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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Chondroitin Sulphate-Chitosan Based Nanogels Loaded with Naringenin-β-Cyclodextrin Complex as Potential Tool for the Treatment of Diabetic Retinopathy: A Formulation Study

International Journal of Nanomedicine, Journal Year: 2025, Volume and Issue: Volume 20, P. 907 - 932

Published: Jan. 1, 2025

The main purpose of the study was formulation development nanogels (NHs) composed chondroitin sulfate (CS) and low molecular weight chitosan (lCH), loaded with a naringenin-β-cyclodextrin complex (NAR/β-CD), as potential treatment for early-stage diabetic retinopathy. Different formulations NHs were prepared by varying polymer concentration, lCH ratio, pH and, then, characterized particle size, zeta potential, concentration (particles/mL) morphology. Cytotoxicity internalization assessed in vitro using Human Umbilical Vein Endothelial Cells (HUVEC). NAR/β-CD evaluated morphology, complexation efficiency, solubility. Finally, most promising NH prototype (NH@NAR/β-CD) further encapsulation loading capacity, opacity cytotoxicity on HUVEC; release test DPPH assay performed to investigate capability sustain NAR NH@NAR/β-CD antioxidant properties, respectively. properties influenced pH. N3 (0.5 mg/mL; lCH=1.5:1; = 5) N9 lCH=1:1; showed optimal characteristics, including small size (<350 nm) positive facilitating cellular uptake. 71% efficiency enhanced Since superior better biocompatibility, NAR/β-CD. N3@NAR/β-CD release, radical scavenging activity biocompatibility finally demonstrated. physico-chemical responsible their cell uptake, suggesting target retinal endothelial cells. high sustained over 72 hours could guarantee maintenance an effective drug at damage site while reducing injection number. Further studies about safety effectiveness intravitreal NHs@NAR/β-CD will be animal model.

Language: Английский

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Oxidative Stress, Inflammatory, Angiogenic, and Apoptotic molecules in Proliferative Diabetic Retinopathy and Diabetic Macular Edema Patients

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(9), P. 8227 - 8227

Published: May 4, 2023

The aim of this study is to evaluate molecules involved in oxidative stress (OS), inflammation, angiogenesis, and apoptosis, discern which these are more likely be implicated proliferative diabetic retinopathy (PDR) macular edema (DME) by investigating the correlation between them plasma (PLS) vitreous body (VIT), as well examining data obtained from ophthalmological examinations. Type 2 (T2DM) patients with PDR/DME (PDRG/DMEG; n = 112) non-DM subjects surrogate controls (SCG 48) were selected according inclusion/exclusion criteria programming for vitrectomy, either due having or hole (MH)/epiretinal membrane (ERM)/rhegmatogenous retinal detachment. Blood samples collected processed determine glycemic profile, total cholesterol, C reactive protein, malondialdehyde (MDA), 4-hydroxynonenal (4HNE), superoxide dismutase (SOD), catalase (CAT) levels antioxidant capacity (TAC). In addition, interleukin 6 (IL6), vascular endothelial growth factor (VEGF), caspase 3 (CAS3) assayed. VITs measure expression all abovementioned molecules. Statistical analyses conducted using R Core Team (2022) program, including group comparisons analyses. Compared SCG, our findings support presence OS, apoptosis PLS VIT T2DM. PDRG, there was a decrease load (p < 0.001) an increase pro-angiogenic 0.001), but pro-oxidants decline antioxidants intravitreally. DMEG, pro-inflammatory augmented diminished increased decreased Furthermore, we found positive PLS-CAT VIT-SOD (rho 0.5; p 0.01) negative PSD-4HNE VIT-TAC DMEG. Integrative imaging variables showed central subfield foveal thickness (CSFT) 0.01), CSFT VIT-4HNE 0.4; PDRG. displayed VIT-CAT 0.01). Exploring relationship potential biomarkers may help detecting early molecular changes PDR/DME, can used identify at high risk progression, monitor therapeutic outcomes retina.

Language: Английский

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Targeting the Gut–Eye Axis: An Emerging Strategy to Face Ocular Diseases

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(17), P. 13338 - 13338

Published: Aug. 28, 2023

The human microbiota refers to a large variety of microorganisms (bacteria, viruses, and fungi) that live in different body sites, including the gut, oral cavity, skin, eyes. In particular, presence an ocular surface with crucial role maintaining homeostasis by preventing colonization from pathogen species has been recently demonstrated. Moreover, recent studies underline potential association between gut (GM) health. this respect, some evidence supports existence gut-eye axis involved pathogenesis several diseases, age-related macular degeneration, uveitis, diabetic retinopathy, dry eye, glaucoma. Therefore, understanding link GM these disorders might be useful for development new therapeutic approaches, such as probiotics, prebiotics, symbiotics, or faecal transplantation through which could modulated, thus allowing better management diseases.

Language: Английский

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WaveFlex biosensor based on S-tapered and waist-expanded technique for detection of glycosylated hemoglobin

Biomedical Optics Express, Journal Year: 2023, Volume and Issue: 14(11), P. 6100 - 6100

Published: Oct. 25, 2023

Glycosylated hemoglobin (HbA1c) is considered a new standard for the detection of diabetes mellitus because it more accurate than regular blood sugar tests and there no need to take on an empty stomach or at specific time. In this work, we have developed novel optical fiber biosensor, referred as "WaveFlex biosensor," which operates principles localized surface plasmon resonance (LSPR) plasmonic wave. The sensor fabricated using innovative S-tapered waist-expanded technique, enabling effectively detect HbA1c. Compared HbA1c sensors currently in use, possess characteristics high sensitivity, low cost, strong anti-interference ability. gold nanoparticles (AuNPs), cerium oxide (CeO2) nanorods (NRs), tungsten disulfide (WS2) nanosheets (NSs) are functionalized improve effectiveness probe surface. AuNPs utilized generate LSPR by excitation evanescent waves amplify sensing signal. CeO2-NRs can metal-carrier interaction with AuNPs, enhancing cascade AuNPs. WS2-NSs layered fold structure large area. Therefore, combination conducive binding antibodies addition sites. make capable selection. applied test solution over concentrations 0-1000 µg/mL, sensitivity limits 1.195×10-5 a.u./(µg/mL) 1.66 µg/mL obtained, respectively. also evaluated assays reproducibility, reusability, selectivity, pH. According findings, method detecting glucose based biosensor proposed.

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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Integrating network pharmacology: The next-generation approach in ocular drug discovery

Current Opinion in Pharmacology, Journal Year: 2024, Volume and Issue: 74, P. 102425 - 102425

Published: Jan. 5, 2024

With the spread of "omics" sciences, approaches systems biology can be considered as new paradigms pharmacological research for discovery novel targets and/or treatments complex multifactorial diseases. Data from omics sciences used design biologic networks, that in turn quantitatively analyzed to identify targets. In this review, we will introduce concept network pharmacology, particularly application innovative approach field ocular with a focus on retinal diseases such diabetic retinopathy (DR), age-related macular degeneration (AMD) and glaucoma.

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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CADASIL: A NOTCH3-associated cerebral small vessel disease

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

Published: Jan. 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.

Language: Английский

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