Biomolecules最新文献

{"title":"NOX2-Driven Oxidative Stress and Endothelial Dysfunction in Male Elite Adolescent Soccer Players.","authors":"Chiara Fossati, Federica Armeli, Alessandra D'Amico, Giacomo Frati, Giovanni Enrico Casciaro, Elena Cavarretta, Vittoria Testa, Alessio Borrelli, Luigi Sciarra, Chiara Lodoli, Marco Zagarella, Beatrice Oana Paun, Vittorio Picchio, Antonio Gianfelici, Fabio Pigozzi, Stefano Corrado, Fabrizio Perroni, Cristina Nocella, Roberto Carnevale","doi":"10.3390/biom16091301","DOIUrl":"10.3390/biom16091301","url":null,"abstract":"<p><strong>Background: </strong>Intense physical exercise induces oxidative stress and inflammation in adult professional athletes, but data on adolescent elite athletes remain limited.</p><p><strong>Methods: </strong>Twenty-four elite adolescent soccer players were recruited and evaluated three times: pre-season baseline (T0), after one month of pre-season training (T1), and at the end of the first half of the competitive season (T2, approximately 4 months after T0). Saliva samples were collected as non-invasive surrogate indicators reflecting oxidative stress- and endothelial-related signaling. In vitro studies were performed on endothelial cells exposed to H₂O₂ concentrations observed in athletes.</p><p><strong>Results: </strong>Athletes showed a significant increase in salivary oxidative stress markers (NOX2 levels and H₂O₂) at T1 and T2 versus T0. Endothelial impairment was evidenced by reduced salivary NOx concentration and elevated endothelin (ET-1) levels. In vitro, endothelial cells exposed to H₂O₂ (8 μM) showed increased sNOX2-dp and ET-1 levels, reduced eNOS phosphorylation, and impaired tube formation (mesh number and area) compared with untreated cells. NOX2ds-tat treatment reduced cell damage and restored angiogenic capacity.</p><p><strong>Conclusions: </strong>Our findings indicate that adolescent elite athletes experience significant salivary oxidative stress- and endothelial-related alterations, potentially reflecting cardiovascular stress. These results underscore the importance of cardiovascular monitoring and the potential benefits of antioxidant strategies, even in young athletes participating in high-intensity sports.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058183","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"NKR-P1A/CD161: A Multifunctional Immune Receptor at the Crossroads of Antitumor Immunity.","authors":"Chiara Rosa Maria Uras, Martina Taglieri, Linda Di Gregorio, Alessandro Poggi","doi":"10.3390/biom16091302","DOIUrl":"10.3390/biom16091302","url":null,"abstract":"<p><p>The immune response of our body, whether it is directed to infective agents, allergens, or tumors, should support our recovery but can also be dangerous if dysregulated. There are molecular systems that have the role of tuning the immune response, such as activating and inhibitory receptors and co-stimulatory molecules. Among this plethora of receptors, immune-checkpoint receptors (ICRs), as well as natural killer receptors (NKRs), expressed on NK and/or T cells can up- or downregulate the function of activating and inhibitory receptors during immune cell crosstalk. Among NKRs, NKRP1A/CD161 has shown to be a promising target molecule for immunotherapy. This receptor showed inhibiting or co-stimulatory effects depending on the cell type analyzed as well as the analytical procedures, reagents used, and the experimental context. The aim of the following review will be to explore the structural and functional features of this receptor on immune cells, its relevance in the tumor microenvironment and its targeting as an immunotherapeutic tool in cancers.