Targeting epidermal growth factor receptor to recruit newly generated neuroblasts in cortical brain injuries.

Background: Neurogenesis is stimulated in the subventricular zone (SVZ) of mice with cortical brain injuries. In most of these injuries, newly generated neuroblasts attempt to migrate toward the injury, accumulating within the corpus callosum not reaching the perilesional area.

Methods: We use a murine model of mechanical cortical brain injury, in which we perform unilateral cortical injuries in the primary motor cortex of adult male mice.

From Cell to Symptoms: The Role of SARS-CoV-2 Cytopathic Effects in the Pathogenesis of COVID-19 and Long COVID.

Severe Acute Respiratory Syndrome CoronaVirus 2 (SARS-CoV-2) infection triggers various events from molecular to tissue level, which in turn is given by the intrinsic characteristics of each patient. Given the molecular diversity characteristic of each cellular phenotype, the possible cytopathic, tissue and clinical effects are difficult to predict, which determines the heterogeneity of COVID-19 symptoms. The purpose of this article is to provide a comprehensive review of the cytopathic effects of SARS-CoV-2 on various cell types, focusing on the development of COVID-19, which in turn may lead, in some patients, to a persistence of symptoms after recovery from the disease, a condition known as long COVID.

Specific Activation of T Cells by an ACE2-Based CAR-Like Receptor upon Recognition of SARS-CoV-2 Spike Protein.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is the causative agent of the Coronavirus Disease 2019 (COVID-19) pandemic, which is still a health issue worldwide mostly due to a high rate of contagiousness conferred by the high-affinity binding between cell viral receptors, Angiotensin-Converting Enzyme 2 (ACE2) and SARS-CoV-2 Spike protein. Therapies have been developed that rely on the use of antibodies or the induction of their production (vaccination), but despite vaccination being still largely protective, the efficacy of antibody-based therapies wanes with the advent of new viral variants. Chimeric Antigen Receptor (CAR) therapy has shown promise for tumors and has also been proposed for COVID-19 treatment, but as recognition of CARs still relies on antibody-derived sequences, they will still be hampered by the high evasion capacity of the virus.

Systematic Review and Meta-Analyses of Aminopeptidases as Prognostic Biomarkers in Amyotrophic Lateral Sclerosis.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease characterized by the progressive loss of motor neurons in the spinal cord, brain stem, and cerebral cortex. Biomarkers for ALS are essential for disease detection and to provide information on potential therapeutic targets. Aminopeptidases catalyze the cleavage of amino acids from the amino terminus of protein or substrates such as neuropeptides.

Polyphosphate Activates von Willebrand Factor Interaction with Glycoprotein Ib in the Absence of Factor VIII In Vitro.

Polyphosphate (polyP), a phosphate polymer released by activated platelets, may modulate various stages of hemostasis by binding to blood proteins. In this context, we previously reported that polyP binds to the von Willebrand factor (VWF). One of the most significant functions of VWF is to bind to and protect the blood circulating Factor VIII (FVIII).

In Silico Evaluation of Sesquiterpenes and Benzoxazinoids Phytotoxins against M, RNA Replicase and Spike Protein of SARS-CoV-2 by Molecular Dynamics. Inspired by Nature.

In the work described here, a number of sesquiterpenes and benzoxazinoids from natural sources, along with their easily accessible derivatives, were evaluated against the main protease, RNA replicase and spike glycoprotein of SARS-CoV-2 by molecular docking. These natural products and their derivatives have previously shown remarkable antiviral activities. The most relevant compounds were the 4-fluoro derivatives of santamarine, reynosin and 2-amino-3-phenoxazin-3-one in terms of the docking score.

Therapeutic Approach to Alzheimer's Disease: Current Treatments and New Perspectives.

Alzheimer's disease (AD) is the most common cause of dementia. The pathophysiology of this disease is characterized by the accumulation of amyloid-β, leading to the formation of senile plaques, and by the intracellular presence of neurofibrillary tangles based on hyperphosphorylated tau protein. In the therapeutic approach to AD, we can identify three important fronts: the approved drugs currently available for the treatment of the disease, which include aducanumab, donepezil, galantamine, rivastigmine, memantine, and a combination of memantine and donepezil; therapies under investigation that work mainly on Aβ pathology and tau pathology, and which include γ-secretase inhibitors, β-secretase inhibitors, α-secretase modulators, aggregation inhibitors, metal interfering drugs, drugs that enhance Aβ clearance, inhibitors of tau protein hyperphosphorylation, tau protein aggregation inhibitors, and drugs that promote the clearance of tau, and finally, other alternative therapies designed to improve lifestyle, thus contributing to the prevention of the disease.

