Diabetic retinopathy as the leading cause of blindness and early predictor of cascading complications—risks and mitigation

The EPMA Journal, Год журнала: 2023, Номер 14(1), С. 21 - 42

Опубликована: Фев. 13, 2023

Abstract Proliferative diabetic retinopathy (PDR) the sequel of (DR), a frequent complication diabetes mellitus (DM), is leading cause blindness in working-age population. The current screening process for DR risk not sufficiently effective such that often disease undetected until irreversible damage occurs. Diabetes-associated small vessel and neuroretinal changes create vicious cycle resulting conversion into PDR with characteristic ocular attributes including excessive mitochondrial retinal cell damage, chronic inflammation, neovascularisation, reduced visual field. considered an independent predictor other severe complications as ischemic stroke. A “domino effect” highly cascading DM which early indicator impaired molecular signaling. Mitochondrial health control clinically relevant management, multi-omic tear fluid analysis can be instrumental prognosis prediction. Altered metabolic pathways bioenergetics, microvascular deficits disease, tissue remodelling are focus this article evidence-based targets predictive approach to develop diagnosis treatment algorithms tailored individual cost-effective prevention by implementing paradigm shift from reactive medicine predictive, preventive, personalized (PPPM) primary secondary care management.

Язык: Английский

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Personalized Drug Therapy: Innovative Concept Guided With Proteoformics

Molecular & Cellular Proteomics, Год журнала: 2024, Номер 23(3), С. 100737 - 100737

Опубликована: Фев. 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.

Язык: 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, Год журнала: 2024, Номер 15(1), С. 1 - 23

Опубликована: Фев. 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.

Язык: Английский

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Mediterranean diet in the targeted prevention and personalized treatment of chronic diseases: evidence, potential mechanisms, and prospects

The EPMA Journal, Год журнала: 2024, Номер 15(2), С. 207 - 220

Опубликована: Апрель 16, 2024

Язык: Английский

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Significance of flavonoids targeting PI3K/Akt/HIF-1α signaling pathway in therapy-resistant cancer cells – A potential contribution to the predictive, preventive, and personalized medicine

Journal of Advanced Research, Год журнала: 2023, Номер 55, С. 103 - 118

Опубликована: Март 4, 2023

Cancer management faces multiple obstacles, including resistance to current therapeutic approaches. In the face of challenging microenvironments, cancer cells adapt metabolically maintain their supply energy and precursor molecules for biosynthesis thus sustain rapid proliferation tumor growth. Among various metabolic adaptations observed in cells, altered glucose metabolism is most widely studied. The aberrant glycolytic modification has been associated with cell division, growth, progression, drug resistance. higher rates glycolysis as a hallmark modulated by transcription factor hypoxia inducible 1 alpha (HIF-1α), downstream target PI3K/Akt signaling, deregulated pathway cancer. We provide detailed overview current, primarily experimental, evidence on potential effectiveness flavonoids combat glycolysis-induced conventional targeted therapies. manuscript focuses reducing via affecting PI3K/Akt, HIF-1α (as critical that regulated pathway), key mediators PI3K/Akt/HIF-1α signaling (glucose transporters enzymes). working hypothesis proposes – an attractive application mitigate Phytochemicals represent source promising substances applicable primary, secondary, tertiary care. However, accurate patient stratification individualized profiling crucial steps paradigm shift from reactive predictive, preventive, personalized medicine (PPPM / 3PM). article focused targeting molecular patterns natural provides evidence-based recommendations 3PM relevant implementation.

Язык: Английский

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Mini-encyclopedia of mitochondria-relevant nutraceuticals protecting health in primary and secondary care—clinically relevant 3PM innovation

The EPMA Journal, Год журнала: 2024, Номер 15(2), С. 163 - 205

Опубликована: Апрель 18, 2024

Despite their subordination in humans, to a great extent, mitochondria maintain independent status but tightly cooperate with the "host" on protecting joint life quality and minimizing health risks. Under oxidative stress conditions, healthy promptly increase mitophagy level remove damaged "fellows" rejuvenating mitochondrial population sending fragments of mtDNA as SOS signals all systems human body. As long metabolic pathways are under systemic control well-concerted together, adaptive mechanisms become triggered increasing protection, activating antioxidant defense repair machinery. Contextually, attributes patho-/physiology instrumental for predictive medical approach cost-effective treatments tailored individualized patient profiles primary (to protect vulnerable individuals again health-to-disease transition) secondary affected disease progression) care. Nutraceuticals naturally occurring bioactive compounds demonstrating health-promoting, illness-preventing, other health-related benefits. Keeping mind health-promoting properties nutraceuticals along therapeutic potential safety profile, there is permanently growing demand application mitochondria-relevant nutraceuticals. Application beneficial only if meeting needs at individual level. Therefore, risk assessment creation pivotal importance followed by adapted nutraceutical sets needs. Based scientific evidence available nutraceuticals, this article presents examples frequent which require protective measures targeted holistic following advanced concepts predictive, preventive, personalized medicine (PPPM/3PM)

Язык: Английский

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CADASIL: A NOTCH3-associated cerebral small vessel disease

Journal of Advanced Research, Год журнала: 2024, Номер unknown

Опубликована: Янв. 1, 2024

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common hereditary cerebral small vessel disease (CSVD), pathologically characterized by a non-atherosclerotic non-amyloid diffuse angiopathy primarily involving to medium-sized penetrating arteries leptomeningeal arteries. In 1996, mutation in notch receptor 3 gene (NOTCH3) was identified as cause of CADASIL. However, since that time other genetic CSVDs have been described, including HtrA serine peptidase 1 gene-associated CSVD cathepsin A CSVD, clinically mimic original phenotype. Though NOTCH3-associated now well-recognized disorder number studies investigating this increasing, role NOTCH3 pathogenesis CADASIL remains elusive.

Язык: 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, Год журнала: 2024, Номер 15(2), С. 289 - 319

Опубликована: Апрель 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.

Язык: 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, Год журнала: 2024, Номер 15(3), С. 415 - 452

Опубликована: Авг. 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

Язык: 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, Год журнала: 2023, Номер 14(1), С. 43 - 51

Опубликована: Фев. 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.

Язык: Английский

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