Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Casein Kinase 1α Agonist Pyrvinium Promotes Autophagy to Suppress Endometriosis in Mice","authors":"Aixiu Zhou,&nbsp;Qiongyi Cai,&nbsp;Yating Hong,&nbsp;Yuchun Lv","doi":"10.1002/jbt.70506","DOIUrl":"https://doi.org/10.1002/jbt.70506","url":null,"abstract":"<div>\u0000 \u0000 <p>Endometriosis is a prevalent gynecological disorder characterized by the ectopic presence of endometrial tissue and chronic inflammation. This study aimed to explore the therapeutic potential of the Casein kinase 1 alpha (CK1α) agonist pyrvinium in endometriosis. Human endometrial stromal cells and an in vivo mouse model of endometriosis were employed. Quantitative PCR was used to assess the mRNA levels of CK1α and autophagy-related genes, while Western blot analysis measured their protein expression. Immunohistochemical staining was performed to detect CK1α and Atg7 in ectopic lesion tissues. Additionally, enzyme-linked immunosorbent assay quantified inflammatory cytokine secretion in the culture supernatants and mouse peritoneal fluid. In human endometrial stromal cells, pyrvinium treatment significantly upregulated CK1α and autophagy-related proteins and suppressed inflammatory cytokine secretion under hypoxic conditions. In the in vivo endometriosis model, pyrvinium inhibited the growth of endometriotic lesions and reduced pro-inflammatory cytokine levels. These findings suggest that pyrvinium activates CK1α, induces autophagy, and mitigates inflammatory responses in endometriosis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 10","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145111124","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":"Targeting the hsa_circ_0000253/miR-7/COL5A2 Axis: Unveiling CCT-018159's Role in Halting Osteosarcoma Progression","authors":"Xu Guo,&nbsp;Xiangrui Zhu,&nbsp;Xin Tian,&nbsp;Yunfeng Dai,&nbsp;Batchimeg Tsedenbal,&nbsp;Mahmoud A. A. Ibrahim,&nbsp;Yanshuo Han,&nbsp;Jinzhu Liu","doi":"10.1002/jbt.70464","DOIUrl":"10.1002/jbt.70464","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents, marked by aggressive local invasion and early metastasis. This study investigated the regulatory role of the hsa_circ_0000253/miR-7/COL5A2 axis and the therapeutic potential of CCT-018159 in OS progression. Differential expression and ceRNA network analyses identified hsa_circ_0000253 as a key regulator. Functional experiments demonstrated that silencing hsa_circ_0000253 or COL5A2 suppressed OS cell proliferation and migration, whereas inhibition of miR-7 enhanced these processes. Single-cell transcriptomics revealed distinct OS cell subclusters, with high-risk cells characterized by elevated expression of COL5A2, IGF1R, COL1A1, and COL1A2, indicating progression toward aggressive phenotypes. Molecular docking further identified CCT-018159 as a candidate drug capable of markedly reducing OS cell proliferation and migration. These findings highlight the hsa_circ_0000253/miR-7/COL5A2 axis as a critical driver of OS malignancy and suggest CCT-018159 as a promising therapeutic agent, warranting further in vivo validation and clinical exploration.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145086048","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":"Telmisartan Ameliorates Blood-Brain Barrier Disruption in a High-Salt Diet Mouse Model","authors":"Zhanhai He,&nbsp;Jinqiu Gao,&nbsp;Huaihua Guo","doi":"10.1002/jbt.70474","DOIUrl":"10.1002/jbt.70474","url":null,"abstract":"<div>\u0000 \u0000 <p>The disruption of the blood-brain barrier (BBB) in hypertension is a critical pathophysiological event characterized by an increase in barrier permeability, which can potentially lead to severe neurological complications. Telmisartan, an angiotensin II receptor antagonist (ARB), is widely prescribed for the management of hypertension. However, there is limited literature on the specific effects of Telmisartan on BBB disruption associated with high-salt diet (HSD)-induced changes. In this study, a salt-induced hypertensive state was induced in mice using a HSD to investigate the effects of telmisartan on BBB disruption associated with HSD. Our recent findings indicate that Telmisartan mitigates brain vascular endothelial inflammation and reduces BBB permeability in HSD-treated