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Comprehensive genome-wide analysis of retinal vessel caliber reveals microvascular-blood pressure pathways: advancing predictive, preventive, and personalized medicine. 视网膜血管口径的全面全基因组分析揭示了微血管-血压途径:推进预测,预防和个性化医学。
IF 6
The EPMA journal Pub Date : 2025-05-06 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00411-w
Yongyi Niu, Xue Li, Jingze Guo, Songyuan Luo, Xianwen Shang, Jing Liu, Shunming Liu, Mingguang He, Danli Shi, Yu Huang, Hongyang Zhang
{"title":"Comprehensive genome-wide analysis of retinal vessel caliber reveals microvascular-blood pressure pathways: advancing predictive, preventive, and personalized medicine.","authors":"Yongyi Niu, Xue Li, Jingze Guo, Songyuan Luo, Xianwen Shang, Jing Liu, Shunming Liu, Mingguang He, Danli Shi, Yu Huang, Hongyang Zhang","doi":"10.1007/s13167-025-00411-w","DOIUrl":"10.1007/s13167-025-00411-w","url":null,"abstract":"<p><strong>Background: </strong>Retinal vessel caliber is strongly associated with systemic blood pressure (BP); however, the causal relationship between retinal vascular caliber and BP remains unclear. Understanding this relationship is essential for advancing predictive, preventive, and personalized medicine (PPPM) approaches to effectively manage hypertension and its related complications.</p><p><strong>Working hypothesis: </strong>Microvessel morphology is causally related to blood pressure. By integrating genome-wide association studies, Mendelian randomization analysis, transcriptomic data, and multivariate genomic approaches, this study aims to identify predictive biomarkers, uncover preventive strategies, and develop personalized intervention targets, thereby advancing the principles of 3P medicine for improved cardiovascular health management.</p><p><strong>Methods and results: </strong>We conducted a comprehensive investigation into the genetic factors underlying retinal vessel calibers and their complex relationship with BP traits. Our genome-wide association study (GWAS) assess retinal vessel calibers-central retinal arteriolar equivalent (CRAE), central retinal venular equivalent (CRVE), and the arteriole-to-venule ratio (AVR)-in a subset of 36,223 individuals of European descent from the UK Biobank. The analysis identified 9, 5, and 4 SNPs located in <i>TNS</i>, <i>Y_RNA</i>, <i>PBLD</i>, <i>C10orf32-ASMT:AS3MT</i>, <i>GNB3:CDCA3</i>, <i>NTN4</i>, <i>COL4 A2</i>, <i>CTD-2378E21.1</i>, <i>WNT7B</i>, <i>VTA1</i>, <i>FCF1</i>, <i>NPLOC4</i>, <i>FUT1</i> and <i>CSK</i> region, which are significantly associated with CRAE, CRVE, and AVR, respectively. Genetic correlation analysis revealed shared heritability between BP traits and both CRAE and AVR, but not CRVE. Mendelian randomization analysis confirmed bidirectional causal relationships between CRAE and BP traits, whereas CRVE was neither influenced by nor influenced BP traits. To explore the potential regulatory mechanisms, we leveraged transcriptomic data and identified the following causal pathways in vessel tissue: The expression of MRPL23-AS1 and ULK3 was correlated with the elevation of blood pressure SBP and narrowing of the CRAE. Finally, we constructed a multivariable genetic model including CRAE, AVR, SBP, and DBP, suggesting a common driving factor which underlies these traits.</p><p><strong>Conclusions: </strong>Our study elucidates the complex relationship between BP and retinal vessel caliber, highlighting potential intervention targets for lowering BP and vascular narrowing-related diseases. These findings contribute to the development of tailored prevention and treatment strategies aligned with PPPM principles.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-025-00411-w.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"401-417"},"PeriodicalIF":6.0,"publicationDate":"2025-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176345","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mitochondrial medicine: "from bench to bedside" 3PM-guided concept. 线粒体医学:“从实验室到病床”的3pm指导概念。
IF 6
The EPMA journal Pub Date : 2025-04-15 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00409-4
Qianwen Shao, Marie Louise Ndzie Noah, Olga Golubnitschaja, Xianquan Zhan
