Biomedicine & Pharmacotherapy最新文献

{"title":"Therapeutic effect of neural induced-stem cell-derived exosomes by regulating ERK/p38/NF-κB in traumatic brain injury","authors":"Dohee Kim ,&nbsp;Jinsu Hwang ,&nbsp;Eunjae Jang ,&nbsp;Hyong-Ho Cho ,&nbsp;Byeong C. Kim ,&nbsp;Han-Seong Jeong ,&nbsp;Sujeong Jang","doi":"10.1016/j.biopha.2025.118616","DOIUrl":"10.1016/j.biopha.2025.118616","url":null,"abstract":"<div><div>Traumatic brain injury (TBI) can occur because of sudden external forces, such as falls or accidents, and it can cause immediate and long-term damage to the central nervous system. In this study, the therapeutic effects of neural-induced human adipose tissue-derived stem cell-derived exosomes (NI-Exo) on TBI were investigated. Exosomes were isolated and characterized through nanoparticle tracking analysis, cryo-transmission electron microscopy, and western blotting analysis. The therapeutic effects of NI-Exo were assessed in LPS-stimulated human microglial cells and TBI mice via behavioral tests (rotarod, elevated body swing, and cylinder tests), qPCR, western blotting analysis, and immunostaining. In the <em>in vitro</em> study, NI-Exo significantly downregulated pro-inflammatory cytokines (IL-6, IL-1β, and TNF-α) and upregulated anti-inflammatory cytokines (IL-4 and IL-10). In the <em>in vivo</em> study, NI-Exo (1 × 10⁴ or 1 × 10⁵ particles/mL) was administered intracerebroventricularly 1 h post-surgery to verify the effect on the <em>in vivo</em> model. In the TBI mouse model, NI-Exo improved asymmetric behaviors and reduced tissue disruption and cell loss. The protein levels of pro-apoptosis (p53, ROCK1, and Bax) decreased and those of anti-apoptosis (Mcl-1) increased in the NI-Exo group compared with those in the TBI group. Mechanistic investigations revealed that NI-Exo inhibited ERK and p38 phosphorylation, highlighting its role in mitigating neuroinflammation via the ERK/p38/NF-κB signaling pathway. Therefore, NI-Exo promoted anti-inflammation in human microglia and TBI mouse models; it also improved anti-apoptosis in TBI models, thereby offering a promising therapeutic potential for TBI treatment through the ERK/p38/NF-κB pathway.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118616"},"PeriodicalIF":7.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218277","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of acetylcholine level by donepezil hydrochloride attenuates the severity of experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis","authors":"Morena Brazil Sant’Anna ,&nbsp;Leticia Ferreira Carvalho Corcino ,&nbsp;Flavia Souza Ribeiro Lopes ,&nbsp;Gessica Sabrina de Assis Silva ,&nbsp;Ana Maria Boaventura de Oliveira ,&nbsp;Andrea Borrego ,&nbsp;Marcelo De Franco ,&nbsp;Osvaldo Augusto Sant’Anna ,&nbsp;Gisele Picolo","doi":"10.1016/j.biopha.2025.118630","DOIUrl":"10.1016/j.biopha.2025.118630","url":null,"abstract":"<div><div>Multiple sclerosis (MS), is a chronic autoimmune disease characterized by neuroinflammation and demyelination, with no known cure. Previous studies demonstrated that crotoxin, a neurotoxin derived from rattlesnake venom, effectively alleviated hyperalgesia and clinical symptoms in experimental autoimmune encephalomyelitis (EAE) when combined with silica SBA-15 (CTX-SBA-15), an inert nanostructured particle. This combination inhibited disease progression and reduced neuroinflammation. Building on these findings, we conducted a comprehensive gene expression analysis to identify differentially expressed genes (DEGs) and pathways affected by MOG_35–55-induced EAE and modulated by CTX, which could serve as potential targets for disease control. Gene expression in the central nervous system was analyzed using the GeneChip platform. Data were processed using the Transcriptome Analysis Console and the Gene Ontology database. The analysis identified 1055 DEGs, with 238 genes specifically associated with the disease in the EAE vs. CFA comparison. In the CTX-SBA-15 post-treatment group, 695 DEGs were identified, with 204 genes upregulated and 491 downregulated compared to the EAE group. Overrepresentation analysis highlighted acetylcholine receptors pathways as significant targets. For validation, donepezil hydrochloride, an acetylcholinesterase inhibitor, was administered (2 mg/kg/day) initiating 12 days after immunization, with body weight monitored every other day. Donepezil improved clinical symptoms, reduced weight loss, decreased cellular infiltrates, and prevented spinal cord demyelination. In conclusion, our findings highlights that the acetylcholine pathway represents a promising target to be modulated for MS management.