mice. Specifically, it downregulates the messenger RNA (mRNA) and protein expression levels of intercellular adhesion molecule-1 (ICAM-1) and endothelial selectin (E-selectin). Additionally, Telmisartan inhibits BBB permeability as evidenced by reduced extravasation of Evans blue dye and restores the expression of Claudin-1, a crucial tight junction (TJ) protein. In vitro studies further support these findings, demonstrating that Telmisartan effectively reduces Angiotensin II-induced permeability in human brain microvascular endothelial cells (HBMECs). Moreover, Telmisartan treatment leads to an increase in trans-endothelial electrical resistance (TEER), indicative of improved barrier function. It also restores the expression of Claudin-1, prevents endothelial dysfunction, and activates the Wnt/β-catenin signaling pathway. Notably, silencing the β-catenin pathway abrogates the beneficial effects of Telmisartan, suggesting that the protective actions of Telmisartan on BBB integrity in HSD-induced conditions are mediated through the activation of the Wnt/β-catenin signaling pathway. These results collectively suggest that Telmisartan not only effectively manages HSD-induced hypertension but also exerts neuroprotective effects by preserving BBB integrity. This dual functionality positions Telmisartan as a potentially valuable therapeutic agent for patients at risk for neurological complications due to HSD-induced BBB disruption.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080698","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":"Green Synthesis of Sulfonamide Derivatives as Human Carbonic Anhydrase Isoforms I, II, IX, XII Inhibitors and Antioxidants: Comprehensive Insights From Biological Evaluation and In-Depth In Silico Analysis","authors":"KM Abha Mishra,&nbsp;Nutan Kumari,&nbsp;Fabrizio Carta,&nbsp;Gioele Renzi,&nbsp;Harshdeep Singh,&nbsp;Claudiu T. Supuran,&nbsp;Kalyan K. Sethi","doi":"10.1002/jbt.70497","DOIUrl":"10.1002/jbt.70497","url":null,"abstract":"<div>\u0000 \u0000 <p>This study presents the green synthesis, pharmacological evaluation, and <i>in silico</i> analysis of aromatic sulfonamide derivatives for their inhibitory effects on human carbonic anhydrase (hCA) isoforms I, II, IX, and XII and their antioxidant properties. The compounds were synthesized via a one-step green synthetic method using acetic acid as the solvent, providing a straightforward and environmentally considerate approach. The synthesized compounds were confirmed to have 95% to 100% purities via HPLC purity analysis. The inhibition constants (K_i) against hCA I varied between 240 nM and 2185 nM, while inhibition of hCA II was observed with K_i values ranging from 19 to 83 nM. For hCA IX and hCA XII, the K_i values were found from 25 to 882 nM and 8.8 to 175 nM, respectively. These sulfonamides exhibited significant inhibition compared to standard carbonic anhydrase inhibitors such as acetazolamide, ethoxzolamide, zonisamide, methazolamide, dorzolamide, and SLC-0111. The antioxidant activity, assessed using the DPPH assay, was moderate to low, with compound <b>6</b> demonstrating a noteworthy IC₅₀ of 62.8 µg/mL, comparable to the IC₅₀ of ascorbic acid (64.7 µg/mL). Quantum chemical analyses, including FMO, Mulliken population analysis, and electrostatic potential, total electron density, and molecular electrostatic potential analysis, demonstrated significant electrostatic interactions and optimal charge distribution. DFT calculations revealed stable chemical behavior with favorable values for hardness, softness, electronegativity, and electrophilicity. Molecular docking studies provided insights into the binding interactions, while MD simulations (10 ns) revealed the stability of the protein-ligand complexes. ADMET predictions indicated favorable physicochemical properties and compliance with Lipinski's rule. These results highlight the potential of these aromatic sulfonamide derivatives as potent inhibitors of human carbonic anhydrase isoforms, with promising antioxidant activity, suggesting their potential therapeutic applications in conditions such as retinal and cerebral edema, glaucoma, epilepsy, high-altitude sickness, and cancer.