N-palmitoyl-D-glucosamine, a Natural Monosaccharide-Based Glycolipid, Inhibits TLR4 and Prevents LPS-Induced Inflammation and Neuropathic Pain in Mice.

Toll-like receptors (TLRs) are key receptors through which infectious and non-infectious challenges act with consequent activation of the inflammatory cascade that plays a critical function in various acute and chronic diseases, behaving as amplification and chronicization factors of the inflammatory response. Previous studies have shown that synthetic analogues of lipid A based on glucosamine with few chains of unsaturated and saturated fatty acids, bind MD-2 and inhibit TLR4 receptors. These synthetic compounds showed antagonistic activity against TLR4 activation in vitro by LPS, but little or no activity in vivo.

Resolvin D1 attenuates the inflammatory process in mouse model of LPS-induced keratitis.

The aim of this study was to investigate the effects of the lipid mediator Resolvin D1 in experimental keratitis. C57BL/6J mice were injected with lipopolysaccharide (2 µg/eye), and after 24 hours, the corneal damage was assessed. Clinical score was quantified, and corneal inflammatory biomarkers were detected by immunohistochemistry.

Ethanol-Induced Oxidative Stress Modifies Inflammation and Angiogenesis Biomarkers in Retinal Pigment Epithelial Cells (ARPE-19): Role of CYP2E1 and its Inhibition by Antioxidants.

The retinal pigment epithelium (RPE) plays a key role in retinal health, being essential for the protection against reactive oxygen species (ROS). Nevertheless, excessive oxidative stress can induce RPE dysfunction, promoting visual loss. Our aim is to clarify the possible implication of CYP2E1 in ethanol (EtOH)-induced oxidative stress in RPE alterations.

Corrigendum: Resolvin D1 Modulates the Intracellular VEGF-Related miRNAs of Retinal Photoreceptors Challenged With High Glucose.

[This corrects the article DOI: 10.3389/fphar.2020.

Resolvin D1 Modulates the Intracellular VEGF-Related miRNAs of Retinal Photoreceptors Challenged With High Glucose.

Stimulation of retinal photoreceptors with elevated glucose concentration (30 mM) for 96 h, served as diabetic retinopathy model to study Resolvin D1 (50 nM) effects on neovascularization. VEGF and anti-angiogenic miR-20a-3p, miR-20a-5p, miR-106a-5p, and miR-20b expression was assessed either in photoreceptors exposed to HG or in exosomes released by those cells. High glucose increased VEGF levels and concurrently decreased anti-angiogenic miRNAs content in photoreceptors and exosomes.

Oxidative stress-induced angiogenesis is mediated by miR-205-5p.

miR-205-5p is known to be involved in VEGF-related angiogenesis and seems to regulate associated cell signalling pathways, such as cell migration, proliferation and apoptosis. Therefore, several studies have focused on the potential role of miR-205-5p as an anti-angiogenic factor. Vascular proliferation is observed in diabetic retinopathy and the 'wet' form of age-related macular degeneration.

miR302a and 122 are deregulated in small extracellular vesicles from ARPE-19 cells cultured with HO.

Age related macular degeneration (AMD) is a common retina-related disease leading to blindness. Little is known on the origin of the disease, but it is well documented that oxidative stress generated in the retinal pigment epithelium and choroid neovascularization are closely involved. The study of circulating miRNAs is opening new possibilities in terms of diagnosis and therapeutics.

Resolvin D1 reduces mitochondrial damage to photoreceptors of primary retinal cells exposed to high glucose.

No study has investigated the interaction of Resolvin D1 (RvD1) with mitochondrial damage of retinal cells caused by diabetes. This study aims to investigate the effects of RvD1 (50 nM) on morphological and biochemical indicators of mitochondrial damage in primary retinal cells exposed to 30 mM d-glucose high glucose (HG). HG-cells exhibited photoreceptor damage characterized by short and small mitochondria with prevalent mitochondrial disruption, fragmentation, and aggregation.

Addition of the Aldose Reductase Inhibitor Benzofuroxane Derivative BF-5m to Prolonged and Moderate Exercise Training Enhanced Protection of the Rat Heart From Type-1 Diabetes.

Moderate exercise training may not be sufficient to exert beneficial effects on the cardiovascular system because of the long-term multifactorial etiology of diabetic complications. The addition of a proper pharmacological tool to the physical exercise should improve the outcomes of the diabetic damage. Here it is shown that 8 weeks exercise training of type 1 diabetic Sprague-Dawley (SD) rats resulted in a significantly increased heart rate, a 14% increase in the left ventricular ejection fraction (LVEF) increased plasma insulin levels and a 13% decrease in plasma glucose with respect to sedentary animals.

Oral Cannabidiol Prevents Allodynia and Neurological Dysfunctions in a Mouse Model of Mild Traumatic Brain Injury.

Neurological dysfunctions are the most impactful and persistent consequences of traumatic brain injury (TBI). Indeed, previous reports suggest that an association between TBI and chronic pain syndromes, as well anxio-depressive behaviors, tends to be more common in patients with mild forms of TBI. At present, no effective treatment options are available for these symptoms.

Retinal and circulating miRNA expression patterns in diabetic retinopathy: An in silico and in vivo approach.

