Journal of Genetic Engineering and Biotechnology最新文献

{"title":"Identification of high-risk signatures and therapeutic targets through molecular characterization and immune profiling of TP53-mutant breast cancer","authors":"Peter Jerome Ishmael V. Paulino,&nbsp;Mohammad Tasyriq Che Omar","doi":"10.1016/j.jgeb.2025.100574","DOIUrl":"10.1016/j.jgeb.2025.100574","url":null,"abstract":"<div><h3>Background</h3><div>TP53 mutations are commonly observed in aggressive subtypes of breast cancer, influencing the tumor microenvironment (TME) and patient prognosis. In this study, we developed a prognostic gene-based risk model to stratify TP53-mutant breast cancer patients and explore potential therapeutic targets.</div></div><div><h3>Methods</h3><div>We performed comprehensive bioinformatics analyses using TCGA and METABRIC datasets to identify key prognostic genes in TP53-mutant breast cancer. Differential expression and Gene Set Enrichment Analysis (GSEA) revealed dysregulated pathways, while protein–protein interaction (PPI) networks highlighted functional hubs. Survival analysis, followed by univariate Cox regression, LASSO, and multivariate regression, led to the construction of a robust gene-based risk model. Immune landscape profiling was conducted to evaluate tumor microenvironment characteristics. Finally, drug sensitivity analysis and molecular docking were used to identify potential therapeutic agents targeting high-risk patients.</div></div><div><h3>Results</h3><div>TP53 mutations were present in ∼ 35 % of patients and associated with significant transcriptomic alterations. A total of 666 genes were consistently dysregulated, including 333 upregulated (such as <em>A2ML1, CA9, VGLL1, PSAT1</em>) and 333 downregulated (such as <em>AGR3, TFF1, ESR1, CPB1</em>) in TP53 mutated breast cancer patients. GSEA revealed that the cell cycle, DNA replication, and metabolic pathways in in TP53 mutated breast cancer patients. Protein–protein interaction (PPI) network analysis of these genes revealed tightly connected modules related to mitotic regulation and immune signaling, underscoring key functional hubs in TP53-mutant tumors. A four-gene prognostic model (<em>FGFR4, S100P, ADM, CTSC</em>) stratified TP53-mutant patients into high- and low-risk groups with distinct survival outcomes and immune profiles. High-risk patients exhibited a suppressed immune landscape, characterized by lower immune and stromal cell infiltration and higher tumor purity. Drug sensitivity analysis and molecular docking revealed several compounds, including Lapatinib, Docetaxel, and Trametinib, with strong binding affinities to key model genes. These drugs demonstrated potential efficacy in high-expression cells, suggesting their viability as targeted therapies.</div></div><div><h3>Conclusion</h3><div>Our findings underscore the prognostic value of the identified genes and the immunosuppressive TME in TP53-mutant breast cancer. The identification of drug candidates with strong binding affinities to key proteins provides promising avenues for targeted therapy in this high-risk patient population.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100574"},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227466","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Isolation and characterization of peroxidase from potato leaves Solanum tuberosum: Application in glucose diagnostic kit","authors":"Hassan M.M. Masoud ,&nbsp;Mohammed M. Abdel-Monsef ,&nbsp;Mohamed S. Helmy ,&nbsp;Sayed S. Esa ,&nbsp;Doaa A. Darwish","doi":"10.1016/j.jgeb.2025.100584","DOIUrl":"10.1016/j.jgeb.2025.100584","url":null,"abstract":"<div><div>Peroxidases play a pivotal role in many medical applications such as diagnostic kits and ELISA assays. This study reports the purification and biochemical characterization of peroxidase from potato leaves (PLPOD) and its application in the formulation of a glucose diagnostic kit. PLPOD was purified through CM-cellulose ion-exchange and Sephacryl S-300 gel filtration chromatography, achieving an 11.8-fold purification with 48 % recovery and a final specific activity of 705.7 U/mg. Native PAGE and activity