FK506 Attenuates the MRP1-Mediated Chemoresistant Phenotype in Glioblastoma Stem-Like Cells.

Poor response to current treatments for glioblastoma has been attributed to the presence of glioblastoma stem-like cells (GSCs). GSCs are able to expel antitumor drugs to the extracellular medium using the multidrug resistance-associated protein 1 (MRP1) transporter. Tacrolimus (FK506) has been identified as an MRP1 regulator in differentiated glioblastoma (GBM) cells (non-GSCs); however, the effect of FK506 on GSCs is currently unknown. The objective of the following research is to evaluate the effect of FK506 on the MRP1-related chemo-resistant phenotype of GSCs. For this, U87MG and C6 glioma cell lines were used to generate non-GSCs and GSCs. mRNA and MRP1-positive cells were evaluated by RT-qPCR and flow cytometry, respectively. A Carboxyfluorescein Diacetate (CFDA)-retention assay was performed to evaluate the MRP1 activity. Apoptosis and MTT assays were employed to evaluate the cytotoxic effects of FK506 plus Vincristine (MRP1 substrate). GSC-derived subcutaneous tumors were generated to evaluate the in vivo effect of FK506/Vincristine treatment. No differences in transcript levels and positive cells for MRP1 were observed in FK506-treated cells. Lesser cell viability, increased apoptosis, and CFDA-retention in the FK506/Vincristine-treated cells were observed. In vivo, the FK506/Vincristine treatment decreased the tumor size as well as ki67, Glial Fibrillary Acidic Protein (GFAP), and nestin expression. We conclude that FK506 confers a chemo-sensitive phenotype to MRP1-drug substrate in GSCs.

Effects of aerobic exercise on fibroblast growth factor 21 in overweight and obesity. A systematic review.

Fibroblast growth factor 21 (FGF21) has been suggested to improve metabolism during aerobic exercise in obesity. However, the variability of exercise interventions gives rise to discrepancies in the field. Therefore, we aimed to systematically review the available literature regarding the effects of aerobic exercise on FGF21 in the context of overweight and obesity. Our search included original articles published between 2009 and November 2021 found in PubMed, Science Direct, and Medline. Clinical and preclinical studies were included. Studies, where subjects or animals presented with other conditions (e.g., cancer, stroke), were excluded. From an initial 43 studies, 19 (clinical studies = 9; preclinical studies = 10) were eligible for inclusion in this review. The main findings were that acute exercise tended to increase circulatory levels of FGF21. In contrast, chronic exercise programs (≥4 weeks) had the opposite effect along with inducing mRNA and protein increases of FGF receptors and ß-klotho in adipose tissue, liver, and skeletal muscle. In conclusion, both clinical and preclinical studies showed that aerobic exercise exerts changes in circulatory and tissue FGF21, along with its receptors and co-receptor. Future research is needed to elucidate the mechanisms, along with the physiological and clinical implications of these changes.

Bovine A20 gene overexpression during bovine viral diarrhea virus-1 infection blocks NF-κB pathway in MDBK cells.

Viruses have developed cellular strategies to ensure progeny survival. One of the most interesting is immune camouflage, where the virus triggers a controlled-intensity immune response that prevents total destruction of the infected cell, thus "winning time" for the virus. This study explored the regulatory contexts of the bovine A20 gene during bovine viral diarrhea virus (BVDV)-1 infection, using IL-8 as an immune-response sentinel molecule. Assessments were conducted through RT-qPCR, Western blotting, gene silencing/overexpression, luciferase assays, and the use of pharmacological inhibitors, among other approaches. The results demonstrated that a) BVDV-1 increased A20 levels in Madin-Darby bovine kidney cells, b) increased A20 led to decreased IL-8 expression, and c) the virus affected the NF-κB signaling pathway. Collectively, these data identify bovine A20 as a strong regulator of immune marker expression. In conclusion, this is the first report on BVDV-1 modulating bovine IL-8 activation through the NF-κB/A20 pathway.

Critical periods in the variation in body composition in school children.

OBJECTIVE: To identify critical periods in the variation in body composition during a school year and determine possible causes. METHODS: A total of 363 boys and girls aged between 10 and 14 years participated in the study. Before and after the Winter Holidays (WIH) and National Holidays (NAH) (July and September, respectively), measurements were taken of body weight, body fat percentage, waist perimeter, time spent on physical activity and hours of sleep in order to determine the variations. The normality of the data was confirmed and the means were compared with an alpha significance level of p<0.05. RESULTS: The school children increased in weight by 600 g and 510 g in the NAH and WIH, respectively (p<0.0001), and their body fat percentage was significantly increased during both periods (0.51%); however, the waist perimeter measurement saw no significant changes. It can also be seen that in NAH physical activity dropped by an important amount (-41 min, p<0.0001), though this did not occur in WIH. A significant increase in hours of sleep was also seen during the two holiday periods (~1 to 2 hours/day). CONCLUSION: It is concluded that both NAH and WIH can be considered critical periods due to the sharp increase in body weight and body fat percentage in the school children, where a possible cause is the reduction in time spent on physical activity.

