Autophagic-Related anticancer effect of grapes extract and tomatoes extract: Ex-Vivo study

Cells undergo autophagy to save themselves from injury, but progressive autophagy can cause cell death. This study characterized and compared the effect of grape (resveratrol) and tomato (lycopene) extracts and their combination on modulating autophagy-related miRNA and its target gene in squamous cell carcinoma cell line. Docking analysis for extracts and selected genes was performed. Methyl Thiazol Tetrazolium assays were used to assess the cytotoxicity of extracts and their combination toward HEp-2 cells. qRT-PCR was used to quantify changes in gene expression. Data were statistically analyzed. miRNA-20a was identified as a potential effector in laryngeal cancer, and sequestosome-1 (SQSTM1) was its target gene. Docking analysis showed that resveratrol interacted with miRNA-20a and showed less affinity toward SQSTM1. Hydrogen bonds and hydrophobic interactions were predicted. In contrast, lycopene showed less affinity toward miRNA-20a than resveratrol. Increasing doses of resveratrol, lycopene, and their combination induced a statistically significant reduction in mean percent viability and mean fold changes of miRNA-20a and SQSTM1 expression in treated HEp-2 cells. Pearson's correlation showed a statistically significant positive correlation between miRNA-20a and SQSTM1 (R=0.812, p≤0.001). Grape and tomato extracts and their combination display promising cytotoxicity against HEp-2 cells in a dose- and time-dependent fashion. Both extracts reduce the expression of miRNA-20a and SQSTM1 with subsequent inhibition autophagy and promotion of apoptosis in HEp-2 cells.

Las células se someten a autofagia para salvarse de lesiones, pero la autofagia progresiva puede provocar la muerte celular. Este estudio caracterizó y comparó el efecto de los extractos de uva (resveratrol) y tomate (licopeno) y su combinación en la modulación de miARN relacionado con la autofagia y su gen diana en la línea celular de carcinoma de células escamosas. Se realizó análisis de acoplamiento para extractos y genes seleccionados. Se utilizaron ensayos de metil tiazol tetrazolio para evaluar la citotoxicidad de los extractos y su combinación frente a las células HEp-2. qRT-PCR se utilizó para cuantificar los cambios en la expresión génica. Los datos fueron analizados estadísticamente. El miARN-20a se identificó como un efector potencial en el cáncer de laringe y el secuenciasoma-1 (SQSTM1) fue su gen diana. El análisis de acoplamiento mostró que el resveratrol interactuaba con miRNA-20a y mostraba menos afinidad hacia SQSTM1. Se predijeron enlaces de hidrógeno e interacciones hidrofóbicas. Por el contrario, el licopeno mostró menos afinidad hacia el miARN-20a que el resveratrol. El aumento de las dosis de resveratrol, licopeno y su combinación indujo una reducción estadísticamente significativa en el porcentaje medio de viabilidad y los cambios medios en la expresión de miRNA- 20a y SQSTM1 en las células HEp-2 tratadas. La correlación de Pearson mostró una correlación positiva estadísticamente significativa entre miRNA-20a y SQSTM1 (R=0,812, p≤0,001). Los extractos de uva y tomate y su combinación muestran una citotoxicidad prometedora contra las células HEp-2 de forma dependiente de la dosis y el tiempo. Ambos extractos reducen la expresión de miRNA-20a y SQSTM1 con la posterior inhibición de la autofagia y promoción de la apoptosis en células HEp-2.

Bone regeneration and graft material resorption in extraction sockets grafted with bioactive silica-calcium phosphate composite (SCPC) versus non-grafted sockets: clinical, radiographic, and histological findings.

PURPOSE: The purpose of the present study was to evaluate the effect of silica-calcium phosphate composite (SCPC) granules on bone regeneration in extraction sockets. METHODS: Ten patients were selected for a split-model study. In each patient, bone healing in SCPC-grafted and control ungrafted sockets was analyzed through clinical, radiographic, histomorphometric, and immunohistochemical assessments 6 months postoperatively. RESULTS: A radiographic assessment using cone-beam computed tomography showed minimal ridge dimension changes in SCPC-grafted sockets, with 0.39 mm and 1.79 mm decreases in height and width, respectively. Core bone biopsy samples were obtained 6 months post-extraction during implant placement and analyzed. The average percent areas occupied by mature bone, woven bone, and remnant particles in the SCPC-grafted sockets were 41.3%±12%, 20.1%±9.5%, and 5.3%±4.4%, respectively. The percent areas of mature bone and woven bone formed in the control ungrafted sockets at the same time point were 31%±14% and 24.1%±9.4%, respectively. Histochemical and immunohistochemical analyses showed dense mineralized bundles of type I collagen with high osteopontin expression intensity in the grafted sockets. The newly formed bone was well vascularized, with numerous active osteoblasts, Haversian systems, and osteocytes indicating maturation. In contrast, the new bone in the control ungrafted sockets was immature, rich in type III collagen, and had a low osteocyte density. CONCLUSIONS: The resorption of SCPC granules in 6 months was coordinated with better new bone formation than was observed in untreated sockets. SCPC is a resorbable bone graft material that enhances bone formation and maturation through its stimulatory effect on bone cell function. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03897010.