Journal of Biochemical and Molecular Toxicology最新文献

{"title":"Relaxin 2 Suppresses Tumor Growth in Esophageal Squamous Cell Carcinoma EC9706 Cells Through Modulation of the STAT Signaling Pathway","authors":"Juzheng Wang,&nbsp;Lv Wang,&nbsp;Qingshi Wang,&nbsp;Qiang Lu","doi":"10.1002/jbt.70288","DOIUrl":"https://doi.org/10.1002/jbt.70288","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Esophageal carcinoma is a highly aggressive cancer with limited therapeutic options. Relaxin 2 (RLN2) has been identified as a regulator of various physiological processes, but its role in cancer, particularly in esophageal carcinoma, is less understood. This study investigates the anticancer effects of RLN2 in EC9706 esophageal carcinoma cells and explores its involvement in the STAT signaling pathway. The study utilized various assays, including CCK-8 for cell viability, DAPI staining and annexin V-FITC for apoptosis assessment, transwell chambers for cell migration and invasion, tube formation assay for angiogenesis, and western blot analysis for analyzing apoptosis-related and STAT signaling proteins. Additionally, the in vivo anticancer potential of RLN2 was assessed using a mouse model. RLN2 demonstrated significant cytotoxicity against esophageal EC9706 cancer cells, inhibiting cell proliferation in a dose- and time-dependent manner. Apoptosis was markedly increased with higher doses of RLN2, as evidenced by an increase in both early and late apoptotic cells. Proapoptotic proteins (Bad, Bax, Caspase-3, Caspase-9) were upregulated, while antiapoptotic proteins (Bcl-2, Mcl-1, Bcl-xL) were downregulated in response to RLN2 treatment. RLN2 significantly inhibited cell migration, invasion, and angiogenesis in EC9706 cells. Furthermore, RLN2 increased the phosphorylation of STAT-1, while the phosphorylation of STAT-3 was reduced. In the in vivo model, RLN2 effectively suppressed tumor growth. RLN2 exhibits potent anticancer effects against EC9706 cells and in a mouse model, primarily through inducing intrinsic apoptosis, inhibiting cell migration and invasion, and blocking the STAT signaling pathway. These findings highlight RLN2's potential as a therapeutic agent for esophageal carcinoma.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919355","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":"Vinpocetine Mitigates Methotrexate-Induced Liver Injury in Rats Through Modulating Intercellular Communication","authors":"Gellan Alaa Mohamed Kamel,&nbsp;Shaimaa Hussein","doi":"10.1002/jbt.70300","DOIUrl":"https://doi.org/10.1002/jbt.70300","url":null,"abstract":"<div>\u0000 \u0000 <p>Methotrexate (MTX) has been widely implemented in managing several malignancies, inflammatory conditions such as rheumatic arthritis, and autoimmune illnesses. Hepatotoxicity is a significant side effect of MTX, characterized by increased oxidative stress (OS) and inflammation. Vinpocetine (Vinpo) is a prescription medication with a favorable safety profile. It exerts anti-inflammatory and oxidant implications that might be novel candidates for protecting against MTX-induced hepatotoxicity. This study investigates the therapeutic impact of Vinpo against MTX-stimulated liver damage via the nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) and nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) pathways. Rats are allocated into three groups: (1) the Control (saline); (2) the MTX-control (20 mg/kg; injected once i.p.), and (3) the Vinpo + MTX groups. Vinpo was administered orally for 7 days, during which MTX was given intraperitoneally once at the end of Day 3. The liver functions, OS markers, inflammatory mediators, Nrf2, HO-1, NF-κB, and apoptotic signals were estimated. Vinpo lead to enhancement in superoxide dismutase (SOD) enzyme activity, elevation in glutathione (GSH), and a hindrance in malondialdehyde (MDA). It also enhances Nrf2 and HO-1, inhibiting NF-κB (p65) expression and apoptotic markers. Moreover, Vinpo therapy, in conjunction with MTX, restores the normal histological structure of hepatic tissues. Our data suggested that Vinpo exerts a preventive effect against MTX-induced toxicity through anti-oxidative, anti-inflammatory, and apoptotic activities, mediated via Nrf2/HO-1/Nf-κB and caspase-3/Bax/Bcl-2 pathways.