Targeting selective autophagy and beyond: From underlying mechanisms to potential therapies

Journal of Advanced Research, Journal Year: 2024, Volume and Issue: 65, P. 297 - 327

Published: May 14, 2024

Autophagy is an evolutionarily conserved turnover process for intracellular substances in eukaryotes, relying on lysosomal (in animals) or vacuolar yeast and plants) mechanisms. In the past two decades, emerging evidence suggests that, under specific conditions, autophagy can target particular macromolecules organelles degradation, a termed selective autophagy. Recently, accumulating studies have demonstrated that abnormality of closely associated with occurrence progression many human diseases, including neurodegenerative cancers, metabolic cardiovascular diseases. This review aims at systematically comprehensively introducing its role various while unravelling molecular mechanisms By providing theoretical basis development related small-molecule drugs as well treating this seeks to contribute understanding therapeutic potential. review, we introduce dissect major categories been discovered. We also focus recent advances underlying both classical non-classical Moreover, current situation targeting different types further summarized, valuable insights into discovery more candidate future. On other hand, reveal clinically relevant implementations are potentially autophagy, such predictive approaches treatments tailored individual patients.

Language: Английский

---

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

---

Anti-prostate cancer protection and therapy in the framework of predictive, preventive and personalised medicine — comprehensive effects of phytochemicals in primary, secondary and tertiary care

The EPMA Journal, Journal Year: 2022, Volume and Issue: 13(3), P. 461 - 486

Published: July 8, 2022

Abstract According to the GLOBOCAN 2020, prostate cancer (PCa) is most often diagnosed male in 112 countries and leading cancer-related death 48 countries. Moreover, PCa incidence permanently increases adolescents young adults. Also, rates of metastasising continuously grow up populations. Corresponding socio-economic burden enormous: treatment costs increase more rapidly than for any other cancer. In order reverse current trends exploding cases costs, pragmatic decisions should be made, favour advanced populational screening programmes effective anti-PCa protection at level health-to-disease transition (sub-optimal health conditions) demonstrating highest cost-efficacy treatments. For doing this, paradigm change from reactive treatments clinically manifested predictive approach personalised prevention essential. Phytochemicals are associated with potent anti-cancer activity targeting each stage carcinogenesis including cell apoptosis proliferation, invasiveness metastatic disease. example, their positive effects demonstrated stabilising restoring mitochondrial quality, which if compromised strongly sub-optimal conditions strong predisposition aggressive sub-types. Further, phytochemicals significantly enhance response cells therapies radio- chemotherapy. Evident plant-based mitigation negative side-effects frequently observed conventional has been reported. Finally, dual anti-viral such as these silibinin have being highly relevant improved management secondary tertiary care, under pandemic conditions, since PCa-affected individuals per evidence vulnerable towards COVID-19 infection. Here, we present a comprehensive data analysis considered primary care well an disease framework predictive, preventive medicine.

Language: Английский

---

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

---

Phytochemical-based nanodrugs going beyond the state-of-the-art in cancer management—Targeting cancer stem cells in the framework of predictive, preventive, personalized medicine

Frontiers in Pharmacology, Journal Year: 2023, Volume and Issue: 14

Published: March 23, 2023

Cancer causes many deaths worldwide each year, especially due to tumor heterogeneity leading disease progression and treatment failure. Targeted of heterogeneous population cells - cancer stem is still an issue in protecting affected individuals against associated multidrug resistance progression. Nanotherapeutic agents have the potential go beyond state-of-the-art approaches overall management. Specially assembled nanoparticles act as carriers for targeted drug delivery. Several nanodrugs already been approved by US Food Drug Administration (FDA) treating different types. Phytochemicals isolated from plants demonstrate considerable nanomedical applications oncology thanks their antioxidant, anti-inflammatory, anti-proliferative, other health benefits. Phytochemical-based NPs can enhance anticancer therapeutic effects, improve cellular uptake agents, mitigate side effects toxic treatments. Per evidence, phytochemical-based specifically target CSCs decreasing risks relapse metastatic manifestation. Therefore, this review focuses on current outlook targeting research studies consideration framework predictive, preventive, personalized medicine (3PM).

Language: Английский

---

Predictive, preventive and personalised approach as a conceptual and technological innovation in primary and secondary care of inflammatory bowel disease benefiting affected individuals and populations

The EPMA Journal, Journal Year: 2024, Volume and Issue: 15(1), P. 111 - 123

Published: Feb. 9, 2024

Abstract Inflammatory bowel disease (IBD) is a global health burden which carries lifelong morbidity affecting all age groups in populations with the disease-specific peak of ranging between 15 and 35 years, are great economic importance for society. An accelerating incidence IBD reported newly industrialised countries, whereas stabilising but increasing prevalence typical countries Westernised lifestyle, such as European area USA. Although aetiology largely unknown, interplay genetic, environmental, immunological, microbial components decisive manifestation, course, severity individual outcomes. Contextually, creation an individualised patient profile crucial cost-effective management primary secondary care IBD. The proposed pathomechanisms include intestinal pathoflora dysbiosis, chronic inflammation mitochondrial impairments, amongst others, collectively may reveal molecular signatures defining subtypes leading to clinical phenotypes, stratification protection against health-to-disease transition treatments tailored profiles—all pillars advanced 3PM approach. paradigm change from reactive medical services predictive diagnostics, targeted prevention profiles overall holds promise meet needs care, increase life-quality affected individuals improve economy management. This article analyses current achievements provides roadmap future developments context 3P medicine benefiting society at large.