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118630"},"PeriodicalIF":7.5,"publicationDate":"2025-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218278","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modelling-filtered drug repurposing and first-in-protein SPR validation of histone deacetylase 4 inhibitors for Ataxia-telangiectasia","authors":"Alessia Distefano ,&nbsp;Matteo Pappalardo ,&nbsp;Roberta Turco ,&nbsp;Giuseppe Grasso ,&nbsp;Salvatore Guccione","doi":"10.1016/j.biopha.2025.118621","DOIUrl":"10.1016/j.biopha.2025.118621","url":null,"abstract":"<div><div>Ataxia-telangiectasia is a neurodegenerative disorder characterised by ATM deficiency and aberrant nuclear accumulation of Histone deacetylase 4 (HDAC4) in Purkinje neurons. Targeting HDAC4 has thus emerged as a promising therapeutic strategy. Here, we employed a drug-repositioning approach to identify new HDAC4 modulators from an EMA-approved compound library. <em>In silico</em> screening selected asenapine, a second-generation antipsychotic, through consensus scoring across four independent docking functions and low predicted binding free energy (ΔG), positioning it among the most thermodynamically stable candidates. Surface plasmon resonance analysis confirmed high-affinity binding to immobilised HDAC4, enabling extraction of kinetic and thermodynamic parameters that characterise the allosteric mechanism underlying HDAC4–asenapine complex formation. Competitive assay with tasquinimod, a known HDAC4 modulator, revealed that asenapine exhibits higher affinity supporting its candidacy for further pharmacological development. These findings underscore the utility of combining repositioning pipelines with real-time affinity quantification to accelerate the discovery of selective HDAC4-targeted therapeutics for Ataxia–Telangiectasia.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118621"},"PeriodicalIF":7.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218280","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unraveling ferroptosis in infectious diseases: From basics, mechanistic pathways, and its dual role in the infections to potential therapeutic implications","authors":"Niloofar Kiaheyrati ,&nbsp;Amir Mahdi Ghaffari Moaf ,&nbsp;Maedeh Manzari ,&nbsp;Ava Payravand ,&nbsp;Samira Sabzi ,&nbsp;Fatemeh Samiee-Rad ,&nbsp;Abouzar Babaei","doi":"10.1016/j.biopha.2025.118624","DOIUrl":"10.1016/j.biopha.2025.118624","url":null,"abstract":"<div><div>Ferroptosis is an iron-dependent form of regulated cell death characterized by the accumulation of lipid peroxides, distinguishing it from apoptosis, necrosis, and other cell death modalities. Initially examined to cancer and neurodegeneration, the recent data underscore its pivotal role in infectious illnesses. Across bacterial, viral, fungal, and parasitic diseases, this review offers a thorough investigation of how ferroptosis contributes to microbial infections. We investigate how different bacteria either promote pathogenicity, immunological evasion, or survival by using or modifying host ferroptotic processes. Moreover, we examine the host’s ferroptotic response as a potential defense mechanism, its dual role in inflammation and tissue damage, and the interplay with immune signaling pathways. Understanding the mechanistic underpinnings of ferroptosis in infection may uncover novel therapeutic targets and strategies for infectious disease management. By integrating cross-kingdom perspectives, this paper is the first comprehensive review, which aims to highlight ferroptosis as a convergent point in host–pathogen interactions with significant biomedical implications.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118624"},"PeriodicalIF":7.