Hypoxia-Induced Inflammation in In Vitro Model of Human Blood-Brain Barrier: Modulatory Effects of the Olfactory Ensheathing Cell-Conditioned Medium.

Hypoxia compromises the integrity of the blood-brain barrier (BBB) and increases its permeability, thereby inducing inflammation. Olfactory ensheathing cells (OECs) garnered considerable interest due to their neuroregenerative and anti-inflammatory properties. Here, we aimed to investigate the potential modulatory effects of OEC-conditioned medium (OEC-CM) on the response of human brain microvascular endothelial cells (HBMECs), constituting the BBB, when exposed to hypoxia.

Solid Lipid Nanoparticles Encapsulating a Benzoxanthene Derivative in a Model of the Human Blood-Brain Barrier: Modulation of Angiogenic Parameters and Inflammation in Vascular Endothelial Growth Factor-Stimulated Angiogenesis.

Lignans, a class of secondary metabolites found in plants, along with their derivatives, exhibit diverse pharmacological activities, including antioxidant, antimicrobial, anti-inflammatory, and antiangiogenic ones. Angiogenesis, the formation of new blood vessels from pre-existing ones, is a crucial process for cancer growth and development. Several studies have elucidated the synergistic relationship between angiogenesis and inflammation in various inflammatory diseases, highlighting a correlation between inflammation and vascular endothelial growth factor (VEGF)-induced angiogenesis.

Molecular Mechanisms and Therapeutic Implications of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells in an In Vitro Model of Diabetic Retinopathy.

The blood-retinal barrier (BRB) is strongly compromised in diabetic retinopathy (DR) due to the detachment of pericytes (PCs) from retinal microvessels, resulting in increased permeability and impairment of the BRB. Western blots, immunofluorescence and ELISA were performed on adipose mesenchymal stem cells (ASCs) and pericyte-like (P)-ASCs by co-cultured human retinal endothelial cells (HRECs) under hyperglycemic conditions (HG), as a model of DR. Our results demonstrated that: (a) platelet-derived growth factor receptor (PDGFR) and its activated form were more highly expressed in monocultured P-ASCs than in ASCs, and this expression increased when co-cultured with HRECs under high glucose conditions (HG); (b) the transcription factor Nrf2 was more expressed in the cytoplasmic fraction of ASCs and in the P-ASC nuclear fraction, under normal glucose and, even more, under HG conditions; (c) cytosolic phospholipase A activity and prostaglandin E2 release, stimulated by HG, were significantly reduced in P-ASCs co-cultured with HRECs; (d) HO-1 protein content was significantly higher in HG-P-ASCs/HRECs than P-ASCs/HRECs; and (e) VEGF-A levels in media from HG-co-cultures were reduced in P-ASCs/HRECs with respect to ASCs/HRECs.

Polyphenols in Inner Ear Neurobiology, Health and Disease: From Bench to Clinics.

There is substantial experimental and clinical interest in providing effective ways to both prevent and slow the onset of hearing loss. Auditory hair cells, which occur along the basilar membrane of the cochlea, often lose functionality due to age-related biological alterations, as well as from exposure to high decibel sounds affecting a diminished/damaged auditory sensitivity. Hearing loss is also seen to take place due to neuronal degeneration before or following hair cell destruction/loss.

[Corrigendum] Melanogenesis in uveal melanoma cells: Effect of argan oil.

Following the publication of the above article, an interested reader drew to the authors' attention that, in Fig. 7 on p. 1282, a pair of the western blotting bands in the Akt blot positioned adjacent to each other looked strikingly similar.

Antioxidants, Hormetic Nutrition, and Autism.

Autism spectrum disorder (ASD) includes a heterogeneous group of complex neurodevelopmental disorders characterized by atypical behaviors with two core pathological manifestations: deficits in social interaction/communication and repetitive behaviors, which are associated with disturbed redox homeostasis. Modulation of cellular resilience mechanisms induced by low levels of stressors represents a novel approach for the development of therapeutic strategies, and in this context, neuroprotective effects of a wide range of polyphenol compounds have been demonstrated in several in vitro and in vivo studies and thoroughly reviewed. Mushrooms have been used in traditional medicine for many years and have been associated with a long list of therapeutic properties, including antitumor, immunomodulatory, antioxidant, antiviral, antibacterial, and hepatoprotective effects.

Blood-Labyrinth Barrier in Health and Diseases: Effect of Hormetic Nutrients.

The stria vascularis, located in the inner ear, consists of three layers, one of which is the blood-labyrinth barrier (BLB). It is formed by endothelial cells, sealed together to prevent the passage of toxic substances from the blood to the inner ear, by pericytes and perivascular-resident macrophage-like melanocyte. There are various causes that lead to hearing loss, and among these are noise-induced and autoimmune hearing loss, ear disorders related to ototoxic medication, Ménière's disease, and age-related hearing loss.

Protective Effects of Human Pericyte-like Adipose-Derived Mesenchymal Stem Cells on Human Retinal Endothelial Cells in an In Vitro Model of Diabetic Retinopathy: Evidence for Autologous Cell Therapy.