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604327/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058195","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glycoproteomics and Functional Characterization of Novel Variants in Siblings with ALG1-CDG.","authors":"Dongzhi Wei, Hui Wang, Senlin Peng, Yu Huang, Ganglong Yang, Weijie Dong, Xiaodong Gao, Ning Wang","doi":"10.3390/biom16091308","DOIUrl":"10.3390/biom16091308","url":null,"abstract":"<p><p>Congenital disorders of glycosylation (CDGs) are a growing group of inborn errors caused by gene defects in glycan biosynthesis pathways. Genetic testing of two patients from the same family harboring <i>ALG1</i>-related CDG (ALG1-CDG) revealed heterozygous variations in the c.1129 A>C and c.1263+3 A>T. Although most CDGs with abnormal <i>N</i>-glycosylation can be detected by transferrin screening, Western blotting of serum transferrin from the two siblings did not reveal significant glycosylation deficiency. In this study, the biochemical phenotype and pathological molecular basis of the CDGs in the siblings were further explored. Analysis of the patients' <i>ALG1</i> cDNA indicated that the associated heterozygous variants were c.1129 A>C (p.Met377Leu) and c.1188 T>A (p.Cys396X). Single-molecule real-time (SMRT) sequencing indicated that the variant frequencies of M377L and C396X were 50% and 36%, respectively. In addition, glycoproteomics analysis suggested that the glycoforms of transferrin were altered in the patients and that glycosylation site occupancy was decreased. It was also confirmed that <i>N</i>-glycosylation was altered in the patients' serum transferrin. Conserved amino acid variants of yeast Alg1 were recombinantly overexpressed, purified and subjected to an in vitro quantitative activity assay. The results showed that these variants caused a decrease in enzymatic activity, suggesting pathogenicity.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604089/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058175","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Coagulation Assessment and Fibrinogen Thresholds in Therapeutic Plasma Exchange-A Narrative Review.","authors":"Matej Zrimsek, Jakob Gubensek","doi":"10.3390/biom16091304","DOIUrl":"10.3390/biom16091304","url":null,"abstract":"<p><p>Many therapeutic apheresis procedures that remove plasma or plasma components also lower coagulation factor levels, which can increase patients' bleeding risk. In this narrative review, we sum up data on clotting factor removal and the development of dilutional coagulopathy mostly associated with therapeutic plasma exchange (TPE) treatment and consider available tests for coagulation assessment. It is common in clinical practice to check fibrinogen levels regularly during repetitive TPE treatments and use it as a marker of hemostasis because of its long half-life and central role in hemostasis. We discuss the background of current clinical practice regarding fibrinogen thresholds discuss different threshold levels and data on the associated risk of bleeding. We stress the importance of additional bleeding risk assessment when patients are exposed to concomitant invasive procedures. We also describe the possibilities for fibrinogen replacement during TPE treatments with either fresh frozen plasma or fibrinogen concentrate and the associated effect on factor XIII levels. Finally, we briefly discuss alternative apheresis procedures regarding their fibrinogen-sparing potential.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome-Wide CRISPR Screens Identify Genome Stability as Regulator of the Cellular Sensitivity to Environmentally Relevant Bisphenol A Exposure.","authors":"Anastasia Hale, Alexandra Nusawardhana, Claudia M Nicolae, George-Lucian Moldovan","doi":"10.3390/biom16091303","DOIUrl":"10.3390/biom16091303","url":null,"abstract":"<p><p>Bisphenol A (BPA) is a prevalent chemical used in the production of plastics. While adverse effects on the reproductive system have been documented, more recent studies also associated BPA exposure with carcinogenesis as well as genomic instability. However, these studies were generally performed using BPA concentrations much higher than those observed in the serum or urine of the general population, making their relevance unclear. To address this, we report here an unbiased genetic study to identify mechanisms responding to levels of BPA exposure relevant to plastic manufacturers. We performed genome-wide CRISPR knockout screens in HeLa and RPE1 cells upon continuous exposure to 0.5 μM BPA, a concentration similar to the mean BPA concentration found in the urine of plastics manufacturing workers, for 19 days. We found genome stability genes among the top common hits between the two cell lines, suggesting that BPA causes DNA damage at this environmentally relevant exposure dose. We validated the DNA repair gene RAD51C and the RNA helicase DDX21 as genes required for BPA resistance. Our study suggests that BPA exposure at environmentally relevant doses can cause DNA damage, highlighting the relevance of BPA for carcinogenesis.