Modulation of TRPV1 on Odontoblast-like Cells Using Capsazepine-Loaded Nanogels.

The modulation of TRPV1 emerges as a promising strategy for dental pain management. This study aimed to assess TRPV1 modulation in a human odontoblast-like cell model using Capsazepine (CZP) loaded in a nanogel delivery system. Gelatin nanogels, synthesized via the emulsification-gelation technique, were characterized and loaded with the TRPV1 antagonist, CZP. HPLC determined a remarkable 67.5 ± 0.04% CZP loading efficiency, with 71.7% of nanogels falling within the 300-950 nm size range, as evidenced by light microscopy. Moreover, CZP-loaded nanogels had a low cytotoxicity. An FTIR analysis showed no adverse chemical interactions, ensuring stability and active release. When examining biological responses, TRPV1 expression and channel activity were assessed in odontoblast-like cells. On the fifth day post-treatment, cells treated with CZP-loaded nanogels exhibited an increased TRPV1 expression and a reduction in calcium fluxes after agonist stimulus (F/F0 ratio 1.18 ± 0.18), resembling the response in free CZP-treated cells (1.28 ± 0.15). A two-way analysis of variance and the Tukey's test were used to determine statistical significance (p < 0.05). This delivery system, proven to be economical and straightforward, holds promise for dental pain management and potential local use. Local administration minimizes systemic adverse effects, making it a practical solution for releasing molecules in the oral cavity.

Scarce Evidence of Heterosis for Growth Traits in Peruvian Guinea Pigs.

This study aimed to estimate the heterosis for productive traits in a two-way crossbreeding scheme. Four guinea pig lines were originally selected for the following traits: line P1 for the growth rate, P2 for the partial feed conversion rate, M1 for the growth rate of the litter at 10 days of age, and M2 for the litter size at birth. The comparison included 176 purebreds (P1: 46, P2: 43, M1: 54 and M2: 33) and 150 crosses (P1P2: 42, P2P1: 38, M1M2: 11 and M2M1: 59); body weights at birth, 10 days, weaning and 60 days of age were analyzed. A linear fixed-effect model was used, and heterosis was estimated as the difference between the average performance of the crossbred and pure-line animals. The pure line comparisons showed that P2 was lower than P1 for weight at 10 days and weaning weight, while all other comparisons between the paternal and maternal pure lines were not significant. The results indicated significant positive heterosis effects for both types of crosses, but only for birth weight: 3.7% for paternal crosses and 12.7% for maternal crosses. The heterosis estimates were mostly positive but not significant for all other traits. A reason for the low levels of heterosis could be that the lines are not very genetically differentiated. These results suggest that applying a two-way crossbreeding scheme within paternal and maternal guinea pig lines for meat production is not recommended due to the absence of heterosis for growth traits.

Design, Synthesis, and Development of 4-[(7-Chloroquinoline-4-yl)amino]phenol as a Potential SARS-CoV-2 Mpro Inhibitor.

A series of chloroquine analogs were designed to search for a less toxic chloroquine derivative as a potential SARS-CoV-2 Mpro inhibitor. Herein, an ANN-based QSAR model was built to predict the IC50 values of each analog using the experimental values of other 4-aminoquinolines as the training set. Subsequently, molecular docking was used to evaluate each analog's binding affinity to Mpro. The analog that showed the greatest affinity and lowest IC50 values was synthesized and characterized for its posterior incorporation into a polycaprolactone-based nanoparticulate system. After characterizing the loaded nanoparticles, an in vitro drug release assay was carried out, and the cytotoxicity of the analog and loaded nanoparticles was evaluated using murine fibroblast (L929) and human lung adenocarcinoma (A549) cell lines. Results show that the synthesized analog is much less toxic than chloroquine and that the nanoparticulate system allowed for the prolonged release of the analog without evidence of adverse effects on the cell lines used; therefore, suggesting that the analog could be a potential therapeutic option for COVID-19.

Adjustable conduits for guided peripheral nerve regeneration prepared from bi-zonal unidirectional and multidirectional laminar scaffold of type I collagen.

