Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Chemoprotective Potential of Cyanidin-3-Glucoside Against 1,2-Dimethylhydrazine-Induced Colorectal Cancer: Modulation of NF-κB and Bcl-2/Bax/Caspase Pathway","authors":"Miao Wang,&nbsp;Xiaoyong Wang","doi":"10.1002/jbt.70125","DOIUrl":"10.1002/jbt.70125","url":null,"abstract":"<div>\u0000 \u0000 <p>Colorectal cancer (CRC) represents a significant global health challenge, with approximately 1.8 million new cases diagnosed annually and a mortality toll exceeding 881,000 lives each year. This study aimed to evaluate the chemoprotective efficacy of Cyanidin-3-glucoside (C3G) in a rat model of CRC induced by 1,2-dimethylhydrazine (DMH). Rats were stratified into groups and administered C3G at doses of 10 and 15 mg/kg following DMH exposure to initiate CRC. Key parameters, including organ weights, tumor burdens, and biochemical markers, were meticulously assessed. Administration of C3G significantly restored body weight while reducing the weights of colon and spleen tissues. Moreover, C3G treatment substantially suppressed tumor incidence and weight in DMH-induced CRC rats. Biochemical analysis revealed that C3G markedly reduced levels of CFA, CA19.9, LDH, and nitric oxide (NO). It also modulated lipid profiles, antioxidant activities, and the expression of both Phase I and II enzymes. Inflammatory mediators, including TNF-α, IL-1β, IL-1α, IL-2, IL-4, IL-6, IL-10, IL-12, and IL-17, were significantly downregulated. Notably, C3G inhibited inflammatory markers such as COX-2, PGE2, iNOS, and NF-κB while promoting Caspase-3, -6, and -9 activity. Furthermore, it regulated the Bax/Bcl-2 apoptotic axis, reducing the Bcl-2/Bax ratio. Cyanidin-3-glucoside demonstrated potent chemopreventive effects against colorectal cancer in this experimental model. Its mechanism of action is likely mediated through modulation of NF-κB and the Bcl-2/Bax/Caspase pathway, suggesting its potential as a therapeutic agent in CRC management.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143023576","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 Comprehensive Appraisal of Bisbenzylisoquinoline Alkaloids Isolated From Genus Cyclea for Anticancer Potential","authors":"Alisha Valsan,&nbsp;Vishnu K. Omanakuttan,&nbsp;Kokuvayil Vasu Radhakrishnan,&nbsp;Kaustabh Kumar Maiti","doi":"10.1002/jbt.70137","DOIUrl":"10.1002/jbt.70137","url":null,"abstract":"<div>\u0000 \u0000 <p>The pharmaceutical industry and academia are continuously searching for novel and effective anticancer lead compounds to ensure patient safety, provide a cure, and surpass all other obstacles. Given the indeterminate nature of cancer etiology, the importance of drugs capable of targeting multiple pathways cannot be overstated. Among naturally occurring compounds, bisbenzylisoquinoline (BBIQ) alkaloids, such as berberine, tetrandrine, chelidonine, and berbamine, have demonstrated significant anticancer potential by modulating diverse signaling pathways. Several of these compounds are currently in clinical trials, highlighting their relevance in cancer treatment. This review emphasizes the need for further investigation into the anticancer properties of BBIQ alkaloids, particularly those isolated from eight <i>Cyclea</i> species in India. With around 27 BBIQ alkaloids identified, these compounds hold promise, especially in combating multidrug resistance—a critical challenge in cancer therapy. Given the rising cancer incidence, these alkaloids warrant a deeper exploration of their therapeutic potential.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005943","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":"RETRACTION: Infliximab Substantially Re-Silenced Wnt/Β-Catenin Signaling and Ameliorated Doxorubicin-Induced Cardiomyopathy in Rats","authors":"","doi":"10.1002/jbt.70141","DOIUrl":"10.1002/jbt.70141","url":null,"abstract":"<p><b>RETRACTION</b>: H. E. Mohamed, M. E. Askar, M. A. Shaheen, A. E. Salama, R. A. Idris, and N. N. Younis, “Infliximab Substantially Re-Silenced Wnt/Β-Catenin Signaling and Ameliorated Doxorubicin-Induced Cardiomyopathy in Rats,” <i>Journal of Biochemical and Molecular Toxicology</i> 37, no. 5 (2023): e23312, https://doi.org/10.1002/jbt.23312.