Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Hesperidin Reduces Hepatic Injury Induced by Doxorubicin in Rat Model Through Its Antioxidative and Anti-Inflammatory Effects, Focusing on SIRT-1/NRF-2 Pathways","authors":"Alzahraa A. Elhemiely,&nbsp;Shaimaa H. El-Fayoumi,&nbsp;Mohamed H. A. Gadelmawla,&nbsp;Nievin Ahmed Mahran,&nbsp;Amany M. Gad","doi":"10.1002/jbt.70465","DOIUrl":"https://doi.org/10.1002/jbt.70465","url":null,"abstract":"<div>\u0000 \u0000 <p>Doxorubicin (DOX) is a member of the anthracycline class that acts as a chemotherapeutic drug. It causes toxicity by killing both noncancerous cells and cancer cells, even in organs that are not its intended target. Hepatotoxicity from DOX injection is mainly induced by the liver's involvement in the detoxifying process. Exposure to DOX mainly causes inflammatory insult, oxidative stress (OS), and apoptotic cell death, which cause hepatic damage. To lessen the hepatotoxicity caused by DOX, it is essential to comprehend these processes and investigate protective medications. Thus, our goal was to investigate the molecular pathways responsible for DOX-induced hepatotoxicity, focusing on Sirt-1/Nrf2, NFκ-B, and P53. Additionally, our work is designed to assess the potential of Hesperidin to confer protection against liver injury, which is administered orally in two different doses, to estimate the most efficient dose. In vivo investigations were performed on adult male rats arbitrarily allocated to five groups, including a normal control group, Hesperidin 100 mg/kg treated group, DOX exposure, and DOX exposure treated with Hesperidin (50, 100 mg/kg), respectively. Increased MDA and MPO levels and SIRT-1 suppression were indicators of hepatic OS brought on by DOX exposure, which also disrupted antioxidant pathways and triggered inflammatory and apoptotic pathways. Additionally, the elevated liver function biomarkers and observed histological alterations confirmed these results. Both doses effectively modified these effects, with the high dose, 100 mg/kg, revealing superior effectiveness in alleviating Dox-induced biochemical and histological changes. The present research sheds information on the molecular processes that accompany liver damage caused by DOX while also highlighting Hesperidin's hepatoprotective capabilities. These data imply that Hesperidin, especially when administered at 100 mg/kg, has a powerful effect as a therapeutic compound for combating DOX-induced hepatotoxicity.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915105","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":"Inhibition of USP46/ANK2 Axis Alleviates Myocardial Infarction in Hypoxia/Reoxygenation-Treated Cardiomyocytes and Ischemia/Reperfusion-Induced Rat Models","authors":"Zhong Xie,&nbsp;Jiming Zhou,&nbsp;Dan Huang,&nbsp;Wei Luo,&nbsp;Junbi Zhao","doi":"10.1002/jbt.70454","DOIUrl":"https://doi.org/10.1002/jbt.70454","url":null,"abstract":"<div>\u0000 \u0000 <p>Ankyrin2 (ANK2) has been found to be abnormally overexpressed in myocardial infarction (MI) cell models, but its role and related mechanisms in MI progression have not been explored. Cardiomyocytes (AC16) were subjected to hypoxia/reoxygenation (H/R) treatment to mimic MI cell models, and ischemia/reperfusion (I/R)-induced myocardial injury was used to establish MI rat models. Cell viability, apoptosis and mitochondrial membrane potential (MMP) depolarization were analyzed by CCK8 assay, flow cytometry and JC-1 staining. The levels of inflammatory-related factors and ferroptosis-related markers were determined by commercial kits. ANK2 and ubiquitin-specific peptidase 46 (USP46) protein levels were analyzed using western blot. Cycloheximide treatment assay and ubiquitination assay were used to confirm the regulation of USP46 on ANK2 protein stability and ubiquitination level. After H/R treatment, AC16 cell viability was reduced, while apoptosis, inflammation and ferroptosis were enhanced. ANK2 was upregulated in H/R-induced AC16 cells, and its knockdown repressed H/R-induced cardiomyocyte apoptosis, inflammation and ferroptosis. USP46 enhanced ANK2 protein stability and expression by deubiquitination. Overexpression of ANK2 also reversed the inhibition effect of USP46 knockdown on H/R-induced cardiomyocyte injury. In addition, downregulation of USP46 alleviated myocardial injury in I/R-induced rat models by decreasing ANK2 expression. USP46-stabilized ANK2 promoted cardiomyocyte apoptosis, inflammation and ferroptosis to aggravate MI process.