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080714","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":"The Effect of Clozapine on Immune-Related Biomarkers in Schizophrenia Patients","authors":"Jia Wei,&nbsp;Ting Dong","doi":"10.1002/jbt.70503","DOIUrl":"10.1002/jbt.70503","url":null,"abstract":"<div>\u0000 \u0000 <p>Schizophrenia is a prevalent mental disorder that significantly impacts global health, with approximately 1% of the population affected and around 30% of cases classified as treatment-resistant schizophrenia (TRS). Clozapine is established as the gold standard for TRS management, yet its use is often complicated by potential adverse effects and the necessity for rigorous blood monitoring due to the risk of severe neutropenia. Recent studies have revealed that clozapine not only influences psychiatric symptoms but also alters immune system functioning and cytokine profiles in patients with schizophrenia. This interplay between clozapine treatment and immune-related biomarkers warrants deeper investigation to elucidate the underlying mechanisms of the disease and to refine therapeutic approaches. Identifying specific biomarkers could enhance clinical decision-making regarding the initiation of clozapine therapy, allowing for more tailored treatments and improved patient outcomes.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080731","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":"Biomimetic Nanoparticles Loaded With α-Cyperone Alleviating LPS-Induced Inflammation in KGN Cells by Activating Nrf2/HO-1 and Suppressing ROS","authors":"Jialing Li,&nbsp;Fengzhi Li,&nbsp;Xue Chen,&nbsp;Jie Ma,&nbsp;Hua Guo","doi":"10.1002/jbt.70495","DOIUrl":"10.1002/jbt.70495","url":null,"abstract":"<p>Diminished ovarian reserve (DOR) is a leading cause of female infertility, and currently, no effective therapeutic options are available. α-Cyperone (AC) possesses various pharmacological properties, including anti-inflammatory and antioxidant effects. However, its clinical application is hindered by poor water solubility, a short half-life, and nonspecific toxicity. In this study, we utilized nanotechnology to develop a novel dual-targeted nanocomplex, termed PLGA@AC@FSHL-M (PAMF) nanoparticles (NPs), comprising poly(lactic-co-glycolic acid) (PLGA) encapsulating AC and camouflaged with a macrophage membrane modified by the FSHL81-95 peptide. This design enabled efficient delivery of AC while simultaneously targeting granulosa cells (GCs). Our findings demonstrated that PAMF NPs significantly reduced the production of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) in lipopolysaccharide (LPS)-induced KGN cells. Furthermore, AC-loaded PAMF NPs enhanced nuclear translocation of nuclear factor erythroid 2–related factor 2 (Nrf2) and upregulated heme oxygenase-1 (HO-1), while inhibiting NF-κβ activation. These results suggest that biomimetic AC-loaded nanoparticles effectively suppress apoptosis and promote proliferation under inflammatory conditions in KGN cells, offering a promising therapeutic strategy for DOR.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080726","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":"AIF-1 Modulates Endometrial Stromal Cell Proliferation, Invasion, and Migration via Mitochondrial Function","authors":"Bo Zhu,&nbsp;Ying Li,&nbsp;Qigui Xie,&nbsp;Xiuni Liu","doi":"10.1002/jbt.70493","DOIUrl":"10.1002/jbt.70493","url":null,"abstract":"<div>\u0000 \u0000 <p>This study investigates the role of allograft inflammatory factor 1 (AIF-1) in regulating the proliferation, invasion, and migration of endometrial stromal cells (ESCs) in the context of endometriosis, focusing on its impact on mitochondrial function. Ectopic endometrial tissues were collected from patients diagnosed with endometriosis, and normal endometrial tissues served as controls. ESCs were isolated and cultured. AIF-1 expression was knocked down using siRNA and overexpressed using plasmid vectors. Quantitative real-time PCR (qRT-PCR), western blot analysis, CCK-8 assays, flow cytometry, transwell assays, scratch assays, ATP detection, and mitochondrial membrane potential assays were performed to evaluate gene expression, cell proliferation, apoptosis, invasion, and mitochondrial function. AIF-1 mRNA and protein levels were significantly upregulated in ectopic ESCs compared to controls. Overexpressing AIF-1 elevated cell proliferation