Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Pterostilbene Exhibited the Anticancer Effect Against 1, 2-Dimethylhydrazine (DMH)-Induced Colorectal Cancer via Alteration of Oxidative Stress, Inflammation and Gut Microbiota","authors":"Chengyun Guo,&nbsp;Ankit Kumar,&nbsp;Chao Liao","doi":"10.1002/jbt.70123","DOIUrl":"https://doi.org/10.1002/jbt.70123","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is the third leading cause of cancer-related deaths worldwide. The current investigation aimed to assess the chemoprotective effects of pterostilbene against 1,2-dimethylhydrazine (DMH)-induced colorectal cancer in mice. An in-silico study was conducted to perform docking studies against nuclear factor kappa factor (NF-κB). CRC was induced in mice by administering DMH (20 mg/kg) subcutaneously, and the mice were subsequently administered various dosages of pterostilbene (5, 10, and 15 mg/kg). At the end of the study, various biochemical parameters, including inflammatory cytokines, inflammatory markers, and antioxidant enzymes, were examined. Additionally, the mice's stools were collected for the analysis of intestinal microbiota. A total of 5 hydrogen bonds were identified between NF-κB and pterostilbene using LigPlot+. Pterostilbene significantly (<i>p</i> &lt; 0.001) reduced tumor incidence, tumor weight, and increased body weight. Pterostilbene significantly (<i>p</i> &lt; 0.001) altered the levels of lipid peroxidation, reduced glutathione, superoxide dismutase, glutathione peroxidase, and catalase as well as the activity of both phase I and phase II enzymes. Furthermore, pterostilbene significantly (<i>p</i> &lt; 0.001) decreased the levels of proinflammatory cytokines such as tumor necrosis factor-α, interleukin-6, interferon-γ, and interleukin-1β, while increasing the levels of anti-inflammatory cytokines like interleukin-4 and interleukin-10. Pterostilbene considerably suppressed the levels of cyclooxygenase-2 and prostaglandin E2, as well as inducible nitric oxide synthase and simultaneously elevated the levels of apoptosis-related parameters, including caspase-3, caspase-8, and caspase-9. Moreover, pterostilbene significantly reduced the abundance of Staphylococcus in the intestinal microbiota and enhanced the levels of beneficial bacteria, such as <i>Bifidobacterium, Akkermansia,</i> and <i>Lactobacillus</i>. Pterostilbene demonstrated a chemoprotective effect against CRC by effectively reducing oxidative stress, mitigating inflammatory responses, and inducing alterations in gut microbiota levels.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143612454","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":"Resveratrol Alleviates Liver Fibrosis by Targeting Cross-Talk Between TLR2/MyD88/ERK and NF-κB/NLRP3 Inflammasome Pathways in Macrophages","authors":"Jin-qing Lei,&nbsp;Qing-li Xie,&nbsp;Qing-ping Li,&nbsp;Shan-yu Qin,&nbsp;Jiao-hua Wu,&nbsp;Hai-xing Jiang,&nbsp;Bing Yu,&nbsp;Wei Luo","doi":"10.1002/jbt.70208","DOIUrl":"https://doi.org/10.1002/jbt.70208","url":null,"abstract":"<div>\u0000 \u0000 <p>Resveratrol alleviates liver fibrosis in mice by upregulating IL-10 to reprogram the macrophage phenotype; however, the mechanism remains to be elucidated. Building on our previous work, in this study, we aimed to determine the role of the TLR2/MyD88/ERK and NF-κB/NLRP3 inflammasome pathways in mediating the effects of resveratrol on liver fibrosis and macrophage polarization. We investigated the expression of cytokines in these inflammasome pathways in a mouse model of liver fibrosis and resveratrol-treated macrophages. The results showed that expression of TLR2, MyD88, ERK, and NF-κB1 in liver tissues was increased in the fourth week after treatment with resveratrol but decreased in the fifth week. Similar results were obtained for the NF-κB/NLRP3 inflammasome pathway. The results also showed that cytokines in both the TLR2/MyD88/ERK and NF-κB/NLRP3 inflammasome pathways in macrophages were elevated after 24 h and reduced after 36 h of treatment with resveratrol. Immunofluorescence and nucleocytoplasmic separation assays showed that resveratrol inhibited the translocation of NF-κB from the cytoplasm to the nucleus in macrophages, and increased NF-κB1 was associated with inhibition of the TLR2/MyD88/ERK pathway. Silencing NF-κB1 increased the expression of TLR2, MyD88, and ERK. In conclusion, the TLR2/MyD88/ERK