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218301","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Feasibility and efficacy of electromotive intraperitoneal drug delivery: A hybrid study","authors":"Nidda Saeed ,&nbsp;Hooman Salavati ,&nbsp;Jolene Wong Si Min ,&nbsp;Sarah Cosyns ,&nbsp;Katrien Remaut ,&nbsp;Charlotte Debbaut ,&nbsp;Mieke Adriaens ,&nbsp;Annelies Coene ,&nbsp;Wim Ceelen","doi":"10.1016/j.biopha.2025.118619","DOIUrl":"10.1016/j.biopha.2025.118619","url":null,"abstract":"<div><div>Intraperitoneal drug delivery (IPDD) is increasingly used to treat peritoneal metastases (PM). However, the adverse biomechanical properties of tumor tissue, such as elevated interstitial fluid pressure and matrix stiffness, are known to impede the transport and efficacy of small-molecule anticancer drugs and nanoparticles (NPs). Physical methods may enhance tissue penetration after IPDD treatment. In this study, we explored the use of an electrical direct current (DC) field generated by electromotive drug administration (EMDA) as a novel physical method to enhance tissue penetration after IPDD. This method involves the combination of a fluid column with a pulsed DC current. A novel in vitro setup was developed in combination with a computational fluid dynamics (CFD) model to test the effects of different treatment variables on the penetration of 100 and 200 nm positively charged NPs in healthy porcine peritoneal samples. We found that tissue penetration using EMDA improved with increasing current intensity, higher temperature of the carrier fluid, and longer administration time, with a plateau reached at 30 min. Isotonic carrier fluids performed better compared to hypotonic and hypertonic solutions. Using these optimized parameters, in vivo studies were performed in both healthy and tumor-induced rats, where peritoneal tissues from all animals and tumor samples from the tumor-induced group were evaluated. EMDA was well tolerated and resulted in significantly enhanced penetration of 100 nm NPs, achieving deeper and more uniform distribution within healthy peritoneum and tumor nodules, irrespective of the anatomical location. These findings highlight EMDA as a promising approach to overcome intrinsic transport barriers of PM and underscore its potential to improve the efficacy of intraperitoneal NP-based therapy for peritoneal metastases.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118619"},"PeriodicalIF":7.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TAS4464, a neddylation inhibitor, mitigates Staphylococcus aureus-induced periprosthetic joint infection by modulating immunosuppressive cell functions","authors":"Kuo-Ti Peng ,&nbsp;Jiun-Liang Chen ,&nbsp;Yu-Chien Hsieh ,&nbsp;Chun-Yuan Hsiao ,&nbsp;Chia-Ching Yang ,&nbsp;Ju-Fang Liu ,&nbsp;Chiang-Wen Lee ,&nbsp;Yao-Chang Chiang ,&nbsp;Pey-Jium Chang","doi":"10.1016/j.biopha.2025.118622","DOIUrl":"10.1016/j.biopha.2025.118622","url":null,"abstract":"<div><div><em>Staphylococcus aureus</em> (<em>S. aureus</em>) is a leading cause of biofilm-associated periprosthetic joint infections (PJIs), in part due to its ability to induce an immunosuppressive environment. Biofilm formation promotes the expansion of myeloid-derived suppressor cells (MDSCs) and M2 macrophages, which impair host immune responses and facilitate infection persistence. Targeting these immunosuppressive cells offers a promising therapeutic strategy for treating <em>S. aureus</em> biofilm-associated PJIs. Neddylation, a post-translational modification involving the conjugation of the ubiquitin-like protein NEDD8 to target proteins, regulates various cellular processes and may influence immune cell function during infection. Here, we investigated the role of neddylation in <em>S. aureus</em> biofilm-induced immunosuppression. We found that TAS4464, a selective neddylation inhibitor, markedly suppressed the expansion of MDSCs and M2 macrophages in bone marrow cells (BMCs) stimulated by <em>S. aureus</em> biofilm. TAS4464 also reduced the expression of inflammation-associated cytokines in these cells. Mechanistically, <em>S. aureus</em> biofilm upregulated key components of the neddylation pathway and markers of MDSCs and M2 macrophages in a dose-dependent manner; however, this upregulation is effectively counteracted by TAS4464. Furthermore, in a mouse model of PJI, TAS4464 treatment significantly reduced bone destruction and inflammation, which correlates with the inhibition of the neddylation pathway and a decrease in circulating MDSCs and M2 macrophages. These findings suggest that TAS4464 mitigates <em>S. aureus</em> biofilm-associated PJIs by disrupting the immunosuppressive microenvironment and highlight neddylation as a potential therapeutic target.