Objetivo: Identificar periodos críticos en la variación de la composición corporal durante un año escolar y determinar causas posibles. Métodos: Un total de 363 niños y niñas entre 10 y 14 años participaron en el estudio. Antes y después de las Vacaciones de invierno (VI) y Vacaciones nacionales (VN) (julio y septiembre, respectivamente), se tomaron mediciones de peso corporal, porcentaje de grasa corporal, perímetro en la cintura, tiempo dedicado a actividad física y horas de sueño para determinar las variaciones. La normalidad de los datos fue confirmada y las medias fueron comparadas con un nivel de significancia alfa de p.

Estudio del Plano Oclusal de una Población Chilena según los Cefalogramas de Steiner, Ricketts y Delaire / Study of the Occlusal Plane in a Chilean Population Using the Cephalometric Analysis of Steiner, Ricketts and Delaire

El propósito de esta investigación fue comparar la ubicación del Plano Oclusal (PO) en una población eugnásica chilena mediante el análisis cefalométrico de Steiner, Ricketts y Delaire. Estudio transversal. Se analizaron 96 telerradiografías digitales de adultos jóvenes chilenos eugnásicos (47 hombres y 49 mujeres) entre 18 y 35 años. En las telerradiografías de determinó la ubicación del PO de acuerdo a los parámetros cefalométricos de Ricketts, Steiner y Delaire. Todos los trazados cefalométricos fueron realizados utilizando el software Adobe® Photoshop® CC, versión 14.2.1. Para las mediciones angulares correspondientes a los análisis de Steiner y Ricketts se utilizó el software Screen Protractor version 4.0© 2006. Para las mediciones milimétricas correspondientes al análisis de Delaire, se utilizó el software Screen Calipers versión 4.0© 2006. Al aplicar el análisis de Steiner en la muestra se obtuvo un promedio de 17,16° para el ángulo formado entre el plano Silla-Nasion y el PO (norma 14,5±3°). Al utilizar el análisis de Ricketts, el ángulo promedio formado por el plano de Frankfurt y el PO fue 6,98° (norma 7,5±2°) Según el análisis de Delaire, la distancia en milímetros desde el PO al punto medio entre las cúspides vestibulares del primer y segundo premolar inferior fue 1,76 mm (referencia teórica 0±1 mm). El promedio de la angulación del PO se encuentra dentro del rango de normalidad según la norma de Steiner y Ricketts y el promedio de la distancia medida en milímetros del PO al punto medio entre las cúspides vestibulares del primer y segundo premolar inferior difiere en 1,76 mm de la referencia teórica del análisis cefalométrico de Delaire. Se recomienda realizar nuevos estudios que permitan definir las normas cefalométricas apropiadas para la poblacion chilena, lo que podría mejorar tanto diagnóstico como planes de tratamiento en diversas áreas de la odontología.

The aim of this study was to compare the location of the occlusal plane (OP) in a eugnathic Chilean population using Steiner, Ricketts, and Delaire cephalometric analysis. A cross-sectional study was carried out and ninety-six digital cephalometric radiographs from 47 male and 49 female young adults between ages 18 and 35 were analyzed to determine the location of the OP according to Steiner, Ricketts and Delaire cephalometric parameters. Cephalometric tracings were obtained with Adobe® Photoshop® CC, version 14.2.1 for all three analysis. Screen Calipers version 4.0© 2006 software was used to measure the distance in millimeters from the OP to a midpoint between the first and second inferior premolars cusps for Delaire analysis. For Steiner and Ricketts angle measurements, software Screen Protractor version 4.0© 2006 was used. Mean and Standard Deviation Tests for Steiner analysis showed that the mean angle between Sella-Nasion plane and OP was 17.16° (cephalometric norm 14.5±3°). The mean angle between Frankfurt plane and OP was 6.98° (cephalometric norm 7.5±2°) for Ricketts analysis. In Delaire analysis, the distance in millimeters from the OP to a midpoint between the first and second inferior premolars cusps obtained was 1.76 mm, which differs from the theoretical reference (0±1 mm). The mean angle of the occlusal plane obtained is within the average standards for Steiner and Ricketts analysis. The mean distance in millimeters obtained from the OP to a midpoint between the first and second inferior premolars cusps in this study differs from the theoretical reference reported in Delaire analysis. Further studies are recommended to study more appropriate cephalometric norms for the Chilean population that would improve diagnosis and treatment plans in different areas of the dentistry field.