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604100/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058192","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Replication Stress Tolerance in Adult T-Cell Leukemia.","authors":"Yusuke Okamoto, Masayuki Kobayashi, Takashi Sakamoto, Kotaro Shirakawa, Akifumi Takaori-Kondo","doi":"10.3390/biom16091310","DOIUrl":"10.3390/biom16091310","url":null,"abstract":"<p><p>Replication stress (RS) represents a major vulnerability of cancer cells treated with nucleoside analogs and related antimetabolites; however, tumors frequently acquire tolerance mechanisms that permit survival despite persistent DNA lesions. This review examines molecular determinants of RS tolerance, focusing on human T-cell leukemia virus type 1 (HTLV-1)-mediated adult T-cell leukemia/lymphoma (ATL) as a model of virus-mediated rewiring of DNA damage responses. Chain-terminating nucleoside analogs generate aberrant replication intermediates, including blocked 3' DNA termini, mis-incorporated bases, and stalled replication forks. In ATL, viral oncoproteins suppress key components of replication stress response pathways, notably tyrosyl-DNA phosphodiesterase 1 (TDP1) and mismatch repair (MMR), thereby creating exploitable repair deficiencies. Consistent with this vulnerability, ATL cells exhibit marked sensitivity to replication stress-inducing agents such as irinotecan (CPT-11) and the chain-terminating nucleoside analog abacavir. Recent CRISPR-based functional genomics studies further identify Schlafen 11 (SLFN11) as an independent and dominant regulator of RS sensitivity. SLFN11 determines the fate of stressed replication forks independently of lesion processing, acting as an execution factor that converts otherwise tolerable RS into irreversible replication arrest. We conclude by discussing therapeutic strategies that exploit RS tolerance defects in ATL, including biomarker-guided nucleoside analog therapy, and rational combination approaches targeting compensatory RS pathways.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604372/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058286","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Trihelix Genes in <i>Gardenia jasminoides</i> Evolution, Expression Profiles, and Potential Regulatory Functions in Growth, Development, and Multiple Stress Responses.","authors":"Jun Liu, Tingting Cheng, Jiefeng Kou, Lili Wang, Lixin Pei, Yan Yang, Conglong Lian, Jinxu Lan, Fei Zhang, Suiqing Chen","doi":"10.3390/biom16091298","DOIUrl":"10.3390/biom16091298","url":null,"abstract":"<p><p>Trihelix is a class of transcription factors unique to plants that play a major role in abiotic and biotic stress responses, seed isolate development, floral organ morphogenesis, and plant photomorphogenesis. Nevertheless, the Trihelix transcription factor family in <i>Gardenia jasminoides</i> (<i>G. jasminoides</i>) has not been systematically characterized. In this study, 11 <i>GjTrihelix</i> genes were identified from the <i>G. jasminoides</i> genome, unevenly distributed across five chromosomes, and can be classified into four subfamilies: GT-1, GT-2, SIP and SH4. Gene structure and functional motif analyses revealed high conservation within the same subfamily. Cis-acting element analysis showed that these genes are closely related to hormone responses, stress responses, and growth and development processes. Intraspecific synteny analysis showed a segmental duplication between <i>GjTrihelix-3</i> and <i>GjTrihelix-10</i>. Interspecific collinearity analysis revealed that <i>G. jasminoides</i> shared 21 collinear gene pairs with soybean, compared with five pairs with Arabidopsis and 13 with Populus, indicating greater syntenic block conservation between G. jasminoides and soybean. Transcriptome data analysis demonstrated distinct spatiotemporal expression specificity of this gene family. Several genes were constitutively expressed in fruits; <i>GjTrihelix-1</i> and <i>GjTrihelix-3</i> were predominantly expressed in green fruits, while <i>GjTrihelix-11</i> was highly expressed in red fruits. Under melatonin treatment, five <i>GjTrihelix</i> genes showed significant up-regulation and obvious transcriptional suppression of another five genes. Following infection by <i>Botryosphaeria dothidea</i>, <i>GjTrihelix-5</i> and <i>GjTrihelix-7</i> were progressively induced and peaked at 72 h. qRT-PCR results indicated that most <i>GjTrihelix</i> genes were highly expressed in leaves, while <i>GjTrihelix-11</i> was highly expressed in flowers. Most <i>GjTrihelix</i> genes were significantly down-regulated under NaCl, ABA, GA₃ and IAA stresses. This study provides new insights into the potential association of the Trihelix transcription factor family in <i>G. jasminoides</i> growth, development, and stress adaptation, offering theoretical references for stress-resistant <i>G. jasminoides</i> breeding.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604084/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Curcumin Retains Anti-Inflammatory Effects Despite IDO Inhibition-Associated Neutrophilic Shift in OVA-Induced Rat Model.","authors":"Mubeen Fatima, Ali Rafi, Muhammad Shoaib Zafar, Usman Aftab, Khush Bakhat Kiran, Muhammad Shahzad, Safdar Hussain, Hongbo Wang","doi":"10.3390/biom16091295","DOIUrl":"10.3390/biom16091295","url":null,"abstract":"<p><p>Allergic asthma is characterized by Th2-driven airway inflammation. Indoleamine 2,3-dioxygenase (IDO) maintains immune tolerance, but its role in modulating the anti-inflammatory actions of Curcumin (CN) is unclear. This study investigated whether CN retains efficacy in a rat model of Ovalbumin (OVA)-induced airway inflammation under pharmacological IDO inhibition. Rats were sensitized and challenged with OVA and treated with methylprednisolone (MP, 15 mg/kg), CN (200 mg/kg), the IDO inhibitor 1-MT (70 mg/kg), or CN+1-MT. Assessments included systemic and pulmonary leukocyte profile, delayed-type hypersensitivity (DTH), OVA-specific IgE, bronchoalveolar lavage fluid (BALF) inflammatory cells and nitric oxide (NO) levels, lung wet/dry weight ratio, gene expression of tumor necrosis factor alpha (TNF-α), interleukin (IL)-4, IL-6, <i>Cxcr2</i> and transcription factor Nfkb1 and lung histopathology. CN alone or combined with 1-MT normalized leukocyte counts, suppressed eosinophilic and neutrophilic infiltration, restored BALF NO levels, reduced DTH response and OVA-specific IgE, decreased pulmonary edema, and preserved pulmonary vascular integrity. CN significantly attenuated TNF-α, IL-4, IL-6, and <i>Cxcr2</i> gene expression despite pharmacological IDO inhibition. Histopathology revealed reduced inflammatory infiltration and maintained alveolar structure. CN maintains anti-inflammatory, immunomodulatory and tissue-protective efficacy in allergic airway inflammation despite pharmacological IDO inhibition. These findings call for future research on CN as a potential adjunctive therapy method for inflammatory airway diseases. However, to elucidate the underlying processes, more research on IDO activity and downstream immunometabolic pathways is needed.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058091","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Comprehensive Bioinformatic and miRNA-Driven Analysis of the Multimeric Canonical I Kappa B Kinase (IKK) Complex in Uterine Corpus Endometrial Carcinoma (UCEC).","authors":"Yasemin Dadas, Enes Karaman, Ergul Bayram, Durmus Ayan","doi":"10.3390/biom16091296","DOIUrl":"10.3390/biom16091296","url":null,"abstract":"<p><p>Uterine corpus endometrial carcinoma (UCEC) is the most common gynecologic malignancy, and aberrant canonical NF-κB signaling is implicated in uterine corpus endometrial carcinoma (UCEC), yet the expression, epigenetic, and prognostic profile of IκB kinase (IKK) complex subunits CHUK (IKKα), IKBKB (IKKβ), and IKBKG (NEMO) remains undefined. This study assessed expression, methylation, miRNA regulation, and clinical relevance of IKK-complex genes in UCEC using public datasets. RNA-seq expression (TCGA-UCEC; GEPIA2) showed significant downregulation of IKBKB in tumors versus normal endometrium (unpaired Wilcoxon), whereas CHUK and IKBKG showed non-significant increases; immunohistochemistry (Human Protein Atlas) illustrated heterogeneity and suggested possible mRNA-protein discordance for IKBKB. Promoter methylation analysis (UALCAN; Illumina 450K) identified