{"title":"Mitochondrial medicine: \"from bench to bedside\" 3PM-guided concept.","authors":"Qianwen Shao, Marie Louise Ndzie Noah, Olga Golubnitschaja, Xianquan Zhan","doi":"10.1007/s13167-025-00409-4","DOIUrl":"10.1007/s13167-025-00409-4","url":null,"abstract":"<p><p>Mitochondria are the primary sites for aerobic respiration and play a vital role in maintaining physiologic function at the cellular and organismal levels. Physiologic mitochondrial homeostasis, functions, health, and any kind of mitochondrial impairments are associated with systemic effects that are linked to the human health and pathologies. Contextually, mitochondria are acting as a natural vital biosensor in humans controlling status of physical and mental health in a holistic manner. So far, no any disorder is known as happening to humans independently from a compromised mitochondrial health as the cause (primary mitochondrial dysfunction) or a target of collateral damage (secondary mitochondrial injury). This certainty makes mitochondrial medicine be the superior instrument to reach highly ambitious objectives of predictive, preventive, and personalized medicine (PPPM/3PM). 3PM effectively implements the paradigm change from the economically ineffective reactive medical services to a predictive approach, targeted prevention and treatments tailored to individualized patient profiles in primary (protection against health-to-disease transition) and secondary (protection against disease progression) healthcare. Mitochondrial DNA (mtDNA) properties differ significantly from those of nuclear DNA (nDNA). For example, mtDNA as the cell-free DNA molecule is much more stable compared to nDNA, which makes mtDNA be an attractive diagnostic target circulating in human body fluids such as blood and tear fluid. Further, genetic variations in mtDNA contribute to substantial individual differences in disease susceptibility and treatment response. To this end, the current gene editing technologies, such as clustered regularly interspaced short palindromic repeats (CRISPR)/Cas, are still immature in mtDNA modification, and cannot be effectively applied in clinical practice posing a challenge for mtDNA-based therapies. In contrast, comprehensive multiomics technologies offer new insights into mitochondrial homeostasis, health, and functions, which enables to develop more effective multi-level diagnostics and targeted treatment strategies. This review article highlights health- and disease-relevant mitochondrial particularities and assesses involvement of mitochondrial medicine into implementing the 3PM objectives. By discussing the interrelationship between 3PM and mitochondrial medicine, we aim to provide a foundation for advancing early and predictive diagnostics, cost-effective targeted prevention in primary and secondary care, and exemplify personalized treatments creating proof-of-concept approaches for 3PM-guided clinical applications.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"239-264"},"PeriodicalIF":6.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106218/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Beyond hormones: 3PM approach to vaginal microbiota dynamics in postmenopausal women. 超越激素:绝经后妇女阴道微生物群动态的下午三点方法。
IF 6
The EPMA journal Pub Date : 2025-04-15 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00406-7
Panchita Pongsupasamit, Chanisa Thonusin, Suchaya Luewan, Nipon Chattipakorn, Siriporn C Chattipakorn
{"title":"Beyond hormones: 3PM approach to vaginal microbiota dynamics in postmenopausal women.","authors":"Panchita Pongsupasamit, Chanisa Thonusin, Suchaya Luewan, Nipon Chattipakorn, Siriporn C Chattipakorn","doi":"10.1007/s13167-025-00406-7","DOIUrl":"10.1007/s13167-025-00406-7","url":null,"abstract":"<p><p>Menopause marks a critical transition characterized by ceased ovarian function and declining estrogen levels, affecting multiple systems with vasomotor symptoms and genitourinary syndrome of menopause (GSM). Recent evidence shows vaginal microbiota undergoes significant alterations during menopause, influencing GSM severity. This comprehensive review examined vaginal microbiota dynamics in postmenopausal women through Predictive, Preventive, and