and NF-κB/NLRP3 inflammasome pathways are involved in the effect of resveratrol on macrophage polarization and the subsequent modulation of liver fibrosis. NF-κB1 acts as the common cytokine that coordinates the crosstalk between the two pathways. Our findings highlight the potential of the members of these pathways as therapeutic targets toward the treatment of liver fibrosis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602687","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":"N-Acetyltransferase 10 Promotes Gastric Cancer Progression by Mediating the N4-Acetylcytidine Modification of Lactate Dehydrogenase A","authors":"Juan Liang,&nbsp;Peng Zhai,&nbsp;Guohua Cheng,&nbsp;Jinlong Han,&nbsp;Xiang Song","doi":"10.1002/jbt.70227","DOIUrl":"https://doi.org/10.1002/jbt.70227","url":null,"abstract":"<div>\u0000 \u0000 <p>The N4-acetylcytidine (ac4C) modification, which is catalyzed by NAT10, represents a significant posttranscriptional modification of mRNA in multiple cancers. However, the significance of this modification in gastric cancer (GC) progression remains unclear. To evaluate the potential of differential NAT10 expression in GC, RT-qPCR and western blot were employed. Dot blot and acRIP were utilized for total ac4C and <i>LDHA</i> mRNA ac4C detection. Subsequently, the effects of NAT10 on GC cell viability and glycolysis were assessed by Cell Counting Kit-8 and glycolysis-related indicator detection Kits. Furthermore, rescue experiments and mice xenograft experiments were conducted to investigate the mechanism underlying the NAT10/LDHA signaling axis in GC. This study identified upregulated NAT10 and ac4C levels in GC. Knockdown of NAT10 led to inhibited cell viability and glycolysis. Additionally, NAT10 directly bound to <i>LDHA</i> mRNA. NAT10 silencing decreased the expression and stability of <i>LDHA</i> mRNA, as well as its ac4C modification level. Interestingly, LDHA overexpression partially reversed the effects of NAT10 knockdown on cell viability and glycolysis. Eventually, the oncogenic effect of NAT10/ac4C/LDHA axis was confirmed in xenograft experiments. NAT10 promoted the GC progression by mediating the ac4C modification of <i>LDHA</i> mRNA, which could serve as a potential therapeutic target for GC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602688","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":"Development of 1,2,3-Triazolopyridazinone Derivatives as Potential Caspase 3 and Apoptosis Inducers: Design, Synthesis and Anticancer Activity Studies","authors":"Guler Yagiz Erdemir,&nbsp;Ali Kuruçay,&nbsp;Burhan Ates,&nbsp;Aliye Altundas","doi":"10.1002/jbt.70216","DOIUrl":"https://doi.org/10.1002/jbt.70216","url":null,"abstract":"<p>Herein, the synthesis, anticancer activity and apoptotic pathways of 1,2,3-triazolopyridazinones compounds, which are similar to DNA bases not previously found in the literature have been investigated. To achieve this goal, it is designed the hybrid molecules combining triazole and pyridazinone/pyridazithione structures, bearing a lipophilic group (benzyl/phenyl) at the one position and benzene with electron withdrawing or donating groups at five positions, with high pharmacophoric properties on the same scaffold structure. The representative compounds in this series <b>5a, 5c, 6a</b> and <b>8c</b> exhibited higher anticancer activity than other compounds and cisplatin control against breast (MCF-7) and lung (A549) cell lines. These compounds were less toxic when tested against the noncancerous L929 cell line. In addition, the apoptotic effect mechanisms of these compounds were confirmed by AO/EB staining and caspase 3 activity results. These findings indicate that some derivatives of these compounds could be effective therapeutic agents for the treatment of cancer disease with an apoptosis-promoting.