CHUK hypomethylation and IKBKG hypermethylation in tumors, with no significant change for IKBKB. Stratification showed IKBKB suppression across clinicopathological strata and TP53 mutant/wild-type tumors; IKBKG decreased across subtypes and stages. Pan-cancer profiling (TIMER2.0) highlighted IKBKB as the broadly dysregulated IKK member across malignancies. STRING networks indicated connectivity with NF-κB mediators (e.g., RELA, NFKB1, TRAF6). miRNA predictions (miRDB/TargetScan) revealed shared regulation (CHUK-IKBKB: 14 miRNAs; CHUK-IKBKG: 2; IKBKB-IKBKG: 0). Kaplan-Meier analysis indicated that elevated IKBKG expression correlated with reduced overall survival (HR = 1.85, <i>p</i> = 0.0037), while CHUK expression did not correlate with survival, and IKBKB exhibited a non-significant trend. In a multivariable Cox regression analysis, high IKBKG expression continued to show a significant association with reduced overall survival, even after adjusting for age, histological type, histological grade, and TCGA molecular subtype (adjusted HR = 1.58, 95% CI = 1.00-2.47, <i>p</i> = 0.048). These findings collectively suggest the potential prognostic significance of IKBKG in UCEC, although independent validation in larger, comprehensively annotated cohorts is still required. Collectively, these findings suggest IKBKG as a candidate negative prognostic marker and indicator in UCEC, warranting experimental validation.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604377/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058121","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigallocatechin Gallate Modulates the Cellular Response to Doxorubicin in HeLa Cervical Cancer Cells.","authors":"Mehmet Emin Ayağ, Mehmet Cudi Tuncer, Şamil Öztürk","doi":"10.3390/biom16091299","DOIUrl":"10.3390/biom16091299","url":null,"abstract":"<p><p>Cervical cancer remains a major cause of cancer-related mortality worldwide, highlighting the need for strategies that may improve responses to conventional chemotherapeutics. Epigallocatechin gallate (EGCG), a green-tea polyphenol with diverse biological activities, has been investigated as a potential chemosensitizing agent. This study evaluated the interaction between EGCG and doxorubicin (DOX) in HeLa cervical cancer cells, with HaCaT keratinocytes included as a non-malignant comparator. Cell viability and drug interactions were assessed using the CCK-8 assay and Chou-Talalay combination index (CI) analysis. Complementary assays evaluated membrane integrity, wound closure, apoptosis, cell-cycle distribution, intracellular DCF-associated fluorescence with or without N-acetylcysteine (NAC) pretreatment, caspase-3 immunoreactivity, and <i>EGFR</i>, <i>FOXP3</i>, <i>CASP3</i>, and <i>CASP7</i> mRNA expression. Network-based analyses were additionally used to identify candidate molecular associations and pathways. CI analysis demonstrated synergistic EGCG-DOX interactions in HeLa cells under the tested conditions, whereas additive or antagonistic interactions predominated in HaCaT cells. Combined treatment produced the greatest reduction in viable cells, increased apoptosis, altered cell-cycle distribution, and reduced wound closure. It also produced the highest viability-normalized DCF-associated fluorescence, which was attenuated by NAC pretreatment, indicating an antioxidant-sensitive change in intracellular oxidative status without establishing a causal role in cytotoxicity. Combined treatment was further associated with increased total caspase-3 immunoreactivity and altered <i>EGFR</i>, <i>FOXP3</i>, <i>CASP3</i>, and <i>CASP7</i> transcript levels. Overall, EGCG and DOX exhibited synergistic interactions and multiple treatment-associated cellular and transcriptional responses in HeLa cells under the present in vitro conditions. These findings do not establish cancer-specific selectivity or a definitive molecular mechanism but provide a basis for validation in additional cervical cancer models and at clinically relevant exposures.</p>","PeriodicalId":8943,"journal":{"name":"Biomolecules","volume":"16 9","pages":""},"PeriodicalIF":5.6,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13604874/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149058117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}