Structural analysis of peptide binding to integrins for cancer detection and treatment.

Integrins are cell receptors involved in several metabolic pathways often associated with cell proliferation. Some of these integrins are downregulated during human physical development, but when these integrins are overexpressed in adult humans, they can be associated with several diseases, such as cancer. Molecules that specifically bind to these integrins are useful for cancer detection, diagnosis, and treatment. This review focuses on the structures of integrin-peptidic ligand complexes to dissect how the binding occurs and the molecular basis of the specificity and affinity of these peptidic ligands. Understanding these interactions at the molecular level is fundamental to be able to design new peptides that are more specific and more sensitive to a particular integrin. The integrin complexes covered in this review are α5ß1, αIIbß3, αvß3, αvß6, and αvß8, because the molecular structures of the complex have been experimentally determined and their presence on tumor cancer cells are associated with a poor prognosis, making them targets for cancer detection and treatment.

Three-dimensional neuroimmune co-culture system for modeling Parkinson's disease microenvironmentsin vitro.

Parkinson's disease (PD) is a complex and multifaceted neurodegenerative disorder that results from multiple environmental factors and multicellular interactions. Although several PD neuropathologies have been identified and described, the thorough understanding of PD pathophysiology and research has been largely limited by the absence of reliablein vitromodels that truly recapitulate PD microenvironments. Here, we propose a neuroimmune co-culture system that models PD neuropathologies by combining relevant multicellular interactions with environments that mimic the brain. This system is composed of: (i) 3D bioprinted cultures of mature human dopaminergic (DA) neurons grown on extracellular matrix (ECM)-derived scaffolds doped with electroconductive nanostructures, and (ii) a direct co-culture of human astrocytes and differentiated monocytes that models neuroinflammatory responses. When co-cultured in a transwell format, these two compartments recreate relevant multicellular environments that model PD pathologies after exposure to the neurotoxin A53Tα-synuclein. With immunofluorescent staining and gene expression analyses, we show that functional and mature DA 3D networks are generated within our ECM-derived scaffolds with superior performance to standard 2D cultures. Moreover, by analyzing cytokine secretion, cell surface markers, and gene expression, we define a human monocyte differentiation scheme that allows the appearance of both monocyte-derived macrophages and dendritic cell phenotypes, as well as their optimal co-culture ratios with human astrocytes to recreate synergistic neuroinflammatory responses. We show that the combined response of both compartments to A53Tα-synuclein stimulates the formation of intracellularα-synuclein aggregates, induces progressive mitochondrial dysfunction and reactive oxygen species production, downregulates the expression of synaptic, DA, and mitophagy-related genes, and promotes the initiation of apoptotic processes within the DA networks. Most importantly, these intracellular pathologies were comparable or superior to those generated with a rotenone-stimulated 2D control that represents the current standard forin vitroPD models and showed increased resilience towards these neurotoxic insults, allowing the study of disease progression over longer time periods than current models. Taken together, these results position the proposed model as a superior alternative to current 2D models for generating PD-related pathologiesin vitro.

Correlación de la distancia recorrida en la caminata de 6 minutos y puntajes de comorbilidad Charlson y Elixhauser / Correlation of distance traveled in the 6 minute walk and Charlson and Elihauser comorbidity scores

Introduction: The walking test of 6 minutes (6MW) is a test that merges the answer of different systems (respiratory, cardiovascular, metabolic, skeletal muscle and neurosensorial) and offers an useful objective result to lead therapeutic measurements and stablish a prognosis, it's possible that the comorbid patient lowers their functional reserve and alters the result of the test not only because of the presence of pathologies cardiorespiratory, nevertheless, information about the correlation between the scores of comorbidity and the traveled distance in the 6MW is limited. Objective: Determine the correlation between the traveled distance in the 6MW and the scores of comorbidities of Charlson and Elixhauser. Methods: A cross-sectional study was made, in patients taken to the 6MW made between 2006 until March 2020, in a hospital of high complexity; there were included patients older than 18 years old, whose clinic history record and walk of 6 minutes were available. The index of Charlson and Elixhauser were calculated in the 6MW, a bivariate analysis was made between the antecedents of pathologies and the traveled distance, independently and adjusted, the spearman correlation coefficient was calculated for the different scores and the distance in meters of the 6MW, was considerate a significative p: <0,05. Results: to the final analysis 491 subjects entered, the average age was of 69 years old (sd: 14,9), 54% male, the 15,3% had an abnormal walk less than the 80% of the expected, the diseases that were considered had a statistically significant relation with the decrease of the distance in the 6MW were arterial hypertension (p: <0,001), chronic heart failure (p=0,037), heart arrhythmia (p=0,003), smoking (p=0,022), chronic pulmonary obstruction disease (p: <0,001), dementia (p=0,03diabetes mellitus with target organ damage (p=0,01), moderate to severe chronic kidney disease (p=0,012), obesity (p=0,036) y lymphoma (p=0,038 the spearman correlation coefficient between the traveled distances and Charlson was of -0,343 (IC95%:-0,420 -0,264)(p: < 0,001) and -0,213(IC95%:-0,285 -0,116)(p: <0,001) with the Elixhauser index. Conclusion: The distances walked in meters in the 6MW has a reverse low correlation with the comorbidity index, the diseases that were not cardiopulmonary and that related independently with changes in the traveled dist ance are smoking, dementia, diabetes mellitus, chronic kidney disease, obesity, and lymphoma. Key words: Comorbidities, Walk, Test, Cardiopulmonary, Charlson, Elixhauser