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

The EPMA Journal, Journal Year: 2023, Volume and Issue: 14(1), P. 21 - 42

Published: Feb. 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.

Language: Английский

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

The EPMA Journal, Journal Year: 2024, Volume and Issue: 15(2), P. 207 - 220

Published: April 16, 2024

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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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, Journal Year: 2023, Volume and Issue: 55, P. 103 - 118

Published: March 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.

Language: 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, Journal Year: 2024, Volume and Issue: 15(2), P. 163 - 205

Published: April 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)

Language: Английский

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Systemic Inflammation as the Health-Related Communication Tool Between the Human Host and Gut Microbiota in the Framework of Predictive, Preventive, and Personalized Medicine

Advances in predictive, preventive and personalised medicine, Journal Year: 2024, Volume and Issue: unknown, P. 203 - 241

Published: Jan. 1, 2024

Language: Английский

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Quercetin, a natural flavonoid, protects against hepatic ischemia–reperfusion injury via inhibiting Caspase-8/ASC dependent macrophage pyroptosis

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: unknown

Published: May 1, 2024

Hepatic ischemia–reperfusion injury (IRI) is an inevitable adverse event following liver surgery, leading to damage and potential organ failure. Despite advancements, effective interventions for hepatic IRI remain elusive, posing a significant clinical challenge. The innate immune response significantly contributes the pathogenesis of by promoting inflammatory cytotoxic cycle. We have reported that blocking GSDMD-induced pyroptosis in immunity cells protected from injury. However, search inhibitors continues. This study aims evaluate whether quercetin, natural flavonoid, can inhibit mitigate IRI. established murine model cellular efficacy quercetin. Quercetin effectively alleviated IRI-induced tissue necrosis inflammation. found during IRI, cleavage GSDMD occurred macrophages, but not other non-parenchymal cells. inhibited macrophages. Moreover, we quercetin blocked ASC assembly formation NLRP3 inflammasomes AIM2 inflammasomes, suppressing macrophage pyroptosis. Co-immunoprecipitation experiments confirmed interaction between Caspase-8, which mechanism complex inflammasome formation. Overexpression Caspase-8 abolished anti-pyroptosis effect signaling. Furthermore, hepatoprotective activity was reduced myelocytic GSDMD-deficient mice. Our findings suggest has beneficial effects on could attenuate target inhibition via Caspase-8/ASC interaction. recommend might serve as targeted approach prevention personalized treatment perioperative patients.

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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