ABSTRACT
An analogy with our previously published theory on the ionospheric auroral gyroscope provides a new perspective in human eye optics. Based on cone cells' real distribution, we model the human eye macula as a pseudospherical surface. This allows the rigorous description of the photoreceptor cell densities in the parafoveal zones modeled further by an optimized paving method. The hexagonal photoreceptors' distribution has been optimally projected on the elliptical pseudosphere, thus designing a prosthetic array counting almost 7000 pixel points. Thanks to the high morphological similarities to a normal human retina, the visual prosthesis performance in camera-free systems might be significantly improved.
Subject(s)
Macula Lutea/physiology , Retina/physiology , Retinal Cone Photoreceptor Cells/physiology , Humans , Models, Anatomic , Models, Theoretical , Movement , Photoreceptor Cells/cytology , Prosthesis Design , Prosthesis Implantation/methods , Retinal Diseases/surgery , Vision, Ocular , Visual ProsthesisABSTRACT
The number of colon cancer cases is increasing worldwide, and type II diabetes patients have an increased risk of developing colon cancer. Diet-borne advanced glycation end-products (AGEs) may promote neoplastic transformation; however, the mechanisms involved remain elusive. The present study helped to define the relationship between dietary AGEs and cancer progression. C2BBe1 adenocarcinoma enterocytes were exposed to 200 µg/mL glycated casein (AGEs-Csn) for up to 24 h. AGEs-Csn exposure resulted in increased cell proliferation, maladaptative changes in SOD and CAT activity and moderate levels of hydrogen peroxide (H2O2) intracellular accumulation. AGEs-Csn activated pro-survival and proliferation signalling, such as the phosphorylation of mTOR (Ser2448) and Akt (Ser473). GSK-3ß phosphorylation also increased, potentially inducing extracellular matrix remodelling and thus enabling metastasis. Moreover, AGEs-Csn induced MMP-1, -3, -7, -9 and -10 expression and activated MMP-2 and MMP-9, which are regulators of the extracellular matrix and cytokine functions. AGEs-Csn induced inflammatory responses that included extracellular IL-1ß at 6 h; time-dependent increases in IL-8; RAGE and NF-κB p65 upregulation; and IκB inhibition. Co-treatment with anti-RAGE or anti-TNF-α blocking antibodies and AGEs-Csn partially counteracted these changes; however, IL-8, MMP-1 and -10 expression and MMP-9 activation were difficult to prevent. AGEs-Csn perpetuated signalling that led to cell proliferation and matrix remodelling, strengthening the link between AGEs and colorectal cancer aggressiveness.
Subject(s)
Caseins/pharmacology , Enterocytes/drug effects , Gene Expression Regulation, Neoplastic , Glycation End Products, Advanced/pharmacology , Adenocarcinoma/etiology , Adenocarcinoma/genetics , Adenocarcinoma/metabolism , Adenocarcinoma/pathology , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , Caseins/chemistry , Catalase/genetics , Catalase/metabolism , Cell Line, Tumor , Colonic Neoplasms/etiology , Colonic Neoplasms/genetics , Colonic Neoplasms/metabolism , Colonic Neoplasms/pathology , Enterocytes/metabolism , Enterocytes/pathology , Extracellular Matrix/drug effects , Extracellular Matrix/metabolism , Glycogen Synthase Kinase 3 beta/genetics , Glycogen Synthase Kinase 3 beta/metabolism , Glycosylation , Humans , I-kappa B Proteins/genetics , I-kappa B Proteins/metabolism , Interleukin-1beta/genetics , Interleukin-1beta/metabolism , Interleukin-8/genetics , Interleukin-8/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/genetics , Matrix Metalloproteinase 9/metabolism , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , Models, Biological , NF-kappa B/genetics , NF-kappa B/metabolism , Phosphorylation , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Signal Transduction , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolism , TOR Serine-Threonine Kinases/genetics , TOR Serine-Threonine Kinases/metabolismABSTRACT
Dairy technology used to produce sweetened milk products might introduce additional advanced glycation end products (AGEs) into the diet. These molecular messengers are linked to detrimental health effects. Using a model accurate to the thermal treatment, reducing sugars, main protein content, and prolonged storage of ultra-high-temperature-sterilized (UHT) milk, we studied the behaviour of milk proteins during glycation. Two-dimensional electrophoresis (2-DE) profiles and western blots of glycated total casein revealed the major contributions of αs2-casein and ß-casein and the relatively minor contributions of κ-casein towards the formation of Nε-carboxymethyllysine (CML)-positive aggregates. Glycated κ-casein had the lowest furosine (FUR), 5-hydroxymethylfurfural (HMF) and AGEs content. Conversely, the α-casein fraction demonstrated a high susceptibility to glycation, having the highest FUR, HMF and AGE levels. The gel-filtration elution profiles and the corresponding fraction fluorescence revealed that glycated casein aggregates were highly fluorescent, while the ß-lactoglobulin glycation profile was similar to that of bovine serum albumin, and fluorescence was detected mainly in tetramers. Although CML is not a cross-linking AGE, it was only detected in large molecular aggregates and not in glycated monomers. Our results also indicate that in casein, glycation-induced changes in the UHT conditions were less deleterious than the subsequent 90 day storage period.