Optical imaging spectroscopy for rapid, primary screening of SARS-CoV-2: a proof of concept.

Effective testing is essential to control the coronavirus disease 2019 (COVID-19) transmission. Here we report a-proof-of-concept study on hyperspectral image analysis in the visible and near-infrared range for primary screening at the point-of-care of SARS-CoV-2. We apply spectral feature descriptors, partial least square-discriminant analysis, and artificial intelligence to extract information from optical diffuse reflectance measurements from 5 µL fluid samples at pixel, droplet, and patient levels.

The Role of Glycosyltransferases in Colorectal Cancer.

Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Post-translational modifications (PTMs) have been extensively studied in malignancies due to its relevance in tumor pathogenesis and therapy. This review is focused on the dysregulation of glycosyltransferase expression in CRC and its impact in cell function and in several biological pathways associated with CRC pathogenesis, prognosis and therapeutic approaches.

MicroRNAs overexpressed in Crohn's disease and their interactions with mechanisms of epigenetic regulation explain novel aspects of Crohn's disease pathogenesis.

Background: In this review, we were interested to identify the wide universe of enzymes associated with epigenetic modifications, whose gene expression is regulated by miRNAs with a high relative abundance in Crohn's disease (CD) affected tissues, with the aim to determine their impact in the pathogenesis and evolution of the disease.

Methods: We used HMDD and Bibliometrix R-package in order to identify the miRNAs overexpressed in CD. The identified enzymes associated with epigenetic mechanisms and post-translational modifications, regulated by miRNAs upregulated in CD, were analyzed using String v11 database.

KIR+ CD8+ T Lymphocytes in Cancer Immunosurveillance and Patient Survival: Gene Expression Profiling.

Killer-cell immunoglobulin-like receptors (KIR) are expressed by natural killer (NK) and effector T cells. Although KIR+ T cells accumulate in oncologic patients, their role in cancer immune response remains elusive. This study explored the role of KIR+CD8+ T cells in cancer immunosurveillance by analyzing their frequency at diagnosis in the blood of 249 patients (80 melanomas, 80 bladder cancers, and 89 ovarian cancers), their relationship with overall survival (OS) of patients, and their gene expression profiles.

Increased Protein Stability and Interleukin-2 Production of a LAT Variant With Possible Implications for T Cell Anergy.

The adaptor LAT plays a crucial role in the transduction of signals coming from the TCR/CD3 complex. Phosphorylation of some of its tyrosines generates recruitment sites for other cytosolic signaling molecules. Tyrosine 132 in human LAT is essential for PLC-γ activation and calcium influx generation.

Aerobic fitness, Mediterranean diet and cardiometabolic risk factors in adults.

Introduction: Unhealthy lifestyle and inadequate diet could influence the development of future cardiometabolic disease. The main aim of this study was to determine the association between aerobic fitness and cardiometabolic risk factors in adults, whether this relation is depends of adherence to Mediterranean diet (MD). A secondary aim was to study the combined effect of aerobic capacity and adherence to MD on global cardiometabolic risk score (CMRS).

Influence of size and surface capping on photoluminescence and cytotoxicity of gold nanoparticles.

Hydrophilic and homogeneous sub-10 nm blue light-emitting gold nanoparticles (NPs) functionalized with different capping agents have been prepared by simple chemical routes. Structure, average, size, and surface characteristics of these NPs have been widely studied, and the stability of colloidal NP solutions at different pH values has been evaluated. Au NPs show blue PL emission, particularly in the GSH capped NPs, in which the thiol-metal core transference transitions considerably enhance the fluorescent emission.

Specific inhibition of ADAM17/TACE promotes neurogenesis in the injured motor cortex.

