Personalized Drug Therapy: Innovative Concept Guided With Proteoformics

Molecular & Cellular Proteomics, Journal Year: 2024, Volume and Issue: 23(3), P. 100737 - 100737

Published: Feb. 13, 2024

Personalized medicine can reduce adverse effects, enhance drug efficacy, and optimize treatment outcomes, which represents the essence of personalized in pharmacy field. Protein drugs are crucial field therapy currently mainstay, possess higher target specificity biological activity compared to small-molecule chemical drugs, making them efficient regulating disease-related processes, have significant potential development drugs. Currently, protein designed developed for specific targets based on patient-specific data. However, due rapid two-dimensional gel electrophoresis (2DGE) mass spectrometry (MS), it is now widely recognized that a canonical actually includes multiple proteoforms, differences between these proteoforms will result varying responses The variation effects different be impact even alter intended benefit drug, potentially harmful instead lifesaving. As result, we propose should shift from being targeted through lens (proteomics) proteoform (proteoformics). This enable better equipped meet patients' needs disease characteristics. With further proteoformics, individualized therapy, especially aimed at as target, improve understanding mechanisms, discovery new signaling pathways, provide theoretical basis aid doctors conducting health risk assessments more cost-effective prevention strategies conducted by artificial intelligence/machine learning, promote technological innovation, convenient tailored patient profile, affected individuals society large.

Language: Английский

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The paradigm change from reactive medical services to 3PM in ischemic stroke: a holistic approach utilising tear fluid multi-omics, mitochondria as a vital biosensor and AI-based multi-professional data interpretation

The EPMA Journal, Journal Year: 2024, Volume and Issue: 15(1), P. 1 - 23

Published: Feb. 27, 2024

Worldwide stroke is the second leading cause of death and third disability combined. The estimated global economic burden by over US$891 billion per year. Within three decades (1990-2019), incidence increased 70%, deaths 43%, prevalence 102%, DALYs 143%. Of 100 million people affected stroke, about 76% are ischemic (IS) patients recorded worldwide. Contextually, moves into particular focus multi-professional groups including researchers, healthcare industry, economists, policy-makers. Risk factors demonstrate sufficient space for cost-effective prevention interventions in primary (suboptimal health) secondary (clinically manifested collateral disorders contributing to risks) care. These risks interrelated. For example, sedentary lifestyle toxic environment both mitochondrial stress, systemic low-grade inflammation accelerated ageing; inflammageing a associated with ageing poor outcomes. Stress overload, decreased bioenergetics hypomagnesaemia vasospasm lesions heart brain all age teenagers. Imbalanced dietary patterns folate but rich red processed meat, refined grains, sugary beverages hyperhomocysteinaemia, inflammation, small vessel disease, IS risks. Ongoing 3PM research towards vulnerable population promoted European Association Predictive, Preventive Personalised Medicine (EPMA) demonstrates promising results holistic patient-friendly non-invasive approach utilising tear fluid-based health risk assessment, mitochondria as vital biosensor AI-based data interpretation reported here EPMA expert group. Collected that IS-relevant corresponding molecular pathways examples, there an evident overlap between involved diabetic retinopathy early indicator patients. Just exemplify some them such 5-aminolevulinic acid/pathway, which also characteristic altered mitophagy patterns, insomnia, stress regulation modulation microbiota-gut-brain crosstalk. Further, ceramides considered mediators oxidative cardiometabolic negatively affecting respiratory chain function fission/fusion activity, sleep-wake behaviour, vascular stiffness remodelling. Xanthine/pathway homeostasis stress-driven anxiety-like behaviour well mechanisms arterial stiffness. In order assess individual risks, application machine learning (AI tool) essential accurate performed multiparametric analysis. Aspects presented paper include needs young populations elderly, personalised assessment care, cost-efficacy, innovative technologies screening programmes, advanced education measures professionals general population-all pillars paradigm change from reactive medical services overall management EPMA.