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919388","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":"lncRNA AK159072 Promotes Myoblast Proliferation and Muscle Regeneration Through Activation of Akt/Foxo1 Pathway","authors":"Si Lei,&nbsp;Rui Chen,&nbsp;Huacai Shi,&nbsp;Shanyao Zhou,&nbsp;Yanling She","doi":"10.1002/jbt.70292","DOIUrl":"https://doi.org/10.1002/jbt.70292","url":null,"abstract":"<div>\u0000 \u0000 <p>Long non-coding RNAs (lncRNAs) are significant regulators of myoblast proliferation, migration and regeneration. In our previous research, we identified that lncRNA AK159072 was differentially expressed during myoblast development. In this study, we would like to explore the regulatory role and the mechanisms of AK159072 in proliferation. We discovered that AK159072 was increasingly expressed during myoblast proliferation and was located in both the nucleus and cytoplasm of proliferating C2C12 myoblast<b>s</b>. Overexpression of AK159072 promoted the expression of proliferation-related genes c-Myc, cyclin-dependent kinase 2 (CDK2), CDK4, and CDK6 in C2C12 myoblasts. Additionally, the cell viability and EdU-positive cells were increased, while the wound size was decreased after overexpression AK159072. In contrast, cell proliferation was attenuated when AK159072 was successfully silenced. Furthermore, the cross sectional area (CSA) and proliferative markers were decreased after knockdown of AK159072 in the mouse hind leg muscles with CTX-induced injury in vivo, indicating that knockdown of AK159072 may delay muscle regeneration. The study further demonstrated that Akt/Foxo1 pathway mediated the effects of AK159072 overexpression and knockdown in myoblasts. Taken together, our results suggested that AK159072 may regulate myoblast proliferation and muscle regeneration via Akt/Foxo1 pathway. The study suggestd that modulating the expression of AK159072 could be a potential therapeutic strategy for muscle injuries, this could have significant clinical relevance for conditions such as muscular dystrophy, sarcopenia, and other muscle disorders.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919389","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":"GOT2 Elevation Mediated by YY1 Promotes the Tumorigenesis and Immune Escape of Lung Adenocarcinoma","authors":"Hongjun Guan,&nbsp;Changpeng Sun,&nbsp;Yinfeng Gu,&nbsp;Jinjin Li,&nbsp;Jie Ji,&nbsp;Yongxian Zhu","doi":"10.1002/jbt.70256","DOIUrl":"https://doi.org/10.1002/jbt.70256","url":null,"abstract":"<div>\u0000 \u0000 <p>Glutamate-oxaloacetate transaminase 2 (GOT2) has been demonstrated to contribute to lung cancer cell growth, invasion, migration and angiogenesis. Herein, we further probed the functions of GOT2 on lung adenocarcinoma (LUAD) cell ferroptosis and immune escape and its associated mechanism. qRT-PCR and Western blot analysis analyses were used to detect the levels of GOT2, and Yin Yang 1 (YY1). A mouse xenograft model was established for in vivo analysis. CCK-8, 5-ethynyl-2′-deoxyuridine, and wound healing assays were applied for the detection of cell proliferation and migration. Cell ferroptosis was evaluated by flow cytometry and the levels of malondialdehyde (MDA) and Fe2+. Immune escape was assessed by measuring CD8+ T cell apoptosis and programmed death-1 ligand 1 (PD-L1) levels. The interaction between GOT2 and YY1 was determined using Chromatin immunoprecipitation and dual luciferase reporter assays. GOT2 expression was higher in LUAD tissues and cells, and the silencing of GOT2 impeded LUAD growth in vivo. Further loss-of-function assays showed that GOT2 silencing suppressed LUAD cell proliferation, migration and immune escape, and induced ferroptosis. Mechanically, we found that YY1 activated the transcription of GOT2 and could elevate GOT2 expression. Moreover, YY1 silencing repressed LUAD cell proliferation, migration and immune escape, and evoked ferroptosis, while theses effects could be reversed by GOT2 overexpression. YY1 activated GOT2 and elevated the expression of GOT2, which then promoted LUAD cell growth, migration and immune escape, and suppressed cell ferroptosis, suggesting a novel perceptivity for the treatment of LUAD.