</p><p>The above article, published online on January 13, 2023, in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Hari K. Bhat; and Wiley Periodicals LLC. The retraction has been agreed upon following an investigation into concerns raised by a third party, which revealed inappropriate image section duplications between this (Figure 5A) and other articles that were previously published by an overlapping group of authors in a different scientific context. The authors were unable to provide the original unmodified images upon request, therefore, the editors have lost confidence in the data presented and decided to retract the article. The authors do not agree with the retraction.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70141","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005972","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":"Arginase Activity Inhibition With Thymoquinone Induces a Hybrid Type of Cell-Death in MDA-MB-231 Cell Line","authors":"Jaweher Bday,&nbsp;Moufida Souid,&nbsp;Vivien Pires,&nbsp;Sallouha Gabbouj,&nbsp;Anne Véjux,&nbsp;Gérard Lizard,&nbsp;Elham Hassen","doi":"10.1002/jbt.70130","DOIUrl":"10.1002/jbt.70130","url":null,"abstract":"<p>Arginase plays a crucial role in the urea cycle; it also has immunosuppressive and pro-tumor effects. The present study aimed to assess the effects of arginase inhibition by thymoquinone (2-Isopropyl-5-methyl-1,4-benzoquinone), an active compound of <i>Nigella sativa</i>, on cell death in the MDA-MB-231 triple-negative breast tumor cell line. Cell viability assays, Western blot analysis, and flow cytometry analysis were used to characterize oxidative stress and cell death. Our results showed that inhibition of arginase activity with thymoquinone significantly increased intracellular nitric oxide levels and resulted in overproduction of cellular and mitochondrial reactive oxygen species. Reductions in cell viability, cycle arrest, and increased cell death were also observed. Loss of transmembrane mitochondrial potential, activation of caspase-3, -7, and -9, cleavage of PARP, condensation and/or fragmentation of the nuclei, suggest that this cell death involved apoptosis. Furthermore, a cytoplasm vacuole formation and an increase in the ratio of [LC3-II/LC3-I] suggests a concomitant activation of autophagy with apoptosis. Altogether, the present study highlighted that arginase inhibition with thymoquinone induces a hybrid type of cell death defined as oxiapoptophagy. Thus, arginase inhibition with thymoquinone in the MDA-MB-231 cell line could be, in part, involved in the anticancer effect of thymoquinone.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005889","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":"Synthesis and Characterization of Schiff Bases and Their Ag(I) Complexes Containing 2,5,6-Trisubstituted Imidazothiadiazole Derivatives: Molecular Docking and In Vitro Cytotoxic Effects Against Nonsmall Lung Cancer Cell Line","authors":"Ahmed Hamdi Mirghani,&nbsp;Suray Pehlivanoglu,&nbsp;Hakan Alici,&nbsp;Hakan Tahtaci,&nbsp;Saban Uysal","doi":"10.1002/jbt.70142","DOIUrl":"10.1002/jbt.70142","url":null,"abstract":"<p>In this study, four novels 2,5,6-trisubstituted imidazothiadiazole derivative ligands and their Ag(I) complexes were synthesized and characterized using various spectroscopic analysis techniques. First, imidazo[2,1-<i>b</i>][1,3,4]thiadiazole derivative <b>(3)</b> was obtained from the reaction of 5-amino-1,3,4-thiadiazole-2-thiol with benzyl bromide in the presence of KOH in an ethanolic medium. In the next step, the resultant compound reacted sequentially with four substituted phenacyl bromide derivatives <b>(4a–4d)</b> under refluxed ethanol for 24 h to obtain substituted 2-(benzylthio)-6-phenylimidazo[2,1-<i>b</i>][1,3,4]thiadiazole derivatives <b>(5–8)</b>. Compounds <b>(9–12)</b> were obtained by attaching a carbonyl group to carbon number 5 of the imidazothiadiazole group in these compounds with the help of Vilsmeier–Haack reagent. The resultant compounds were reacted in an ethanolic medium to synthesize