Experimental Biology and Medicine最新文献

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Pan-immune-inflammation value predicts survival in inflammatory breast cancer patients. 泛免疫炎症值预测炎症性乳腺癌患者的生存。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-05-01 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10493
Yingjia Hu, Jian Li, Mingyu Wang, Xinyi Wang, Jiankang Li, Hongfei Ji, Xingjian Niu
{"title":"Pan-immune-inflammation value predicts survival in inflammatory breast cancer patients.","authors":"Yingjia Hu, Jian Li, Mingyu Wang, Xinyi Wang, Jiankang Li, Hongfei Ji, Xingjian Niu","doi":"10.3389/ebm.2025.10493","DOIUrl":"https://doi.org/10.3389/ebm.2025.10493","url":null,"abstract":"<p><p>Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer subtype with poor survival. Identifying novel biomarkers is needed to predict survival for this highly progressive form of breast cancer. In this retrospective study, we investigated pan-immune-inflammation value (PIV), a novel immune-inflammation-based biomarker which combined the peripheral blood parameters (lymphocytes, monocytes, neutrophils, and platelets) in a retrospective cohort of 143 IBC patients. Then we explored the difference of PIV levels in IBC and non-IBC cohorts and the relationship between PIV and clinical characteristics in IBC patients. The survival rates of disease-free survival (DFS) and overall survival (OS) in IBC patients were analyzed and univariate and multivariate statistics were used to evaluate the prognostic value. PIV had the most significantly predictive value in IBC patients compared with other peripheral blood parameters. The mean PIV value in IBC patients was significantly higher than non-IBC patients, and the significant difference between the IBC and non-IBC was also observed in subgroups with different clinical stages and pathologic types. Furthermore, PIV performed an extensive systemic immune prognostic factor on both DFS and OS in IBC patients, and PIV was identified an independent prognostic indicator for survival outcome in IBC patients in univariate and multivariate models. Our retrospective study demonstrated the prognostic value of PIV in IBC patients, suggesting the potential application of PIV in IBC treatment outcomes. PIV would also provide some insights into the mechanisms underlying the role of immune and inflammation in IBC development and progression.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10493"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078184/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Critical role of alpha spectrin in DNA repair: the importance of μ-calpain and Fanconi anemia proteins. α谱蛋白在DNA修复中的关键作用:μ-calpain和Fanconi贫血蛋白的重要性。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-05-01 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10537
Muriel W Lambert
{"title":"Critical role of alpha spectrin in DNA repair: the importance of μ-calpain and Fanconi anemia proteins.","authors":"Muriel W Lambert","doi":"10.3389/ebm.2025.10537","DOIUrl":"https://doi.org/10.3389/ebm.2025.10537","url":null,"abstract":"<p><p>Nonerythroid spectrins are proteins important in maintaining the structural integrity and flexibility of the cell and nuclear membranes and are essential for a number of functionally important cellular processes. One of these proteins, nonerythroid α spectrin (αSpII), plays a critical role in DNA repair, specifically repair of DNA interstrand crosslinks (ICLs), where it acts as a scaffold, recruiting repair proteins to sites of damage. Loss or breakdown of αSpII is an important factor in a number of disorders. One of these is Fanconi anemia (FA), a genetic disorder characterized by bone marrow failure, chromosome instability, cancer predisposition, congenital abnormalities and a defect in DNA ICL repair. Significantly, breakdown of αSpII occurs in cells from a number of FA complementation groups, due to excessive cleavage by the protease, μ-calpain, leading to defective repair of DNA ICLs in telomeric and non-telomeric DNA. Knockdown of μ-calpain in FA cells by μ-calpain siRNA results in restoration of αSpII levels to normal and repair of DNA ICLs in telomeric and non-telomeric DNA, demonstrating the importance of αSpII stability in the repair process. It is hypothesized that there is a mechanistic link between excessive cleavage of αSpII by μ-calpain and defective DNA ICL repair in FA and that FA proteins, which are deficient in FA, play a key role in maintaining the stability of αSpII and preventing its cleavage by μ-calpain. All of these events are proposed to be important key factors involved in the pathophysiology of FA and suggest new avenues for potential therapeutic intervention.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10537"},"PeriodicalIF":2.8,"publicationDate":"2025-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12078185/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076911","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Aberrant DNMT1-mediated DACH1 methylation is associated with colorectal adenoma-to-carcinoma progression. 异常dnmt1介导的DACH1甲基化与结直肠腺瘤向癌的进展有关。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-04-30 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10469
Yan Zhang, Honggang Liu
