BNIP3P1 overexpression inhibited trophoblast cell proliferation, invasion, and migration while promoting apoptosis, effects that were reversed by miR-128-3p overexpression. In Vivo, BNIP3P1 overexpression exacerbated PE-like symptoms, including hypertension and proteinuria, while knockdown of BNIP3 alleviated these symptoms. Mechanistically, bioinformatics analysis and experimental validation confirmed that BNIP3P1 regulates miR-128-3p, which in turn modulates BNIP3 expression. Additionally, BNIP3P1 expression was shown to be regulated by DNA methylation, with hypermethylation of its promoter observed in PE placental tissues. Inhibition of DNA methylation with 5-Azacytidine enhanced trophoblast proliferation, invasion, and migration, while reducing apoptosis and ameliorating PE-like symptoms In Vivo. BNIP3P1 regulates trophoblast function through the miR-128-3p/BNIP3 axis and is epigenetically controlled by DNA methylation in PE. Targeting the BNIP3P1/miR-128-3p/BNIP3 axis may provide novel therapeutic strategies for PE treatment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085368","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":"Hypericin Regulates Inflammation Levels and Improves Depressive Symptoms in Rats With Post-Stroke Depression Through the MEK/ERK/CREB Pathway","authors":"Kui Jia,&nbsp;Wenlong Li,&nbsp;Yifan Li,&nbsp;Lingling Qian","doi":"10.1002/jbt.70295","DOIUrl":"https://doi.org/10.1002/jbt.70295","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To investigate the effect of hypericin on ameliorating depressive behaviour in post-stroke depression (PSD) rats.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Rats underwent a middle cerebral artery occlusion and chronic mild stress for 28 days to create a PSD model. Behavioural tests included the open field test (OFT) and the elevated plus maze test. Hypericin at a low (100 mg/kg) and a high (400 mg/kg) dose was administered via gavage. Lipopolysaccharide (LPS) was used to establish a microglia-injury model, with hypericin treatment at 0.25, 0.5, 1, and 2 μmol/L, and ELISA was used to measure serotonin (5-HT), interleukin (IL)-6 and IL-10 levels. Additionally, Western blot analysis and immunohistochemistry analysed protein levels and the expression of iNOS and Arg-1 in the hippocampus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Following the PSD model preparation, the rats showed substantially reduced movement in the OFT and spent less time in the open arms of the elevated plus maze, whereas treatment with hypericin and fluoxetine improved depressive behaviour in these tests. In addition, hypericin decreased IL-6, increased IL-10 and 5-HT and enhanced p-MEK/MEK, p-ERK/ERK and p-CREB/CREB expression in the serum of the PSD rats and the LPS cell model. Hypericin also reduced iNOS but increased Arg-1 expression in the PSD rat hippocampus.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Hypericin promotes M2 microglial polarisation, reduces inflammation and improves depressive behaviour in PSD rats by activating the MEK/ERK/CREB pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085372","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":"MicroRNA-487b-3p Represses Cell Functions and Epithelial-Mesenchymal Transition and Acts as a Prognostic Predictor for Breast Cancer","authors":"Yang Wang,&nbsp;Jianhong Liu,&nbsp;Haizhen Yu,&nbsp;Shizhen Li,&nbsp;Wenyan Wang","doi":"10.1002/jbt.70310","DOIUrl":"https://doi.org/10.1002/jbt.70310","url":null,"abstract":"<div>\u0000 \u0000 <p>Our aim was to ascertain the clinical implications of microRNA-487b-3p (miR-487b-3p) in breast cancer. MiR-487b-3p level was measured in breast cancer tissues (<i>n</i> = 102) and adjacent noncancerous tissues (<i>n</i> = 102) using quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier method and Cox regression analysis were conducted for evaluating the clinical performance of miR-487b-3p. Cell counting kit-8 (CCK-8) and Transwell assay were utilized for cellular functions. Bioinformatics tools and luciferase reporter assay were performed for the target predication and confirmation. MiR-487b-3p was remarkably diminished in breast cancer tissues. Aberrant miR-487b-3p was tightly in relation to Ki67 (<i>p</i> = 0.003), human epidermal growth factor receptor (HER2) status (<i>p</i> = 0.025), tumor node metastasis (TNM) stage (<i>p</i> = 0.028) and lymph node metastasis (<i>p</i> = 0.002). Moreover, a better progression free survival rate was found in patients expressing high miR-487b-3p (<i>n</i> = 51, <i>p</i> &lt; 0.001) than those with low