the novel <b>(13–16)</b> ligands by adding ethylenediamine in a 1:2 molar ratio. The Ag(I) complexes of the resultant ligands were synthesized by mixing silver acetate with the ligands in a dimethyl sulfoxide medium to obtain <b>(17–20)</b> complexes. All the synthesized compounds were analyzed using FTIR, ¹H NMR, ¹³C NMR, mass spectroscopy, magnetic susceptibility, ICP-OES, and thermogravimetric analysis techniques. The study also investigates the in vitro cytotoxic effect of the ligands and complexes on A549 (nonsmall cell lung cancer) cells using the MTT assay and shows that the <b>13</b>, <b>15</b>, and <b>16</b> ligands, together with their complexes, exhibit potent cytotoxicity. In addition, in silico molecular docking simulations were conducted both to support the in vitro cytotoxicity experiments and to ascertain the active binding sites and interactions of the ligands and complexes on the EGFR receptor. The result indicates that ligands and complexes may serve as promising candidates for further investigation as anticancer agents.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11744420/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056014","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":"TWIST1 Regulates FOXM1/β-Catenin to Promote the Growth, Migration, and Invasion of Ovarian Cancer Cells by Activating MFAP2","authors":"Lingqin Zhao,&nbsp;Qian Song,&nbsp;Chao Zheng,&nbsp;Wei Sun,&nbsp;Yaqing Chen","doi":"10.1002/jbt.70140","DOIUrl":"10.1002/jbt.70140","url":null,"abstract":"<div>\u0000 \u0000 <p>TWIST1 is aberrantly expressed in ovarian cancer (OC). MFAP2 is a downstream target of TWIST1, and we previously found MFAP2 facilitated OC development by activating FOXM1/β-catenin. We planned to investigate the mechanisms of TWIST1 in OC. GEPIA (a database for gene expression analysis) and UALCAN (a database containing comprehensive cancer transcriptome and clinical patient data) investigated TWIST1's connection to MFAP2 and patient survival in ovarian serous cystadenocarcinoma (OV). Human OC cells (A2780 and CAOV3) were transfected with si-TWIST1, oe-TWIST1, oe-MFAP2, or si-TWIST1 + oe-MFAP2. Cellular apoptosis, viability, migration, and invasion were detected. TWIST1, MFAP2, FOXM1, and β-catenin protein expressions were tested. Dual-luciferase and ChIP-qPCR validated the correlation between MFAP2 and TWIST1. Moreover, OC mice were established by injecting OC cells subcutaneously. The pathology, apoptosis, as well as Ki67, TWIST1, MFAP2, FOXM1, and β-catenin protein levels of tumors were assessed. TWIST1 expression positively correlated with MFAP2 expression, but negatively related to patients' survival in OV. TWIST1 overexpression promoted malignant behaviors, and increased MFAP2, FOXM1, and β-catenin protein levels for OC cells. TWIST1 knockdown exhibited the opposite trend. In vivo, TWIST1 knockdown disrupted tissue structure, induced apoptosis, decreased Ki67, TWIST1, MFAP2, FOXM1, and β-catenin protein levels in tumor. Interestingly, MFAP2 overexpression reversed the effects of TWIST1 knockdown in vitro and in vivo. Additionally, dual-luciferase and ChIP-qPCR confirmed MFAP2 was a downstream target for TWIST1 in OC. TWIST1 regulated FOXM1/β-catenin to promote the growth, migration, and invasion of OC cells by activating MFAP2, indicating that targeting TWIST1 may be effective for treating OC.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005977","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":"Hypoxia-Inducible Factor-1α Regulates BNIP3-Dependent Mitophagy and Mediates Metabolic Reprogramming Through Histone Lysine Lactylation Modification to Affect Glioma Proliferation and Invasion","authors":"Feng Dong,&nbsp;Haichang Yin,&nbsp;Zhixing Zheng","doi":"10.1002/jbt.70069","DOIUrl":"10.1002/jbt.70069","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>Gliomas are the predominant form of malignant brain tumors. We investigated the mechanism of hypoxia-inducible factor-1α (HIF-1α) affecting glioma metabolic reprogramming, proliferation and invasion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>Human glioma cell U87 was cultured under hypoxia