RESVEGA,a Nutraceutical Omega-3/Resveratrol Supplementation,Reduces Angiogenesis in a Preclinical Mouse Model of Choroidal Neovascularization

Age-related macular degeneration (AMD) is an eye disease that is characterized by damage to the central part of the retina, the macula, and that affects millions of people worldwide. At an advanced stage, a blind spot grows in the center of vision, severely handicapping patients with this degenerative condition. Despite therapeutic advances thanks to the use of anti-VEGF, many resistance mechanisms have been found to accentuate the visual deficit. In the present study, we explored whether supplementation with Resvega^®, a nutraceutical formulation composed of omega-3 fatty acids and resveratrol, a well-known polyphenol in grapes, was able to counteract laser-induced choroidal neovascularization (CNV) in mice. We highlight that Resvega^® significantly reduced CNV in mice compared with supplementations containing omega-3 or resveratrol alone. Moreover, a proteomic approach confirmed that Resvega^® could counteract the progression of AMD through a pleiotropic effect targeting key regulators of neoangiogenesis in retina cells in vivo. These events were associated with an accumulation of resveratrol metabolites within the retina. Therefore, a supplementation of omega-3/resveratrol could improve the management or slow the progression of AMD in patients with this condition.     

Tumor-Promoting Activity and Proteomic Profiling of Cisplatin/Oxaliplatin-Derived DAMPs in Cholangiocarcinoma Cells

Damage-associated molecular patterns (DAMPs) are well recognized as the molecular signature of immunogenic cell death (ICD). The efficacy of drug-induced ICD function may be impacted by the precise ratio between immunostimulatory and immunoinhibitory DAMPs. Tumor-derived DAMPs can activate tumor-expressed TLRs for the promotion of tumor cell motility, invasion, metastatic spread and resistance to chemotherapeutic treatment. Herein, drug-induced DAMPs’ expression and their role in tumor progression are utilized as one crucial point of evaluation regarding chemotherapeutic treatment efficacy in our study. Cisplatin and oxaliplatin, the conventional anticancer chemotherapy drugs, are emphasized as a cause of well-known DAMPs’ release from cholangiocarcinoma (CCA) cells (e.g., HSP family, S100, CRT and HMGB1), whereby they trigger Akt, ERK and Cyclin-D1 to promote tumor activities. These findings strengthen the evidence that DAMPs are not only involved in immunomodulation but also in tumor promotion. Therefore, DAMP molecules should be considered as either targets of cancer treatment or biomarkers to evaluate treatment efficacy and tumor recurrence.     

Proteomics of Aqueous Humor as a Source of Disease Biomarkers in Retinoblastoma

Aqueous humor (AH) can be easily and safely used to evaluate disease-specific biomarkers in ocular disease. The aim of this study was to identify specific proteins biomarkers in the AH of retinoblastoma (RB) patients at various stages of the disease. We analyzed the proteome of 53 AH samples using high-resolution mass spectrometry. We grouped the samples according to active vitreous seeding (Group 1), active aqueous seeding (Group 2), naive RB (group 3), inactive RB (group 4), and congenital cataracts as the control (Group 5). We found a total of 889 proteins in all samples. Comparative parametric analyses among the different groups revealed three additional proteins expressed in the RB groups that were not expressed in the control group. These were histone H2B type 2-E (HISTH2B2E), InaD-like protein (PATJ), and ubiquitin conjugating enzyme E2 V1 (UBE2V1). Upon processing the data of our study with the OpenTarget Tool software, we found that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and CD44 were more highly expressed in the RB groups. Our results provide a proteome database regarding AH related to RB disease that may be used as a source of biomarkers. Further prospective studies should validate our finding in a large cohort of RB patients.     

