Biology subjects

Pujol, J.

Publications and source records attributed to Pujol, J..

4 recordsLinked to original sources

bioRxiv2024

Wnt/β-catenin signaling improves oxidative metabolism in skeletal muscle of obese ob/ob mice

BackgroundCanonical Wnt signaling is involved in many physiological and pathological states. As it regulates lipid metabolism and glucose homeostasis, its misregulation may lead to the development of diabetes and obesity. We have already reported that activation of the Wnt/{beta}-catenin canonical signaling pathway increased insulin sensitivity and prevented lipid deposits in rat skeletal muscle through a reciprocal regulation of Wnt10b and the lipogenic factor SREBP-1c. ResultsHere we have studied the role of Wnt/{beta}-catenin canonical signaling in skeletal muscle of genetically obese and diabetic (ob/ob) mice and their control ob/+ mice. We showed that Wnt10b and SREBP-1c expressions were conversely regulated in cultured mouse myoblasts isolated from lean ob/+ or obese ob/ob mice. Activation of the Wnt/{beta}-catenin pathway using Wnt10b overexpression or the selective GSK3 inhibitor 6-Bromo-indirubin-3oxime (BIO) was sufficient to decrease lipogenic genes expression in cultured myoblasts isolated from control and obese mice. In vivo, we performed direct electrotransfection of Wnt10b cDNA or BIO injections in Tibialis Anterior (TA) muscles of ob/ob and ob/+ mice. Both up-regulated Wnt10b gene expression and down-regulated SREBP-1c expression. Canonical Wnt signaling increased slow Myosin Heavy Chain-I (MHC-I) oxidative fiber number as well as fast Myosin Heavy Chain-IIA (MHC-IIA) oxidative fiber number, while decreasing fast glycolytic fiber number in TA muscle. In addition, Wnt signaling increased mitochondrial oxidative metabolism and respiratory reserve capacity by 2- and 3-fold in myotubes cultured from ob/ob and ob/+ mice muscles respectively. Surprisingly, the activation of the Wnt pathway was sufficient to reduce hyperglycemia by 30% within 3 weeks in ob/ob mice. ConclusionsOur results show that activation of Wnt/{beta}-catenin signaling in skeletal muscle induced a shift towards a more oxidative metabolism in myofibers, thus mimicking the effects of exercise training. Wnt10b could be a valuable candidate to develop therapeutic drugs for the treatment of obesity and/or type 2 diabetes.

cell biology↗

bioRxiv2023

Graded changes in local functional connectivity of the brain in young people with depression

Major depressive disorder (MDD) is marked by significant changes to the coupling of spontaneous neural activity within various brain regions. However, many methods for assessing this local connectivity use fixed or arbitrary neighborhood sizes, resulting in a decreased capacity to capture smooth changes to the spatial gradient of local correlations. A newly developed method sensitive to classical anatomo-functional boundaries, Iso-Distant Average Correlation (IDAC), was therefore used to examine depression associated alterations to the local functional connectivity of the brain. One-hundred and forty-five adolescents and young adults with MDD and 95 healthy controls underwent a resting-state fMRI scan. Whole-brain functional connectivity maps of intracortical neural activity within iso-distant local areas (5-10mm, 15-20mm, and 25-30mm) were generated to characterize local fMRI signal similarities. Across all spatial distances, MDD participants demonstrated greater local functional connectivity of the bilateral posterior hippocampus, retrosplenial cortex, dorsal insula, fusiform gyrus, and supplementary motor area. Additionally, in the short and medium range connections there were depression associated alterations in the midcingulate (15-20mm and 25-30mm) and subgenual anterior cingulate (15-20mm). Our study identified increased synchrony of the neural activity in several regions commonly implicated in the neurobiology of depression; however, a subset of identified effects was dependent on the spatial distance under consideration. Longitudinal examination of these effects will clarify whether these differences are also found in other age groups and if this synchrony is additionally altered by continued disease progression.

neuroscience↗

bioRxiv2023

Combination of NY-ESO-1-TCR-T-cells coengineered to secrete SiRPalpha decoys with anti-tumor antibodies to augment macrophage phagocytosis

The adoptive transfer of T cell receptor (TCR)-engineered T cells (ACT) targeting the HLA-A2 restricted cancer-testis epitope NY-ESO-1157-165 (A2/NY) has yielded favorable clinical responses against a variety of cancers. Two promising approaches to improve ACT efficacy are TCR affinity-optimization and combinatorial treatment strategies to reprogram the tumor microenvironment (TME). By computational design, we previously developed a panel of affinity-enhanced A2/NY-TCRs. Here, we have demonstrated improved tumor control and engraftment by T cells gene-modified to express one such TCR comprising a single amino acid replacement in CDR3{beta} (A97L). To harness macrophages in the TME, we coengineered TCR-T cells to constitutively or inducibly secrete a high-affinity signal regulatory protein alpha (SiRP) decoy (CV1) to block the CD47 dont eat me signal. We demonstrated better control of tumor outgrowth by CV1-Fc coengineered TCR-T cells but in subcutaneous xenograft tumor models we observed depletion of both CV1-Fc and CV1 coengineered T cells. Importantly, CV1 coengineered T cells were not depleted by human macrophages in vitro. Moreover, Avelumab and Cetuximab enhanced macrophage-mediated phagocytosis in vitro in the presence of CV1, and augmented tumor control upon ACT. Taken together, our study indicates important clinical promise for harnessing macrophages by combining CV1 coengineered TCR-T cells with tumor-targeting monoclonal antibodies.

bioengineering↗

bioRxiv2019

Measurement of ocular transmission in living human eyes with a double-pass system

PurposeTo develop a methodology based on a double-pass system to obtain useful information about the transmission of ocular media, performing noninvasive measures in vivo.\n\nMethodsThis noninvasive procedure consists of recording double-pass images at different voltages of a laser diode of 780 nm and the determination of the scattering in an area between 25 and 35 arc minutes of each image.\n\nResultsOcular scattering showed a linear behavior respect to the voltage of the laser and the slope of the linear fit was proportional to the transmittance squared of the media evaluated. The relationship between the ocular light scattering of the images and the transmittance values of several filters located into an artificial eye was used as a calibration function. The measurements performed in a group of ten subjects with ages between 25 and 45 years old presented a mean direct transmittance of the whole eye including retina of 42.7 %, which agrees with the bibliography. No differences between dark eyes and light eyes were found.\n\nConclusionWe have developed a method to determine the transmittance of the human eye in vivo for a wavelength of 780 nm using the double-pass method, commonly used for the determination of the optical quality of an eye.

bioengineering↗