Shortness of donor nerves has led to the development of nerve conduits that connect sectioned peripheral nerve stumps and help to prevent the formation of neuromas. Often, the standard diameters of these devices cannot be adapted at the time of surgery to the diameter of the nerve injured. In this work, scaffolds were developed to form filled nerve conduits with an inner matrix with unidirectional channels covered by a multidirectional pore zone. Collagen type I dispersions (5 mg/g and 8 mg/g) were sequentially frozen using different methods to obtain six laminar scaffolds (P1 to P5) formed by a unidirectional (U) pore/channel zone adjacent to a multidirectional (M) pore zone. The physicochemical and microstructural properties of the scaffolds were determined and compared, as well as their biodegradability, residual glutaraldehyde and cytocompatibility. Also, the Young's modulus of the conduits made by rolling up the bizonal scaffolds from the unidirectional to the multidirectional zone was determined. Based on these comparisons, the proliferation and differentiation of hASC were assessed only in the P3 scaffolds. The cells adhered, aligned in the same direction as the unidirectional porous fibers, proliferated, and differentiated into Schwann-like cells. Adjustable conduits made with the P3 scaffold were implanted in rats 10 mm sciatic nerve lesions to compare their performance with that of autologous sciatic nerve grafted lesions. The in vivo results demonstrated that the tested conduit can be adapted to the diameter of the nerve stumps to guide their growth and promote their regeneration.

Evaluation of collagen type I scaffolds including gelatin-collagen microparticles and Aloe vera in a model of full-thickness skin wound.

Research on collagen type I scaffolds with Aloe vera is sparse. The aim of this work was to develop collagen type I scaffolds with gelatin-collagen microparticles and loaded with a dispersion of A. vera, to assess their performance as grafting material for healing of skin wounds. Scaffolds were evaluated in a Cavia porcellus model with full-thickness skin wound and compared with wounds healed by secondary intention (controls). Animals grafted with scaffolds without A. vera and their control wounds were also included in the study. Evaluation of enzymatic degradation and percentage of the scaffolds' free amino groups-as an indirect assessment of their cross-linking-were also carried out because A. vera contains compounds which affect their stability. We found that dispersions of lyophilized A. vera extract loaded on scaffolds do not have cytotoxic potential, and they decrease collagenase degradation of scaffolds in the range of 0.1 to 0.3% w/v in a dose-dependent manner. Only the A. vera dispersion with the highest concentration (0.3% w/v) decreased the percentage of free amino groups, which are the ones involved in the cross-link of collagen fibers. This finding suggests that cross-linking is not the mechanism by which the tested dispersions stabilize the scaffolds. Preclinical, histochemical, and histomorphometric analyses of repaired wound tissue indicate that loading collagen type I scaffolds, including microparticles of gelatin-collagen, with A. vera in the concentrations tested does not improve wound healing. Low biodegradability of the tested scaffolds caused by the inhibition of collagenase activity might account for these results.

Controlled release of an extract of Calendula officinalis flowers from a system based on the incorporation of gelatin-collagen microparticles into collagen I scaffolds: design and in vitro performance.

Aiming to develop biological skin dresses with improved performance in the treatment of skin wounds, acellular collagen I scaffolds were modified with polymeric microparticles and the subsequent loading of a hydroglycolic extract of Calendula officinalis flowers. Microparticles made of gelatin-collagen were produced by a water-in-oil emulsion/cross-linking method. Thereafter, these microparticles were mixed with collagen suspensions at three increasing concentrations and the resulting mixtures lyophilized to make microparticle-loaded porous collagen scaffolds. Resistance to enzymatic degradation, ability to associate with the C. officinalis extract, and the extract release profile of the three gelatin-collagen microparticle-scaffold prototypes were assessed in vitro and compared to collagen scaffolds without microparticles used as control. Data indicated that the incorporation of gelatin-collagen microparticles increased the resistance of the scaffolds to in vitro enzymatic degradation, as well as their association with the C. officinalis flower extract. In addition, a sharp decrease in cytotoxicity, as well as more prolonged release of the extract, was attained. Overall results support the potential of these systems to develop innovative dermal substitutes with improved features. Furthermore, the gelatin-collagen mixture represents a low-cost and scalable alternative with high clinical transferability, especially appealing in developing countries.