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118622"},"PeriodicalIF":7.5,"publicationDate":"2025-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218279","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Autophagy inhibition enhances sensitivity of alpelisib in PI3K–mutated non-small cell lung cancer","authors":"Jinyoung Kim ,&nbsp;Chandani Shrestha ,&nbsp;Tae Woo Kim ,&nbsp;Sang-Bin Lee ,&nbsp;Gwangbin Lee ,&nbsp;Dasom Jung ,&nbsp;Min Hwang ,&nbsp;Shinwon Kang ,&nbsp;Hyung Soon Park ,&nbsp;Hyunho Kim ,&nbsp;Ho Jung An ,&nbsp;Dongwoo Chae ,&nbsp;Byoung Yong Shim ,&nbsp;Jiyoon Kim","doi":"10.1016/j.biopha.2025.118620","DOIUrl":"10.1016/j.biopha.2025.118620","url":null,"abstract":"<div><div>Non-small cell lung cancer (NSCLC) is a prevalent and lethal form of lung cancer with few effective treatment options, and targeted therapies for PI3K–mutated NSCLC remain particularly limited. The phosphatidylinositol 3-kinase (PI3K) pathway, frequently activated in NSCLC, is a viable therapeutic target, especially in tumors harboring PI3K mutations. Alpelisib (BYL719), a selective PI3Kα inhibitor, has shown promise, but its efficacy is often hampered by compensatory survival mechanisms, including autophagy. This study assesses the therapeutic potential of alpelisib as a monotherapy and in combination with an autophagy inhibitor for PI3K–mutated NSCLC. Alpelisib significantly reduced cell viability in human NSCLC cell lines in a dose- and time-dependent manner, with enhanced markers of autophagy and apoptosis, with pronounced effects in PI3K–mutant H460 cells. Co-treatment with alpelisib and chloroquine (CQ) further suppressed tumor cell growth, viability, migration, and colony formation more effectively than alpelisib alone, owing to increased apoptosis, elevated early and late apoptotic populations, and increased levels of cleaved PARP and caspase-3. In xenograft mouse models, the combination of alpelisib and CQ significantly inhibited tumor growth and reduced EGFR-Ras signaling compared to monotherapy. These findings suggest that combining alpelisib with autophagy inhibition significantly enhances its antitumor activity in PI3K–mutated NSCLC, highlighting a promising therapeutic strategy to address unmet clinical needs in this molecular subset. This discovery opens new possibilities for developing innovative targeted therapies for challenging NSCLC.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118620"},"PeriodicalIF":7.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218281","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Letter to the Editor regarding “Integrative systems biology, transcriptomic profiling, and experimental validation reveal enterolactone as a multi-target inhibitor of metastatic signalling in triple-negative breast cancer”","authors":"Parth Aphale,&nbsp;Shashank Dokania,&nbsp;Himanshu Shekhar","doi":"10.1016/j.biopha.2025.118605","DOIUrl":"10.1016/j.biopha.2025.118605","url":null,"abstract":"","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118605"},"PeriodicalIF":7.