staining confirmed the enzyme’s purity and homogeneity. PLPOD molecular weight was estimated from gel filtration column as 64 kDa, but on SDS gel, there were three PLPOD isoforms of approximated molecular weights ranging from ∼ 40–60 kDa. PLPOD exhibited optimal activity at pH 5.2, with Zn²⁺ and Ni²⁺ enhancing activity, while Ca²⁺ and Fe²⁺ inhibited it. Inhibitor analysis confirmed the heme-dependent nature of the enzyme. The <em>K_m</em> values for guaiacol and H₂O₂ were 0.067 mM and 40 mM, respectively, consistent with typical plant peroxidases. A glucose diagnostic kit developed using PLPOD showed strong concordance with a commercial glucose kit when tested on normal and diabetic serum samples demonstrating its clinical applicability. These findings suggest that PLPOD is a viable cost-effective for use in diagnostic assays and kits.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100584"},"PeriodicalIF":2.8,"publicationDate":"2025-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227468","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NR5A1 gene variants in infertile Senegalese men: Discovery of a novel missense variant and genotype-phenotype correlation","authors":"Adji Dieynaba Diallo ,&nbsp;Arame Ndiaye ,&nbsp;Ndiaga Diop ,&nbsp;Fatou Diop Gueye ,&nbsp;Mame Venus Gueye ,&nbsp;Yacouba Dia ,&nbsp;Amath Thiam ,&nbsp;Abdoulaye Séga Diallo ,&nbsp;Rokhaya Ndiaye ,&nbsp;Oumar Faye ,&nbsp;Mama Sy","doi":"10.1016/j.jgeb.2025.100578","DOIUrl":"10.1016/j.jgeb.2025.100578","url":null,"abstract":"<div><div>The <em>NR5A1</em> gene, encoding Steroidogenic Factor 1 (SF-1), plays a critical role in sex differentiation and spermatogenesis. However, data on <em>NR5A1</em> variants in sub-Saharan African populations remain limited. This exploratory pilot study aimed to identify and characterize <em>NR5A1</em> variants in infertile Senegalese men and to assess genotype–phenotype correlations. We conducted a cross-sectional study in 23 infertile Senegalese men, and exons 2 –7 of <em>NR5A1</em> were sequenced using the Sanger method. Detected variants were analyzed with in silico prediction tools and filtered for rarity (minor allele frequency &lt; 1 %) using the gnomAD database. Genotype–phenotype associations were analyzed using Fisher’s exact test.</div><div>Eighty-three percent of patients harbored at least one <em>NR5A1</em> variant. A novel heterozygous missense variant, c.584C &gt; T (p.Ser195Phe), located in the hinge region of SF-1, was identified in three unrelated individuals presenting with micropenis, testicular hypotrophy, and azoospermia. Several previously described variants were also detected. Genotype–phenotype correlation analysis revealed significant associations between <em>NR5A1</em> variants and spermatogenic failure, the most common clinical feature (60.8 %). These findings demonstrate substantial genetic variability in <em>NR5A1</em> among Senegalese men with infertility, and identify a novel missense variant. Our study highlights the relevance of <em>NR5A1</em> in male infertility screening and emphasizes the importance of incorporating African populations into reproductive genetics research.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100578"},"PeriodicalIF":2.8,"publicationDate":"2025-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145227469","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Utilizing deep learning algorithms for the early identification and categorization of skin cancer","authors":"Junaid Iqbal ,&nbsp;Mohammad Faisal ,&nbsp;Subhan Ullah ,&nbsp;Zareen A. Khan ,&nbsp;Zeeshan Ali ,&nbsp;Noor zaman Bawari","doi":"10.1016/j.jgeb.2025.100576","DOIUrl":"10.1016/j.jgeb.2025.100576","url":null,"abstract":"<div><div>Skin cancer is one of the utmost global challenges for today human being. Diverse forms of skin cancer found in humans, but current research work focuses on malignancy. The malignant can be treated easily if detected in the early stage. To achieve this goal, image processing and deep learning techniques were performed for the distinguished melanoma in early stages. Utilizing three models such as EfficientNet-B0, VGG16, and