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915044","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 Involvement of RIPK-3/Caspase-8 Inhibition and Nrf2/HO-1 Upregulation in the Protective Effect of Umbelliferone Against Chlorpyrifos-Induced Pulmonary Toxicity","authors":"Wesam H. Abdulaal,&nbsp;Nourelhuda A. Mohammed,&nbsp;Ehab S. Taher,&nbsp;Zuhier A. Awan,&nbsp;Mustafa Adnan Zeyadi,&nbsp;Tarek S. Ibrahim,&nbsp;Fares E. M. Ali,&nbsp;Emad H. M. Hassanein","doi":"10.1002/jbt.70467","DOIUrl":"https://doi.org/10.1002/jbt.70467","url":null,"abstract":"<div>\u0000 \u0000 <p>Chlorpyrifos (CPF) is a pesticide commonly used for pest management. Regretfully, there is evidence that pesticides can cause pulmonary toxicity. The phytochemical umbelliferone (UMB) possesses anti-inflammatory and antioxidant bioactivities. This investigation aimed to determine whether UMB protects against pulmonary toxicity induced by CPF. Rats were divided into four groups: group I (control), group II (30 mg/kg of UMB), group III (10 mg/kg of untreated CPF), and group IV (30 mg/kg of CPF + UMB). Interestingly, UMB reduced pulmonary intoxication, as evidenced by the attenuation of CPF-induced histopathological alterations and the lowering of ALP, LDH, and CRP levels. Furthermore, UMB decreased CPF-induced pulmonary oxidative damage by reducing malondialdehyde (MDA) content and increasing GSH and SOD levels, which was mediated by the upregulation of Nrf2, HO-1, PPAR-γ, and cytoglobin expression. UMB decreased CPF-induced lung inflammation by lowering MPO, TNF-α, and IL-1β levels, as well as NF-κB expression. Additionally, UMB counteracted lung necroptosis by downregulating RIPK-1, RIPK3, mixed-lineage kinase domain-like pseudokinase (MLKL), and Caspase-8, as confirmed by in silico studies. Accordingly, UMB could be a sound therapeutic strategy for mitigating CPF-induced lung intoxication, as it balances antioxidants and oxidants, reduces cellular inflammation, and prevents lung tissue necroptosis.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144915107","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":"Decreased lncRNA TMEM51-AS1 Facilitates TNBC Progression and Its Diagnostic Value of Recurrence with Preoperative DCE-MRI Characteristics","authors":"Tian Song,&nbsp;Zhenfang Zhu,&nbsp;Kanhua Wu","doi":"10.1002/jbt.70436","DOIUrl":"https://doi.org/10.1002/jbt.70436","url":null,"abstract":"<div>\u0000 \u0000 <p>Long noncoding RNAs (lncRNAs) participate in various physiological and pathological processes of tumors and have a significant correlation with MRI radiomics. This study investigated the role of lncRNA TMEM51-AS1 in TNBC and probed the role of preoperative DCE-MRI combined with TMEM51-AS1 in risk stratification of postoperative recurrence of TNBC. Real-time quantitative PCR was used to detect the tissue TMEM51-AS1 expression after operation. According to the recurrence and metastasis of patients 1 year after surgery, patients were grouped into high-risk and low-risk groups. The value of preoperative DCE-MRI and TMEM51-AS1 in the assessment of postoperative recurrence and metastasis was analyzed using the receiver operating characteristic curve. CCK-8 and Transwell assays were performed to evaluate the influence of TMEM51-AS1 on TNBC cellular capacities. TMEM51-AS1 was decreased in TNBC tissues, especially in high-risk groups. TMEM51-AS1 expression, Max Slope, and Max Cone were risk factors associated with postoperative recurrent metastasis, and combined three had a high diagnostic value in predicting postoperative recurrent metastasis. Increased TMEM51-AS1 weakened TNBC cell proliferation, migration, and invasion by regulating miR-19a-3p. Combined preoperative DCE-MRI and TMEM51-AS1 testing may be used to predict the risk of postoperative recurrent metastasis in patients with TNBC. TMEM51-AS overexpression may repress TNBC progression by miR-19a-3p, which may guide the subsequent clinical management and improve the survival of TNBC patients.