and treated with small interfering (si)HIF-1α, si-B cell lymphoma-2/adenovirus E1B 19-kDa interacting protein 3 (siBNIP3), si-YT521-B homology domain 2 (siYTHDF2), 3-methyladenine and 2-deoxyglucose, with exogenous sodium lactate-treated normally-cultured cells as a lactate-positive control. Cellular hexokinase 2, lactate dehydrogenase A and pyruvate dehydrogenase kinase 1 enzyme activities, glucose uptake, and levels of lactic acid and adenosine triphosphate (ATP), and HIF-1α, glycolysis-related proteins, mitophagy-related proteins, histone H3 lysine 18 lactylation (H3K18la) and YTHDF2 were determined by ELISA, 2-NBDG, kits, and Western blot. Extracellular acidification rate (ECAR), and cell proliferation, invasion, apoptosis and mitophagy were evaluated by extracellular flux analysis, CCK-8, Transwell, flow cytometry, and immunofluorescence staining. H3K18la-YTHDF2 relationship and YTHDF2-BNIP3 interaction were assessed by ChIP and Co-IP assays.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Hypoxia-induced highly-expressed HIF-1α in glioma cells increased glycolysis-related protein levels, glycolytic enzyme activities, glucose uptake, lactic acid production, ATP level and ECAR, thereby promoting metabolic reprogramming, invasion and proliferation. HIF-1α mediated metabolic reprogramming, proliferation and invasion through BNIP3-dependent mitophagy, which were partly negated by mitophagy inhibition. HIF-1α induced histone Kla modification to upregulate YTHDF2. YTHDF2 downregulation impeded YTHDF2-BNIP3 interaction and inhibited HIF-1α-induced BNIP3-dependent mitophagy, curbing glioma cell metabolic reprogramming, proliferation and invasion.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusions</h3>\u0000 \u0000 <p>Hypoxia-induced high HIF-1α expression upregulated YTHDF2 through hH3K18la modification, enhanced YTHDF2-BNIP3 interaction, and regulated BNIP3-dependent mitophagy-mediated metabolic reprogramming to affect glioma proliferation and invasion.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 2","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143005970","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":"Investigation of the Effects of Silymarin on Ovarian Ischemia Reperfusion via Nrf-2/HO-1/NQO1, Ki-67 and Wnt Signaling Pathways","authors":"Ayşe Betül Öztürk,&nbsp;Nurhan Akaras,&nbsp;Hasan Şimşek,&nbsp;Fatih Mehmet Kandemir","doi":"10.1002/jbt.70138","DOIUrl":"10.1002/jbt.70138","url":null,"abstract":"<p>Ovarian ischemia is a pathological condition that usually occurs due to ovarian torsion, resulting in the interruption of blood supply to the ovaries and oxygen deficiency. Silymarin (SLM) is a flavonoid complex of plant origin with pharmacological properties such as antioxidant, anti-inflammatory, and antiapoptotic effects. In this study, we investigated the effects of SLM through different pathways in rats subjected to experimental ovarian ischemia/reperfusion (I/R). Female Wistar rats were divided into five groups: Control, SLM (50 mg/kg), I/R, I/R + SLM25 (25 mg/kg), and I/R + SLM50 (50 mg/kg). SLM was given orally for 7 days, followed by ischemia (2 h) and reperfusion (2 h) on day 8. Biochemical (MDA, GSH, SOD, CAT, GPx) and histological (H&amp;E, Ki-67 IHC) analyses were performed. Also, molecular (qRT-PCR) analyses were performed to evaluate oxidative stress, inflammation, apoptosis, and Wnt signaling. I/R increased MDA and NO levels in ovarian tissue while decreasing SOD, CAT, GPx, and GSH. Antioxidant defense genes (Nrf-2, HO-1, NQO1) were suppressed, and inflammation markers (NF-ĸB, IL-1β, TNF-α) along with apoptotic markers (Bax, Caspase-3) were elevated, while Bcl-2 decreased. The Wnt signaling pathway was inhibited, particularly at Wnt-3A, LRP5, Dvl-2, and Cyclin-1, reducing Ki-67 protein levels and IHC positivity. Silymarin has shown a therapeutic effect on ovarian ischemia reperfusion injury with its antioxidant, antiapoptotic and anti-inflammatory effects and cell cycle regulatory activity.