Inception-V3, the process involved initial preprocessing of image followed by training these models for 30 epochs on the PH2 and ISIC datasets. All three models demonstrated strong performance on both dataset; however, EfficientNet-B0 outperformed the other two models with an accuracy of 92 %, while Inception-V3 achieved 87 % accuracy and VGG-16 achieved 85 % accuracy. It has been established from the results that we aspire to enhance our suggested idea by incorporating it into a mobile platform in forthcoming endeavors. This modification will allow users to access and employ the model’s capabilities on the go, enhancing its reach and impact. The mobile platform will have an easy-to-use interface, allowing users to provide data and get reliable outcomes. This integration will not only increase the accessibility of the model, but also improve its value, making it easier for individuals to adopt it into their daily lives. By doing so, we hope to boost the model’s adoption and utilization, resulting in more accurate predictions and better decision-making.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100576"},"PeriodicalIF":2.8,"publicationDate":"2025-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene editing using gamma modified PNA: HBB gene as a model","authors":"Noha Eltaweel ,&nbsp;Ghada Elkamah ,&nbsp;Nesma Elaraby ,&nbsp;Iman Hassan ,&nbsp;Ahmed Wassel ,&nbsp;Nahla Abdel-Aziz ,&nbsp;Khalda Amr","doi":"10.1016/j.jgeb.2025.100562","DOIUrl":"10.1016/j.jgeb.2025.100562","url":null,"abstract":"<div><div>PNAs have emerged as a powerful tool in gene editing, particularly for correcting monogenic disorders by enhancing targeted recombination and genomic modifications. This study <strong>aimed to</strong> establish a gene editing technique using Peptide Nucleic Acid (PNA)/donor DNA-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles at our genomic facilities, with the ultimate goal of correcting disease-causing mutations. <strong>Methods</strong> involved culturing skin fibroblasts from a healthy Egyptian volunteer without HBB gene mutations in two separate 12-well plates. Oligonucleotides were designed, and nanoparticles were formulated and characterized before being used to treat the cultured fibroblasts. DNA and RNA were extracted from treated cells, followed by molecular analyses to confirm the edits. <strong>Results</strong> indicated successful encapsulation of nanoparticles and modest, sustained introduction of the desired mutation, accompanied by functional impairment in HBB gene expression. The study successfully established PNA gene editing technology, potentially paving the way for future treatment studies of single-gene disorders.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100562"},"PeriodicalIF":2.8,"publicationDate":"2025-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In-silico, in-vitro, and proteomics analyses on repurposed drugs in targeting the small GTPase, Rho subfamily protein (Rho GTPase), and putative Rho GTPase-activating protein (RhoGAP) of Giardia lamblia","authors":"Nurhana Jasni ,&nbsp;Khairul Bariyyah Abd. Halim ,&nbsp;Wong Weng Kin ,&nbsp;Darren Lau ,&nbsp;Clifford Young ,&nbsp;Peter Hoffmann ,&nbsp;Nurulhasanah Othman","doi":"10.1016/j.jgeb.2025.100573","DOIUrl":"10.1016/j.jgeb.2025.100573","url":null,"abstract":"<div><div><em>Giardia lamblia</em> is a globally prevalent protozoan responsible for Giardiasis, an intestinal disease commonly treated with nitroimidazoles such as metronidazole, tinidazole, and albendazole. However, increasing drug resistance has reduced treatment efficacy. Rho GTPase and its regulator, putative Rho GTPase-activating protein (RhoGAP), play crucial roles in <em>Giardia</em>’s encystation, membrane trafficking, and metabolism. This study explores these proteins as potential drug targets. We employed sequence-based target prediction, molecular docking, molecular dynamics (MD) simulations, minimal inhibitory concentration (MIC) assays, and label-free quantitative proteomics (LFQ) to identify and validate potential inhibitors. Target sequence analysis revealed Dextromethorphan and Azathioprine as candidate Rho