Diabetic retinopathy (DR) is characterized by morphologic and metabolic alterations in endothelial cells (ECs) and pericytes (PCs) of the blood-retinal barrier (BRB). The loss of interendothelial junctions, increased vascular permeability, microaneurysms, and finally, EC detachment are the main features of DR. In this scenario, a pivotal role is played by the extensive loss of PCs.

Pericytes of Stria Vascularis Are Targets of Cisplatin-Induced Ototoxicity: New Insights into the Molecular Mechanisms Involved in Blood-Labyrinth Barrier Breakdown.

The stria vascularis (SV) contributes to cochlear homeostasis and consists of three layers, one of which contains the blood-labyrinthic barrier (BLB), with a large number of bovine cochlear pericytes (BCPs). Cisplatin is a chemotherapeutic drug that can damage the SV and cause hearing loss. In this study, cell viability, proliferation rate, cytotoxicity and reactive oxygen species production were evaluated.

Antioxidant Activity of Cyanidin-3-O-Glucoside and Verbascoside in an Model of Diabetic Retinopathy.

Background: Reactive oxygen species (ROS) accumulation plays a pivotal role in the onset of cell damage induced by hyperglycemia and represents one of the major factors in the pathogenesis of diabetic retinopathy. In this study, we tested the antioxidants cyanidin-3-O-glucoside (C3G) and verbascoside (Verb) in the protection of retinal endothelium against glucose toxicity "".

Methods: Increasing amounts (5-50 μM) of C3G, Verb or the combination of both compounds were tested in Human Retinal Endothelial Cells (HREC) grown with normal glucose (5 mM, NG) or high glucose (25 mM, HG).

Melatonin loaded hybrid nanomedicine: DoE approach, optimization and in vitro study on diabetic retinopathy model.

Melatonin (MEL) is a pleiotropic neurohormone of increasing interest as a neuroprotective agent in ocular diseases. Improving the mucoadhesiveness is a proposed strategy to increase the bioavailability of topical formulations. Herein, the design and optimization of MEL-loaded lipid-polymer hybrid nanoparticles (mel-LPHNs) using Design of Experiment (DoE) was performed.

Vitamin D preserves blood retinal barrier integrity in an model of diabetic retinopathy.

The impairment of the blood retinal barrier (BRB) represents one of the main features of diabetic retinopathy, a secondary microvascular complication of diabetes. Hyperglycemia is a triggering factor of vascular cells damage in diabetic retinopathy. The aim of this study was to assess the effects of vitamin D on BRB protection, and to investigate its regulatory role on inflammatory pathways.

The Anti-Inflammatory Effect of the β1-Adrenergic Receptor Antagonist Metoprolol on High Glucose Treated Human Microvascular Retinal Endothelial Cells.

Hyperglycemia-induced impairment of the blood-retinal barrier represents the main pathological event in diabetic retinopathy that is elicited by a reduced cellular response to an accumulation of reactive oxygen species (ROS) and increased inflammation. The purpose of the study was to evaluate whether the selective β1-adrenoreceptor (β1-AR) antagonist metoprolol could modulate the inflammatory response to hyperglycemic conditions. For this purpose, human retinal endothelial cells (HREC) were treated with normal (5 mM) or high glucose (25 mM, HG) in the presence of metoprolol (10 μM), epinephrine (1 μM), or both compounds.

Haloperidol Metabolite II Valproate Ester ()-(-)-MRJF22: Preliminary Studies as a Potential Multifunctional Agent Against Uveal Melanoma.

Increased angiogenesis and vascular endothelial growth factor (VEGF) levels contribute to higher metastasis and mortality in uveal melanoma (UM), an aggressive malignancy of the eye in adults. , a prodrug of the sigma (σ) ligand haloperidol metabolite II conjugated with the histone deacetylase (HDAC) inhibitor valproic acid, has previously demonstrated a promising antiangiogenic activity. Herein, the asymmetric synthesis of and was performed to investigate their contribution to antiangiogenic effects in human retinal endothelial cells (HREC) and to assess their therapeutic potential in primary human uveal melanoma (UM) 92-1 cell line.

Potential therapeutic applications of mesenchymal stem cells for the treatment of eye diseases.

Stem cell-based treatments have been extensively explored in the last few decades to develop therapeutic strategies aimed at providing effective alternatives for those human pathologies in which surgical or pharmacological therapies produce limited effects. Among stem cells of different sources, mesenchymal stem cells (MSCs) offer several advantages, such as the absence of ethical concerns, easy harvesting, low immunogenicity and reduced tumorigenesis risks. Other than a multipotent differentiation ability, MSCs can release extracellular vesicles conveying proteins, mRNA and microRNA.

Glucose-impaired Corneal Re-epithelialization Is Promoted by a Novel Derivate of Dimethyl Fumarate.

Glucose induces corneal epithelial dysfunctions characterized by delayed wound repair. Nuclear erythroid 2-related factor 2 (Nrf2) mediates cell protection mechanisms even through the Heme oxygenase-1 (HO-1) up-regulation. Here, we synthesized new HO-1 inducers by modifying dimethyl fumarate (DMF) and used docking studies to select VP13/126 as a promising compound with the best binding energy to Kelch-like ECH-associated protein 1 (keap1), which is the the regulator of Nrf2 nuclear translocation.