Personalized Medicine (3PM/PPPM), revealing characteristic shifts-increased alpha diversity, reduced <i>Lactobacillus</i> dominance, and transitions toward non-<i>Lactobacillus</i> species-that serve as potential predictive biomarkers for the menopausal state, premature ovarian insufficiency, and GSM symptoms. The analysis evaluated microbiota-based risk stratification strategies for vaginal dysbiosis and demonstrated the effectiveness of both hormonal interventions (systemic/local estrogen, tibolone, ospemifene) and non-hormonal alternatives (probiotics, energy-based devices, pessary) in normalizing microbiota composition and improving vaginal health. The application of PPPM/3PM transformed menopausal healthcare from reactive to proactive precision-based care by establishing microbiota-based biomarkers that predict health risks, enable early targeted interventions tailored to specific microbiota profiles, and guide personalized treatment approaches based on individual microbial compositions. While this paradigm shift significantly advances gynecological medicine, research gaps remain in validating baseline microbiota signatures as predictive biomarkers and establishing standardized screening protocols. Further studies are needed to validate interventions such as probiotics and prebiotics, optimizing strain selection for personalized, evidence-based preventive and therapeutic strategies. Developing standardized yet personalized protocols to restore a balanced vaginal microbiome could help alleviate menopause-related symptoms. Advancing microbiota-based personalized therapeutic approaches is crucial to enhancing the quality of life for postmenopausal women through targeted and individualized vaginal health management.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"299-350"},"PeriodicalIF":6.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106263/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
IgG N-glycosylation contributes to different severities of insulin resistance: implications for 3P medical approaches. IgG n -糖基化有助于不同程度的胰岛素抵抗:对3P医疗方法的影响
IF 6
The EPMA journal Pub Date : 2025-04-15 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00410-x
Xiaohong Chen, Lois Balmer, Kun Lin, Weijie Cao, Ziyu Huang, Xiang Chen, Manshu Song, Yongsong Chen
{"title":"IgG N-glycosylation contributes to different severities of insulin resistance: implications for 3P medical approaches.","authors":"Xiaohong Chen, Lois Balmer, Kun Lin, Weijie Cao, Ziyu Huang, Xiang Chen, Manshu Song, Yongsong Chen","doi":"10.1007/s13167-025-00410-x","DOIUrl":"10.1007/s13167-025-00410-x","url":null,"abstract":"<p><strong>Background: </strong>Reliable biomarkers capturing immunometabolic processes in insulin resistance (IR) remain limited. IgG N-glycosylation modulates immune responses and reflects metabolic disorders, yet its role in IR remains unclear. This study investigated its potential for early detection, risk stratification, and targeted prevention within the framework of predictive, preventive, and personalised medicine (PPPM/3PM).</p><p><strong>Methods: </strong>A total of 313 participants were categorized into three groups based on the homeostatic model assessment for insulin resistance (HOMA-IR): insulin-sensitive (HOMA-IR < 2.69 without diabetes, n = 75), mild IR (HOMA-IR ≥ 2.69 without diabetes, n = 155), and severe IR (HOMA-IR ≥ 2.69 with type 2 diabetes, n = 83). Canonical correlation analysis was conducted to explore the overall relationship between IgG N-glycosylation and IR-related inflammation, indicated by tumour necrosis factor-α, interleukin- 6, C-reactive protein, and adiponectin. Mediation analysis was performed to evaluate the effect of IgG N-glycans on IR. Ordinal logistic regression was used to assess the association between IgG N-glycans and IR severity, with discriminative power evaluated using receiver operating characteristic curves.