Forecasting the Pharmacological Mechanisms of Plumbago zeylanica and Solanum xanthocarpum in Diabetic Retinopathy Treatment: A Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Study DOI Creative Commons
Nilanchala Sahu, Rama Tyagi,

Neeraj Kumar

и другие.

Biology, Год журнала: 2024, Номер 13(9), С. 732 - 732

Опубликована: Сен. 18, 2024

(1) Background: Diabetic retinopathy (DR) is a major complication of diabetes, marked by abnormal angiogenesis, microaneurysms, and retinal hemorrhages. Traditional Ayurvedic medicine advocates multi-target strategies for DR management. However, the mechanisms which Solanum xanthocarpum (SX) Plumbago zeylanica (PZ) exert therapeutic effects are not well understood; (2) Methods: To investigate these mechanisms, we employed network pharmacology molecular docking techniques. Phytochemicals from SX PZ were identified using IMPPAT database Swiss Target Prediction tool. DR-related protein targets sourced GeneCards database, common through Venn diagram analysis. STRING Cytoscape used to construct analyze protein–protein interaction networks. Pathway enrichment was performed with Gene Ontology KEGG databases; (3) Results: We 28 active phytoconstituents, targeting proteins such as EGFR, SRC, STAT3, AKT1, HSP90AA1. Molecular dynamics simulations confirmed strong binding affinities compounds their targets; (4) Conclusions: The study highlights activity PZ, particularly in pathways related EGFR tyrosine kinase inhibitor resistance PI3K–AKT signaling. These findings provide valuable insights into potential DR, suggesting effective modulation key involved disease.

Язык: Английский

An update on chronic complications of diabetes mellitus: from molecular mechanisms to therapeutic strategies with a focus on metabolic memory DOI Creative Commons

Tongyue Yang,

Qi Feng, Feng Guo

и другие.

Molecular Medicine, Год журнала: 2024, Номер 30(1)

Опубликована: Май 26, 2024

Abstract Diabetes mellitus, a chronic metabolic disease, often leads to numerous complications, significantly contributing global morbidity and mortality rates. High glucose levels trigger epigenetic modifications linked pathophysiological processes like inflammation, immunity, oxidative stress, mitochondrial dysfunction, senescence various kinds of cell death. Despite glycemic control, transient hyperglycemia can persistently harm organs, tissues, cells, latent effect termed "metabolic memory" that contributes diabetic complications. Understanding memory's mechanisms could offer new approach mitigating these However, key molecules networks underlying memory remain incompletely understood. This review traces the history research, highlights its features, discusses recent involved in mechanisms, summarizes confirmed potential therapeutic compounds. Additionally, we outline vitro vivo models memory. We hope this work will inform future research on regulatory facilitate development effective compounds prevent

Язык: Английский

Процитировано

21
Microglia in retinal angiogenesis and diabetic retinopathy DOI Creative Commons
Aiyan Hu, Mirko H. H. Schmidt,

Nora Heinig

и другие.

Angiogenesis, Год журнала: 2024, Номер 27(3), С. 311 - 331

Опубликована: Апрель 2, 2024

Abstract Diabetic retinopathy has a high probability of causing visual impairment or blindness throughout the disease progression and is characterized by growth new blood vessels in retina at an advanced, proliferative stage. Microglia are resident immune population central nervous system, known to play crucial role regulating retinal angiogenesis both physiological pathological conditions, including diabetic retinopathy. Physiologically, they located close essential for forming (neovascularization). In retinopathy, microglia become widely activated, showing distinct polarization phenotype that leads their accumulation around neovascular tufts. These activated induce pathogenic through secretion various angiogenic factors status endothelial cells. Interestingly, some subtypes simultaneously promote regression neovascularization tufts normal lesions. Modulating state microglial activation ameliorate thus appears as promising potential therapeutic approach managing Graphical abstract

Язык: Английский

Процитировано

16
Diabetic retinopathy features in Lund MetS rats DOI Creative Commons

María José Canz,

Júlia Baguña Torres, Jordi Huerta

и другие.

Experimental Eye Research, Год журнала: 2025, Номер unknown, С. 110274 - 110274

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

1
The ideal treatment timing for diabetic retinopathy: the molecular pathological mechanisms underlying early-stage diabetic retinopathy are a matter of concern DOI Creative Commons
Wenjie Sun, Xuedong An, Yuehong Zhang

и другие.

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 9, 2023

Diabetic retinopathy (DR) is a prevalent complication of diabetes, significantly impacting patients’ quality life due to vision loss. No pharmacological therapies are currently approved for DR, excepted the drugs treat diabetic macular edema such as anti-VEGF agents or steroids administered by intraocular route. Advancements in research have highlighted crucial role early intervention DR halting delaying disease progression. This holds immense significance enhancing and alleviating societal burden associated with medical care costs. The non-proliferative stage represents phase DR. In comparison proliferative stage, pathological changes primarily manifest microangiomas hemorrhages, while at cellular level, there loss pericytes, neuronal cell death, disruption components functionality within retinal vascular unit encompassing pericytes neurons. Both neurodegenerative microvascular abnormalities stages Therefore, our focus lies on we initially summarized mechanisms involved its development, including pathways polyols, that revolve around occurring during this stage. We also integrate cutting-edge mechanisms, leukocyte adhesion, neutrophil extracellular traps, multiple RNA regulation, microorganisms, death (ferroptosis pyroptosis), other related mechanisms. current status drug therapy early-stage discussed provide insights development pharmaceutical interventions targeting treatment

Язык: Английский

Процитировано

15
A Narrative Review of the Advances in Screening Methods for Diabetic Retinopathy: Enhancing Early Detection and Vision Preservation DOI Open Access

Tanisha Upadhyay,

Roshan Prasad,

Swapneel Mathurkar

и другие.

