The neuroprotective effect of melatonin in glutamate excitotoxicity of R28 cells and mouse retinal ganglion cells.

Glaucoma is the leading cause of irreversible blindness. The progressive degeneration of retinal ganglion cells (RGCs) is the major characteristic of glaucoma. Even though the control of intraocular pressure could delay the loss of RGCs, current clinical treatments cannot protect them directly.

Nuclear factor erythroid 2-related factor 2 agonist protects retinal ganglion cells in glutamate excitotoxicity retinas.

Objective: To investigate whether tert-Butylhydroquinone (TBHQ) can ameliorate oxidative stress and inflammation induced by glutamate excitotoxicity, and mediate retinal ganglion cell (RGC) damage by activating the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway and inhibiting the nuclear factor kappa B (NF-κB) signaling pathway.

Materials And Methods: TBHQ was used to treat a glutamate excitotoxicity model of retinal cell line 28 and C57 mice. Damage to RGCs and visual function were assessed using flash visual evoked potential (FVEP), immunofluorescence, propidium iodide staining, and hematoxylin and eosin staining.

Molecular investigation of candidate genes for pyroptosis-induced inflammation in diabetic retinopathy.

Background: Diabetic retinopathy is a diabetic microvascular complication. Pyroptosis, as a way of inflammatory death, plays an important role in the occurrence and development of diabetic retinopathy, but its underlying mechanism has not been fully elucidated. The purpose of this study is to identify the potential pyroptosis-related genes in diabetic retinopathy by bioinformatics analysis and validation in a diabetic retinopathy model and predict the microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) interacting with them.

Heat Shock Proteins 70 Regulate Cell Motility and Invadopodia-Associated Proteins Expression in Oral Squamous Cell Carcinoma.

Background: Many studies have shown that diabetes is often closely related to oral squamous cell carcinoma (OSCC) occurrence and metastasis. Heat shock protein 70 (Hsp70) is a molecular chaperone related to diabetes complications. This study aims to investigate the role of Hsp70 in OSCC in expression of invadopodia-associated proteins.

Identification and Validation of Autophagy-Related Genes in Diabetic Retinopathy.

Background: Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes, which is associated with damage of blood-retinal barrier and ischemia of retinal vasculature. It devastates visual acuity due to leakage of retinal vessels and aberrant pathological angiogenesis in diabetic patients. The etiology of DR is complex, accumulated studies have shown that autophagy plays an important role in the pathogenesis of DR, but its specific mechanism needs to be further studied.

Long-Term Oral Administration of Salidroside Alleviates Diabetic Retinopathy in db/db Mice.

Diabetic retinopathy (DR), a microvascular complication of diabetes mellitus, is the leading cause of vision loss in the working-age population worldwide. Unfortunately, current clinical treatments cannot completely prevent the occurrence and development of DR. Salidroside (Sal) is a medicinal supplement that has antioxidative and cytoprotective properties.

Peroxisome Proliferator-Activated Receptor α Activation Protects Retinal Ganglion Cells in Ischemia-Reperfusion Retinas.

Retinal ischemia-reperfusion (IR) leads to massive loss of retinal ganglion cells (RGC) and characterizes several blind-causing ophthalmic diseases. However, the mechanism related to retinal IR is controversial, and a drug that could prevent the RGC loss caused by IR is still lacking. This study aimed to investigate the role of endogenous retinal peroxisome proliferator-activated receptor (PPAR)α and the therapeutic effect of its agonist, fenofibric acid (FA), in IR-related retinopathy.

DNMT1-mediated PPARα methylation aggravates damage of retinal tissues in diabetic retinopathy mice.

Background: Peroxisome proliferator-activated receptor alpha (PPARα) is associated with diabetic retinopathy (DR), and the underlying mechanism is still unclear. Aim of this work was to investigate the mechanism of PPARα in DR.