{"title":"Aberrant DNMT1-mediated DACH1 methylation is associated with colorectal adenoma-to-carcinoma progression.","authors":"Yan Zhang, Honggang Liu","doi":"10.3389/ebm.2025.10469","DOIUrl":"https://doi.org/10.3389/ebm.2025.10469","url":null,"abstract":"<p><p>Colorectal cancer (CRC) remains a major contributor to cancer-related morbidity and mortality. While Dachshund homolog 1 (DACH1) was recognized as a critical regulator in cancer progression, its role in promoting or suppressing tumor development remains a subject of ongoing debate. This study aimed to elucidate the role of DACH1 in CRC progression and its underlying regulation mechanisms. The expression levels of Methyltransferase 1 (DNMT1) and DACH1, as well as its methylation status were assessed through a combination of TCGA data analysis and experimental validation using immunohistochemistry, PCR, methylation-specific PCR, and bisulfite sequencing RCR on 120 clinical samples, comprising normal mucosa, adenomas, and adenocarcinomas. The relationships among them were evaluated using Pearson or Spearman correlation analysis. The associations between the DACH1 and DNMT1 levels and clinicopathological parameters were examined to determine their clinical relevance. A progressive decrease in DACH1 expression and a concomitant increase in DACH1 promoter methylation and DNMT1 expression were observed from normal mucosa to adenoma and adenocarcinoma tissues. Higher DNMT1 expression and lower DACH1 expression were associated with poorer clinical outcomes, including worse tumor differentiation, lymphatic metastasis, and advanced tumor stages. Paired analysis of tissues from the same patient further validated their inverse expression patterns during CRC progression. DNMT1-mediated DACH1 epigenetic silencing plays a critical role in CRC progression, suggesting that the DNMT1-DACH1 regulatory axis may serve as a potential biomarker and therapeutic target in CRC.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10469"},"PeriodicalIF":2.8,"publicationDate":"2025-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12075005/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144076910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Primary cilia and inflammatory response: unveiling new mechanisms in osteoarthritis progression. 原发性纤毛和炎症反应:揭示骨关节炎进展的新机制。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-04-28 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10490
Yuyan Sun, Ziyu Luo, Yuanyuan Fu, ThaiNamanh Ngo, Wen Wang, Yuanrong Wang, Ying Kong
{"title":"Primary cilia and inflammatory response: unveiling new mechanisms in osteoarthritis progression.","authors":"Yuyan Sun, Ziyu Luo, Yuanyuan Fu, ThaiNamanh Ngo, Wen Wang, Yuanrong Wang, Ying Kong","doi":"10.3389/ebm.2025.10490","DOIUrl":"https://doi.org/10.3389/ebm.2025.10490","url":null,"abstract":"<p><p>Osteoarthritis (OA) is a common degenerative joint disease that can lead to chronic pain and disability. The pathogenesis of OA involves chronic low-grade inflammation, characterized by the degradation of chondrocytes, inflammation of the synovium, and systemic low-grade inflammation. This inflammatory response accelerates the progression of OA and contributes to pain and functional impairment. Primary cilia play a crucial role in cellular signal transduction and the maintenance of cartilage matrix homeostasis, and their dysfunction is closely linked to inflammatory responses. Given these roles, primary cilia may significantly contribute to the pathogenesis of OA. This review explores inflammation-associated signaling pathways in OA, including NF-κB, MAPK, JAK/STAT, and PI3K/AKT/mTOR signaling. In addition, we place particular emphasis on cilia-mediated inflammatory modulation in OA. Primary cilia mediate chondrocyte responses to mechanical loading and inflammatory cytokines via pathways including NF-κB, MAPK, TRPV4, and Hedgehog signaling. Notably, alterations in the length and incidence of primary cilia in chondrocytes during OA further underscore their potential role in disease pathogenesis. The identification of biomarkers and therapeutic targets related to primary cilia and inflammatory pathways offers new potential for the treatment and management of OA.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10490"},"PeriodicalIF":2.8,"publicationDate":"2025-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12066368/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143958356","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors. 慢病毒载体肝基因治疗临床前的性别差异
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-04-25 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10422
Efrain Guzman, Cheen Khoo, Deirdre O'Connor, Gayathri Devarajan, Sharifah Iqball, Bernard Souberbielle, Kyriacos Mitrophanous, Yatish Lad