Brain injuries in the adult mammalian brain are accompanied by a fast neurogenic response inside neurogenic niches. However, this response does not contribute to the generation of new neurons within damaged tissues like the cerebral cortex, which are essentially non-neurogenic. This occurs because injuries create a hostile environment that favors gliogenesis.

A Stretch of Negatively Charged Amino Acids of Linker for Activation of T-Cell Adaptor Has a Dual Role in T-Cell Antigen Receptor Intracellular Signaling.

The adaptor protein linker for activation of T cells (LAT) has an essential role transducing activatory intracellular signals coming from the TCR/CD3 complex. Previous reports have shown that upon T-cell activation, LAT interacts with the tyrosine kinase Lck, leading to the inhibition of its kinase activity. LAT-Lck interaction seemed to depend on a stretch of negatively charged amino acids in LAT.

Ultrastructural Localization and Molecular Associations of HCV Capsid Protein in Jurkat T Cells.

Hepatitis C virus core protein is a highly basic viral protein that multimerizes with itself to form the viral capsid. When expressed in CD4 T lymphocytes, it can induce modifications in several essential cellular and biological networks. To shed light on the mechanisms underlying the alterations caused by the viral protein, we have analyzed HCV-core subcellular localization and its associations with host proteins in Jurkat T cells.

The atheroma plaque secretome stimulates the mobilization of endothelial progenitor cells ex vivo.

Endothelial progenitor cells (EPCs) constitute a promising alternative in cardiovascular regenerative medicine due to their assigned role in angiogenesis and vascular repair. In response to injury, EPCs promote vascular remodeling by replacement of damaged endothelial cells and/or by secreting angiogenic factors over the damaged tissue. Nevertheless, such mechanisms need to be further characterized.

Sensitivity of dendritic cells to NK-mediated lysis depends on the inflammatory environment and is modulated by CD54/CD226-driven interactions.

Previous studies have suggested that NK cells may limit T cell responses by their ability to eradicate dendritic cells, as demonstrated by NK cell-mediated killing of dendritic cells generated from mouse bone marrow cells or human monocytes with GM-CSF. In the present study, we demonstrated that conventional dendritic cells, generated in vitro with Flt3 ligand or from spleens, were resistant to NK cell-mediated lysis. However, upon stimulation with GM-CSF, NK cells could mediate lysis of these dendritic cells.

Non-T cell activation linker (NTAL) proteolytic cleavage as a terminator of activatory intracellular signals.

Non-T cell activation linker is an adaptor protein that is tyrosine phosphorylated upon cross-linking of immune receptors expressed on B lymphocytes, NK cells, macrophages, basophils, or mast cells, allowing the recruitment of cytosolic mediators for downstream signaling pathways. Fas receptor acts mainly as a death receptor, and when cross-linked with Fas ligand, many proteins are proteolytically cleaved, including several signaling molecules in T and B cells. Fas receptor triggering also interferes with TCR intracellular signals, probably by means of proteolytic cleavage of several adaptor proteins.

N-glycosylation profile analysis of Trastuzumab biosimilar candidates by Normal Phase Liquid Chromatography and MALDI-TOF MS approaches.

Unlabelled: The pharmaceutical market has entered an era in which the production of new therapeutics is being often replaced by "biosimilars", copies of already commercialized products waiting for the patents to expire in order to be distributed in a more competitive and affordable manners. Due to its relevance, the ErbB2-targeted monoclonal antibody Trastuzumab (Herceptin) used as breast cancer therapy is one of the main targets in the production of biosimilars. A major challenge is to produce antibodies with the same or the closest N-glycosylation pattern seen in the commercialized drug.

[Diet and exercise influence on the proteomic profile of an athlete population].

Introduction: Nutrition has emerged as a fundamental tool included in the training program of athletes. Body composition seeks different objectives depending on type of sport, position, or time of the season. Furthermore, analysis proteomics allows us to know the structure and function of proteins.

CD4+ primary T cells expressing HCV-core protein upregulate Foxp3 and IL-10, suppressing CD4 and CD8 T cells.

Adaptive T cell responses are critical for controlling HCV infection. While there is clinical evidence of a relevant role for regulatory T cells in chronic HCV-infected patients, based on their increased number and function; mechanisms underlying such a phenomena are still poorly understood. Accumulating evidence suggests that proteins from Hepatitis C virus can suppress host immune responses.