Biotechnology and applied biochemistry最新文献

{"title":"A Fluorescent Aptamer Sensor for Detecting Golgi Protein 73 Based on Magnetic Ferroferric Oxide@Boron, Nitrogen-Doped Graphene Quantum Dots.","authors":"Guiyin Li, Wei He, Ruijie Yan, Xuanlong Su, Tingting Yu, Xiaohong Tan, Yong Huang","doi":"10.1002/bab.70006","DOIUrl":"https://doi.org/10.1002/bab.70006","url":null,"abstract":"<p><p>In this paper, a fluorescent aptamer sensor based on magnetic ferroferric oxide@boron, nitrogen-doped graphene quantum dots (Fe₃O₄@B,N-GQDs) was developed to detect Golgi protein 73 (GP73). GP73 aptamer (GP73_Apt) functioned with Fe₃O₄@B,N-GQDs (Fe₃O₄@B,N-GQDs-GP73_Apt) and was used as the fluorescent donor, while molybdenum disulfide (MoS₂) with a large surface served as the fluorescent acceptor. The fluorescence of Fe₃O₄@B,N-GQDs-GP73_Apt was quenched by MoS₂ based on the fluorescence resonance energy transfer (FRET) principle. However, in the presence of GP73, Fe₃O₄@B,N-GQDs-GP73_Apt could specifically bind to GP73, forming a Fe₃O₄@B,N-GQDs-GP73_Apt-GP73 complex. This binding event caused Fe₃O₄@B,N-GQDs-GP73_Apt to move away from the surface of MoS₂, thus blocking the FRET process and recovering the fluorescence. Under optimal conditions, a linear relationship was established between the fluorescence recovery and the concentration of GP73 within the range of 10-1000 ng/mL (R²= 0.9918), and the limit of detection was 7.37 ng/mL. Additionally, when the sensor was applied to test actual samples, the recovery rates were in the range of 98.80%-101.18%, and the relative standard deviations were between 0.29%-3.04%. These findings demonstrated the excellent detection performance of the proposed fluorescent aptamer sensor.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of MDM4 as a Prognostic Biomarker and a Target for Therapeutics in Colorectal Cancer.","authors":"Xiao Shang, Xiaoqiang Zheng, Aimin Jiang, Ni Zhao, Yuru Chen, Na Liu, Min Chen, Xuan Liang, Zhiping Ruan, Tao Tian, Xiao Fu, Yu Yao","doi":"10.1002/bab.70002","DOIUrl":"https://doi.org/10.1002/bab.70002","url":null,"abstract":"<p><p>Colorectal cancer (CRC) is a serious global health problem. Even with improvements in CRC diagnosis and treatment, many patients are diagnosed with metastatic disease, indicating the tumor has metastasized, and the survival rate for those with advanced CRC is still low. Immune checkpoint inhibitors (ICIs) have shown some promise for certain groups of CRC patients, specifically for those with mismatch repair deficiencies or microsatellite instability, but their overall effectiveness is still limited. Novel biomarkers and treatment targets are critically needed for the improvement of the diagnosis and treatment of CRC, ultimately improving patient outcomes. MDM4 (murine double minute 4) protein is important in controlling the tumor suppressor p53. MDM4 is similar in structure to MDM2 and is known to block p53's transcriptional ability, which can contribute to tumorigenesis. MDM4 is often found at higher levels in many cancers, including CRC, and has been linked to cancer progression through mechanisms that don't involve p53. However, MDM4's role in the tumor immune microenvironment of CRC remains unclear; its role in CRC prognosis and response to immunotherapy isn't fully understood. This study explores the biological, clinical, and immunological impact of MDM4 in CRC, focusing on its potential as a marker for prognosis and treatment target. This study is the first to comprehensively link MDM4 overexpression in CRC to immune evasion through reduced infiltration of CD8+ T cells and dendritic cells, establishing its role as an independent prognostic marker and a potential immunotherapy target. We explored the role of MDM4 in CRC by combining bioinformatic analyses and laboratory experiments. We gathered data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databasesWe performed Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Set Enrichment Analysis (GSEA) to identify the key biological pathways linked to MDM4 in CRC. We also explored how MDM4 expression is associated with the immune microenvironment by examining the tumor-infiltrating lymphocytes in CRC tissues. Laboratory experiments were conducted to test the functional role of MDM4 in CRC cell lines. Our analysis