Methods: Human retinal capillary pericytes (HRCPs) were treated with high glucose (HG) to induce DR cell model.

The Anti-apoptotic Role of 3'-Untranslational Region in Response to Angiotensin II via Mcl1 Expression.

Myeloid cell leukemia 1 (Mcl1), an abundant protein in the myocardium, plays an essential role in fibrosis and anti-inflammation in cardiomyocytes to prevent heart failure. However, whether 3'-untranslated regions (3'-UTR) has the cardio-protecting function remains unclear. Down-regulation of Mcl1 was observed in adult mice heart tissues after Angiotensin II (Ang II) treatment.

The 3' Untranslated Region Protects the Heart from Angiotensin II-Induced Cardiac Dysfunction via AGGF1 Expression.

The messenger RNA (mRNA) 3' untranslated regions (3' UTRs), as cis-regulated elements bound by microRNAs (miRNAs), affect their gene translation. However, the role of the trans-regulation of 3' UTRs during heart dysfunction remains elusive. Compared with administration of angiogenic factor with G-patch and forkhead-associate domains 1 (Aggf1), ectopic expression of Aggf1 with its 3' UTR significantly suppressed cardiac dysfunction in angiotensin II-infused mice, with upregulated expression of both Aggf1 and myeloid cell leukemia 1 (Mcl1).

Diabetic nephropathy execrates epithelial-to-mesenchymal transition (EMT) via miR-2467-3p/Twist1 pathway.

Although diabetic nephropathy (DN) is induced by a complicate interplay of multiple factors, the underlying mechanisms remain poorly characterized, even the treatment. Herein, we show that both of DN patients and STZ-induced type 1 diabetic rat exhibit the reduction both of urinary and circulating miR-2467-3p. We identify a negative correlation between miR-2467-3p levels and renal dysfunction.

Diabetic retinopathy: Focus on NADPH oxidase and its potential as therapeutic target.

Diabetic retinopathy is a common complication of diabetes that affects the retina due to a sustained high blood sugar level. Recent studies have demonstrated that high glucose-driven oxidative stress plays an important role in the microvascular complications of retina in diabetes. Oxidative stress occurs due to the excess of reactive oxygen species, which causes oxidative damage to retina, leading to the leak of tiny blood vessels, or acts as signaling molecules to trigger neovascularization, resulting in new fragile vessels.

Neuroprotective effects of PPARα in retinopathy of type 1 diabetes.

Diabetic retinopathy (DR) is a common neurovascular complication of type 1 diabetes. Current therapeutics target neovascularization characteristic of end-stage disease, but are associated with significant adverse effects. Targeting early events of DR such as neurodegeneration may lead to safer and more effective approaches to treatment.

Pulsatility Index as a Novel Parameter for Perfusion in Mouse Model of Hindlimb Ischemia.

Background/aims: In clinical settings, the pulsatility index (PI) has become a widely used tool for monitoring obstetrics or other vascular diseases. It is based on the maximum Doppler shift waveform derived from ultrasonography. However, it remains unclear whether the PI levels are correctly predicted from the perfusion in mouse model of hindlimb ischemia.

Renal Resistive Index as a Novel Indicator for Renal Complications in High-Fat Diet-Fed Mice.

Background/aims: The renal resistive index (RI) is a novel candidate as a renal injury prognostic indicator, but it remains unclear how renal RI levels correspond to renal injury in diabetic nephropathy.

Methods: To examine this issue, we compared 8-week-old male C57BL/6 mice fed with high-fat diet (HFD) versus chow diet (CHD) for 16 weeks. At 8 and 12 weeks, the glomerular filtration rate (GFR), urinary albumin-to-creatinine ratio (UACR), and inflammatory factors (IL-1β, IL-6, TNFα, and MCP-1) were measured, along with the increase in renal RI.

Interaction of PPARα With the Canonic Wnt Pathway in the Regulation of Renal Fibrosis.

