Biology subjects

Arias, F.

Publications and source records attributed to Arias, F..

4 recordsLinked to original sources

bioRxiv2024

Functional high capacity exosome-encapsulating bioinspired hydrogel promotes microvascularbed expansion in diabetic mice

Chronic wounds present a significant clinical challenge due to impaired skin microvasculature, particularly in diabetes. The tissue engineering study introduces therapeutic Exo-Q, a unique thermoresponsive polymer hydrogel created with Q protein nanofibers and cultured human bone marrow multipotent stromal cell exosomes with consistent gene signature. Limited, local and topical application of Exo-Q hydrogel is feasible for maximum neovascularization during murine diabetic wound closure in a xenotransplantation model, as well as compatibility and vascular delivery in human skin in a xenograft model. Exo-Q hydrogel treatment significantly reduces diabetic wound closure time within ranges of non-diabetic wounds. This innovative, non-invasive tissue engineered therapeutic option offers a promising approach to addressing the complex pathologies of non-healing wounds.

bioengineering↗

bioRxiv2023

Reelin plasma levels predict cognitive decline in Alcohol Use Disorder: peak levels in patients expressing plasma APOE4 protein

BackgroundHuman apolipoprotein (APO)-E4 has been related to neuropsychiatric disorders such as Alzheimers disease and cognitive decline. Reelin and Clusterin share the VLDLR and ApoER2 receptors with APOE4. Here we checked the role of these components in Alcohol Use Disorder (AUD)-induced cognitive decline. MethodsThis is a cross-sectional study with AUD-diagnosed patients (DSM-5) (n=24) recruited from an outpatient Alcohol Programme and matched controls (n=34). Participants were assessed by the validated Test of Detection of Cognitive Impairment in Alcoholism (TEDCA). APOE4 presence in plasma (distinguishing APOE4 carriers and no carriers subjects) and its levels were performed by e4Quant technique. The rest of biological markers were tested by Enzyme-Linked Immunosorbent Assay kits. ResultsPlasma APOE4 isoform was present in 37.5% and 58.8% of patients and controls, respectively. Quantification analyses revealed that APOE4 reached similar plasma levels in carriers independently if they were AUD subjects or controls. Circulant plasma APOE4 had a negative effect on AUDs cognition, specifically affecting Memory/Learning (p<0.01, {eta}2=0.15). Plasma Clusterin and Reelin increased in patients but, interestingly, Reelin plasma levels peaked in patients expressing APOE4 (p<0.05, {eta}2=0.09), who showed reduced VLDL and ApoER2 expression in peripheral blood mononuclear cells (PBMCs). Reelin was a good predictor of cognitive loss in patients, accounting for the 42.3% and 54.0% of general intelligence and executive function impairments, respectively. ConclusionsReelin plasma levels are increased in AUD patients who express the APOE4 isoform, predicting cognitive deterioration to a great extent. Remarkably, plasma Reelin helps to differentiate between AUD patients with and without cognitive decline. Significance StatementFinding biological markers that predict a worse evolution in neuropsychiatric disorders may help to assist vulnerable patients appropriately. In this sense, in this study we found a biological marker, Reelin, which is elevated in patients with diagnosis of alcohol use disorder (AUD) that underwent an outpatient treatment. Interestingly, Reelin plasma levels were elevated in patients that also express APOE4, an aberrant protein present only in a small percentage of the population which is related to neuroinflammation and cognitive impairment (i.e. it is involved in Alzheimers disease). We observed that Reelin plasma levels negatively correlate with cognitive scores, being Reelin a good predictor of cognitive impairment in patients. These results may have implications for the follow-up of AUD patients in outpatient treatment.

neuroscience↗

bioRxiv2018

Radiopotentiation of Enzalutamide over Human Prostate Cancer Cells as Assessed by Real-Time Cell Monitoring

While radiotherapy is the first line of treatment for prostate cancer, androgen blockade therapies are demonstrating significant survival benefit as monotherapies. As androgen blockade can cause cell death by apoptosis, it is likely that androgen blockade will potentiate the cytotoxic activities of radiotherapy. Here we tested the potential synergistic effects of these two treatments over two human metastatic prostate cancer cells by real time growth monitoring (RTCA), androgen-sensitive LNCaP cells and androgen-resistant PC-3. Both cell lines were highly resistant to high doses of radiotherapy. A pre-treatment of LNCaP cells with IC50 concentrations of enzalutamide significantly sensitized them to radiotherapy through enhanced apoptosis. In contrast, enzalutamide resistant PC-3 cells were not sensitized to radiotherapy by androgen blockade. These results provide evidence that the enzalutamide/radiotherapy combination could maximize therapeutic responses in patients with enzalutamide-sensitive prostate cancer.

cancer biology↗

bioRxiv2017

The Centrosome Controls the Number and Spatial Distribution of Microtubules by Negatively Regulating Alternative MTOCs

In this work, we have investigated in mammalian cells how microtubule nucleation at centrosome and Golgi apparatus are coordinated, using genetic ablation of three {gamma}-TuRC binding proteins -AKAP450, Pericentrin and CDK5Rap2- and the PLK4 inhibitor centrinone. We show that centrosomal microtubule nucleation is independent of Golgi activity whereas the converse is not true: nucleation on the Golgi negatively correlates with the number of centrosomes. In addition, depleting AKAP450 in cells lacking centrioles, that abolishes Golgi nucleation activity, leads to microtubule nucleation from numerous cytoplasmic Golgi-unbound acentriolar structures containing Pericentrin, CDK5Rap2 and y-tubulin. Strikingly, centrosome-less cells display twice higher microtubule density than normal cells, suggesting that the centrosome controls the spatial distribution of microtubules, not only by nucleating them, but also by acting as a negative regulator of alternative MTOCs. Collectively, the data reveals a hierarchical control of microtubule nucleation, with the centrosome regulating this process in a more complex manner than usually thought. It also unveils mechanisms that could help understanding MT network reorganization during cell differentiation.

cell biology↗