</p>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910155","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":"PLK3-Activated Mitochondrial Apoptosis Pathway in the Pathogenesis of Sepsis-Associated Acute Kidney Injury","authors":"Pinlu Jiang,&nbsp;Rui Chen,&nbsp;Keke Wu,&nbsp;Jingying Wang,&nbsp;Miaoliang Chen,&nbsp;Jie Qin,&nbsp;Jiansheng Zhu","doi":"10.1002/jbt.70462","DOIUrl":"https://doi.org/10.1002/jbt.70462","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute kidney injury (AKI), a prevalent complication of sepsis, sorely needs effective interventions. Yet, our grasp of the mechanisms behind sepsis-induced AKI is far from complete, hindering the development of targeted therapies. Cecal ligation and puncture (CLP) was used to induce sepsis in mice, followed by treatment with the PLK3 antagonist R406 to assess the effects of PLK3 inhibition on inflammatory responses and renal damage. A lipopolysaccharide (LPS)-induced injury model in HK-2 cells was developed to explore the impact of LPS on lysosomal membrane permeability (LMP) and PLK3 expression. Knocking down PLK3 in HK-2 cells, we investigated its effects on cell viability, apoptosis, mitochondrial membrane potential (MMP), and mitochondrial reactive oxygen species (mtROS). Through bioinformatics analysis, the upstream transcription factor of PLK3 was screened and identified as MAF BZIP transcription factor F (MAFF). The transcriptional regulatory relationship was validated, and rescue experiments were conducted to investigate the effects of MAFF upregulating PLK3 on cell viability and apoptosis. In our study, inhibiting PLK3 in CLP mice mitigated kidney injury, as evidenced by reduced Scr, BUN, and KIM-1 levels, alongside suppressed cell apoptosis, increased pro-inflammatory cytokines, and reduced oxidative stress. In LPS-stimulated HK-2 cells, PLK3 expression was markedly higher, leading to reduced cell viability and increased lysosomal permeability. Knocking down PLK3 in these cells effectively reversed the LPS-induced effects, including cell apoptosis, MMP decrease, and mtROS accumulation. Finally, the upstream transcription factor of PLK3, MAFF, was identified and confirmed to transcriptionally activate PLK3 expression. The upregulation of PLK3 by MAFF further suppressed cell viability and promoted apoptosis in LPS-treated HK-2 cells. PLK3 is a key driver of sepsis-associated AKI (S-AKI), transcriptionally activated by MAFF, and mediates its effects through the mitochondrial apoptotic pathway. Targeting PLK3 could be an effective strategy to reduce the impact of S-AKI.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144910183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Methyltransferase-like 14 (METTL14)-mediated N6-methyladenosine (m6A) Modification of Forkhead Box Protein 1 (FOXP1) Regulates Trophoblast Inflammation and Function via Transmembrane BAX Inhibitor Motif-Containing 6 (TMBIM6)","authors":"Yanhua Liu,&nbsp;Yingru Liu,&nbsp;Xiaoying Zhang,&nbsp;Xiaoxiong Zhu,&nbsp;Yaping Liu","doi":"10.1002/jbt.70458","DOIUrl":"https://doi.org/10.1002/jbt.70458","url":null,"abstract":"<div>\u0000 \u0000 <p>Pre-eclampsia (PE) represents a serious pregnancy complication characterized by impaired trophoblast function. Although methyltransferase-like 14 (METTL14) has been implicated in PE pathogenesis and trophoblast dysfunction, its precise molecular mechanisms remain unclear. mRNA expression was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Immunoblot analysis was used for protein expression evaluation. Total N6-methyladenosine (m6A) RNA methylation was analyzed using an assay kit. Cell tube formation, invasion and colony formation were assessed by tube formation, transwell and colony formation assays, respectively. Interleukin-8 (IL-8), IL-1beta (IL-1β), and IL-6 levels were quantified by enzyme-linked immunosorbent assay (ELISA). The influence of METTL14 in forkhead box protein 1 (FOXP1) was tested by methylated RNA immunoprecipitation (MeRIP) and mRNA stabilization assays. The FOXP1/transmembrane BAX inhibitor motif-containing 6 (TMBIM6) relationship was validated by chromatin immunoprecipitation (ChIP) and luciferase assays. Total m6A methylation levels and METTL14 expression were significantly increased in placental samples of PE patients. Overexpression of METTL14 diminished cell colony formation, invasion, and tube formation abilities of human HTR-8/SVneo trophoblast cells and promoted their pro-inflammatory cytokine production. METTL14 epigenetically reduced FOXP1 expression via an m6A dependent mechanism. Re-expression of FOXP1 exerted a counteracting impact on METTL14-driven dysfunction and inflammation of HTR-8/SVneo cells. FOXP1 promoted TMBIM6 transcription, and METTL14 reduced TMBIM6 expression by FOXP1. FOXP1 regulated HTR-8/SVneo cell phenotypes and inflammation by TMBIM6. Our findings identify a new epigenetic mechanism, the METTL14/FOXP1/TMBIM6 axis, with the ability to affect trophoblast function and inflammation.