Peroxisome proliferator-activated receptor-α (PPARα) displays renoprotective effects with an unclear mechanism. Aberrant activation of the canonical Wnt pathway plays a key role in renal fibrosis. Renal levels of PPARα were downregulated in both type 1 and type 2 diabetes models.

Nanoparticle-mediated expression of a Wnt pathway inhibitor ameliorates ocular neovascularization.

Objective: The deficiency of very low-density lipoprotein receptor resulted in Wnt signaling activation and neovascularization in the retina. The present study sought to determine whether the very low-density lipoprotein receptor extracellular domain (VLN) is responsible for the inhibition of Wnt signaling in ocular tissues.

Approach And Results: A plasmid expressing the soluble VLN was encapsulated with poly(lactide-co-glycolide acid) to form VLN nanoparticles (VLN-NP).

CD82 restrains pathological angiogenesis by altering lipid raft clustering and CD44 trafficking in endothelial cells.

Background: Angiogenesis is crucial for many pathological processes and becomes a therapeutic strategy against diseases ranging from inflammation to cancer. The regulatory mechanism of angiogenesis remains unclear. Although tetraspanin CD82 is widely expressed in various endothelial cells (ECs), its vascular function is unknown.

Peroxisome proliferator-activated receptor α protects capillary pericytes in the retina.

Pericyte degeneration is an early event in diabetic retinopathy and plays an important role in progression of diabetic retinopathy. Clinical studies have shown that fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, has robust therapeutic effects on diabetic retinopathy in type 2 diabetic patients. We evaluated the protective effect of PPARα against pericyte loss in diabetic retinopathy.

PPARα regulates mobilization and homing of endothelial progenitor cells through the HIF-1α/SDF-1 pathway.

Purpose: The mechanism for the antiangiogenic activity of peroxisome proliferator-activated receptor alpha (PPARα) remains incompletely understood. Endothelial progenitor cells (EPC) are known to participate in neovascularization (NV). The purpose of this study was to investigate whether PPARα regulates EPC during retinal NV.

Protective and antioxidant effects of PPARα in the ischemic retina.

Purpose: Previous studies have demonstrated that peroxisome proliferator-activated receptor-alpha (PPARα) agonists have therapeutic effects in diabetic retinopathy, although the mechanism of action remains incompletely understood. The purpose of this study was to evaluate PPARα's protective effects in the ischemic retina, and to delineate its molecular mechanism of action.

Methods: For the oxygen-induced retinopathy (OIR) model, wild-type (WT), and PPARα knockout (PPARα(-/-)) mice were exposed to 75% O₂ from postnatal day 7 (P7) to P12 and treated with the PPARα agonist fenofibric acid (Feno-FA) from P12 to P16.

Pathogenic role of diabetes-induced PPAR-α down-regulation in microvascular dysfunction.

Two independent clinical studies have reported that fenofibrate, a peroxisome proliferator-activated receptor α (PPARα) agonist, has robust therapeutic effects on microvascular complications of diabetes, including diabetic retinopathy (DR) in type 2 diabetic patients. However, the expression and function of PPARα in the retina are unclear. Here, we demonstrated that PPARα is expressed in multiple cell types in the retina.

Therapeutic potential of a monoclonal antibody blocking the Wnt pathway in diabetic retinopathy.

Dysregulation of Wnt/β-catenin signaling contributes to the development of diabetic retinopathy by inducing retinal inflammation, vascular leakage, and neovascularization. Here, we evaluated the inhibitory effect of a monoclonal antibody (Mab) specific for the E1E2 domain of Wnt coreceptor low-density lipoprotein receptor-related protein 6, Mab2F1, on canonical Wnt signaling and its therapeutic potential for diabetic retinopathy. Mab2F1 displayed robust inhibition on Wnt signaling with a half-maximal inhibitory concentration (IC₅₀) of 20 μg/mL in retinal pigment epithelial cells.