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143919387","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":"Circ_0003520/miR-205-5p/CUL4B Axis Drives the Progression of Clear Cell Renal Carcinoma","authors":"Xiangdi Yang,&nbsp;Xiaochun Zeng,&nbsp;Nengxing Xia,&nbsp;Xuecheng Xie,&nbsp;Yingjie Long","doi":"10.1002/jbt.70263","DOIUrl":"https://doi.org/10.1002/jbt.70263","url":null,"abstract":"<div>\u0000 \u0000 <p>Many circular RNAs (circRNAs) are frequently expressed in cancers and involved in cancer progression. Clear cell renal cell carcinoma (ccRCC) is a malignancy with a high mortality rate. A previous study has shown that circ_0003520 is increased in ccRCC. However. The action of circ_0003520 in ccRCC progression and its possible mechanisms remain unclear. Levels of circ_0003520, miR-205-5p and cullin 4B (CUL4B) were examined by qRT-PCR and western blot. Cell counting kit-8 (CCK-8), 5-ethynyl-2′ -deoxyuridine (EdU), flow cytometry, transwell, tube formation, and xenograft tumor assays were conducted to detect the effects of circ_0003520 on cRCC cell proliferation, apoptosis, migration, invasion, angiogenesis In Vitro, as well as tumor formation In Vivo. The binding between circ_0003520 or CUL4B and miR-205-5p was analyzed using dual-luciferase activity reporter assay and RNA immunoprecipitation (RIP) assay. We found that circ_0003520 and CUL4B expression was increased and miR-205-5p expression was decreased in ccRCC tissues compared to normal tissues. Circ_0003520 knockdown inhibited the proliferation, migration, invasion, and angiogenesis and promoted apoptosis in ccRCC cells in vitro, as well as inhibited tumor formation In Vivo. Further mechanism analysis showed that the miR-205-5p/CUL4B axis was the downstream target pathway of circ_0003520. Circ_0003520 could up-regulate CUL4B through sequestering miR-205-5p. Functionally, miR-205-5p inhibition or CUL4B overexpression could recover the inhibition mediated by circ_0003520 knockdown on ccRCC cell proliferation, migration, invasion, and angiogenesis, as well as the enhancement of cell apoptosis. Besides that, circ_0003520 also hindered tumor growth In Vivo via miR-205-5p/CUL4B axis. Circ_0003520 acts as an oncogene to promote ccRCC progression by regulating the miR-205-5p/CUL4B axis, indicating a promising strategy for suppressing ccRCC growth.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905262","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":"Kallistatin Improves Lipid Metabolism and Alleviates Cardiac Hypertrophy via the SIRT1/PPAR Pathway: An Experimental Study","authors":"Bing Li,&nbsp;Yanping Wu,&nbsp;Ya Li,&nbsp;Yonggang Yuan,&nbsp;Xianbo Zhou,&nbsp;Zesheng Xu,&nbsp;JinKun Wen","doi":"10.1002/jbt.70274","DOIUrl":"https://doi.org/10.1002/jbt.70274","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 <p>Cardiovascular disease is a major health concern, with cardiac hypertrophy (CH) leading to heart failure and increased mortality. Although kallistatin has shown a protective effect against cardiovascular diseases, its role in CH remains unclear. The effects of kallistatin on myocardial lipid metabolism, inflammation, and hypertrophy via the SIRT1/PPARα pathway in both animal model and cell culture were assessed. The rat model of CH was induced by Angiotensin II (Ang II). Plasma kallistatin and inflammatory indicators (IL-6, TNF-α, MCP-1) were measured using ELISA. <i>In Vitro</i>, Ang II-treated NRVMs were divided into control, Ang II, and Ang II + kallistatin groups. WGA-Oregon Red staining was used to assess cell size, and CO-IP was performed to evaluate SIRT1/PPARα interactions. Gene (ANF, α-SKA, PDK4, mCPT-I, MCAD) and protein expression in NRVMs and heart tissues were analyzed via qRT-PCR and Western blot. Kallistatin levels were decreased in patients with CH and rats with Ang II-induced CH. <i>In Vivo</i>, kallistatin treatment decreased the HW/BW ratio, SBP, DBP and MAP, cardiomyocyte size, and arrhythmias. <i>In Vitro</i>, kallistatin reversed Ang II-induced hypertrophy, evidenced by smaller cell size (via WGA-Oregon Red staining), reduced ANF and α-SKA expression, and decreased lipid accumulation. Kallistatin inhibited inflammatory markers (IL-6, TNF-α, MCP-1) and enhanced fatty acid oxidation by upregulating PDK4, mCPT-I, and MCAD. CO-IP demonstrated interactions between SIRT1 and PPARα, and pathway inhibition confirmed that kallistatin's protective effects were mediated through the SIRT1/PPARα pathway. Kallistatin protects against CH and arrhythmias reducing inflammation and improving lipid metabolism by modulating the SIRT1/PPARα pathway.