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894114","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":"Protective Potential of Hispidulin Against Oleic Acid-Induced Acute Kidney Injury: Investigation of Oxidative Stress, Inflammation and Cellular Death Mechanisms","authors":"Bahri Avci,&nbsp;Handan Uguz,&nbsp;Esra Palabiyik,&nbsp;Ayse Nurseli Sulumer,&nbsp;Hakan Askin","doi":"10.1002/jbt.70461","DOIUrl":"https://doi.org/10.1002/jbt.70461","url":null,"abstract":"<div>\u0000 \u0000 <p>Hispidulin is a natural flavonoid extracted from many plants such as <i>Saussurea involucrata</i> by different methods. The present study aims to evaluate the histopathologic, antioxidant and molecular effects of hispidulin in oleic acid-induced male <i>Spraque Dawley</i> rats. Accordingly, rats were divided into three separate groups HC: Healthy Control Group OA: Oleic Acid Group and H + OA Group. Oxidative stress markers superoxide dismutase (SOD), catalase (CAT), glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) were evaluated in kidney tissues obtained from the animals of the treatment groups. The same tissues were subjected to histopathologic examination. Moreover, gene expression levels of critical regulators of apoptosis, cellular metabolism and inflammation were examined by real-time PCR to identify the molecular structure responsible for the nephrotoxic impact of oleic acid. It was observed that oleic acid (OA) led to decrease in GSH level and an increase in MPO and MDA levels in rat kidney tissues. The levels of SOD and CAT, which are among the antioxidant system components, were found to decrease. In addition, kidney damage biomarker (<i>Kim-1</i>), inflammation genes <i>(Il-6</i>, <i>Nf-Kß</i>), apoptotic gene (<i>Casp3</i>) and gene involved in extracellular matrix renewal (<i>Mmp2</i>) were negatively affected by OA exposure. However, it was observed that hispidulin was able to reverse all the deregulations induced by OA administration. In conclusion, oleic acid, used as an inducer of acute kidney injury, caused tissue damage by disrupting the oxidant and antioxidant balance and dysfunction in renal tissues by increasing the levels of inflammatory mediators. Hispidulin, which we use as a renoprotective agent in acute kidney injury, may be considered as an alternative, versatile and effective technique to alleviate renal injury by inhibiting inflammation, tubular cell death and oxidative stress.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894415","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":"Sinomenine Hydrochloride Activates Podocyte Autophagy by Attenuating PI3K/AKT/mTOR Pathways to Protect Diabetic Nephropathy","authors":"Lihan Xie,&nbsp;Weinan Li,&nbsp;Shiqi Fan,&nbsp;Jinsong Jin","doi":"10.1002/jbt.70455","DOIUrl":"https://doi.org/10.1002/jbt.70455","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic kidney disease (DKD) is a common complication of diabetes, often characterized by podocyte injury, proteinuria, and eventual renal failure. Sinomenine hydrochloride (SH), an active component derived from traditional Chinese medicine, is clinically effective in treating kidney diseases. This study investigates the protective effects of SH on podocytes under high-glucose conditions and its mechanism of action. Mouse podocytes (MPC-5) were treated with SH at concentrations of 50, 200, and 600 μg/mL under high-glucose conditions (30 mmol/L) for 24 h to establish a DKD model. Cell viability was assessed using CCK-8 assays, and apoptosis rates were measured using flow cytometry. Autophagy levels were evaluated by detecting LC3-II, Beclin-1, and P62 proteins via Western blot analysis, while the involvement of the PI3K/AKT/mTOR pathway was analyzed by examining phosphorylated AKT and mTOR. Transmission electron microscopy was employed to observe autophagosomes. SH improved podocyte viability, reduced apoptosis, and enhanced autophagic activity by increasing LC3-II and Beclin-1 expression while decreasing P62 levels. SH also downregulated p-AKT and p-mTOR, indicating inhibition of the PI3K/AKT/mTOR pathway. Electron microscopy confirmed increased autophagosomes in SH-treated groups. SH protects podocytes in a high-glucose environment by enhancing autophagy through inhibition of the PI3K/AKT/mTOR pathway. These findings provide insights into SH as a potential therapeutic agent for DKD management.