Background And Purpose: Diabetic retinopathy, a secondary complication of diabetes mellitus, can lead to irreversible vision loss. Currently, no treatment is approved for early phases of diabetic retinopathy. Modifications of the expression pattern of miRNAs could be involved in the early retinal damage of diabetic subjects.

Curcumin prevents high glucose damage in retinal pigment epithelial cells through ERK1/2-mediated activation of the Nrf2/HO-1 pathway.

To study the effects of curcumin on human retinal pigment epithelial (RPE) cells exposed to high glucose (HG) insult, we performed in vitro studies on RPE cells cultured both in normal and HG conditions to assess the effects of curcumin on the cell viability, nuclear factor erythroid 2-related factor 2 (Nrf2) expression, HO-1 activity, and ERK1/2 expression. RPE cells exposed to HG insult were treated with curcumin. The cell viability, apoptosis, HO-1 activity, ERK, and Nrf2 expression were evaluated.

ARPE-19-derived VEGF-containing exosomes promote neovascularization in HUVEC: the role of the melanocortin receptor 5.

ARPE-19 retinal pigment epithelial cells cultured in a medium containing 35 mM D-glucose led to an augmented ROS formation and release of vascular endothelial factor (VEGF)-containing exosomes compared to ARPE-19 cells cultured in a medium containing 5 mM D-glucose (standard medium). Exposing these cells to the melanocortin 5 receptor agonist (MCR) PG-901 (10M), for 9 d reduced ROS generation, the number of exosomes released and their VEGF content. In contrast, incubating the cells with the melanocortin receptor MCR agonist BMS-470539 (10 M) or with the mixed MCR agonist MTII (0.

The activation of retinal HCA2 receptors by systemic beta-hydroxybutyrate inhibits diabetic retinal damage through reduction of endoplasmic reticulum stress and the NLRP3 inflammasome.

Objective: The role of the hydroxycarboxylic acid receptor 2 (HCA2) in the retinal damage induced by diabetes has never been explored. In this context, the present study highlights an upregulation of retinal HCA2 receptors in diabetic C57BL6J mice. Moreover, we illustrate that HCA2 receptors exert an anti-inflammatory effect on the retinal damage induced by diabetes when activated by the endogenous ligand β-hydroxybutyrate.

The Melanocortin MC5R as a New Target for Treatment of High Glucose-Induced Hypertrophy of the Cardiac H9c2 Cells.

The study explored the anti-hypertrophic effect of the melanocortin MC5R stimulation in H9c2 cardiac myocytes exposed to high glucose. This has been done by using α-MSH and selective MC5R agonists and assessing the expression of GLUT4 and GLUT1 transporters, miR-133 and urotensin receptor levels as a marker of cardiac hypertrophy. The study shows for the first time an up-regulation of MC5R expression levels in H9c2 cardiomyocytes exposed to high glucose medium (33 mM D-glucose) for 48 h, compared to cells grown in normal glucose medium (5.

Structural insight into the optimization of ethyl 5-hydroxybenzo[g]indol-3-carboxylates and their bioisosteric analogues as 5-LO/m-PGES-1 dual inhibitors able to suppress inflammation.

The release of pro-inflammatory mediators, such as prostaglandines (PGs) and leukotrienes (LTs), arising from the arachidonic acid (AA) cascade, play a crucial role in initiating, maintaining, and regulating inflammatory processes. New dual inhibitors of 5-lipoxygenase (5-LO) and microsomal prostaglandin E synthase-1 (mPGES-1), that block, at the same time, the formation of PGE and LTs, are currently emerged as a highly interesting drug candidates for better pharmacotherapie of inflammation-related disorders. Following our previous studies, we here performed a detailed structure-based design of benzo[g]indol-3-carboxylate derivatives, disclosing several new key factors that affect both enzyme activity.

Intraperitoneal Administration of Oxygen/Ozone to Rats Reduces the Pancreatic Damage Induced by Streptozotocin.

The rat model of streptozotocin (STZ)-induced pancreatic damage was used to examine whether a systemic oxygen/ozone mixture could be beneficial for the pancreas by reducing the machinery of the local detrimental mediators released by STZ. The results showed that oxygen/ozone administration (150 µg/Kg i.p.

High Levels of Serum Ubiquitin and Proteasome in a Case of HLA-B27 Uveitis.

In this paper, the authors describe a case of high serum levels of ubiquitin and proteasome in a woman under an acute attack of autoimmune uveitis. The woman was 52 years old, diagnosed as positive for the Human leukocyte antigen-B27 gene, and came to our observation in January 2013 claiming a severe uveitis attack that involved the right eye. During the acute attack of uveitis, this woman had normal serum biochemical parameters but higher levels of serum ubiquitin and proteasome 20S subunit, with respect to a healthy volunteer matched for age and sex.

Melanocortin receptor agonists MCR protect photoreceptors from high-glucose damage and restore antioxidant enzymes in primary retinal cell culture.

Retinal photoreceptors are particularly vulnerable to local high-glucose concentrations. Oxidative stress is a risk factor for diabetic retinopathy development. Melanocortin receptors represent a family of G-protein-coupled receptors classified in five subtypes and are expressed in retina.