{"title":"Gender difference in pre-clinical liver-directed gene therapy with lentiviral vectors.","authors":"Efrain Guzman, Cheen Khoo, Deirdre O'Connor, Gayathri Devarajan, Sharifah Iqball, Bernard Souberbielle, Kyriacos Mitrophanous, Yatish Lad","doi":"10.3389/ebm.2025.10422","DOIUrl":"https://doi.org/10.3389/ebm.2025.10422","url":null,"abstract":"<p><p>Viral vector-based therapies are effective therapeutics for the correction of several disorders, both in mouse models and in humans. Several pre-clinical studies have demonstrated differences in transduction efficiencies and therapeutic effect between male and female mice dosed with AAV-based gene therapy product candidates. Here, we report gender-specific transduction and transgene expression differences in mice dosed systemically with lentiviral vectors (LVV). Male mice systemically dosed with LVV carrying the reporter gene luciferase showed at least a 12-fold higher expression of luciferase and a higher vector copy number (VCN) in their livers compared with female mice. Lastly, PAH<sup>Enu2</sup> male mice dosed with a LVV carrying the human phenylalanine hydroxylase (PAH) transgene were observed to have a higher VCN than their female littermates. These findings suggest that sex-based differences initially observed in AAV-mediated therapies also apply to LVV, but the exact mechanism remains to be determined.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10422"},"PeriodicalIF":2.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061785/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986198","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Research on the online service mechanism of internet hospital in infectious disease prevention and control. 网络医院传染病防治在线服务机制研究。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-04-25 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10349
Xin Zhao, Haitao Huang, Guojun Zeng, Qingke Shi, Peijia Zhu, Longhao Zhang, Lei Li, Lunxu Liu, Nan Huang, Wenguang Liu, Kexin Yu
{"title":"Research on the online service mechanism of internet hospital in infectious disease prevention and control.","authors":"Xin Zhao, Haitao Huang, Guojun Zeng, Qingke Shi, Peijia Zhu, Longhao Zhang, Lei Li, Lunxu Liu, Nan Huang, Wenguang Liu, Kexin Yu","doi":"10.3389/ebm.2025.10349","DOIUrl":"https://doi.org/10.3389/ebm.2025.10349","url":null,"abstract":"<p><p>Infectious diseases can sometimes lead to pandemics, often transmitted through public and social gatherings, including in-person hospital visits. Consequently, there is an urgent need for innovative approaches to prevent their spread. Taking COVID-19 as an example, we have explored a remote, contactless hospital online model that offers the public online medical consultations, professional psychological counseling, and chronic disease management consultations, thereby mitigating the risk of new transmissions resulting from hospital visits. This model was implemented, validated, and practiced at West China Hospital in China from 29 January 2020, to 12 March 2020. It was also applicable to other infectious diseases, such as influenza A. In this research, we utilized the hospital's internet platform, supplemented by telephone services, to offer the following to the public: 1) General medical education and consultation related to epidemics and psychological anxiety; 2) Online screening for at-risk populations; 3) Online prescription and medication delivery services for patients with chronic diseases. Consequently, over a period of more than 1 month, the online epidemic platform completed a total of 32,755 cases, including 8,783 internet consultations and 1,082 telephone consultations for the public, as well as 22,890 internet consultations for chronic disease patients. Among these, 289 high-risk individuals were identified, with 3 cases confirmed as COVID-19 during follow-up diagnoses, while no infections were detected in the remaining individuals. In conclusion, this innovative medical model serves as a significant supplement to existing healthcare systems and has the potential to be expanded to other hospitals and other infectious diseases. It is particularly beneficial in scenarios where medical resources are limited, populations are under quarantine, and there is a large demand for medical services and anxiety management during infectious disease pandemics.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10349"},"PeriodicalIF":2.8,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12061786/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143990641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Erratum: Retraction: Pyridoxal 5' phosphate protects islets against streptozotocin-induced beta-cell dysfunction - in vitro and in vivo. 更正:撤回:吡哆醛5'磷酸保护胰岛免受链脲佐菌素诱导的β细胞功能障碍-在体外和体内。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-04-24 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10614
{"title":"Erratum: Retraction: Pyridoxal 5' phosphate protects islets against streptozotocin-induced beta-cell dysfunction - <i>in vitro</i> and <i>in vivo</i>.","authors":"","doi":"10.3389/ebm.2025.10614","DOIUrl":"https://doi.org/10.3389/ebm.2025.10614","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.3389/ebm.2024.10441.].</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10614"},"PeriodicalIF":2.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058543/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143986193","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Artificial intelligence for children with attention deficit/hyperactivity disorder: a scoping review. 儿童注意缺陷/多动障碍的人工智能:范围综述。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-04-24 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10238
Bo Sun, Fei Cai, Huiman Huang, Bo Li, Bing Wei