GTPase inhibitors, and Imatinib, Dasatinib, and Ponatinib as RhoGAP inhibitors. Molecular docking using AutoDock Vina yielded binding energies ranging from −5.3 to −8.5 kcal/mol. MD simulations via GROMACS confirmed structural compactness and complex stability. <em>In vitro</em> MIC assays demonstrated that Dasatinib and Imatinib inhibited RhoGAP at concentrations of 12.5 µM and 100 µM, respectively, while azathioprine inhibited Rho GTPase at 500 µM. Dextromethorphan showed no inhibitory activity. LFQ proteomic analysis further confirmed Dasatinib’s significant impact on protein expression profiles. These findings highlight RhoGAP as a promising therapeutic target in <em>G. lamblia</em>, with Dasatinib showing potential as a repurposed treatment for Giardiasis. Proteomic data are publicly available in the MASSIVE database under identifier MSV000097321.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100573"},"PeriodicalIF":2.8,"publicationDate":"2025-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145158221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"In vitro antiproliferative effects of green synthesized silver nanoparticles from Brassica carinata microgreens on DU-145 prostate cancer cells and In vivo safety assessment","authors":"Dogfounianalo Somda ,&nbsp;Joel L. Bargul ,&nbsp;Sabina Wangui Wachira ,&nbsp;John M. Wesonga","doi":"10.1016/j.jgeb.2025.100552","DOIUrl":"10.1016/j.jgeb.2025.100552","url":null,"abstract":"<div><h3>Background</h3><div>Prostate cancer ranks among the most lethal malignancies affecting men globally. Conventional therapeutic approaches for this disease encounter limitations due to adverse side effects and the emergence of drug resistance, making its management challenging. Green-synthesized silver nanoparticles (AgNPs) have emerged as an attractive alternative to address the shortcomings of existing anticancer treatments.</div></div><div><h3>Objective</h3><div>This study was undertaken to evaluate the anticancer potential and safety profile of <em>BCM-</em>AgNPs, focusing on DU-145 inhibition and sub-acute toxicity in Wistar rats.</div></div><div><h3>Methods</h3><div>Previously synthesized <em>Brassica carinata</em> microgreen silver nanoparticles (<em>BCM</em>-AgNPs) alongside <em>Brassica carinata</em> microgreen crude extract (BCME) were used. The antiproliferative activity was investigated through the MTT assay on DU-145 prostate cancer cells and normal Vero E6 cells to determine the IC₅₀ and CC₅₀. Subsequently, a series of bioassays, including cell migration assays, clonogenic assays, cell cycle assays, and DNA fragmentation assays, were conducted. Furthermore, RT-qPCR was performed to delineate the molecular mechanism of <em>BCM</em>-AgNPs on DU-145 cells. Finally, a subacute toxicity study was carried out to assess the safety of <em>BCM</em>-AgNPs.</div></div><div><h3>Results</h3><div>Both <em>BCM</em>-AgNPs and BCME exhibited potent antiproliferative activity against DU-145 cells with an IC₅₀ of 33.47 μg/mL and 46.25 μg/mL, respectively, while sparing normal Vero E6 cells with selectivity indices of 3.50 for <em>BCM</em>-AgNPs and 4.62 for BCME. <em>BCM-AgNPs</em> demonstrated anti-migratory effects and hindered colony formation in DU-145 cells. They further induced S-phase cell cycle arrest through DNA fragmentation. RT-qPCR analysis revealed the upregulation of pro-apoptotic genes and the downregulation of genes involved in cell survival and proliferation pathways. <em>BCM</em>-AgNPs showed no toxicity in Wistar rats during 28-day oral administration.</div></div><div><h3>Conclusion</h3><div>This study demonstrates for the first time the selective and prominent antiproliferative effects of <em>BCM</em>-AgNPs against DU-145, as well as their safety and biocompatibility, underscoring their potential as a promising candidate for anticancer therapy.