showed that MDM4 expression was higher in CRC than in normal colorectal tissues, with even higher levels found in more advanced tumor stages. Increased MDM4 expression was linked to poorer progression-free survival (PFS) in CRC patients and was identified as an independent predictor of prognosis. Through pathway enrichment analyses, we found that MDM4 was involved in important tumor-related and immune pathways, including those regulating cell cycle progression and immune response. Notably, overexpression of MDM4 was associated with lower infiltration of CD8 T cells, natural killer (NK) cells, and dendritic cells in the tumor microenvironment, suggesting that MDM4 might help the tumor evade the immune system. In vitro","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144246570","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Relationship Between Aldose Reductase and Isoxazole Derivatives: An In Vitro and In Silico Approach to Its Correlation With Diabetic Conditions.","authors":"Ahmet Esat Göner, Hatice Esra Duran","doi":"10.1002/bab.70003","DOIUrl":"https://doi.org/10.1002/bab.70003","url":null,"abstract":"<p><p>Diabetes mellitus (DM), which can result in a number of problems such as cataracts, neuropathy, retinopathy, nephropathy, and several cardiovascular illnesses, continues to be a growing issue despite major advancements in treatment approaches. Numerous scientists have targeted the polyol pathway as a target for intervention since it includes aldose reductase (ALR2, AR (E.C.1.1.1.21)), a crucial enzyme. Oxidative damage, NADPH depletion, and intracellular sorbitol buildup result from the overactivation of ALR2 brought on by hyperglycemia. Interest in creating novel ALR2 inhibitors (ALR2Is) with enhanced therapeutic characteristics has increased as a result of this circumstance. The amazing biological capabilities of isoxazole molecules led us to look into the biological properties of isoxazole and related compounds. We examined these isoxazoles' binding affinities and interactions in the ALR2 active site using thorough in vitro and in silico techniques. In comparison to the reference pharmaceutical epalrestat (EPR, K_I 232.70 ± 15.51 nM), our results demonstrate that these isoxazoles efficiently inhibit ALR2 at nanomolar doses, with inhibition constants (K_I) ranging from 12.13 ± 1.24 nM to 89.51 ± 4.68 nM. Important interactions between these isoxazoles and ALR2 are highlighted by the combined in vitro and in silico studies, indicating their potential as therapeutic agents against a range of pathological diseases. Furthermore, these substances that have ALR2 inhibitory properties could be useful as stand-in treatments or preventative measures for diabetes problems.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144233255","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Development of Salvianolic Acid A-Loaded Gelatin Nanoparticles for Effective Suppression of Inflammation and Oxidative Stress in Blood-Brain Barrier to Ischemic Stroke Therapy.","authors":"Chaoming Li, Haixin Li, Haichun Zhou","doi":"10.1002/bab.2766","DOIUrl":"https://doi.org/10.1002/bab.2766","url":null,"abstract":"<p><p>Ischemic stroke (ICS) represents a treatment emergency for which efficient therapeutic options remain insufficient. Salvianolic acid A (SAA) is a naturally occurring polyphenol recognized as an effective neuroprotective agent. Compared with developed drugs, SAA demonstrates low side effects and displays several modes of action, providing considerable benefits in managing ICS. Yet, limitations of inadequate transmembrane permeability and water solubility hinder the effectiveness of SAA. Recently, nanodelivery methods have garnered significant attention in ICS as an efficient to penetrate the blood-brain barrier and enhance drug solubility. This investigation developed a new nanomedicine (SAA@GRH NPs) for ICS treatment, utilizing SAA-loaded gelatin nanoparticles (SAA@GNPs) that were functionalized and altered with brain tissue target rabies virus glycoprotein (RVG29). The stability, antioxidant, antibacterial, neuroprotective effects, cellular uptake, and cytocompatibility of SAA@GRH NPs were examined. The in vivo efficacy of SAA@GRH NPs on ICS was studied in a rat model of middle cerebral artery occlusion (MCAO) with histological