Language: Английский

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Ischemic stroke of unclear aetiology: a case-by-case analysis and call for a multi-professional predictive, preventive and personalised approach

The EPMA Journal, Journal Year: 2022, Volume and Issue: 13(4), P. 535 - 545

Published: Nov. 17, 2022

Due to the reactive medical approach applied disease management, stroke has reached an epidemic scale worldwide. In 2019, global prevalence was 101.5 million people, wherefrom 77.2 (about 76%) suffered from ischemic stroke; 20.7 and 8.4 intracerebral subarachnoid haemorrhage, respectively. Globally in year 2019 - 3.3, 2.9 0.4 individuals died of stroke, During last three decades, absolute number cases increased substantially. The current is 110 patients worldwide with more than 60% below age 70 years. Prognoses by World Stroke Organisation are pessimistic: globally, it predicted that 1 4 adults over 25 will suffer their lifetime. Although best known contributing factor, 16% all strokes occur teenagers young aged 15-49 years incidence trend this population increasing. corresponding socio-economic burden which leading cause disability, enormous. Global costs estimated at 721 billion US dollars, 0.66% GDP. Clinically manifested only "tip iceberg": total about 14 times greater currently capable identify manage. Specifically, lacunar (LS), characteristic for silent brain infarction, represents up 30% strokes. Silent LS, diagnosed mainly routine health check-up autopsy without history, a reported infarction 55% investigated populations. To end, independent predictor stroke. Further, small vessel considered strong contributors cognitive impairments, dementia, depression suicide, amongst others general population. sub-populations such as diabetes mellitus type 2, proliferative diabetic retinopathy According various statistical sources, cryptogenic account 15 40% entire incidence. question consider here is, whether fully referable unidentifiable aetiology or rather underestimated risks. Considering latter, translational research might be great clinical utility realise innovative predictive preventive approaches, potentially benefiting high risk society large. position paper, consortium combined multi-professional expertise provide clear statements towards paradigm change predictive, personalised medicine crucial elements are:Consolidation multi-disciplinary including family medicine, in-depth diagnostics followed targeted primary secondary (e.g. treated cancer) prevention infarctionApplication assessment focused on sub-optimal conditions effectively prevent health-to-disease transitionApplication AI machine learning treatment algorithms tailored robust biomarker patternsApplication screening programmes adequately needs

Language: Английский

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Energy metabolism as the hub of advanced non-small cell lung cancer management: a comprehensive view in the framework of predictive, preventive, and personalized medicine

The EPMA Journal, Journal Year: 2024, Volume and Issue: 15(2), P. 289 - 319

Published: April 8, 2024

Abstract Energy metabolism is a hub of governing all processes at cellular and organismal levels such as, on one hand, reparable vs. irreparable cell damage, fate (proliferation, survival, apoptosis, malignant transformation etc.), and, the other carcinogenesis, tumor development, progression metastazing versus anti-cancer protection cure. The orchestrator mitochondria who produce, store invest energy, conduct intracellular systemically relevant signals decisive for internal environmental stress adaptation, coordinate corresponding levels. Consequently, quality mitochondrial health homeostasis reliable target risk assessment stage reversible damage to followed by cost-effective personalized against health-to-disease transition as well targeted disease (secondary care cancer patients growing primary tumors metastatic disease). energy reprogramming non-small lung (NSCLC) attracts particular attention clinically instrumental paradigm change from reactive medical services predictive, preventive medicine (3PM). This article provides detailed overview towards mechanisms biological pathways involving metabolic (MR) with respect inhibiting synthesis biomolecules blocking common NSCLC anti-NSCLC therapeutic strategies. For instance, mitophagy recycles macromolecules yield substrates nucleotide synthesis. Histone modification DNA methylation can predict onset diseases, plasma C7 analysis an efficient service potentially resulting in optimized healthcare economy areas. MEMP scoring guidance immunotherapy, prognostic assessment, drug development. Metabolite sensing nutrients their derivatives are potential MR-related therapy NSCLC. Moreover, miR-495-3p sphingolipid rheostat targeting Sphk1, 22/FOXM1 axis regulation, A2 receptor antagonist highly promising TFEB biomarker predicting immune checkpoint blockade redox-related lncRNA signature (redox-LPS) considered predictive approaches. Finally, exemplified this phenotyping innovative population screening, multi-level diagnostics, prevention, treatment algorithms tailored patient profiles—all essential pillars 3PM approach overall management cancers. highlights innovation focused advance benefiting vulnerable subpopulations, affected patients, large.

Language: Английский

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Digital biomarkers: 3PM approach revolutionizing chronic disease management — EPMA 2024 position