expression (<i>n</i> = 51). Additionally, miR-487b-3p was an independent predictor for the prognosis of breast cancer (<i>p</i> &lt; 0.001; HR = 2.971; 95% CI = 1.721–5.131). Enforced miR-487b-3p expression obviously restrained cell activities and epithelial-mesenchymal transition (EMT), while apposite effects were observed posttransfection with miR-487b-3p inhibitor (<i>p</i> &lt; 0.001). Notably, low-density lipoprotein receptor-related protein 6 (LRP6) was a potential target gene of miR-487b-3p, an adverse relevance of which was discovered (<i>r</i> = −0.5811; <i>p</i> &lt; 0.001). MiR-487b-3p was an underlying indicator for the prognosis in breast cancer. It impacted on cell activities and EMT via regulating LRP6 in breast cancer development.</p>\u0000 <p><b>Clinical trial registration:</b> Not applicable.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085373","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":"Hydroxytyrosol Inhibits BPS-Induced NF-κB Signaling Pathway Activation, Mitigates Oxidative Stress, and Reduces Neuronal Apoptosis","authors":"Hongyu Zhang,&nbsp;Guoshun Lin,&nbsp;Yang Yang,&nbsp;Yifei Wang,&nbsp;Xiushuo Yang,&nbsp;Guige Hou,&nbsp;Zhenbo Wang,&nbsp;Qingguo Meng,&nbsp;Yun Hou","doi":"10.1002/jbt.70303","DOIUrl":"https://doi.org/10.1002/jbt.70303","url":null,"abstract":"<div>\u0000 \u0000 <p>Hydroxytyrosol (HT), a primary phenolic compound in olive oil, exhibits antioxidant and antiapoptotic effects in various cell types, including cardiomyocytes and human umbilical vein endothelial cells. Contrastingly, bisphenol S (BPS) is known to induce apoptosis in myocardial and endothelial cells via oxidative stress. BPS increases reactive oxygen species (ROS) production and reduces the viability of hippocampal HT22 cells. In this study, we explored whether HT could protect neurons from BPS-induced oxidative stress and apoptosis. Our results showed that HT effectively inhibited oxidative stress responses in the brains of BPS-treated mice and significantly decreased ROS production in BPS-treated HT22 and PC12 cells. Additionally, HT reduced BPS-induced neuronal apoptosis in the cortical regions of mice as well as in HT22 and PC12 cells. Further analysis revealed that BPS activates the NF-κB signaling pathway, a key mediator of oxidative stress and neuronal apoptosis, while HT counteracted these effects. In summary, this study demonstrates the antioxidant and antiapoptotic properties of HT in BPS-exposed neurons. These findings provide compelling experimental evidence supporting the potential dietary inclusion of HT-rich compounds to alleviate oxidative stress-related neuronal damage.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085367","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":"Alyssin Modulates Inflammatory Mediators Expression in Interleukin-1β-Stimulated Human Periodontal Ligament Cells","authors":"Ikuko Hosokawa,&nbsp;Yoshitaka Hosokawa,&nbsp;Risa Okamoto,&nbsp;Kazumi Ozaki,&nbsp;Keiichi Hosaka","doi":"10.1002/jbt.70314","DOIUrl":"https://doi.org/10.1002/jbt.70314","url":null,"abstract":"<div>\u0000 \u0000 <p>Alyssin is an isothiocyanate found in cruciferous plants. It has been reported to have physiologically active effects. However, no attempts have been made to use alyssin for the treatment of periodontitis. In addition, there are no reports investigating the effects of alyssin on periodontal tissue constituent cells. In the present study, experiments were carried out to determine whether alyssin has an anti-inflammatory effect on human periodontal ligament cells (HPDLCs). We found that alyssin suppressed the interleukin (IL)-1β-induced production of IL-6, IL-8, C−C motif chemokine ligand (CCL)2, CCL20, and C−X−C motif chemokine ligand (CXCL)10 and the expression of intercellular adhesion molecule (ICAM)-1 and cyclooxygenase (COX)-2 in HPDLCs. It was also found that alyssin inhibited the IL-1β-induced activation of nuclear factor (NF)-κB and the phosphorylation of p70S6 kinase (p70S6K) in HPDLCs. Furthermore, we found that the expression of the antioxidant enzymes hemeoxygenase (HO)-1 and NAD(P)H:quinone oxidoreductase (NQO)-1 was enhanced by alyssin treatment of HPDLC. This study suggests that by suppressing the activation of NF-κB and p70S6K, alyssin may attenuate the expression of inflammatory mediators in HPDLCs. In addition, alyssin also increased the expression of antioxidant enzymes.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 6","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144085369","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}