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70216","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602849","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":"Linagliptin Mitigates DMH-Induced Colorectal Cancer in Rats: Crosstalk Between NFAT and IL-6/JAK2/STAT3/NF-κB Signaling Hubs","authors":"Mohamed O. Mahmoud,&nbsp;Hager Abd Al-Hamid,&nbsp;Noha F. Hassan,&nbsp;Mona R. El-Ansary,&nbsp;Safaa B. Gomaa","doi":"10.1002/jbt.70206","DOIUrl":"https://doi.org/10.1002/jbt.70206","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) is a multicomponent disease and the second most frequent root of cancer-related deaths globally. Linagliptin is a dipeptidyl peptidase-4 (DPP-4) inhibitor. It has been repurposed in recent experimental studies due to its marked anti-inflammatory activities. This study aimed to evaluate the ameliorative role of linagliptin in 1,2-dimethylhydrazine (DMH)-induced CRC via modulation of NFAT-mediated IL-6 and JAK2/STAT3/NF-κB signaling pathways. CRC model has been successfully established via a dose equal 40 mg/kg two times a week of DMH for 8-week duration. Twenty-four Wistar rats were segregated into three groups of eight rats each; normal control, DMH-induced CRC and DMH + linagliptin (10 mg/kg; p.o). Linagliptin attenuated DMH-induced oxidative stress by restoring the declined levels of some antioxidant enzymes. Linagliptin suppressed the elevated nuclear factor kappa B (NF-κB) induced by DMH which is highlighted using immunohistochemistry analysis. The anti-inflammatory role of linagliptin has been fortified by the decline in nuclear factor of activated T-cells (NFAT) mRNA expression level along with the reduction in vascular endothelial growth factor (VEGF), interlukin-6 (IL-6) and cyclooxygenase-2 (COX-2) levels. Linagliptin mitigate the protein expression of DMH-activated oncogenic janus-activated kinase/signal transducers and activators of transcription (JAK2/STAT3). Linagliptin exerted a proapoptotic effect to tumor cells manifested by a remarkable decline in B-cell lymphoma 2 (Bcl-2) and a significant elevation in Bcl-2-associated X protein (Bax) expression levels. The histopathological analysis revealed that linagliptin has inhibitory potential against the DMH induced dysplastic aberrant crypt foci (ACF) and adenocarcinoma. Linagliptin ameliorated CRC by modulating NFAT-mediated IL-6 with JAK2/STAT3/NF-κB signaling cascades.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143602450","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":"Simvastatin Enhances the Cytotoxic Effects of Doxorubicin in a Mammary Adenocarcinoma Cell Model by Involving Connexin 43","authors":"Roberta Vitale,&nbsp;Stefania Marzocco,&nbsp;Ada Popolo","doi":"10.1002/jbt.70214","DOIUrl":"https://doi.org/10.1002/jbt.70214","url":null,"abstract":"<p>Gap Junctions channels formed by Connexins (Cx) provide intercellular communication enabling the coordination of cell growth, differentiation, and metabolism, and their reduction has been shown in many tumor types. Expression levels of Cx43, the most extensively studied Gap Junctions forming protein, are reduced or completely absent in breast cancer cells, while their overexpression correlates with increased cellular permeability to anticancer agents and, consequently, reduced resistance to drug treatments. So, drug associations targeting Cx43 are being considered to overcome chemoresistance. Previous studies demonstrated that Simvastatin (Sim) interferes with Cx43 expression and localization, and chemo-sensitizing effects of Sim in several tumor cell lines treated with antineoplastic chemotherapeutics have been shown. This study aimed to evaluate whether Sim cotreatment enhances Doxorubicin-induced cytotoxicity by affecting Cx43 expression and/or phosphorylation, so MCF-7 cells were treated with Sim (10 µM) for 4 h and then coexposed to Sim and Doxorubicin (1 µM) for 20 h. In Sim cotreated cells, increased membrane levels of Cx43 have been shown; moreover, decreased levels of Cx43 phosphorylated on Ser368 and Ser262 residues, involved in channel closure and disruption of cell–cell communication, have been demonstrated in these cells. In Sim cotreated cells increased Doxorubicin uptake and enhanced Doxorubicin-induced cytotoxic effects have been demonstrated together with reduced migratory capacity. Our data support the notion that Sim cotreatment could be a possible strategy to overcome chemoresistance, since the observed increase in Cx43 membrane levels, and the concomitant reduction of Cx43 phosphorylation, could be responsible for increased sensitization of cells to Doxorubicin treatment.