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100552"},"PeriodicalIF":2.8,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Biosynthesis, characterization, antibacterial, antibiofilm, and antioxidant activities of sodium nanoparticles from Escherichia coli metabolites","authors":"Malak Mezher ,&nbsp;Mahmoud I. Khalil ,&nbsp;Taymour A. Hamdalla ,&nbsp;Dalia El Badan","doi":"10.1016/j.jgeb.2025.100575","DOIUrl":"10.1016/j.jgeb.2025.100575","url":null,"abstract":"<div><div>This study emphasizes the need for strategies to tackle multi-drug resistant pathogens by investigating the antibacterial, antibiofilm, and antioxidant properties of sodium nanoparticles (NaNPs) derived from metabolites of <em>Escherichia coli</em>. The configuration of the NaNPs was examined through X-ray diffraction (XRD), Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), Photoluminescence (PL), and Ultraviolet–visible spectroscopy (UV–Vis). XRD and TEM analyses revealed that NaNPs possess a grain size around 125 nm, exhibiting a crystallinity of 63.45 % and a rod-shaped morphology. The UV–Vis revealed considerable absorbance at 280 nm, leading to an optical bandgap of 4.125 eV. To evaluate antibacterial and antibiofilm characteristics, clinical bacteria including <em>Streptococcus pneumonia</em>, <em>Enterococcus faecium</em>, <em>Klebsiella pneumonia</em>, and <em>Salmonella</em> Typhimurium were identified and examined for multidrug resistance using antibiogram testing. The antibacterial activity was assessed through agar well diffusion, minimum inhibitory and bactericidal concentrations (MIC and MBC) tests, and a time-kill assay. The antibiofilm effect was assessed by preventing biofilm formation and removing established biofilm assays. The antioxidant potential was assessed through the 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay. Antibacterial results demonstrated a bactericidal effect on <em>Enterococcus faecium</em> and <em>Salmonella</em> Typhimurium (MBCs 0.0625 and 0.125 mg/mL, respectively). Inhibition zones ranged from 7.3 to 10.5 mm. NaNPs inhibited bacterial growth following 5 h of incubation. Antibiofilm results revealed an inhibitory effect on biofilm development (with an inhibition percentage of 62 %) and a minimal impact on biofilm elimination (showing a destruction percentage of 21 %). Antioxidant results showed a significant scavenging effect, with the percentage of radical scavenging reaching 23 %. The results suggest positive effects of the NaNPs in biomedical applications.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100575"},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105181","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal correlation between inflammatory cytokines and hypertrophic scar based on two-sample Mendelian randomization","authors":"Lujia Mao ,&nbsp;Juan Huang ,&nbsp;Yixun Zhang ,&nbsp;Weiqiang Zhang ,&nbsp;Xiaoxiang Wang ,&nbsp;Ronghua Yang","doi":"10.1016/j.jgeb.2025.100572","DOIUrl":"10.1016/j.jgeb.2025.100572","url":null,"abstract":"<div><div>Hypertrophic scars result from the abnormal proliferation of fibroblasts and the accumulation of collagen after skin injury. In this process, inflammatory cytokines act as crucial regulators. The large − scale release of inflammatory cytokines aberrantly activates fibroblasts. It promotes the proliferation of fibroblasts and the synthesis of collagen, and simultaneously inhibits collagen degradation. The purpose of this study is to investigate the causal correlation between inflammatory cytokines and hypertrophic scars (<em>HS</em>). This study applied a two-sample Mendelian randomization approach (<em>TSMR</em>), leveraging summarized data gathered by genome-wide association studies (GWAS). The inflammatory cytokines (8293 samples) and hypertrophic scar (HS, 207,482 samples) summary data were analyzed to figure out whether there was a causal connection of the two.The inverse variance-weighted (IVW) method was implemented to undertake causal analysis, also sensitivity, heterogeneity, and pleiotropy analyses were performed to further evaluate the results’ stability and dependability.Two inflammatory cytokines, IL-2 and CCL4, were identified as being associated with HS. The IVW analysis demonstrated a positive relationship between IL-2 and the risk of HS (OR = 1.51, 95 % CI = 1.06–2.15, <em>P</em> = 0.02), indicating that IL-2 is a risk factor for hypertrophic scarring, with elevated