</p><p><strong>Results: </strong>Pro-inflammatory IgG N-glycoforms, characterized by reduced sialylation and galactosylation, along with increased bisecting N-acetylglucosamine, were observed as IR severity increased. IgG N-glycosylation significantly correlated with inflammatory markers in the insulin-sensitive (<i>r</i> = 0.599, <i>p</i> < 0.05), mild (<i>r</i> = 0.461, <i>p</i> < 0.05), and severe (<i>r</i> = 0.666, <i>p</i> < 0.01) IR groups. IgG N-glycosylation significantly influenced IR (<i>β</i> = 0.406) partially via modulation of inflammation. Increased glycoforms FA2[6]G1 (OR: 0.86, 95% CI: 0.78-0.96) and A2G2S2 (OR: 0.88, 95% CI: 0.82-0.94) were associated with a lower IR risk, with respective area under the curves (AUCs) of 0.752, 0.683, and 0.764 for the insulin sensitive, mild, and severe IR groups.</p><p><strong>Conclusions: </strong>IgG N-glycosylation contributes to IR by modulating inflammatory responses. Glycoforms FA2[6]G1 and A2G2S2 emerge as protective biomarkers, offering potential for predicting and preventing IR through primary prevention strategies within the PPPM framework.</p><p><strong>Supplementary information: </strong>The online version contains supplementary material available at 10.1007/s13167-025-00410-x.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"419-435"},"PeriodicalIF":6.0,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106251/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting the MAPK signaling pathway: implications and prospects of flavonoids in 3P medicine as modulators of cancer cell plasticity and therapeutic resistance in breast cancer patients. 靶向MAPK信号通路:黄酮类化合物在3P药物中作为乳腺癌患者癌细胞可塑性和治疗耐药调节剂的意义和前景
IF 6
The EPMA journal Pub Date : 2025-04-10 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00407-6
Peter Kubatka, Bianka Bojkova, Natalia Nosalova, Mykhailo Huniadi, Samson Mathews Samuel, Bini Sreenesh, Gabriela Hrklova, Karol Kajo, Slavomir Hornak, Dasa Cizkova, Rostyslav Bubnov, Ivica Smokovski, Dietrich Büsselberg, Olga Golubnitschaja
{"title":"Targeting the MAPK signaling pathway: implications and prospects of flavonoids in 3P medicine as modulators of cancer cell plasticity and therapeutic resistance in breast cancer patients.","authors":"Peter Kubatka, Bianka Bojkova, Natalia Nosalova, Mykhailo Huniadi, Samson Mathews Samuel, Bini Sreenesh, Gabriela Hrklova, Karol Kajo, Slavomir Hornak, Dasa Cizkova, Rostyslav Bubnov, Ivica Smokovski, Dietrich Büsselberg, Olga Golubnitschaja","doi":"10.1007/s13167-025-00407-6","DOIUrl":"10.1007/s13167-025-00407-6","url":null,"abstract":"<p><p>Cancer drug resistance poses a significant challenge in oncology, primarily driven by cancer cell plasticity, which promotes tumor initiation, progression, metastasis, and therapeutic evasion in many different cancers. Breast cancers (BCs) are a prominent example of that, with an estimated 2.3 million new cases and 670,000 BC-related deaths registered worldwide annually. Triple-negative BC is especially challenging for treatments demonstrating particularly aggressive disease course, an early manifestation of metastatic disease, frequent drug-resistant cancer types, and poor individual outcomes. Although chemosensitizing agents have been developed, their clinical utility in oncology remains unproven. The mitogen-activated protein kinase (MAPK) pathway is considered a critical regulator of intracellular and extracellular signaling highly relevant for both - genetic and epigenetic modifications. Dysregulation of the MAPK signaling pathways plays a significant role in conferring chemoresistance in BC. Contextually, targeting the MAPK pathway represents a promising strategy for overcoming drug resistance and enhancing the therapeutic efficacy of anticancer agents in BC treatment. On the other hand, flavonoids, a prominent class of phytochemicals, are key modulators of MAPK signaling. Flavonoids interact with the ERK, JNK, p38, and ERK5 pathways of the MAPK signaling cascade and present a promising avenue for developing novel anti-cancer therapies and re-sensitizing agents for the treatment of BC. Compounds such as quercetin, kaempferol, genistein, luteolin, myricetin, EGCG, baicalein, baicalin, nobiletin, morin, delphinidin, acacetin, isorhamnetin, apigenin, silymarin, among others, have been identified as specific modulators of MAPK signaling, exerting complex downstream effects in BC cells increasing therewith drug efficacy and suppressing tumor growth and aggressivity. These properties reflect mechanisms of great clinical relevance to overcome therapeutic resistance in overall BC management. This article highlights corresponding mechanisms and provides clinically relevant illustrations in the framework of 3P medicine for primary (protection of individuals at high risk against health-to-disease transition) and secondary care (protection against metastatic BC progression). 