Language: Английский

---

Targeting mitochondria for ovarian aging: new insights into mechanisms and therapeutic potential

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: June 17, 2024

Ovarian aging is a complex process characterized by decline in oocyte quantity and quality, directly impacting fertility overall well-being. Recent researches have identified mitochondria as pivotal players the of ovaries, influencing various hallmarks pathways governing this intricate process. In review, we discuss multifaceted role determining ovarian fate, outline mechanisms through which contribute to aging. Specifically, emphasize potential targeting mitochondrial dysfunction innovative therapeutic approaches, including antioxidants, metabolic improvement, biogenesis promotion, mitophagy enhancement, transfer, traditional Chinese medicine. These strategies hold promise effective means mitigate age-related preserve health. Drawing insights from advanced field, review provides deeper understanding interplay between function aging, offering valuable perspectives for development novel interventions aimed at preserving enhancing reproductive

Language: Английский

---

Pre-pregnancy check-up of maternal vascular status and associated phenotype is crucial for the health of mother and offspring

The EPMA Journal, Journal Year: 2022, Volume and Issue: 13(3), P. 351 - 366

Published: Aug. 17, 2022

Cardiovascular disease remains the leading cause of burden globally with far-reaching consequences including enormous socio-economic to healthcare and society at large. health is decisive for reproductive function, healthy pregnancy postpartum. During pregnancy, maternal cardiovascular system exposed highly increased haemodynamic stress that significantly impacts status mother offspring. Resulting from sub-optimal conditions overlooked in pre-pregnancy time, progressive abnormalities can be expected during Contextually, there are two main concepts follow framework predictive, preventive personalised medicine, namely develop:1. advanced screening young populations predict prevent individual risks prior planned pregnancies2. in-depth companion diagnostics long-lasting postpartum offspring.Data collected current study demonstrate group-specific complications offspring clinical relevance related phenotyping pre-pregnant mothers. Diagnostic approach proposed this revealed its great utility demonstrating important synergies between maladaptation connective tissue dysfunction. Co-diagnosed low BMI mother, dysfunction, stiffness peripheral vessels decreased blood pressure considered a specific phenotype useful innovative programmes severe This crucial discovery brings together systemic effects characteristic, example, individuals Flammer syndrome predisposed phenotype-specific primary vascular dysregulation, pregnancy-associated risks, normal tension glaucoma, ischemic stroke age, impaired wound healing associated disorders. Proposed effectively protect both against health-to-disease transition. Pre-pregnancy check-up focused on utilising here described phenotypes pivotal policy.Cardiovascular function pregnancy. may transition relevant affected Overlooked lifelong. Here we co-diagnosed bodyweight which increase eye heart disorders amongst others. Innovative mitigate an essential innovation policy proposed.

Language: Английский

---

Machine learning–couched treatment algorithms tailored to individualized profile of patients with primary anterior chamber angle closure predisposed to the glaucomatous optic neuropathy

The EPMA Journal, Journal Year: 2023, Volume and Issue: 14(3), P. 527 - 538

Published: Aug. 17, 2023

Primary angle closure glaucoma (PACG) is still one of the leading causes irreversible blindness, with a trend towards an increase in number patients to 32.04 million by 2040, 58.4% compared 2013. Health risk assessment based on multi-level diagnostics and machine learning-couched treatment algorithms tailored individualized profile primary anterior chamber are considered essential tools reverse protect vulnerable subpopulations against health-to-disease progression.To develop methodology for personalized choice effective method (PAC) comparing prognosis intraocular pressure (IOP) changes due laser peripheral iridotomy (LPI) or lens extraction (LE).The multi-parametric data analysis was used models predicting individual outcomes LPI LE. For doing this, we suggested positive dynamics after treatment, as objective measure successful treatment. Thirty-seven anatomical parameters have been applying artificial intelligence prospective study 30 (LE) + PAC.Based topographic features PAC, mathematical developed that provide LE Multi-level key tool overall advanced approach. To this end, future application AI area, it strongly recommended consider following:Clinically relevant phenotyping applicable population screeningSystemic effects causing suboptimal health conditions order cost-effectively affected individuals transitionClinically utilizing health/disease-specific molecular patterns detectable body fluids high predictive power such comprehensive tear fluid analysis.The online version contains supplementary material available at 10.1007/s13167-023-00337-1.

Language: Английский

---

Vascular dysregulation in glaucoma: retinal vasoconstriction and normal neurovascular coupling in altitudinal visual field defects

The EPMA Journal, Journal Year: 2023, Volume and Issue: 14(1), P. 87 - 99

Published: Feb. 16, 2023

Vision loss in glaucoma is not only associated with elevated intraocular pressure and neurodegeneration, but vascular dysregulation (VD) a major factor. To optimize therapy, an improved understanding of concepts predictive, preventive, personalized medicine (3PM) needed which based on more detailed VD pathology. Specifically, to learn if the root cause glaucomatous vision neuronal (degeneration) or origin, we now studied neurovascular coupling (NVC) vessel morphology their relationship glaucoma.In patients primary open angle (POAG) (n = 30) healthy controls 22), NVC was using dynamic analyzer quantify retinal diameter before, during, after flicker light stimulation evaluate dilation response following activation. Vessel features were then related branch level visual field impairment.Retinal arterial venous vessels had significantly smaller diameters POAG comparison controls. However, both reached normal values during activation despite diameters. This largely independent depth varied among patients.Because dilation/constriction normal, can be explained by chronic vasoconstriction limits energy supply (and brain) neurons subsequent hypo-metabolism ("silent" neurons) cell death. We propose that primarily origin. help better personalize therapy targeting eye also prevent low vision, slowing its progression supporting recovery restoration.ClinicalTrials.gov, # NCT04037384 July 3, 2019.

Language: Английский

---