Paralelismo entre plano oclusal y plano de Camper / Parallelism between the occlusal plane and the Camper's line

Objetivo: El propósito de este estudio fue verificar la relación de paralelismo entre el plano oclusal y 3 definiciones de plano de Camper en una población eugnásica chilena. Material y métodos Estudio transversal. Se seleccionaron 60 adultos jóvenes chilenos eugnásicos (32 hombres y 28 mujeres) entre 18 y 35 años. Se utilizaron telerradiografías de perfil digitales y fotografías faciales laterales estandarizadas. Se superpuso la cefalometría en las fotografías laterales con el programa Quick-Ceph®. Los planos de Camper se trazaron desde 3 diferentes puntos de inicio en el tragus (superior, medio e inferior) hacia el punto más inferior del ala de la nariz. Se midieron los ángulos formados entre el plano oclusal y los 3 planos de Camper resultantes con el programa Screen Protractor®. Resultados El análisis ANOVA muestra diferencias significativas entre los 3 ángulos. El ángulo promedio entre el plano de Camper medio y el plano oclusal fue -0,63°. En hombres, el plano de Camper medio fue más paralelo al plano oclusal (1,11°) y en mujeres el plano de Camper superior fue el más paralelo con el plano oclusal (1,39°). Conclusión El paralelismo fue verificado para el plano de Camper medio en hombres y para el plano de Camper superior en mujeres.

Objective: The aim of this study was to verify the parallelism between the occlusal plane and three different Camper's line definitions in a Chilean eugnathic population. Material and methods Cross-sectional study was conducted on 60 Chilean eugnathic young adults (32 males and 28 females) between 18 and 35 years old. Lateral digital standardised cephalometric radiographs and facial photographs were used. The cephalometric analysis was superimposed over the lateral photographs with Quick-Ceph® software. The Camper's line was traced from three different starting points at the Tragus (upper, middle and lower) to the lowest point below the nostrils. The angles obtained between the occlusal plane and the resulting Camper's lines were measured with Screen Protractor® software. Results The ANOVA test showed significant differences for the obtained angles. The mean parallelism between the medium Camper's line and the occlusal plane was -0.63°. In males, the medium Camper's line was more parallel to the occlusal plane (1.11°), and for females, the upper Camper's line was the most parallel to the occlusal plane (1.39°). Conclusion The parallelism was verified for the medium Camper's line in males, and for the upper Camper's line in females.

Paralelismo entre plano oclusal y 3 planos cefalométricos / Parallelism between the occlusal plane and 3 cephalometric planes

Objetivo: El propósito de este estudio fue comprobar si existe paralelismo entre el plano oclusal según la definición de Ricketts y 3 planos cefalométricos propuestos, en una población eugnásica chilena. Material y método Estudio transversal. Se incluyeron 96 adultos jóvenes chilenos eugnásicos entre 18 y 35 años, a los cuales se les tomaron telerradiografías de perfil estandarizadas. Se trazaron manualmente los planos cefalométricos propuestos A, B y C para medir los ángulos formados entre ellos y el plano oclusal. El plano A va desde el punto de unión del plano biespinal y el plano mandibular de Downs, hasta Stomion. El plano B se trazó desde el punto Xi de Ricketts hasta Stomion. El plano C va desde el punto medio entre R3 y R4 de Ricketts hasta Stomion. Resultados El promedio de angulación para el plano A es 0,42°, mientras que los plano B y C presentan en promedio un ángulo de −1,71° respecto el plano oclusal. ANOVA muestra diferencias significativas entre los planos propuestos y el plano oclusal. Se obtuvo un coeficiente de correlación r > 0,7 para los 3 planos propuestos. Conclusión El plano A es el que presenta mayor cercanía al paralelismo con el plano oclusal. Los planos B y C, aun cuando presentan una ligera discrepancia con el plano oclusal, podría ser utilizado igualmente.

Purpose The aim of this study was to verify the parallelism between the occlusal plane defined by Ricketts and 3 new different definitions of cephalometric lines in a Chilean eugnathic population. Material and method A cross-sectional study was conducted on 96 Chilean eugnathic young adults between 18 and 35 years old. Lateral digital standardised cephalometric radiographs were used. The cephalometric tracings for suggested lines A, B, and C were drawn by hand. Line A extends from the junction between the palatal plane and Downs's mandibular plane to Stomion. Line B was drawn from the Ricketts's Xi point to Stomion. Line C goes from Ricketts's R3 and R4 midpoint to Stomion. Results The ANOVA test shows significant differences between the suggested lines and the occlusal plane. The mean angle obtained for line A is 0.42° to the occlusal plane, while lines B and C showed a mean angle of −1.71°. A correlation coefficient r > 0.7 was obtained. Conclusion Line A is the most parallel line to the occlusal plane. Although lines B and C show a little discrepancy with the occlusal plane, they may be used anyway.