3PM novelty makes good use of patient phenotyping and stratification, predictive multi-level diagnostics, and application of Artificial Intelligence (AI) tools to the individualized interpretation of big data - all proposed for cost-effective treatments tailored to individualized patient profiles with clear benefits to patients and advanced BC management.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"437-463"},"PeriodicalIF":6.0,"publicationDate":"2025-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106287/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176341","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Development and validation of a prediction model for the depressive symptom risk in commercial airline pilots. 商业航空公司飞行员抑郁症状风险预测模型的建立与验证。
IF 6
The EPMA journal Pub Date : 2025-04-03 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00408-5
Jie Zhang, Xuhua Chen, Lin Zhang, Haodong Qi, Erliang Zhang, Minzhi Chen, Yiran Wang, Yunfei Li, Yan Chen, Qingqing Duan, Feng Shi, Linlin Wang, Qingqing Jin, Bin Ren, Yong Lu, Ya Su, Mi Xiang
{"title":"Development and validation of a prediction model for the depressive symptom risk in commercial airline pilots.","authors":"Jie Zhang, Xuhua Chen, Lin Zhang, Haodong Qi, Erliang Zhang, Minzhi Chen, Yiran Wang, Yunfei Li, Yan Chen, Qingqing Duan, Feng Shi, Linlin Wang, Qingqing Jin, Bin Ren, Yong Lu, Ya Su, Mi Xiang","doi":"10.1007/s13167-025-00408-5","DOIUrl":"10.1007/s13167-025-00408-5","url":null,"abstract":"<p><strong>Background/aims: </strong>Shift workers, such as medical personnel, and pilots, are facing an increased risk of depressive symptoms. Depressive symptoms significantly impact an individual's quality of life and affect work performance, decision-making abilities, and overall public safety. This study aims to establish a multidimensional depressive symptom prediction model based on a large sample of commercial airline pilots to facilitate early identification, prevention, and personalized intervention strategies.</p><p><strong>Methods: </strong>This population-based study included 11,111 participants, with 7918 pilots in the training set and 3193 pilots in the external validation set. Depressive symptom severity was assessed using the Patient Health Questionnaire-9 (PHQ-9). Physiological, psychological, and lifestyle factors potentially associated with depressive symptom risk were collected. The optimal predictors for model development were selected using the Boruta algorithm combined with the LASSO method, and a nomogram was developed using multivariate logistic regression to predict depressive symptoms in pilots. The model performance was evaluated using Receiver Operating Characteristic (ROC) curves, calibration curves, and accuracy measures, such as the Brier score and Spiegelhalter <i>z</i>-test. Additionally, decision curve analysis (DCA) was performed to assess the model's clinical utility.</p><p><strong>Results: </strong>A total of 7918 pilots were included in the training set and 3193 were included in the external validation set. Five characteristic indicators were selected based on their significance in the prediction of depressive symptom risk: living status, alcohol drinking, family history of mental health disorder, subjective health, and subjective sleep quality. The model showed acceptable overall discrimination (AUC<sub>train</sub> = 0.836, 95%CI 0.818 to 0.854; AUC<sub>validation</sub> = 0.840, 95%CI 0.811 to 0.868) and calibration (Brier score<sub>train</sub> = 0.048; Brier score<sub>validation</sub> = 0.051). The decision curve analysis showed that the net benefit was superior to intervening on all participants or not intervening on all participants.