Cureus, Год журнала: 2024, Номер unknown

Опубликована: Фев. 4, 2024

Diabetes mellitus (DM) is putting a great burden worldwide. This rise in DM cases, both type 1 and 2, significantly impacts public health. India has grappled with diabetes epidemic for several years, leading to many misdiagnosed untreated cases. remains significant factor adult-onset blindness despite improvements management. increases the danger of diabetic retinopathy (DR) permanent loss sight those affected. The screening DR aims identify persons complications arising from or DR, which could potentially result blindness, so that treatment can be started immediately avoided. A comprehensive health system approach required ensure sector effectively screens DR. Improving patient outcomes avoiding visual depends on early identification treatment. article discusses actions should implemented establish national effort systematic screening. It also highlights importance its impact effectiveness. Regular screenings enable detection retinopathy, allowing timely intervention Early helps prevent associated such as macular edema retinal detachment. Screening assists healthcare providers planning, optimizing approaches, monitoring Meanwhile, essential enhancing outcomes, thus chances preserving vision preventing further progression disease. improving overall management this sight-threatening complication.

Язык: Английский

Процитировано

6
Hybrid Explainable Artificial Intelligence Models for Targeted Metabolomics Analysis of Diabetic Retinopathy DOI Creative Commons
Fatma Hilal Yağın, Cemil Çolak, Abdulmohsen Algarni

и другие.

Diagnostics, Год журнала: 2024, Номер 14(13), С. 1364 - 1364

Опубликована: Июнь 27, 2024

Diabetic retinopathy (DR) is a prevalent microvascular complication of diabetes mellitus, and early detection crucial for effective management. Metabolomics profiling has emerged as promising approach identifying potential biomarkers associated with DR progression. This study aimed to develop hybrid explainable artificial intelligence (XAI) model targeted metabolomics analysis patients DR, utilizing focused identify specific metabolites exhibiting varying concentrations among individuals without (NDR), those non-proliferative (NPDR), proliferative (PDR) who have type 2 mellitus (T2DM). A total 317 T2DM patients, including 143 NDR, 123 NPDR, 51 PDR cases, were included in the study. Serum samples underwent using liquid chromatography mass spectrometry. Several machine learning models, Support Vector Machines (SVC), Random Forest (RF), Decision Tree (DT), Logistic Regression (LR), Multilayer Perceptrons (MLP), implemented solo models two-stage ensemble approach. The trained validated 10-fold cross-validation. SHapley Additive exPlanations (SHAP) employed interpret contributions each feature predictions. Statistical analyses conducted Shapiro-Wilk test normality, Kruskal-Wallis H group differences, Mann-Whitney U Bonferroni correction post-hoc comparisons. SVC + MLP achieved highest performance, an accuracy 89.58%, precision 87.18%, F1-score 88.20%, F-beta score 87.55%. SHAP revealed that glucose, glycine, age consistently important features across all classes, while creatinine various phosphatidylcholines exhibited higher importance class, suggesting their severe DR. XAI particularly ensemble, demonstrated superior performance predicting progression compared models. application facilitates interpretation importance, providing valuable insights into metabolic physiological markers different stages These findings highlight combined techniques detection, interventions, personalized treatment strategies

Язык: Английский

Процитировано

6
Research progress of VEGFR small molecule inhibitors in ocular neovascular diseases DOI

D.Y. Jiang,

Ting Xu, Lei Zhong

и другие.

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 257, С. 115535 - 115535

Опубликована: Май 29, 2023

Язык: Английский

Процитировано

12
Beyond Glucose: The Dual Assault of Oxidative and ER Stress in Diabetic Disorders DOI

Tamsheel Fatima Roohi,

Syed Faizan, Zahoor Ahmad Parray

и другие.

High Blood Pressure & Cardiovascular Prevention, Год журнала: 2023, Номер 30(6), С. 513 - 531

Опубликована: Дек. 2, 2023

Язык: Английский

Процитировано

11
Macular pigments produced from microalga Chlorella sp. and applied to alleviate the pathogenic process in diabetic mice DOI

M. C. Lin,

Wei-Hong Chiu,

Cheng‐Han Lin

и другие.

Algal Research, Год журнала: 2024, Номер 78, С. 103414 - 103414

Опубликована: Янв. 30, 2024

Язык: Английский

Процитировано

3
Müller Glia Co-Regulate Barrier Permeability with Endothelial Cells in an Vitro Model of Hyperglycemia DOI Open Access
Juan S. Peña, François Berthiaume, Maribel Vázquez

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(22), С. 12271 - 12271

Опубликована: Ноя. 15, 2024

Diabetic retinopathy is a complex, microvascular disease that impacts millions of working adults each year. High blood glucose levels from Diabetes Mellitus lead to the accumulation advanced glycation end-products (AGEs), which promote inflammation and breakdown inner retinal barrier (iBRB), resulting in vision loss. This study used an vitro model hyperglycemia examine how endothelial cells (ECs) Müller glia (MG) collectively regulate molecular transport. Changes cell morphology, expression junctional proteins, reactive oxygen species (ROS) ECs MG were examined when exposed hyperglycemic medium containing AGEs. Trans-endothelial resistance (TEER) assays measure changes response inflammatory conditions, with without anti-VEGF compound. Both types responded conditions significant area ROS, proteins ZO-1, CX-43, CD40, as well receptor for The resistivities individual dual barriers decreased within but restored basal, normoglycemic treated anti-VEGF. illustrated phenotypic responses hyperglycemia, key cell–cell communication. results highlight important, synergistic relationships between they contribute function combination conventional treatments.

Язык: Английский

Процитировано

3