Fibroma ameloblástico asociado a un odontoma compuesto. La importancia del estudio histopatológico / Ameloblastic fibroma associated with a compound odontoma. Importance of the histopathological study

El fibroma ameloblástico es un tumor odontogénico mixto benigno de rara aparición, que constituye el 2% de todos los tumores odontogénicos, es de crecimiento lento, más común en niños y adultos jóvenes, compuesto por tejido conjuntivo fibroso embrionario y epitelio odontogénico primitivo, se caracteriza por la proliferación de tejido epitelial y mesenquimático. Aparece con más frecuencia en la mandíbula en zona de molares y premolares de pacientes jóvenes sin predilección de sexo, asociándose a veces a un diente incluido. El presente artículo tiene como objetivo describir un caso clínico de un paciente en la segunda década de vida, con aparente anodoncia en el maxilar superior, que se encontraba asintomático y en el cual fue diagnosticado fibroma ameloblástico en maxilar superior, zona de incisivos anteriores, lado izquierdo, se realiza una breve revisión de la literatura y diagnósticos diferenciales, se analizan sus características clínicas e histológicas y la actitud terapéutica a tomar. El tratamiento quirúrgico conservador con extirpación seguida de curetaje parece ser la opción terapéutica más adecuada, y teniendo presente que el porcentaje de recidiva es del 18,3% principalmente debido a escisión incompleta de la lesión, se deben realizar controles radiográficos postoperatorios 6 meses después y cada año por los siguientes 5 años (AU)

The ameloblastic fibroma is a benign mixed, rare odontogenic tumour, which accounts for 2% of all odontogenic tumours. It is slow growing, and more common in children and young adults. It is composed of embryonic fibrous connective tissue and early odontogenic epithelium, and characterised by the proliferation of epithelial and mesenchymal tissue. It appears most frequently in the jaw area of molars and premolars of young patients with no sex predilection, and is sometimes associated with an impacted tooth. This article aims to describe a clinical case of a child in the second decade of life, with apparent anodontia in the maxilla, which was asymptomatic and later diagnosed as an ameloblastic fibroma in the left side maxilla incisors area. A brief review of the literature and differential diagnoses was carried out, including an analysis of its clinical and histological features, and the therapeutic approach to take. Conservative surgical excision followed by curettage seems to be the most appropriate treatment option. It should be noted that the recurrence rate is 18.3%, mainly due to incomplete excision of the lesion. Radiographic controls should be performed six months postoperatively, and every year for the following five years (AU)

The Mycobacterium tuberculosis membrane protein Rv0180c: Evaluation of peptide sequences implicated in mycobacterial invasion of two human cell lines.

The identification and characterization of hypothetical membrane proteins from Mycobacterium tuberculosis have led to a better understanding of the mechanisms used by this pathogen to invade and survive inside host cells. This study assessed the presence, transcription, localization and possible biological activity of the conserved hypothetical protein Rv0180c from M. tuberculosis. Bioinformatics analyses indicated that Rv0180c contains a signal peptide, six possible transmembrane helices and a Plasmodium Export Element (PEXEL)-like motif. PCR analyses showed the presence of the Rv0180c gene in strains from the M. tuberculosis complex; but transcription was not detected in Mycobacterium microti. Sera against synthetic peptides of Rv0180c recognized two protein bands in M. tuberculosis H37Rv sonicate: a ∼48-kDa band close to the predicted molecular mass of Rv0180c (47.6 kDa), and a 63-kDa band probably caused by protein modifications. Moreover, the same sera located the protein on the surface of M. tuberculosis H37Rv bacilli by immunoelectron microscopy. Twenty-three synthetic peptides spanning the entire length of Rv0180c were tested for their ability to bind to U937 and A549 cells, finding nine high-activity binding peptides (HABPs) specific for both cell types, two HABPs specific for A549 cells (namely 31032 and 31044) and two HABPs specific for U937 cells (namely 31025 and 31041). HABPs inhibited invasion of M. tuberculosis H37Rv into A549 or U937 cells by significant percentages and facilitated internalization of latex beads in A549 cells. The Rv0180c HABPs herein reported could be preliminary candidates to be assessed as components of a multiepitope, chemically synthesized, subunit-based vaccine against tuberculosis.