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70214","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595090","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":"Preparation, Spectral Characterization and Antioxidant Activities of Aminothiophene-Containing Schiff Base and Co(II) and Pd(II) Complexes","authors":"Naki Çolak,&nbsp;Ahmet Savcı,&nbsp;Nevin Turan,&nbsp;Kenan Buldurun","doi":"10.1002/jbt.70215","DOIUrl":"https://doi.org/10.1002/jbt.70215","url":null,"abstract":"<p>This research focused on synthesizing a Schiff base (L) and its Co(II) and Pd(II) complexes under appropriate conditions to contribute to enhancing antioxidant activity. The ligand was synthesized by reacting methyl 2-amino-4-ethyl-5-methylthiophene-3-carboxylate with 5-bromo-2-hydroxybenzaldehyde. Various analytical techniques were employed to characterize the ligand and its resulting complexes, including microanalysis, ¹H and ¹³C NMR spectroscopy, FTIR, electronic spectra, mass spectrometry, magnetic susceptibility, molar conductance, and thermo-gravimetric analysis. Electronic spectra and magnetic moment values were used to confirm the geometric structures of the synthesized compounds. Thermo-gravimetric analyses (TGA-DTA) were conducted to evaluate the thermal stability of the complexes. The Pd(II) complex was found to have a square planar structure, while a tetrahedral structure was suggested for the Co(II) complex. The results from the elemental analysis were consistent with both the ligand and metal complexes, showing good agreement between calculated and experimental values. The in vitro antioxidant activities of the newly synthesized compounds were examined using different antioxidant methods. Experiment results exhibited that the Pd(II) complex had better activities than the Schiff base and Co(II) complex. According to ABTS experimental results, Pd(II) complex (IC50:1.25) showed similar activity to the standards. In contrast, CUPRAC results revealed that Pd(II) complex (7.55 µg TE/mL) showed better activity than the standards. The results indicate that Pd(II) complex has strong potential as effective antioxidants, making them valuable for food and medicine applications.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70215","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595322","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":"Long Noncoding RNA E2F1 Messenger RNA Stabilizing Factor (EMS) Promotes Sorafenib Resistance in Renal Cell Carcinoma by Regulating miR-363-3p and Dual-Specificity Phosphatase 10 Expression","authors":"Pinxiao Wang,&nbsp;Qian Deng,&nbsp;Siyuan Pan,&nbsp;Weiping Dong","doi":"10.1002/jbt.70153","DOIUrl":"https://doi.org/10.1002/jbt.70153","url":null,"abstract":"<div>\u0000 \u0000 <p>Renal cell carcinoma (RCC) is a common kidney disease associated with high mortality. Sorafenib is a protein kinase inhibitor that targets multiple kinases and is used for treating different cancers, including RCC. However, sorafenib resistance in patients with RCC hampers its use. Therefore, elucidating the molecular mechanisms underlying sorafenib resistance in RCC and developing novel therapeutic strategies to overcome drug resistance are vital. In this study, we found that the expression level of the long noncoding RNA (lncRNA) E2F1 messenger RNA stabilizing factor (EMS) was significantly higher in sorafenib-resistant RCC tissues and cell lines than in sorafenib-sensitive RCC tissues and cell lines. <i>lncRNA EMS</i> knockdown improved the sensitivity of sorafenib-resistant RCC cells to sorafenib treatment, as evidenced by decreased cell proliferation and increased apoptosis. Additionally, <i>lncRNA EMS</i> silencing combined with sorafenib treatment markedly inhibited RCC tumor development in vivo. Moreover, it was systematically shown that lncRNA EMS sponged <i>miR-363-3p</i>, whose expression was decreased in sorafenib-resistant RCC. Notably, <i>miR-363-3p</i> negatively regulated the expression of dual-specificity phosphatase 10 (<i>DUSP10</i>) by targeting its 3′-UTR. Furthermore, <i>miR-363-3p</i> overexpression restored sorafenib sensitivity, whereas upregulated <i>DUSP10</i> expression promoted sorafenib resistance in sorafenib-resistant cell lines. In conclusion, the lncRNA EMS/miR-363-3p/DUSP10 axis regulates sorafenib resistance in RCC, and these molecules are promising biomarkers and therapeutic targets for patients with sorafenib-resistant RCC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595323","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":"Exosomatic miR-1246 Promotes Hepatocellular Carcinoma Progression via FSTL5 and ERK/p38 MAPK Pathway","authors":"Wen-ju Chen,&nbsp;Ying-jie Dai,&nbsp;Wan-hong Gu,&nbsp;Chun-ling Zhang,&nbsp;Yi-chao Wang","doi":"10.1002/jbt.70148","DOIUrl":"https://doi.org/10.1002/jbt.70148","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Hepatocellular carcinoma (HCC) is one of the most common malignant tumors worldwide. Unfortunately, the effective targeted therapies for HCC are lacking at present. While the regulation of microRNA-1246 (miR-1246) has been identified in HCC, its specific mechanism in exosomes derived from HCC remains elusive. This study aimed to explore the regulation of tumor-derived exosome miR-1246 in HCC cell invasion, migration, proliferation, and epithelial-mesenchymal transition (EMT).