The EPMA Journal, Journal Year: 2024, Volume and Issue: 15(2), P. 149 - 162

Published: May 11, 2024

Abstract Non-communicable chronic diseases (NCDs) have become a major global health concern. They constitute the leading cause of disabilities, increased morbidity, mortality, and socio-economic disasters worldwide. Medical condition-specific digital biomarker (DB) panels emerged as valuable tools to manage NCDs. DBs refer measurable quantifiable physiological, behavioral, environmental parameters collected for an individual through innovative technologies, including wearables, smart devices, medical sensors. By leveraging healthcare providers can gather real-time data insights, enabling them deliver more proactive tailored interventions individuals at risk patients diagnosed with Continuous monitoring relevant wearable devices or smartphone applications allows clinicians track progression NCDs in real time. With introduction (DBM), new quality primary secondary is being offered promising opportunities assessment protection against health-to-disease transitions vulnerable sub-populations. DBM enables take most cost-effective targeted preventive measures, detect disease developments early, introduce personalized interventions. Consequently, they benefit life (QoL) affected individuals, economy, society large. instrumental paradigm shift from reactive services 3PM approach promoted by European Association Predictive, Preventive, Personalized Medicine (EPMA) involving experts 55 countries This position manuscript consolidates multi-professional expertise area, demonstrating clinically examples providing roadmap implementing concepts facilitated DBs.

Language: Английский

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Body fluid multiomics in 3PM-guided ischemic stroke management: health risk assessment, targeted protection against health-to-disease transition, and cost-effective personalized approach are envisaged

The EPMA Journal, Journal Year: 2024, Volume and Issue: 15(3), P. 415 - 452

Published: Aug. 29, 2024

Because of its rapid progression and frequently poor prognosis, stroke is the third major cause death in Europe first one China. Many independent studies demonstrated sufficient space for prevention interventions primary care ischemic defined as most cost-effective protection vulnerable subpopulations against health-to-disease transition. Although several identified molecular patterns specific IS body fluids, none these approaches has yet been incorporated into treatment guidelines. The advantages disadvantages individual fluids are thoroughly analyzed throughout paper. For example, multiomics based on a minimally invasive approach utilizing blood components recommended real-time monitoring, due to particularly high level dynamics system. On other hand, tear fluid more stable system non-invasive patient-friendly holistic appropriate health risk assessment innovative screening programs management. This article details aspects essential promote practical implementation highlighted achievements 3PM-guided

Language: Английский

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Short communication: unique metabolic signature of proliferative retinopathy in the tear fluid of diabetic patients with comorbidities — preliminary data for PPPM validation

The EPMA Journal, Journal Year: 2023, Volume and Issue: 14(1), P. 43 - 51

Published: Feb. 22, 2023

Type 2 diabetes (T2DM) defined as the adult-onset type that is primarily not insulin-dependent, comprises over 95% of all mellitus (DM) cases. According to global records, 537 million adults aged 20-79 years are affected by DM means at least 1 out 15 persons. This number projected grow 51% year 2045. One most common complications T2DM diabetic retinopathy (DR) with an overall prevalence 30%. The total DR-related visual impairments on rise, due growing population. Proliferative (PDR) progressing DR and leading cause preventable blindness in working-age adults. Moreover, PDR characteristic systemic attributes including mitochondrial impairment, increased cell death chronic inflammation, independent predictor cascading DM-complications such ischemic stroke. Therefore, early a reliable appearing upstream this "domino effect". Global screening, timely identification DM-related complications, insufficiently implemented currently applied reactive medicine. A personalised predictive approach cost-effective targeted prevention shortly - predictive, preventive medicine (PPPM / 3PM) could make good use accumulated knowledge, preventing other severe complications. In order reach goal, stage- disease-specific biomarker panels needed characterised easy way sample collection, high sensitivity specificity analyses. current study, we tested hypothesis non-invasively collected tear fluid robust source for analysis ocular (DM-related complications) patterns suitable differential diagnosis stable versus PDR. Here, report first results comprehensive ongoing which correlate individualised patient profiles (healthy controls patients D well without co-morbidities) their metabolic fluid. Comparative mass spectrometric performed has identified following clusters differentially expressed groups comparison: acylcarnitines, amino acid & related compounds, bile acids, ceramides, lysophosphatidyl-choline, nucleobases phosphatidyl-cholines, triglycerides, cholesterol esters, fatty acids. Our preliminary data strongly support potential clinical utility indicating unique signature stages progression. pilot study creates platform validating stratify T2DM-patients predisposed since T2DM-related stroke, our international project aims create analytical prototype "diagnostic tree" (yes/no) applicable healthrisk assessment care.