{"title":"Artificial intelligence for children with attention deficit/hyperactivity disorder: a scoping review.","authors":"Bo Sun, Fei Cai, Huiman Huang, Bo Li, Bing Wei","doi":"10.3389/ebm.2025.10238","DOIUrl":"10.3389/ebm.2025.10238","url":null,"abstract":"<p><p>Attention deficit/hyperactivity disorder is a common neuropsychiatric disorder that affects around 5%-7% of children worldwide. Artificial intelligence provides advanced models and algorithms for better diagnosis, prediction and classification of attention deficit/hyperactivity disorder. This study aims to explore artificial intelligence models used for the prediction, early diagnosis and classification of attention deficit/hyperactivity disorder as reported in the literature. A scoping review was conducted and reported in line with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews) guidelines. Out of the 1994 publications, 52 studies were included in the scoping review. The included articles reported the use of artificial intelligence for 3 different purposes. Of these included articles, artificial intelligence techniques were mostly used for the diagnosis of attention deficit/hyperactivity disorder (38/52, 79%). Magnetic resonance imaging (20/52, 38%) were the most frequently used data in the included articles. Most of the included articles used data sets with a size of <1,000 samples (28/52, 54%). Machine learning models were the most prominent branch of artificial intelligence used for attention deficit/hyperactivity disorder in the studies, and the support vector machine was the most used algorithm (34/52, 65%). The most commonly used validation in the studies was k-fold cross-validation (34/52, 65%). A higher level of accuracy (98.23%) was found in studies that used Convolutional Neural Networks algorithm. This review provides an overview of research on artificial intelligence models and algorithms for attention deficit/hyperactivity disorder, providing data for further research to support clinical decision-making in healthcare.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10238"},"PeriodicalIF":2.8,"publicationDate":"2025-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12058481/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143992996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Retraction: Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats. 收缩:富氢盐水对大鼠心肌缺血再灌注损伤的保护作用。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-04-10 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10605
{"title":"Retraction: Hydrogen-rich saline protects myocardium against ischemia/reperfusion injury in rats.","authors":"","doi":"10.3389/ebm.2025.10605","DOIUrl":"https://doi.org/10.3389/ebm.2025.10605","url":null,"abstract":"<p><p>[This retracts the article DOI: 10.3181/0812-RM-349.].</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10605"},"PeriodicalIF":2.8,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12023914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144000745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Developing predictive models for µ opioid receptor binding using machine learning and deep learning techniques. 利用机器学习和深度学习技术开发微阿片受体结合的预测模型。
IF 2.8 4区 医学
Experimental Biology and Medicine Pub Date : 2025-03-19 eCollection Date: 2025-01-01 DOI: 10.3389/ebm.2025.10359
Jie Liu, Jerry Li, Zoe Li, Fan Dong, Wenjing Guo, Weigong Ge, Tucker A Patterson, Huixiao Hong
{"title":"Developing predictive models for µ opioid receptor binding using machine learning and deep learning techniques.","authors":"Jie Liu, Jerry Li, Zoe Li, Fan Dong, Wenjing Guo, Weigong Ge, Tucker A Patterson, Huixiao Hong","doi":"10.3389/ebm.2025.10359","DOIUrl":"10.3389/ebm.2025.10359","url":null,"abstract":"<p><p>Opioids exert their analgesic effect by binding to the µ opioid receptor (MOR), which initiates a downstream signaling pathway, eventually inhibiting pain transmission in the spinal cord. However, current opioids are addictive, often leading to overdose contributing to the opioid crisis in the United States. Therefore, understanding the structure-activity relationship between MOR and its ligands is essential for predicting MOR binding of chemicals, which could assist in the development of non-addictive or less-addictive opioid analgesics. This study aimed to develop machine learning and deep learning models for predicting MOR binding activity of chemicals. Chemicals with MOR binding activity data were first curated from public databases and the literature. Molecular descriptors of the curated chemicals were calculated using software Mold2. The chemicals were then split into training and external validation datasets. Random forest, k-nearest neighbors, support vector machine, multi-layer perceptron, and long short-term memory models were developed and evaluated using 5-fold cross-validations and external validations, resulting in Matthews correlation coefficients of 0.528-0.654 and 0.408, respectively. Furthermore, prediction confidence and applicability domain analyses highlighted their importance to the models' applicability. Our results suggest that the developed models could be useful for identifying MOR binders, potentially aiding in the development of non-addictive or less-addictive drugs targeting MOR.</p>","PeriodicalId":12163,"journal":{"name":"Experimental Biology and Medicine","volume":"250 ","pages":"10359"},"PeriodicalIF":2.8,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11961360/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143771836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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