</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Exosomes secreted by HepG2 cells were characterized via Western blotting, nanoparticle tracking analysis, and transmission electron microscopy, followed by transfection with a miR-1246 inhibitor. RT-qPCR was employed for measuring the miR-1246 levels. Also, the impacts of the exosome miR-1246 inhibitor on HepG2 cell migration, invasion, proliferation, and EMT were evaluated.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>The findings revealed elevated miR-1246 levels in HCC tissues relative to adjacent non-cancerous tissues, with a greater enrichment of miR-1246 in HepG2-derived exosomes than in HepG2 cells. HCC cell invasion, migration, proliferation, and EMT were significantly enhanced by HCC-derived exosomes, while exosomes loaded with miR-1246 inhibitor inhibited these biological functions. Further mechanistic studies illustrated an association of the regulatory role of miR-1246 with FSTL5 and ERK/p38 MAPK signaling.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>In conclusion, tumor-derived miR-1246 enters hepatocellular carcinoma cells in the form of exosomes and promotes cancer cell invasion, EMT, and migration. The potential mechanism of miR-1246 is potentially relevant to the targeted gene FSTL5 as well as the ERK/p38 signaling.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595037","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 Anti-Inflammatory Potential of SLC-0111: A Carbonic Anhydrase Inhibitor Targeting Cyclooxygenase-Mediated Inflammatory Pathways in a Carrageenan-Induced Rat Model","authors":"Aslınur Doğan,&nbsp;Elif Merve Betül Yanılmaz,&nbsp;Gulcin Karakoc,&nbsp;Ali Parlar,&nbsp;Ebru Annaç,&nbsp;Nebih Lolak,&nbsp;Suleyman Akocak","doi":"10.1002/jbt.70217","DOIUrl":"https://doi.org/10.1002/jbt.70217","url":null,"abstract":"<p>Inflammation is a fundamental physiological reaction that leads to the development of many diseases, including tissue damage, asthma, diabetes, atherosclerosis, inflammatory bowel disease, and cancer. The enzyme COX is a vital mediator in inflammatory processes. Interestingly, the COX enzyme possesses multiple structural similarities to the carbonic anhydrase enzyme. SLC-0111, a molecule known for its potent and selective inhibition of carbonic anhydrase, has not yet been studied for its potential effects on acute inflammation, proinflammatory cytokine levels, or oxidative stress parameters. Our study seeks to assess the binding affinity of SLC-0111 to the COX enzyme, as well as its possible anti-inflammatory properties. We treated rats SLC-0111 at dosages of 50, 100, and 200 mg/kg for 3 days before generating inflammation with carrageenan (CAR). Following CAR delivery, paw thickness was evaluated at 4-h intervals to assess inflammatory levels. Additionally, protein extravasation in paw tissue has been examined using Evans Blue (EB) dye. MDA and glutathione (GSH) levels in paw tissue were measured to assess oxidative stress. Carrageenan enhanced edema, protein extravasation, and proinflammatory cytokines TNF-α, IL-1β, IL-6, IL-4, and IL-13. SLC-0111 decreased all of these, except for IL-4. Similarly, the histological findings of our research indicated that SLC-0111 had an anti-inflammatory effect at a dose of 200 mg/kg. However, SLC-0111 had no significant effect on MDA or GSH levels. These data represent that SLC-0111 may have anti-inflammatory properties and could be used as a treatment for inflammation-related disorders.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 3","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-03-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70217","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143595091","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}