Language: Английский

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Integrating oculomics with genomics reveals imaging biomarkers for preventive and personalized prediction of arterial aneurysms

The EPMA Journal, Journal Year: 2023, Volume and Issue: 14(1), P. 73 - 86

Published: Feb. 13, 2023

Arterial aneurysms are life-threatening but usually asymptomatic before requiring hospitalization. Oculomics of retinal vascular features (RVFs) extracted from fundus images can reflect systemic properties and therefore were hypothesized to provide valuable information on detecting the risk aneurysms. By integrating oculomics with genomics, this study aimed (i) identify predictive RVFs as imaging biomarkers for (ii) evaluate value these in supporting early detection context predictive, preventive personalized medicine (PPPM).This involved 51,597 UK Biobank participants who had available extract RVFs. Phenome-wide association analyses (PheWASs) conducted associated genetic risks main types aneurysms, including abdominal aortic aneurysm (AAA), thoracic (TAA), intracranial (ICA) Marfan syndrome (MFS). An aneurysm-RVF model was then developed predict future The performance assessed both derivation validation cohorts compared other models employing clinical factors. RVF score derived our patients an increased aneurysms.PheWAS identified a total 32 that significantly Of these, number vessels optic disc ('ntreeA') AAA (β = -0.36, P 6.75e-10) ICA -0.11, 5.51e-06). In addition, mean angles between each artery branch ('curveangle_mean_a') commonly 4 MFS genes (FBN1: β -0.10, 1.63e-12; COL16A1: -0.07, 3.14e-09; LOC105373592: -0.06, 1.89e-05; C8orf81/LOC441376: 0.07, 1.02e-05). showed good discrimination ability predicting cohort, C-index 0.809 [95% CI: 0.780-0.838], which similar (0.806 [0.778-0.834]) higher than baseline (0.739 [0.733-0.746]). Similar observed 0.798 (0.727-0.869) model, 0.795 (0.718-0.871) 0.719 (0.620-0.816) model. participant. individuals upper tertile those lower (hazard ratio 17.8 [6.5-48.8], 1.02e-05).We significant certain revealed impressive capability using by PPPM approach. Our finds have great potential support not only diagnosis also more screening plan may benefit healthcare system.The online version contains supplementary material at 10.1007/s13167-023-00315-7.

Language: Английский

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Maternal metabolic health And Mother and Baby health Outcomes (MAMBO): Protocol of a prospective observational study (Preprint)

Published: Feb. 11, 2025

Metabolic disease is increasingly impacting women of reproductive age. In pregnancy, uncontrolled metabolic can result in offspring with major congenital anomalies, preterm birth, and abnormal fetal growth. Pregnancy also accelerates the complications diseases mothers resulting an increased risk premature cardiovascular events. Despite convincing evidence that pre-conception care largely mitigate risks there are few data about how to identify highest enable them be connected appropriate services.The aim study determine maternal phenotype represents having adverse neonatal pregnancy outcomes. This will a prospective cohort 500 recruited early pregnancy. The primary outcome composite born small or large for gestational age (customized birthweight ≤10th ≥90th centile age). Secondary outcomes (1) birth (SGA, LGA, abnormalities, (<37 weeks’ gestation)) (2) new (gestational diabetes, diabetes Type 2 Diabetes pre-diabetes; hypertension, preeclampsia, eclampsia essential hypertension after pregnancy; weight gain ≥20kg overweight/obesity at 12–18-months post-partum visit). A multivariable logistic regression analysis conducted candidate predicators poor due disease. From this model, model coefficients associated 95% confidence intervals (CI) extracted derive score predicting delivery LGA/SGA (primary outcome) composites (secondary outcomes). has been approved by institutional Human Research Ethics Committee (HREC/90080/MH-2022). Findings disseminated through peer reviewed publications conference presentations, national international networks involved maternity high-risk populations. registered Australian New Zealand Clinical Trials Registry (ACTRN12623000037606).

Language: Английский

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Mitochondria in cutaneous health, disease, ageing and rejuvenation—the 3PM-guided mitochondria-centric dermatology

The EPMA Journal, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Association of both intrinsic and extrinsic risk factors leading to accelerated skin ageing is reflected in excessive ROS production ir/reversible mitochondrial injury burnout, as abundantly demonstrated by accumulating research data. Due the critical role stress pathophysiology disorders, maintained (primary care) restored (secondary health, rejuvenation homoeostasis are considered most effective holistic approach advance dermatological treatments based on systemic health-supportive stimulating measures. Per evidence, an anti-ageing protection, wound healing scarring quality - all strongly depend sustainable functionality well-balanced homoeostasis. The latter can be objectively measured and, if necessary, a manner pre- rehabilitation algorithms tailored individualised patient profiles. entire spectrum corresponding innovations area includes natural rejuvenation, aesthetic reconstructive medicine, protection targeted disorders. Contextually, mitochondria-centric dermatology instrumental for advanced 3PM-guided which makes good use predictive multi-level diagnostics against health-to-disease transition progression relevant Cost-effective new treatment avenues focused health physiologic proposed article including in-depth analysis cases exemplified care with detailed mechanisms expert recommendations presented.

Language: Английский

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