Calciprotein Particles Cause Physiologically Significant Pro-Inflammatory Response in Endothelial Cells and Systemic Circulation

Calciprotein particles (CPPs) represent an inherent mineral buffering system responsible for the scavenging of excessive Ca²⁺ and PO₄³⁻ ions in order to prevent extraskeletal calcification, although contributing to the development of endothelial dysfunction during the circulation in the bloodstream. Here, we performed label-free proteomic profiling to identify the functional consequences of CPP internalisation by endothelial cells (ECs) and found molecular signatures of significant disturbances in mitochondrial and lysosomal physiology, including oxidative stress, vacuolar acidification, accelerated proteolysis, Ca²⁺ cytosolic elevation, and mitochondrial outer membrane permeabilisation. Incubation of intact ECs with conditioned medium from CPP-treated ECs caused their pro-inflammatory activation manifested by vascular cell adhesion molecule 1 (VCAM1) and intercellular adhesion molecule 1 (ICAM1) upregulation and elevated release of interleukin (IL)-6, IL-8, and monocyte chemoattractant protein-1/ C-C motif ligand 2 (MCP-1/CCL2). Among the blood cells, monocytes were exclusively responsible for CPP internalisation. As compared to the co-incubation of donor blood with CPPs in the flow culture system, intravenous administration of CPPs to Wistar rats caused a considerably higher production of chemokines, indicating the major role of monocytes in CPP-triggered inflammation. Upregulation of sICAM-1 and IL-8 also suggested a notable contribution of endothelial dysfunction to systemic inflammatory response after CPP injections. Collectively, our results demonstrate the pathophysiological significance of CPPs and highlight the need for the development of anti-CPP therapies.     

Proteomics in neurosciences

This review provides an outline of the most important proteomic applications in the study of neurodegenerative disorders including Alzheimer's (AD), Parkinson's (PD), Huntington's (HD), and prion diseases, and also discusses advances in cancer and addiction. One of the scopes is to illustrate the potential of proteomics in the biomarkers discovery of these diseases. Finally, this article comments the advantages and drawbacks of the most commonly used techniques and methods for samples preparation.     

Proteomic identification and physicochemical characterisation of paramyosin and collagen from octopus (Octopus vulgaris) and jumbo squid (Dosidicus gigas)

To perform improvements in food science, it is fundamental to understand the physicochemical properties of proteins since their interaction with other macromolecules plays an essential role in food systems. Collagen and paramyosin help in the maintenance of the matrix structure cells, the textural behaviour and the technical functionality of the protein concentrates; because of this, their identification and characterisation are necessary. Cephalopods species have shown differences in the distribution of its muscle fibres. The amino acid profile of jumbo squid showed a high content of glycine and hydroxyproline, while octopus showed a high content of acidic amino acids. The thermal profile of jumbo squid showed an endothermic transition at 117 °C, which octopus did not present. Moreover, the proteomic identification confirms the identity of paramyosin with 33% coverage to paramyosin from Dosidicus gigas and a 4% coverage to collagen type II from Sepia pharaonis on octopus and jumbo squid, respectively.     

A Proteomic Study Suggests Stress Granules as New Potential Actors in Radiation-Induced Bystander Effects

Besides the direct effects of radiations, indirect effects are observed within the surrounding non-irradiated area; irradiated cells relay stress signals in this close proximity, inducing the so-called radiation-induced bystander effect. These signals received by neighboring unirradiated cells induce specific responses similar with those of direct irradiated cells. To understand the cellular response of bystander cells, we performed a 2D gel-based proteomic study of the chondrocytes receiving the conditioned medium of low-dose irradiated chondrosarcoma cells. The conditioned medium was directly analyzed by mass spectrometry in order to identify candidate bystander factors involved in the signal transmission. The proteomic analysis of the bystander chondrocytes highlighted 20 proteins spots that were significantly modified at low dose, implicating several cellular mechanisms, such as oxidative stress responses, cellular motility, and exosomes pathways. In addition, the secretomic analysis revealed that the abundance of 40 proteins in the conditioned medium of 0.1 Gy irradiated chondrosarcoma cells was significantly modified, as compared with the conditioned medium of non-irradiated cells. A large cluster of proteins involved in stress granules and several proteins involved in the cellular response to DNA damage stimuli were increased in the 0.1 Gy condition. Several of these candidates and cellular mechanisms were confirmed by functional analysis, such as 8-oxodG quantification, western blot, and wound-healing migration tests. Taken together, these results shed new lights on the complexity of the radiation-induced bystander effects and the large variety of the cellular and molecular mechanisms involved, including the identification of a new potential actor, namely the stress granules.