analysis. The resultant SAA@GRH NPs enhanced the solubility of SAA and demonstrated effective dispersion. In vitro studies indicate that SAA@GRH NPs possess significant antibacterial activities, antioxidant capabilities, and protection against intracellular reactive oxygen species. RVG29 markedly improved the absorption of SAA@GRH NPs by IMR32 cells. Moreover, in vivo investigations confirmed the efficacy of SAA@GRH NPs in mitigating nerve injury and facilitating neurological recovery. In the MCAO model, SAA@GRH NPs markedly diminished neuroinflammation, substantially recovered behavioral functions and decreased neuronal death. Collectively, our data suggested that SAA@GRH NPs may offer an innovative and promising strategy for the successful treatment of ICS.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2766"},"PeriodicalIF":3.2,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purification and Characterization of Hyaluronidase From Streptomyces graminisoli.","authors":"Doha Nassir, Dalia A El-Ebeedy, Osama A M Said, Omar S Keshk, Seham Sater Alhelaify, Ohud Muslat Alharthy, Dalal Sulaiman Alshaya, Ahmed Z Abdel Azeiz","doi":"10.1002/bab.2789","DOIUrl":"https://doi.org/10.1002/bab.2789","url":null,"abstract":"<p><p>Hyaluronidases (HAase) are a family of hydrolytic enzymes that degrade hyaluronic acid (HA) and have gained significant attention in medical and pharmaceutical applications. This study presents an optimized approach for isolating and characterizing a novel HAase-producing actinomycete strain. Using HA-supplemented minimal salt medium (MSM) as the sole carbon and nitrogen source, we isolated and identified Streptomyces graminisoli by 16S-rRNA sequencing. The enzyme was purified using an improved DEAE-Sephadex G50 column chromatography method, yielding a molecular weight of 35 kDa. Kinetic analysis results revealed a K_m value of 0.28 mg/mL and a V_max value of 24.9 U/mL, indicating high substrate affinity. The results of advanced bioinformatics analysis using both nucleotide (Basic Local Alignment Search Tool nucleotide [BLASTN]) and amino acid (Basic Local Alignment Search Tool protein [BLASTP]) sequences demonstrated significant conservation across actinomycetes, with sequence identity and query coverage exceeding 75% and 90%, respectively. This study provides new insights into microbial HAase production and characterization, with potential applications in biotechnology and medicine.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144214994","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Matrix Metalloproteinases 9 Contributes to Inflammatory Responses in Helicobacter pylori-Positive Gastric Cancer.","authors":"Wen-Jie Kong, Wei-Dong Liu, Man Wang, Wen-Jia Hui, Huan He, Lin Yu, Feng Gao","doi":"10.1002/bab.70000","DOIUrl":"https://doi.org/10.1002/bab.70000","url":null,"abstract":"<p><p>Helicobacter pylori-induced inflammatory microenvironment plays a pivotal role in the development of gastric cancer (GC). This study investigates whether matrix metallopeptidase 9 (MMP9) mediates H. pylori-induced effects in GC progression. GC patients were stratified on the basis of H. pylori infection status. MMP9 levels were measured using enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, and RT-PCR. AGS and MKN45 GC cell lines were transfected with MMP9-specific siRNA and cocultured with H. pylori. Cell viability, proliferation, and migration were assessed using 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide assay, colony formation assay, and transwell migration assay, respectively. Expression of pro-inflammatory cytokines in cells and their secretion into coculture supernatants were analyzed by Western blotting and ELISA. MMP9 levels were significantly elevated in the serum of H. pylori-positive GC patients compared to H. pylori-negative patients. Correspondingly, increased MMP9 mRNA and protein expression were detected in H. pylori-positive GC tissues. Serum levels and tissue mRNA expression of interleukin (IL)-1β, tumor necrosis factor (TNF)-α, and IL-8 positively correlated with MMP9 expression. In vitro, H. pylori infection enhanced MMP9 expression and promoted the secretion of IL-1β, TNF-α, and IL-8 in AGS and MKN45 cells. H. pylori stimulation also increased the survival, proliferation, and migration of GC cells, which were significantly attenuated by MMP9 knockdown. MMP9 mediates H. pylori-induced inflammatory responses that contribute to the GC progression. Targeting MMP9 may represent a therapeutic strategy to counteract H. pylori-driven GC development.