Blockade of P2X7 receptors preserves blood retinal barrier integrity by modulating the plasmalemma vesicle‐associated protein: Implications for diabetic retinopathy

British Journal of Pharmacology, Год журнала: 2025, Номер unknown

Опубликована: Фев. 20, 2025

Plasmalemma vesicle-associated protein (PLVAP) regulates transcytosis in vascular endothelial cells. PLVAP expression is increased pathological conditions, such as diabetic retinopathy. P2X7 receptor antagonists have been shown to preserve blood-retinal barrier (BRB) integrity. Here, we tested the hypothesis that tightly linked activity, leading breakdown of BRB an vitro model We integrated network approaches with retinopathy using primary human retinal microvascular cells (HRMECs). Cells were treated a antagonist, JNJ47965567, and several genes predicted belong signalling assessed. Levels localisation PLVAP, VE-cadherin zonula occludens-1 (ZO-1) HRMECs evaluated. In vivo, effects JNJ47965567 on retinas mice High levels glucose HRMECs, which was blocked by JNJ47965567. Furthermore, preserved ZO-1. choroidal vasculature mice, immunostaining increased, compared non-diabetic mice. This increase significantly attenuated treatment CONCLUSIONS AND IMPLICATIONS: study showed important component complex gene regulatory network, including mediating pathophysiology The antagonist good pharmacodynamic profile, suggesting this approach could be value

Язык: Английский

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Screening of Active Substances Regulating Alzheimer’s Disease in Ginger and Visualization of the Effectiveness on 6-Gingerol Pathway Targets

Foods, Год журнала: 2024, Номер 13(4), С. 612 - 612

Опубликована: Фев. 18, 2024

Ginger has been reported to potentially treat Alzheimer’s disease (AD), but the specific compounds responsible for this biological function and their mechanisms are still unknown. In study, a combination of network pharmacology, molecular docking, dynamic simulation technology was used screen active substances that regulate AD explore mechanisms. The TCMSP, GeneCards, OMIM, DisGeNET databases were utilized obtain 95 cross-targets related ginger’s ingredients as key targets. A functional enrichment analysis revealed pathways in which may be involved regulating include response exogenous stimuli, oxidative stress, toxic substances, lipid metabolism, among others. Furthermore, drug-active ingredient–key target interaction diagram constructed, highlighting 6-Gingerol is associated with 16 Additionally, protein–protein (PPI) mapped targets, HUB genes (ALB, ACTB, GAPDH, CASP3, CAT) identified. Based on results pharmacology cell experiments, selected ingredient further investigation. Molecular docking performed between its top three proteins strongest binding affinities (ACHE, MMP2, PTGS2) chosen dynamics together CASP3 protein gene. findings indicate exhibits strong ability these suggesting potential role at level, well abnormal cholinesterase metabolism apoptosis, other regulatory pathways. These provide solid theoretical foundation future vitro experiments using actual cells animal investigate application 6-Gingerol.

Язык: Английский

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Comprehensive analysis of the effects of the traditional stir-fry process on the dynamic changes of volatile metabolites in Hainan camellia oil

Food Chemistry X, Год журнала: 2024, Номер 23, С. 101747 - 101747

Опубликована: Авг. 17, 2024

The traditional stir-fry process before pressing is crucial to manufacture Hainan camellia oil. To assess the effects of on oil, six samples across different stages were analyzed. modified odors, volatile metabolite profiles, and human health-promoting functions Totally, 350 metabolites detected, heterocyclic compounds revealed as main contributors strong aroma. Potential indicators for monitoring degree established. Eight key aroma identified, including three new ones (1-octen-3-one, 2,3-butanedione, vanillin). Lipids degradation Millard reaction are probably pathways generation. Over-stir-fry treatment diminished contents some important but increased risk arising burnt odor. Our work offered insights into over-stir-fry which meaningful improving hot-pressing technique.

Язык: Английский

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Mechanistic insights into pachymic acid’s action on triple-negative breast Cancer through TOP2A targeting

Scientific Reports, Год журнала: 2025, Номер 15(1)

Опубликована: Янв. 22, 2025

Язык: Английский

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α1D Adrenergic Receptor Antagonism Protects Against High Glucose-Induced Mitochondrial Dysfunction and Blood Retinal Barrier Breakdown in ARPE-19 Cells

International Journal of Molecular Sciences, Год журнала: 2025, Номер 26(3), С. 967 - 967

Опубликована: Янв. 24, 2025

Diabetic retinopathy (DR) is a microvascular complication of diabetes mellitus and leading cause blindness in the working-age population. Current pharmacological treatments counteract DR’s later stages without targeting earlier disease phases. Using computational approaches, our group previously identified α1D α2C adrenoceptors (α1DR α2CR) as new putative drug targets for DR. Therefore, aim this work was to validate role these receptors an vitro model DR, i.e., retinal pigmented epithelial cells (ARPE-19) challenged with high glucose (HG, 50 mM). We examined effects selective α1DR α2CR agonists antagonists on hyperglycemia-induced mitochondrial dysfunction blood barrier breakdown. Seahorse XFe employed assess oxygen consumption rate extracellular acidification rate. The integrity ARPE-19 evaluated through transepithelial electrical resistance measurements sodium fluorescein permeability test. modulation antagonist BMY 7378 (0.1–1 µM, 24 h), but not α2CR, significantly attenuated HG-induced dysfunction. 48 h) also prevented HG-mediated damage integrity. In contrast, agonist phenylephrine (1–10 μM, further reduced activity compared HG, indicating that activation directly implicated DR-mediated conclusion, current study validated target

Язык: Английский

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Protective effect of A-type ECG dimer on oxidative damage of retinal pigment epithelial cell

Food Bioscience, Год журнала: 2025, Номер unknown, С. 106443 - 106443

Опубликована: Март 1, 2025

Язык: Английский

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Metabolomics combined with network pharmacology reveals the regional and variety heterogeneity of grape metabolites and their potential antioxidant mechanisms

Food Research International, Год журнала: 2025, Номер 211, С. 116443 - 116443

Опубликована: Апрель 19, 2025

Язык: Английский

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Recent Advances on Modeling Retinal Disease: Towards Efficient Gene/Drug Therapy

Experimental Eye Research, Год журнала: 2025, Номер unknown, С. 110416 - 110416

Опубликована: Май 1, 2025

Язык: Английский

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Mechanistic exploration of BPA-induced hepatotoxicity and the therapeutic potential of Kedrostis foetidissima: A network pharmacology and molecular docking study incorporating in silico and in vitro approach

South African Journal of Botany, Год журнала: 2025, Номер 183, С. 265 - 280

Опубликована: Май 30, 2025

Язык: Английский

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Syringin as a novel therapeutic agent for renal cell carcinoma by targeting EGFR/PI3K/Akt pathway and enhancing sunitinib efficacy

Journal of Functional Foods, Год журнала: 2024, Номер 123, С. 106556 - 106556

Опубликована: Ноя. 13, 2024

Язык: Английский

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