Ferulic Acid-Loaded Polymeric Nanoparticles for Potential Ocular Delivery.

Ferulic acid (FA) is an antioxidant compound that can prevent ROS-related diseases, but due to its poor solubility, therapeutic efficacy is limited. One strategy to improve the bioavailability is nanomedicine. In the following study, FA delivery through polymeric nanoparticles (NPs) consisting of polylactic acid (NPA) and poly(lactic-co-glycolic acid) (NPB) is proposed.

Effects of High Glucose Concentration on Pericyte-Like Differentiated Human Adipose-Derived Mesenchymal Stem Cells.

A pericyte-like differentiation of human adipose-derived mesenchymal stem cells (ASCs) was tested in in vitro experiments for possible therapeutic applications in cases of diabetic retinopathy (DR) to replace irreversibly lost pericytes. For this purpose, pericyte-like ASCs were obtained after their growth in a specific pericyte medium. They were then cultured in high glucose conditions to mimic the altered microenvironment of a diabetic eye.

The GAUGAA Motif Is Responsible for the Binding between circSMARCA5 and SRSF1 and Related Downstream Effects on Glioblastoma Multiforme Cell Migration and Angiogenic Potential.

Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1.

Poly 2-methacryloyloxyethyl Phosphorylcholine Protects Corneal Cells and Contact Lenses from Desiccation Damage.

Significance: Contact lens (CL) wearing may cause discomfort and eye dryness. We describe here the efficacy of a synthetic polymer in protecting both the corneal epithelial cells and the CL from desiccation damage. Artificial tears containing this polymer might be helpful to treat or prevent ocular surface damage in CL wearers.

The double effect of walnut septum extract (Juglans regia L.) counteracts A172 glioblastoma cell survival and bacterial growth.

Walnut (Juglans regia L.) is considered to be a 'superfood' for its multiple protective actions on human health. Walnut extracts have proven antitumor activity in different cancer cell lines.

Activation of the VEGF-A/ERK/PLA2 Axis Mediates Early Retinal Endothelial Cell Damage Induced by High Glucose: New Insight from an In Vitro Model of Diabetic Retinopathy.

Early blood retinal barrier (BRB) dysfunction induced by hyperglycemia was related to increased pro-inflammatory activity of phospholipase A2 (PLA2) and the upregulation of vascular endothelial growth factor A (VEGF-A). Here, we tested the role of VEGF-A in high glucose (HG)-induced damage of human retinal endothelial cells (HRECs) mediated by Ca++-dependent (cPLA2) and Ca++-independent (iPLA2) PLA2s. HRECs were treated with normal glucose (5 mM, NG) or high glucose (25 mM, HG) for 48 h with or without the VEGF-trap Aflibercept (Afl, 40 µg/mL), the cPLA2 inhibitor arachidonoyl trifluoromethyl ketone (AACOCF3; 15 µM), the iPLA2 inhibitor bromoenol lactone (BEL; 5 µM), or VEGF-A (80 ng/mL).

Anti-Angiogenic and Anti-Proliferative Graphene Oxide Nanosheets for Tumor Cell Therapy.

Graphene oxide (GO) is a bidimensional novel material that exhibits high biocompatibility and angiogenic properties, mostly related to the intracellular formation of reactive oxygen species (ROS). In this work, we set up an experimental methodology for the fabrication of GO@peptide hybrids by the immobilization, via irreversible physical adsorption, of the Ac-(GHHPH)-NH peptide sequence, known to mimic the anti-angiogenic domain of the histidine-proline-rich glycoprotein (HPRG). The anti-proliferative capability of the graphene-peptide hybrids were tested in vitro by viability assays on prostate cancer cells (PC-3 line), human neuroblastoma (SH-SY5Y), and human retinal endothelial cells (primary HREC).

Uveal Melanoma Cells Elicit Retinal Pericyte Phenotypical and Biochemical Changes in an in Vitro Model of Coculture.

Vascular pericytes are an important cellular component in the tumor microenvironment, however, their role in supporting cancer invasion is poorly understood. We hypothesized that PDGF-BB could be involved in the transition of human retinal pericytes (HRPC) in cancer-activated fibroblasts (CAF), induced by the 92.1 uveal melanoma (UM) cell line.

Isolation and Characterization of a New Human Corneal Epithelial Cell Line: HCE-F.

Purpose: To isolate and characterize an epithelial cell (EC) line from a human donor cornea, which may serve as a reliable test cell line to address biomolecular issues and study the response of corneal epithelium to stressing events and therapeutic treatments.

Methods: A corneal button from a donor patient was treated with enzymes to separate the epithelial sheet and to free EC, which were put in tissue culture. ECs were characterized by optic and electronic microscopies, cytokeratins and PAX6 were detected by SDS-PAGE and western immunoblotting, the barrier function was evaluated by transepithelial electric resistance and by the immune detection of membrane junction proteins, and the karyotype was characterized according to the classical methods.