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144183593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigation of PB1-F2 Protein-Derived Peptide Effects on Clinical Symptoms and Inflammatory Factors in an Animal Model of Multiple Sclerosis.","authors":"Seyed Hossein Khatami, Saeed Karima, Bahman Jalali Kondori, Mojtaba Sepandi, Zohreh Jangravi","doi":"10.1002/bab.2790","DOIUrl":"https://doi.org/10.1002/bab.2790","url":null,"abstract":"<p><p>Multiple sclerosis (MS) is an autoimmune condition affecting the central nervous system (CNS), resulting in immune-mediated demyelination and neurodegeneration. The NF-κB signaling pathway is pivotal in the inflammatory processes that drive MS pathogenesis. Recent research has underscored the therapeutic potential of peptides owing to their low immunogenicity, high specificity, and minimal side effects. PB1-F2, a protein from the influenza virus, has shown the capacity to modulate inflammation by inhibiting the NF-κB pathway. Synthetic peptides were designed on the basis of the C-terminal region of PB1-F2 and evaluated for their ability to suppress NF-κB-mediated inflammatory responses. Among these peptides, RZV8 emerged as the most potent peptide and was selected for further investigation. This study aimed to explore the therapeutic effects of the intraperitoneal administration of RZV8 in experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Following EAE induction in female C57BL/6J mice, the animals were treated with RZV8. Various serum inflammatory mediators, motor functions, myelination, and inflammatory cell infiltration levels were then assessed. Our results demonstrated that RZV8 administration alleviated EAE clinical severity, reducing inflammation, demyelination, and gliosis in EAE mice. We propose that the therapeutic effects of RZV8 are primarily due to its neuroprotective and anti-inflammatory properties. These results could offer new perspectives for treating neuroinflammatory diseases, such as MS, highlighting RZV8 as a potential therapeutic candidate.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156992","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dihydroartemisinin Alleviates Ulcerative Colitis via Target Identification and Pathway Modulation: A Cyberpharmacology Approach.","authors":"Yu Zhang, Yiqing Zhao, Yan Qin, Ruiya Zhang, Zhiqiang Zhang, Qin Zhang, Junping Wang","doi":"10.1002/bab.2793","DOIUrl":"https://doi.org/10.1002/bab.2793","url":null,"abstract":"<p><p>Ulcerative colitis (UC) is a long-term inflammatory condition impacting the bowel with an unclear cause. It is categorized as a refractory condition due to the limited efficacy and adverse effects of existing treatments. Dihydroartemisinin (DHA), a semi-synthetic derivative and primary active metabolite of artemisinin, exhibits anti-inflammatory and antioxidant properties. To assess the therapeutic effects of DHA on UC and elucidate its possible mechanisms of action. A dextran sulfate sodium (DSS)-induced UC mouse model (2.5% DSS for 30 days) was used to evaluate the therapeutic effects of DHA (20 mg/kg/day) through assessment of disease activity, colon damage, and inflammation. Key targets were identified using network pharmacology, followed by pathway analysis (GO and Kyoto Encyclopedia of Genes and Genomes [KEGG]), molecular docking, and western blotting to validate interactions and signaling modulation. DHA treatment significantly improved disease activity index (DAI) scores, reduced colon shortening, and ameliorated histopathological injury in the DSS-induced UC mouse model. Seven core targets of DHA were identified: EGFR, MMP9, PTGS2, MMP2, mitogen-activated protein kinase 3 (MAPK3), MAPK1, and ERBB2. Enrichment analyses revealed critical mechanisms and pathways implicated in its therapeutic effects. Molecular docking demonstrated robust binding between DHA and its targets, whereas western blot analysis confirmed that DHA mitigated UC via modulation of the MAPK inflammatory signaling pathway. The research highlights DHA's therapeutic potential in UC treatment by identifying its core targets and mechanisms of action, paving the way for future research and drug development in managing UC.