</p><p><strong>Conclusions: </strong>This study provides a reliable tool for early prediction and customized management of depressive symptoms among commercial airline pilots. This approach promotes the development of the field by transitioning from passive mental health care to active mental health prevention, emphasizing personalized prevention strategies.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"285-298"},"PeriodicalIF":6.0,"publicationDate":"2025-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106183/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176352","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Acute mountain sickness prediction: a concerto of multidimensional phenotypic data and machine learning strategies in the framework of predictive, preventive, and personalized medicine. 急性高原病预测:多维表型数据和机器学习策略在预测,预防和个性化医学框架的协奏曲。
IF 6
The EPMA journal Pub Date : 2025-03-31 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00404-9
Wenhui Li, Meng Zhang, Yangyi Hu, Pan Shen, Zhijie Bai, Chaoji Huangfu, Zhexin Ni, Dezhi Sun, Ningning Wang, Pengfei Zhang, Li Tong, Yue Gao, Wei Zhou
{"title":"Acute mountain sickness prediction: a concerto of multidimensional phenotypic data and machine learning strategies in the framework of predictive, preventive, and personalized medicine.","authors":"Wenhui Li, Meng Zhang, Yangyi Hu, Pan Shen, Zhijie Bai, Chaoji Huangfu, Zhexin Ni, Dezhi Sun, Ningning Wang, Pengfei Zhang, Li Tong, Yue Gao, Wei Zhou","doi":"10.1007/s13167-025-00404-9","DOIUrl":"10.1007/s13167-025-00404-9","url":null,"abstract":"&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;Acute mountain sickness (AMS) is a self-limiting illness, involving a complex series of physiological responses to rapid ascent to high altitudes, where the body is exposed to lower oxygen levels (hypoxia) and changes in atmospheric pressure. AMS is the mildest and most common form of altitude sickness; however, without adequate preparation and adherence to ascent guidelines, it can progress to life-threatening conditions.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Aims: &lt;/strong&gt;Due to the multi-factorial predisposition of AMS among individuals, identifying AMS biomarkers before high altitude exposure from multiple dimensions (e.g., clinical, metabolic, and proteomic markers) and integrating them to build an AMS predictive model enables early diagnosis and personalized interventions, which allows targeted allocation of medical resources, such as prophylactic medications (e.g., acetazolamide) and supplemental oxygen, to those who need them most and prevention of unnecessary complications. Consequently, predicting AMS utilizing biomarkers from multidimensional phenotypic data before high-altitude exposure is essential for the paradigm change in high-altitude medical research from currently applied reactive services to the cost-effective predictive, preventive, and personalized medicine (PPPM/3PM) in primary (reversible damage to health and targeted protection against health-to-disease transition) and secondary (personalized protection against disease progression) care.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;To this end, this study recruited 83 Han Chinese male volunteers and obtained clinical, proteomic, and metabolomic profiles for analysis before they ascended to high altitudes. The Mann-Whitney &lt;i&gt;U&lt;/i&gt; test was used to identify clinical features distinguishing AMS from non-AMS. The proteomic and metabolomic features were concatenated and clustered to find co-expression modules associated with AMS. A machine learning model, Mutual Information-radial kernel-based Support Vector Machine-Recursive Feature Elimination (MI-radialSVM-RFE) was employed for biomarkers selection and AMS prediction. A molecular docking technique was used to select molecular biomarkers that can bind with Traditional Chinese Medicine (TCM) ingredients.