Biology subjects

Velloso, L. A.

Publications and source records attributed to Velloso, L. A..

5 recordsLinked to original sources

bioRxiv2020

Glutamic acid promotes hair growth in mice

Glutamic Acid is the main excitatory neurotransmitter in neurons. Abnormal distributions of the glutamic acid receptors have been shown in hyper proliferative models such as psoriasis and skin regeneration. However, the biological function of glutamic acid in the skin remains unclear. Using ex vivo, in vivo and in silico approaches, we showed for the first time that exogenous glutamic acid promotes hair growth and keratinocyte proliferation. Topical application of glutamic acid decreased expression of genes related to apoptosis signaling in the skin. Also, we showed Glutamic acid increased viability and proliferation in cultured human keratinocyte. For the first time, we identified the excitotoxic GA concentration and we provided evidence for the existence of a novel skin signaling pathway mediated by a neurotransmitter controlling keratinocyte and hair follicle proliferation. In perspective, we anticipate our results could be the starting point to elucidate how exogenous glutamic acid from food intake or even endogenous GA from neuropsychiatric disorders modulate skin diseases.

pharmacology and toxicology↗

bioRxiv2020

A smartphone app for individual anesthetic calculation decreased anesthesia-related mortality in mice

Annually, millions of animals are used for experimental purposes. Despite the recommended anesthetic doses being well-known worldwide, the final amounts applied to mice could be different than those calculated. Here, we developed, tested, and validated a mobile app where researchers and operators were able to use personal devices to process body weight, calculate a master anesthetic cocktail, and then apply the individual volume to each mouse. Our objective was to refine anesthesia procedures using information technologies. Our data showed that the "Labinsane" mobile app decreased anesthetic-related deaths upon using weight-adjusted doses of ketamine and xylazine. Also, we validated that the Labinsane mobile app matched all calculations of anesthetic doses. To our knowledge, this is the first report with hundreds of anesthetized mice records and validation and implementation of a mobile app to solve an old but transversal challenge for researchers working with experimental mice.

pharmacology and toxicology↗

bioRxiv2020

POMC-specific knockdown of Tril reduces body adiposity and increases hypothalamic leptin responsiveness

In a public dataset of transcripts differentially expressed in selected neuronal subpopulations of the arcuate nucleus, we identified TLR4-interactor with leucine-rich repeats (Tril) as a potential candidate for mediating the harmful effects of a high-fat diet in proopiomelanocortin (POMC) neurons. The non-cell-specific inhibition of Tril in the arcuate nucleus resulted in reduced hypothalamic inflammation, protection against diet-induced obesity associated with increased whole-body energy expenditure and increased systemic glucose tolerance. The inhibition of Tril, specifically in POMC neurons, resulted in a trend for protection against diet-induced obesity, increased energy expenditure and increased hypothalamic sensitivity to leptin. Thus, Tril emerges as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental diet-induced obesity.

neuroscience↗

bioRxiv2020

Demonstration of re-epithelialization in a bioprinted human skin equivalent wound model

ObjectiveThe development of an in vitro platform for modeling human skin injury and the re-epithelization process. ApproachA fibrin provisional matrix (FPM) was installed into a wound facsimile of a bioprinted human skin equivalent (HSE). A mixture of plasma-derived fibrinogen-containing factor XIII, fibronectin, thrombin, and macrophages (an FPM "bioink") was extruded into the wound site. The surrounding in vitro tissue culture became a source of keratinocytes to achieve wound closure by a re-epithelialization process signaled by the FPM. ResultsAn in vitro analog of wound closure and re-epithelialization by keratinocytes occurred over the FPM after a normal migration initiation at 3 days. InnovationA physiologic mixture of macrophage/fibrinogen/fibronectin that supports macrophage differentiation was applied to a mechanically wounded, bioprinted dermal tissue. We developed a transitional culture medium to mimic the changing microenvironment during the initial phases of wound healing. As a reference, we temporally compared our in vitro model with a murine skin wound healing. ConclusionThis co-culture model was shown to temporally synchronize a re-epithelization process for initiation of keratinocyte migration from a surrounding tissue and the migration process over the top of an FPM. A future study of the analogous subepithelial healing pathway is envisioned using the same in vitro bioprinted tissue study platform for co-culture of keratinocytes, melanocytes, fibroblasts, endothelial cells, and macrophages using more specialized FPMs.

bioengineering↗

bioRxiv2020

Three-Dimensional (3D) Fibronectin Nano-Array Presented on Fibrin Matrix Accelerates Mice Skin Wound Healing

Plasma fibrinogen (F1) and fibronectin (pFN) polymerize to form a fibrin clot that is both a hemostatic and provisional matrix for wound healing. About 90% of plasma F1 has a homodimeric pair of {gamma} chains ({gamma}{gamma}F1) and 10% has a heterodimeric pair of {gamma} and more acidic {gamma} chains ({gamma}{gamma}F1). We have synthesized a novel fibrin matrix exclusively from a 1:1 (molar ratio) complex of {gamma}{gamma}F1 and pFN in the presence of highly active thrombin and recombinant Factor XIII (rFXIIIa). In this matrix, the fibrin nanofibers were wrapped with periodic 200-300 nm wide pFN nanobands (termed {gamma}{gamma}F1:pFN fibrin). In contrast, fibrin made from 1:1 mixture of {gamma}{gamma}F1 and pFN formed a sporadic distribution of "pFN droplets" (termed {gamma}{gamma}F1 +pFN fibrin). The {gamma}{gamma}F1:pFN fibrin enhanced the adhesion of primary human umbilical vein endothelium cells (HUVECs) relative to the {gamma}{gamma}F1+FN fibrin. Three dimensional (3D) culturing showed that the {gamma}{gamma}F1:pFN complex fibrin matrix enhanced the proliferation of both HUVECs and primary human fibroblasts. HUVECs in the 3D {gamma}{gamma}F1:pFN fibrin exhibited a starkly enhanced vascular morphogenesis while an apoptotic growth profile was observed in the {gamma}{gamma}F1 +pFN fibrin. Relative to {gamma}{gamma}F1 +pFN fibrin, mouse dermal wounds that were sealed by {gamma}{gamma}F1:pFN fibrin exhibited accelerated and enhanced healing. This study suggests that a 3D pFN nano-array presented on a fibrin matrix can promote wound healing.

bioengineering↗