levels potentially promoting disease progression. In contrast, CCL4 was negatively associated with HS risk (OR = 0.86, 95 % CI = 0.74–0.99, <em>P</em> = 0.03), pointing to the fact CCL4 might function as a protective agent, where lower levels of CCL4 could inhibit scar formation. Sensitivity analyses verified the dependability of the TSMR results (<em>P</em> &gt; 0.05). Our MR analysis indicates a causal correlation between inflammatory cytokines and hypertrophic scars. Specifically, IL-2 promotes hypertrophic scar formation, whereas CCL4 exerts a protective effect, reducing the risk of scar formation. These discoveries imply that inflammatory cytokines have a considerable part to play in the pathogenesis of hypertrophic scarring through modulating its formation.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100572"},"PeriodicalIF":2.8,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fmp45 promotes Rad53 dephosphorylation via Ptc2 interaction to attenuate checkpoint signaling and maintain genome stability","authors":"Zhongyi Cong ,&nbsp;Jingyuan Jiang ,&nbsp;Mengyuan Li ,&nbsp;Chenqi Yan,&nbsp;Jiayin Li,&nbsp;Xinmin Zhang","doi":"10.1016/j.jgeb.2025.100567","DOIUrl":"10.1016/j.jgeb.2025.100567","url":null,"abstract":"<div><h3>Background</h3><div>Double-strand breaks (DSBs) are repaired through the coordinated action of DNA damage checkpoint pathways, homologous recombination (HR), and non-homologous end joining (NHEJ) mechanisms. Given the complexity of DSB repair networks, the identification of novel regulatory factors remains essential for a comprehensive understanding of genomic stability maintenance. Fmp45, a membrane protein previously implicated in salt stress response but with no known role in DNA repair, was found to be upregulated in multiple DNA damage-related transcriptomic datasets (GEO: GSE83454, GSE155701, GSE74642). This observation led us to hypothesize that Fmp45 might represent a previously unrecognized component of the DSB repair machinery. In this study, we demonstrate that Fmp45 functions as a zeocin-specific modulator of the DSB response in Saccharomyces cerevisiae.</div></div><div><h3>Methods</h3><div>Growth phenotypes were analysed to investigate FMP45 deletion (<em>fmp</em>45Δ) and its genetic interactions with other genes, protein expression and Rad53 phosphorylation was assessed by Western blotting, protein localization was analysed by Laser confocal microscopy, cell cycle progression was determined by flow cytometry, and protein–protein interactions was probed yeast two-hybrid assays.</div></div><div><h3>Results</h3><div>Growth assays revealed that <em>fmp</em>45Δ mutants exhibited hypersensitivity to DSBs induced by zeocin but not to other DNA lesions caused by hydroxyurea, methyl methanesulfonate, 4-nitroquinoline-1-oxide, or camptothecin. Genetic interaction analysis showed that <em>Fmp45</em> cooperated with checkpoint gene <em>Rad9</em> but not with HR-related genes (<em>Sae2</em>, <em>Exo1</em>) or NHEJ factor <em>yku70</em>. Laser confocal microscopy confirmed that <em>FMP45</em> deletion did not impair nuclear localization of Rad51, a key mediator of HR-mediated DNA strand invasion. Further analysis of Rad53 phosphorylation/dephosphorylation dynamics, growth phenotypes of <em>fmp</em>45Δ with phosphatase (<em>ptc</em>2Δ, <em>pph</em>3Δ) and checkpoint effector (<em>rad</em>9Δ, <em>mrc</em>1Δ) mutants, cell cycle profiling, and yeast two-hybrid assays demonstrated that Fmp45 interacts with Ptc2 to promote Rad53 dephosphorylation, thereby preventing excessive cell cycle arrest.</div></div><div><h3>Conclusion</h3><div>These findings elucidate a critical checkpoint-phosphatase coordination mechanism ensuring timely DNA damage recovery and genomic stability, identifying Fmp45 as a key regulator balancing DNA repair fidelity with cell cycle resumption following DSBs.</div></div>","PeriodicalId":53463,"journal":{"name":"Journal of Genetic Engineering and Biotechnology","volume":"23 4","pages":"Article 100567"},"PeriodicalIF":2.8,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145105180","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}