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results: &lt;/strong&gt;Among 83 participants, 66 were selected for detailed analysis after quality control steps. Six protein-metabolite co-expression modules were identified as significantly associated with AMS. The MI-radialSVM-RFE model selected 12 biomarkers (two clinical features: systolic blood pressure (SBP) and peak expiratory flow (PEF); six proteins: Acyl-CoA synthetase long-chain family member 4 (ACSL4), immunoglobulin kappa variable 1D-16 (IGKV1D-16), coagulation factor XIII B subunit (F13B), prosaposin (PSAP), poliovirus receptor (PVR), and multimerin-2 (MMRN2); and four metabolites: 2-Methyl-1,3-cyclohexadiene, calcitriol, 4-Acetamido-2-amino-6-nitrotoluene, and 20-Hydroxy-PGE2) for the AMS prediction mode","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"265-284"},"PeriodicalIF":6.0,"publicationDate":"2025-03-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176269","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Microalgae and exercise: from molecular mechanisms and brain health to clinical perspectives in the context of 3P medicine. 微藻与运动:从分子机制和脑健康到3P医学背景下的临床观点。
IF 6
The EPMA journal Pub Date : 2025-03-26 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00405-8
Xuanyu Bo
{"title":"Microalgae and exercise: from molecular mechanisms and brain health to clinical perspectives in the context of 3P medicine.","authors":"Xuanyu Bo","doi":"10.1007/s13167-025-00405-8","DOIUrl":"10.1007/s13167-025-00405-8","url":null,"abstract":"<p><p>Microalgae are emerging as innovative bioresources with diverse therapeutic applications, particularly in cardiovascular health, neuroprotection, anti-inflammatory, and antioxidant responses. These bioactive compounds effectively reduce inflammatory mediators, mitigate oxidative stress, and support mitochondrial health-critical factors in exercise performance, recovery, and chronic disease management. Notably, microalgae such as <i>Spirulina</i> and <i>Chlorella</i> exhibit promising biological activities in preclinical and limited clinical studies, including anti-inflammatory and neuroprotective effects. However, large-scale, randomized controlled trials (RCTs) remain scarce, limiting their clinical translation. Although preliminary evidence suggests potential benefits for sports performance, oxidative stress reduction, and cognitive function, most studies are small-scale, preclinical, or observational. Large, well-powered RCTs are needed to confirm their efficacy and safety. Within the framework of Predictive, Preventive, and Personalized Medicine (PPPM/3PM), this review explores microalgae's potential in predictive diagnostics, targeted prevention, and individualized supplementation strategies. Despite promising findings, clinical application requires a cautious approach due to insufficient high-quality trials supporting microalgae-based interventions in medical practice. Future research should prioritize RCTs, pharmacokinetic studies, and long-term safety assessments to establish evidence-based guidelines for their use in health and disease management.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"351-386"},"PeriodicalIF":6.0,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106266/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Monoclonal antibody immune therapy response instrument for stratification and cost-effective personalized approaches in 3PM-guided pan cancer management. 单克隆抗体免疫治疗反应仪在3pm引导下的泛癌治疗中分层和成本效益个性化方法。
IF 6
The EPMA journal Pub Date : 2025-03-22 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00403-w
Salem Baldi, Mohammed Alnaggar, Maged Al-Mogahed, Khalil A A Khalil, Xianquan Zhan
{"title":"Monoclonal antibody immune therapy response instrument for stratification and cost-effective personalized approaches in 3PM-guided pan cancer management.","authors":"Salem Baldi, Mohammed Alnaggar, Maged Al-Mogahed, Khalil A A Khalil, Xianquan Zhan","doi":"10.1007/s13167-025-00403-w","DOIUrl":"10.1007/s13167-025-00403-w","url":null,"abstract":"<p><strong>Background: </strong>Immune checkpoint inhibitors (ICIs), such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 therapies, have revolutionized cancer treatment by harnessing the body's immune system to eliminate cancer cells. Despite their considerable promise, the efficacy of ICIs significantly differs based on tumor types and specific patient conditions, highlighting the necessity for personalized approaches in the framework of predictive preventive personalized medicine (PPPM; 3PM).