and invasion and decreased apoptosis. Additionally, AIF-1 knockdown decreased mitochondrial DNA copy number, membrane potential, and ATP levels, whereas its overexpression had the opposite effects. AIF-1 plays a crucial role in ESCs proliferation, invasion, and migration by modulating mitochondrial function, potentially via the AIF-1 pathway. These findings suggest that targeting AIF-1 could be a novel therapeutic approach for managing endometriosis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080681","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":"Oxygen Deprivation and Brain Inflammation: The Mitochondrial Link to Alzheimer's Progression","authors":"Salvatore Nesci","doi":"10.1002/jbt.70527","DOIUrl":"10.1002/jbt.70527","url":null,"abstract":"","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080688","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":"Gaining Biological Insights Into Deltamethrin-Induced Toxicity and Resistance at the Molecular Level","authors":"Mustafa Yavuz,&nbsp;Recep Anil Kaya,&nbsp;Ceyhun Bereketoglu,&nbsp;Beste Turanli","doi":"10.1002/jbt.70469","DOIUrl":"10.1002/jbt.70469","url":null,"abstract":"<div>\u0000 \u0000 <p>Deltamethrin (DM), a type II pyrethroid, is one of the most widely used insecticides around the world. The link between diseases including obesity, neurodevelopmental disorders, liver fibrosis and DM treatment has been elucidated in organisms that exposed DM. Also, in aquatic organisms, hepatopancreatic necrosis disease, impaired cellular development, and decreased mobility could be related to DM treatment for pond cleaning and fending off arthropods causing diseases such as Caligidosis. Apart from that, DM resistance in target organisms has been a staggering issue due to the prevalence of DM-resistant insects, which make challenging to overcome vector-borne diseases, agricultural corps' yield, and economic loss in aquaculture. Using omics analysis in organisms exposed to DM, systems biology tools have provided a detailed understanding of the interactions among genes, proteins, metabolites, and microbiota at molecular level. This review underscores the mechanisms of how DM leads to toxicity in model and nontarget organisms, and how target organisms evolve from being susceptible to resistant as a molecular response. Overall, an in-depth analysis of the molecular mechanisms behind DM exposure will provide a comprehensive understanding of the DM application for its risk assessment.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080667","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":"Comparison of Antioxidant Effects of 3-Hydroxybutyrate and Sodium 3-Hydroxybutyrate Through SIRT3/FOXO3A Pathway: Implications for In Vitro and In Vivo Research","authors":"Yu Liu,&nbsp;Jianfei Wu,&nbsp;Duanfang Cai,&nbsp;Kezhi Liu,&nbsp;Mingming Liu,&nbsp;Shiyan Li,&nbsp;Daixu Wei","doi":"10.1002/jbt.70502","DOIUrl":"10.1002/jbt.70502","url":null,"abstract":"<div>\u0000 \u0000 <p>3-hydroxybutyrate (3HBH) and sodium 3HBH (3HBNa) have been used in many studies, leading to confusion about their roles. The present study aimed to compare the antioxidant effects of 3HBH and 3HBNa. The CCK8 was used to assess the antioxidant effect of 3HBH and 3HBNa on H₂O₂-induced BV2 cells. Total-glutathione (T-GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were measured. Apoptosis was evaluated by flow cytometry. Western blot and RT-qPCR were used to detect the protein and mRNA expression levels of BCL-2, BAX, CASPASE-3, SIRT3, and FOXO3A. Blood ketone concentrations of the mice were recorded at different time points after administration of the same dose of 3HBNa and 3HBH. Both 3HBH and 3HBNa showed anti-oxidative and anti-apoptotic ability on H₂O₂-induced BV2 cells, but the ability of 3HBH was stronger than that of 3HBNa. 3HBH exhibited a stronger ability to activate the sirtuin 3 (SIRT3)/forkhead box O3 (FOXO3A) pathway. The ability of ketogenic effects was no significant difference between 3HBH and 3HBNa in in vivo studies. These findings suggest prioritizing 3HBH over 3HBNa in in vitro research. However, both options are available in in vivo studies from a ketogenic perspective.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145080678","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}