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Targeting metabolic syndrome with ALIAmides: A novel multi-mechanistic approach","authors":"Irene Palenca ,&nbsp;Maria Masulli ,&nbsp;Sara Rurgo ,&nbsp;Giovanni Sarnelli ,&nbsp;Giuseppe Esposito","doi":"10.1016/j.biopha.2025.118611","DOIUrl":"10.1016/j.biopha.2025.118611","url":null,"abstract":"<div><div>Metabolic syndrome (MetS) represents a growing clinical challenge worldwide, significantly increasing cardiovascular disease and type 2 diabetes risk, and all-cause mortality. Defined by a constellation of risk factors, including central obesity, dyslipidemia, hypertension, and insulin resistance, MetS is frequently associated with hepatic involvement such as metabolic dysfunction-associated fatty liver disease (MAFLD) and non-alcoholic steatohepatitis (NASH). A growing body of evidence also highlights intestinal barrier dysfunction called \"leaky-gut syndrome\" and gut microbiota dysbiosis as key contributors to the chronic low-grade inflammation that underlies MetS. Current therapies, including statins, GLP-1 receptor agonists, SGLT2 inhibitors, and antihypertensives, target individual components of the syndrome but fail to address its multifactorial pathophysiology. Additionally, these therapies often demonstrate tolerability issues, limited long-term adherence and compliance, and potential side effects particularly in hepatic and metabolic contexts. ALIAmides such as palmitoylethanolamide (PEA) and oleoylethanolamide (OEA) are emerging as promising adjunctive agents for MetS. By activating PPARs, modulating immune responses, and restoring gut barrier integrity, these compounds provide a multi-targeted strategy that addresses the complex pathophysiology of MetS. This review summarizes current evidence on ALIAmides, highlighting their potential to complement standard care and improve long-term metabolic outcomes.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118611"},"PeriodicalIF":7.5,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145218302","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interferon signature predicts chemotherapy resistance in acute myeloid leukaemia","authors":"Ela Cerovska ,&nbsp;David Kundrat ,&nbsp;Zdenek Krejcik ,&nbsp;Cyril Salek ,&nbsp;Jan Musil ,&nbsp;Eliska Cechova ,&nbsp;Michaela Dostalova Merkerova ,&nbsp;Monika Belickova ,&nbsp;Hana Remesova","doi":"10.1016/j.biopha.2025.118612","DOIUrl":"10.1016/j.biopha.2025.118612","url":null,"abstract":"<div><h3>Background</h3><div>Despite advances in therapeutic development, an anthracycline-cytarabine induction regimen remains the gold standard for acute myeloid leukaemia (AML) treatment. However, reliable predictive markers for assessing treatment sensitivity, adjusting therapy intensity, and guiding the use of experimental therapies are still lacking. This study aimed to develop a predictive model of AML chemoresistance.</div></div><div><h3>Methods</h3><div>Transcriptome sequencing and DNA methylation analysis of leukaemic blasts were performed to identify differentially expressed and methylated genes between responding (RES) and non-responding (non-RES) patients. A logistic regression nomogram model was developed using obtained data to predict complete remission (CR) and was further validated.</div></div><div><h3>Results</h3><div>Compared to RES patients, non-RES patients exhibited a significant overexpression of interferon-related DNA damage resistance signature (IRDS) genes at diagnosis. Based on the expression of three IRDS genes (<em>IFIT5</em>, <em>IFI44L</em>, <em>IFI44</em>), we developed the IRDS score, which demonstrated high predictive accuracy, with calculated probabilities of CR of 0.71 for RES patients and 0.31 for non-RES patients. Downregulation of histone and chromatin remodelling genes following therapy administration was a hallmark of a successful treatment response. Integrative analysis revealed 1108 genes with concordant changes in both gene expression and DNA methylation between RES and non-RES patients, including IRDS genes <em>IFIT5</em> and <em>IFI44L</em>.</div></div><div><h3>Conclusions</h3><div>The IRDS score-based model predicts AML chemoresistance with high accuracy and feasibility. It is quick, cost effective, and requires readily available biological material. This tool shows promise for guiding treatment decisions and identifying candidates for intensified or experimental therapies.</div></div>","PeriodicalId":8966,"journal":{"name":"Biomedicine & Pharmacotherapy","volume":"192 ","pages":"Article 118612"},"PeriodicalIF":7.5,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145214681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}