</p><p><strong>Main body: </strong>This review proposes a stratification instrument within the 3PM framework to enhance the therapeutic efficacy of ICIs across Pan-cancer. Predictive approaches need to be utilized to enhance the effectiveness of ICIs. For example, biomarkers such as particular genetic alterations and metabolic pathways provide key information on patient treatment responses. To predict treatment outcomes, uncover resistance mechanisms, and tailor medications, we examine biomarkers including PDL-1 and CTLA4. Focusing on cancers like melanoma, bladder, and renal cell carcinoma, we highlight advances in combination therapies and cellular approaches to overcome resistance. We conducted an analysis of clinical trials and public datasets (TCGA, GEO) to evaluate ICI responses across number of cancer types. Survival analysis employed Kaplan-Meier curves and Cox regression. Pan-cancer analysis shows response rates ranging from 19.8% in bladder cancer to > 39% in melanoma when combination therapy is used, emphasizing the potential of 3PM to improve outcomes. By exploring resistance mechanisms and emerging therapeutic innovations, we propose a cost-effective model for better patient stratification and care. Validation of this model requires standardized biomarkers and prospective trials, promising a shift toward precision oncology.</p><p><strong>Conclusion: </strong>Within the 3PM framework, this review addresses the urgent need for cost-effective stratification tools and adaptive combinatorial strategies to optimize outcomes.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"465-503"},"PeriodicalIF":6.0,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176395","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Characterization of the gut microbiota in drug abuse: prediction, prevention, and personalized medicine to benefit affected populations. 药物滥用中肠道微生物群的特征:预测、预防和个性化医疗以使受影响人群受益。
IF 6
The EPMA journal Pub Date : 2025-03-15 eCollection Date: 2025-06-01 DOI: 10.1007/s13167-025-00402-x
Xin Wang, Ya-Jie Yu, Cai Liao, Xiao-Ru Liu, Rui Yu, Yun Wang
{"title":"Characterization of the gut microbiota in drug abuse: prediction, prevention, and personalized medicine to benefit affected populations.","authors":"Xin Wang, Ya-Jie Yu, Cai Liao, Xiao-Ru Liu, Rui Yu, Yun Wang","doi":"10.1007/s13167-025-00402-x","DOIUrl":"10.1007/s13167-025-00402-x","url":null,"abstract":"<p><p>Drug abuse poses an enormous threat to global public health. Long-term drug abuse can reduce the quality of life of patients and increase the healthcare burden on society. There is growing interest in developing new methods to mitigate the effects of drug abuse. The gut microbiota plays a key role in maintaining homeostasis within the brain-gut-lung axis, which is critical in drug-abusing patients. The microbiota-brain-gut-lung axis refers to the interactions of microbes with the brain, gut, and lung. The effects of drug abuse on the gut microbiota are increasingly recognized, especially the pathogenesis by which the microbiota-brain-gut-lung axis is involved in regulating organ-organ communication, to explore new therapeutic approaches for clinical drug abuse. Currently, in addition to antibiotics, antiviral drugs, anti-tumor drugs, corticosteroids, drugs for the treatment of neurodegenerative diseases, and anesthetics also cause gut microbiota imbalance. This review summarizes the effects of drug abuse on gut microbiota and the important role of the microbiota-brain-gut-lung axis in drug abuse. Identifying changes in the gut microbiota associated with drug abuse and their underlying mechanisms under the principles of predictive, preventive, and personalized medicine (PPPM) is a critical step toward achieving PPPM. These strategies include FMT, probiotic supplements, and engineered bacteria that can benefit sub-healthy individuals with gut dysbiosis caused by drug abuse.</p>","PeriodicalId":94358,"journal":{"name":"The EPMA journal","volume":"16 2","pages":"505-517"},"PeriodicalIF":6.0,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12106171/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","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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