</p>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894116","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 Applications of Mesenchymal Stem Cell-Derived Extracellular Vesicles in Diabetic Neuropathy; Challenges and Future Prospective","authors":"Lei Shi,&nbsp;Hong xia Che,&nbsp;Huan Yang,&nbsp;Yang yang Li,&nbsp;Yuan yuan Jin","doi":"10.1002/jbt.70459","DOIUrl":"https://doi.org/10.1002/jbt.70459","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetes, a collection of metabolic syndromes, is a significant global health issue. One of the most prevalent microvascular complications of diabetes that is linked to excessive blood sugar levels is diabetic neuropathy (DN). DN frequently necessitates prolonged therapy and may persist following treatment, which could have a negative impact on the individual's quality of life. The crucial management of DN still requires the development of efficient therapies, regardless of the continuous discovery of new drugs. A novel innovation and advancement in the treatment of diabetes and diabetes-related complications has been the emergence of mesenchymal stem cells (MSCs). Compared to their parent donors, MSC-derived extracellular vesicles (MSC-EVs) have shown considerable potential as a unique cell-free method that reprograms damaged cells by initiating regenerative processes. Increasingly, research has demonstrated that MSC-EVs transfer a variety of biological compounds to establish a beneficial microenvironment, thereby playing an important role in alleviating diabetic complications. The objective of this review was to offer a comprehensive perspective on the utilization of MSC-derived EVs in DN, as well as to discuss recent developments and potential challenges to improve their efficacy in DN.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894413","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":"Knockdown of CDKN1A Suppresses the IL-17 Pathway to Inhibit Oxidative Stress and Alleviate Autism Spectrum Disorder","authors":"Wenda Wang,&nbsp;Qiujin Lin,&nbsp;Liru Liu,&nbsp;Hanhui Mai,&nbsp;Hongmei Tang,&nbsp;Kaishou Xu","doi":"10.1002/jbt.70466","DOIUrl":"https://doi.org/10.1002/jbt.70466","url":null,"abstract":"<div>\u0000 \u0000 <p>Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by impaired social interaction, communication deficits, and repetitive behaviors. However, the underlying molecular mechanisms remain elusive. This study aims to investigate the role of cyclin-dependent kinase inhibitor 1 A (CDKN1A) in ASD. This study integrated multi-omics bioinformatics analysis to identify differentially expressed genes (DEGs) related to oxidative stress in ASD. Hub genes were screened using machine learning models. In vivo, an ASD rat model was established by maternal lipopolysaccharide (LPS) injection. Behavioral tests (open field, three-chamber social, morris water maze) were performed. Histopathology change was observed by hematoxylin-eosin staining. In vitro, LPS-stimulated BV2 microglia were treated with IL-17A for feedback experiments. Enzyme-linked immunosorbent assay was carried out to measure inflammatory factors and oxidative stress indicators. Western blot was used to detect protein expression. Bioinformatics analysis revealed 30 DEGs, with CDKN1A emerging as a prominent hub gene associated with oxidative stress. ASD model rats exhibited behavioral deficits, neuroinflammation, and hippocampal neurodegeneration. CDKN1A knockdown significantly attenuated these phenotypes, improving social interaction, reducing anxiety-like behaviors, and enhancing spatial learning and memory. Moreover, IL-17 pathway was screened as downstream pathway of CDKN1A. CDKN1A silencing suppressed LPS-induced apoptosis, inflammation, and oxidative stress in BV2 microglial cells, which was weakened by IL-17A. CDKN1A drives ASD pathogenesis via IL-17 pathway activation. Its suppression mitigates neuroinflammation, oxidative stress, and behavioral impairments, establishing CDKN1A as a novel therapeutic target for ASD.</p>\u0000 <p><b>Trial Registration:</b> Clinical trial number: Not applicable.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 9","pages":""},"PeriodicalIF":2.8,"publicationDate":"2025-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144894115","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}