</p>\u0000 </section>\u0000 </div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905261","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":"Anti-Inflammatory Effects of Spexin on Acetic Acid‑Induced Colitis in Rats via Modulating the NF-κB/NLRP3 Inflammasome Pathway","authors":"Sevil Arabacı Tamer,&nbsp;Fadime Köse,&nbsp;Sevinç Yanar,&nbsp;Özcan Budak,&nbsp;Cahit Bağcı","doi":"10.1002/jbt.70285","DOIUrl":"https://doi.org/10.1002/jbt.70285","url":null,"abstract":"<p>Ulcerative colitis is a chronic inflammatory bowel disease characterized by inflammation and ulcers in the lining of the colon and rectum. Spexin is a novel peptide with antioxidant and anti-inflammatory properties. This study aims to elucidate the therapeutic effects and underlying mechanisms of spexin in mitigating acetic acid-induced colitis in rats. Male Sprague Dawley rats were assigned to control (<i>n</i> = 14) and colitis (<i>n</i> = 21) groups. Colitis was induced via 5% acetic acid (AA) administration (1 mL, intrarect). Post-induction, rats received subcutaneous saline (1 mL/kg), spexin (50 µg/kg/day), or oral sulfasalazine (500 mg/kg) for 5 days. Control groups received saline or spexin. After 24 h of the final treatment, colons were evaluated macroscopically, and levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-18 were determined by ELISA, oxidative stress markers myeloperoxidase (MPO), malondialdehyde (MDA) and glutathione (GSH) levels were measured spectrophotometrically and NOD-like receptor pyrin domain-containing 3 (NLRP3), nuclear factor-κB (NF-κB), caspase-1 proteins were analyzed with <i>Western Blot</i> alongside histopathological assessments. Colitis induction significantly elevated macroscopic damage scores, stool consistency, inflammatory cytokines, MDA, MPO, and NLRP3, NF-κB, caspase-1, while reducing GSH levels (<i>p</i> &lt; 0.001–0.01). Microscopic evaluations confirmed increased necrosis, submucosal edema, and inflammatory cell infiltration (<i>p</i> &lt; 0.001). Spexin reversed these effects by enhancing GSH levels (<i>p</i> &lt; 0.01), reducing macroscopic/microscopic scores, cytokines, MDA, and MPO levels (<i>p</i> &lt; 0.05–0.001), and suppressing NLRP3, NF-κB, and caspase-1 activation (<i>p</i> &lt; 0.01–0.001). For the first time that spexin ameluates acetic acid-induced colitis in rats by modulating the NF-κB/NLRP3 signaling pathway, reducing oxidative damage, enhancing antioxidant capacity, and suppressing inflammation.</p>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbt.70285","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143905269","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":"Evaluation of Carvacrol Zinc Oxide Quantum Dots in Mitigating Hepatic Inflammation and Function Impairment in DMBA-Induced Mammary Carcinogenesis","authors":"Manoj Kumar Srinivasan,&nbsp;Briska Jifrina Premnath,&nbsp;Nalini Namasivayam","doi":"10.1002/jbt.70262","DOIUrl":"https://doi.org/10.1002/jbt.70262","url":null,"abstract":"<div>\u0000 \u0000 <p>The liver plays a crucial role in metabolizing and purging various substances from the body. Exposure to toxins like DMBA (7,12-dimethylbenz[a]anthracene) can harm the liver, leading to inflammation, impaired function, and the potential development of liver lesions or tumors. The present study explored the protective effect of CVC-ZnO QDs (carvacrol-zinc oxide quantum dots) on the liver by DMBA-induced mammary carcinoma. Female Sprague Dawley rats were used, and mammary cancer was initiated by injecting DMBA near the mammary gland. Different concentrations of CVC-ZnO QDs were administered orally to determine the most effective dosage. Various liver tissue factors were evaluated, including liver marker enzymes, antioxidant status, lipid peroxidation, detoxification enzyme activities and protein bound carbohydrates. Additionally, the inflammatory response of the liver tissue was investigated using immunohistochemistry and PCR. Results revealed that rats treated with CVC-ZnO QDs showed a significant decrease in liver marker enzymes, lipid peroxidation levels, Phase I detoxification enzyme activities and protein bound carbohydrates. CVC-ZnO QDs also increased Phase II detoxification enzyme activity, and antioxidant levels compared to rats treated solely with DMBA. Histopathological analysis confirmed that CVC-ZnO QDs shielded the liver from DMBA-induced damage. Furthermore, CVC-ZnO QDs were found to reduce the expression of IL-6, NF-κB, and COX-2 in DMBA-induced rats. Overall, the study demonstrated that administering CVC-ZnO QDs at a dose of 4 mg/kg b.w had a notable hepatoprotective effect against DMBA-induced mammary cancer in rats.