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156984","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection of HPV-16 by a Simple and Cost-Effective DNA Probe: Polyadenine-Polythymine-Decorated Gold Nanoparticles (PolyA-PolyT@AuNPs).","authors":"Mohamad Ali Saleh, Fatemeh Zahra Zangeneh, Yasaman-Sadat Borghei, Hamid Reza Samadikhah, Maryam Nikkhah, Saman Hosseinkhani","doi":"10.1002/bab.2772","DOIUrl":"https://doi.org/10.1002/bab.2772","url":null,"abstract":"<p><p>HPV-16 identification is crucial for point-of-care molecular diagnosis of cervical cancer. However, the diagnostic methods currently in use are unable to combine both high analytical performance and cost-efficient medical diagnosis. To circumvent this, we have developed a novel nanobiosensor for diagnosis of the HPV-16 L1 gene sequence through colorimetric methods. Using a unique conjugation technique of polyvalent DNA to gold nanoparticles (AuNPs), quickly synthesizing AuNPs synthesis in situ at the particular probe-polyadenine-polythymine (A₁₅-T₁₀) strands was developed. Transmission electron microscopy (TEM), dynamic light scattering (DLS), gel electrophoresis, UV-Vis spectroscopy, and visual detection demonstrate that the Poly(A)₁₅-(T)₁₀ strand can create separate anisotropic AuNPs so that a thick layer of DNA is functionalized on each AuNP, therefore generating polyvalent (p)DNA-AuNPs. Moreover, the hybridization test, UV-Vis spectroscopy, TEM, visual detection, and DLS results further confirmed the innovative sensing applicability, showing more excellent attractiveness of pDNA-AuNPs conjugation in diagnostics in biomedicine and particular sequence detection, such as double-stranded DNA (dsDNA) by employing probe-polyA-polyT extra-strands that are in harmony with the intended sequence. This sensor demonstrated good performance levels with a sensitivity of up to 1.9 nM for pUCm-T. Additionally, the sensor showed intense discrimination against actual clinically collected HPV-16 samples, consistent stability, and good repeatability.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":"e2772"},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Stem Cell Transcription Factor OCT4 Silences Target DNA Methyltransferase 1 to Strengthen DNA Damage Response in Cisplatin-Treated Gastric Cancer Cells.","authors":"Zhengzheng Yan, Xiaoqian Bu, Haixia Chen, Chongren Ren, Ji Li, Yongjie Wu, Jun Xing","doi":"10.1002/bab.2777","DOIUrl":"https://doi.org/10.1002/bab.2777","url":null,"abstract":"<p><p>OCT4 plays a crucial role in the DNA damage response(DDR) mechanism, whereas cisplatin (CDDP) acts as an anti-tumor agent by inducing DDR. This study aimed to investigate the role of OCT4 in regulating DNA methyltransferase 1 (DNMT1) in CDDP-treated gastric cancer (GC). A dual-luciferase reporter assay was performed to detect the relationship between DNMT1 and OCT4. Human GC cell lines HGC-27 and MGC-803 were transfected with siRNA-OCT4 or ov-DNMT1 to construct interfering cell lines; CDDP of 0, 2.5, 5, 10, and 20 µM was used to treat GC cell lines, respectively. As follows, γ-H2AX immunofluorescence was used to detect DDR. The protein expressions of OCT4 and DNMT1 were detected by Western blot (WB), and the effects of CDDP treatment on cell apoptosis and proliferation were assessed using CCK8, cell cloning, and flow cytometry. The IC50 of CDDP-treated GC cells was reduced by OCT4 silence but enhanced by DNMT1 overexpression. A targeted regulatory relationship exists between OCT4 and DNMT1. The expression of OCT4 and DNMT1 was increased in CDDP-treated cells, and DNMT1 was decreased in the siRNA-OCT4 group. In the CDDP-treated GC cells, DNMT1 overexpression significantly reversed the siRNA-OCT4-induced cell apoptosis, γ-H2AX upregulation, and proliferation decrease. OCT4 silence may target DNMT1 to induce DDR in GC cells to strengthen the CDDP-induced cell apoptosis and proliferation inhibition.</p>","PeriodicalId":9274,"journal":{"name":"Biotechnology and applied biochemistry","volume":" ","pages":""},"PeriodicalIF":3.2,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144156993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}