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11733837/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142983077","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":"Design, Synthesis, and In Vitro Evaluation of Aromatic Sulfonamides as Human Carbonic Anhydrase I, II, IX, and XII Inhibitors and Their Antioxidant Activity","authors":"KM Abha Mishra,&nbsp;Nutan Kumari,&nbsp;Fabrizio Carta,&nbsp;Gioele Renzi,&nbsp;Claudiu T. Supuran,&nbsp;Kalyan K. Sethi","doi":"10.1002/jbt.70135","DOIUrl":"10.1002/jbt.70135","url":null,"abstract":"<div>\u0000 \u0000 <p>This study is focused on the design, synthesis, and evaluation of some sulfonamide derivatives for their inhibitory effects on human carbonic anhydrase (hCA) enzymes I, II, IX, and XII as well as for their antioxidant activity. The purity of the synthesized molecules was confirmed by the HPLC purity analysis and was found in the range of 93%–100%. The inhibition constant (K_i) against hCA I ranged from 0.75 nM to 1972 nM. The sulfonamides inhibited isoform hCA II significantly, with a K_i ranging from 0.09 to 56 nM. Similarly, the inhibitory effects on hCA IX and XII were found with K_i spanning from 27.8 to 2099 nM and 9.43 to 509 nM, respectively. Most of the synthesized compounds showed significant inhibition in comparison to standard drugs such as acetazolamide, ethoxzolamide, zonisamide, methazolamide, dorzolamide, and SLC-0111. Antioxidant activity was assessed using the DPPH assay, with compound <b>13</b> showing better antioxidant activity with an IC₅₀ of 54.8 µg/mL, as compared to the standard ascorbic acid (IC₅₀ 64.7 µg/mL). The molecular docking studies provided insights into the binding modes of these compounds. The in silico physicochemical properties, pharmacokinetic/ADME, and toxicity properties evaluations confirmed favorable drug-likeness properties, complying with Lipinski's rule. These findings underscore the therapeutic potential of these compounds for the treatment of retinal/cerebral edema, glaucoma, edema, epilepsy management, high-altitude sickness, and cancer.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143056012","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":"Effectiveness of a Novel PLA2R1 Knock-In Rat Model in Repairing Renal Function Damage","authors":"Bo Huang,&nbsp;Wen-dong Sui,&nbsp;Zi-tong Zhang,&nbsp;Lu Zhao,&nbsp;Yin-yin Li,&nbsp;Dai-he Yang,&nbsp;Yun Zhou","doi":"10.1002/jbt.70056","DOIUrl":"10.1002/jbt.70056","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Phospholipase A2 receptor 1 (PLA2R1) exists in many animals and plays an important role in membranous nephropathy. In this study, we aimed to evaluate a PLA2R1 knock-in rat model with repaired kidney function to study the molecular mechanisms of membranous nephropathy. We constructed the PLA2R1 knockout [PLA2R1(−)] model and PLA2R1 knock in [PLA2R1(+)] model in rats. Consistent complement C3 and IgA expression was confirmed through colocalization studies. Urinary biochemical indicators were performed using Automatic Biochemistry Analyzer. The complement C3, IgG, and Nephrin were detected by immunofluorescence assay. The expression levels of complement C3, IgA, and PLA2R1 were detected by western blot. The differential expression proteins (DEPs) between control and PLA2R1(+) models were detected by liquid chromatography with tandem mass spectrometry. The PLA2R1(−) model showed proteinuria, complement C3 aggregation, and IgA and IgG deposition in the glomerulus. Comparing with the PLA2R1(−) model, the PLA2R1(+) model, the deposition of complement C3 and IgA in the glomerulus did not completely disappear, and IgG expression weakened. Moreover, the absolute value of urinary protein was much lower in the PLA2R1(+) model than in the PLA2R1(−) model, and some of the humanized PLA2R1 gene fragments repaired some of the kidney functions. Humanized PLA2R1-insertion in rats can repair part of the renal function and reduce proteinuria, which will help in studying the molecular mechanisms of membranous nephropathy, as well as the entire membranous nephropathy-related system and complement activation signaling pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 1","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982753","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}