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143897155","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":"Upregulation of PREX1 Expression by POU2F2 Promotes the Malignant Progression of Acute Myeloid Leukemia via the mTOR Pathway","authors":"Md. Eamran Hossain,&nbsp;Huanhuan Li,&nbsp;Yingcai Li,&nbsp;Sidong Zhang,&nbsp;Xiaoyi Wang,&nbsp;Bai Li,&nbsp;Yufeng Liu","doi":"10.1002/jbt.70286","DOIUrl":"https://doi.org/10.1002/jbt.70286","url":null,"abstract":"<div>\u0000 \u0000 <p>Acute myeloid leukemia (AML) is a hematologic neoplasm with heterologous cytology and short-term prognosis. In varying cancers, PREX1 and POU2F2 serve as oncogenes, but whether it influences AML malignant progression is elusive. This project attempted to unravel the influence of PREX1 and POU2F2 on AML malignant progression. Bioinformatics analysis of differential mRNAs in AML was carried out to identify target genes and predict upstream regulatory molecules. Bioinformatics analyzed PREX1 and POU2F2 expressions in AML. Kyoto Encyclopedia of Genes and Genomes (KEGG) analyzed the enriched pathway of PREX1. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) was applied to examine the expressions of PREX1 and POU2F2. Dual-luciferase and Chromatin immunoprecipitation (ChIP) assays were applied to prove the regulatory relationship between PREX1 and POU2F2. Protein expression levels of POU2F2, PREX1, and mTOR in AML cells were examined by Western blot (WB). AML cell proliferation and viability were examined by colony formation assays and CCK-8, respectively. By Transwell assay, we assessed AML cell invasion and migration. The influence of the POU2F2/PREX1 axis on AML was evaluated by a xenograft tumor model. PREX1 was substantially upregulated in AML and enriched in the mTOR pathway. PREX1 knockdown noticeably hampered the proliferation, invasion, and migration of AML cells. Bioinformatics analysis unveiled that POU2F2, a potential upstream transcription factor (TF) of PREX1, was upregulated in AML cells. Dual-luciferase and ChIP proved the binding of PREX1 promoter region to POU2F2. In vivo and In Vitro experiments uncovered that PREX1 knockdown reversed the promoting influence conferred by POU2F2 overexpression on the mTOR pathway as well as the malignant progression of AML cells. POU2F2 modulates the mTOR pathway by upregulating the expression of PREX1 to stimulate the malignant progression of AML cells, suggesting POU2F2 and PREX1 as likely targets for AML therapy.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143896897","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":"GRIA1 Alleviates Sevoflurane-Induced Neurotoxicity by Suppressing Autophagy","authors":"Xue Lei,&nbsp;Jianli Yan,&nbsp;Zhilin Wu,&nbsp;Qiang Li,&nbsp;Mengqiu Liang,&nbsp;Chen Chen","doi":"10.1002/jbt.70281","DOIUrl":"https://doi.org/10.1002/jbt.70281","url":null,"abstract":"<div>\u0000 \u0000 <p>The neurotoxicity caused by inhaled anesthetics has attracted more attention. Sevoflurane (SEV), a common general anesthetic, has a wide range of clinical applications. However, the underlying molecular mechanism of SEV-induced neurotoxicity is blurry.Cell viability and apoptosis were evaluated using CCK-8 and flow cytometry. The abundances of targeted molecules were measured using RT-qPCR, western blot and IF assay. SEV induction reduced cell viability, promoted cell apoptosis and autophagy of HT22 cells, which was positively related with gradually increasing concentrations of SEV. In addition, Glutamate ionotropic receptor AMPA type subunit 1 (GRIA1) expression was evidently decreased by SEV induction and its overexpression abolished SEV-mediated influences on cell viability, apoptosis and autophagy of HT22 cells. Furthermore, the autophagy inducer rapamycin reversed GRIA1 overexpression-mediated promotion of cell viability and suppression of cell apoptosis and autophagy of HT22 cells upon SEV induction. GRIA1 improved SEV-induced neurotoxicity by suppressing autophagy.</p></div>","PeriodicalId":15151,"journal":{"name":"Journal of Biochemical and Molecular Toxicology","volume":"39 5","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143888969","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}