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In current work, we prepared a series of nine 4-benzyloxy-5-benzylidene-1,3-thiazolidine-2,4-diones using a two-step pathway. Compounds 1–9 were tested in vitro using a set of three ...proteins recognized as important targets in diabetes and related diseases: PPARα, PPARγ, and GLUT-4. Compounds 1–3, 5, and 7 showed significant increases in the mRNA expression of PPARγ and GLUT-4, whereas compounds 1–3 did it over PPARα. Compounds 1–3 were identified as a dual PPAR α/γ modulators and were selected for evaluating the in vivo antidiabetic action at 100 mg/kg dose, being orally actives and decreasing blood glucose concentration in a hyperglycemic mice model, as well as reducing the triacylglycerides levels in normolipidemic rats. Docking and molecular dynamics studies were conducted to clarify the dual effect and binding mode of compounds 1–3 on both PPARs. Compounds 2 and 3 exhibited robust in vitro and in vivo efficacy and could be considered dual PPAR modulators with antidiabetic and antidyslipidemic effects.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Colorectal cancer is a heterogeneous disease with multiple genomic changes that influence the clinical management of patients; thus, the search for new molecular targets remains necessary. The aim of ...this study was to identify genetic variants in tumor tissues from Mexican patients with colorectal cancer, using massive parallel sequencing. A total of 4813 genes were analyzed in tumoral DNA from colorectal cancer patients, using the TruSight One Sequencing panel. From these, 192 variants with clinical associations were found distributed in 168 different genes, of which 46 variants had not been previous reported in the literature or databases, although genes harboring those variants had already been described in colorectal cancer. Enrichment analysis of the affected genes was performed using Reactome software; pathway over-representation showed significance for disease, signal transduction, and immune system subsets in all patients, while exclusive subsets such as DNA repair, autophagy, and RNA metabolism were also found. Those characteristics, whether individual or shared, could give tumors specific capabilities for survival, aggressiveness, or response to treatment. Our results can be useful for future investigations targeting specific characteristics of tumors in colorectal cancer patients. The identification of exclusive or common pathways in colorectal cancer patients could be important for better diagnosis and personalized cancer treatment.
We searched for the prevalence of actionable somatic mutations in exon 2 of the KRAS gene in western Mexican patients with CRC. Tumor tissue DNA samples from 150 patients with sporadic CRC recruited ...at the Civil Hospital of Guadalajara were analyzed. Mutations in exon 2 of the KRAS gene were identified using Sanger sequencing, and the data were analyzed considering clinical–pathological characteristics. Variants in codon 12 (rs121913529 G>A, G>C, and G>T) and codon 13 (rs112445441 G>A) were detected in 26 patients (with a prevalence of 17%). No significant associations were found between these variants and clinical–pathological characteristics (p > 0.05). Furthermore, a comprehensive search was carried out in PubMed/NCBI and Google for the prevalence of KRAS exon 2 mutations in Latin American populations. The 17 studies included 12,604 CRC patients, with an overall prevalence of 30% (95% CI = 0.26–0.35), although the prevalence ranged from 13 to 43% across the different data sources. Determining the variation and frequency of KRAS alleles in CRC patients will enhance their potential to receive targeted treatments and contribute to the understanding of the genomic profile of CRC.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
El curso MQ-203 Bioquímica para Microbiología, fue impartido del 2006 al 2010 mediante clases magistrales en donde la evaluación del aprendizaje de los estudiantes se llevó a cabo exclusivamente ...mediante exámenes de selección única. En el primer semestre del 2011, además de las clases magistrales, en este cuso se implementaron varias actividades de aprendizaje cooperativo incluyendo trabajos en grupo, el estudio y la discusión de casos clínicos y el desarrollo de un trabajo de investigación en grupo. Estas actividades tuvieron un valor de 25% en la nota final del curso. En este artículo se analizan las opiniones de los estudiantes sobre estos cambios y el efecto de estos en su desempeño. Los estudiantes expresaron sentir un mayor compromiso con el proceso de aprendizaje, tanto individual como el de sus compañeros y mostraron una gran satisfacción con respecto al desarrollo del curso. Además, los estudiantes obtuvieron mejores notas que en años anteriores y aumentó significativamente el porcentaje de aprobación del curso. De esta manera, la implementación de actividades cooperativas contribuyó a una mejora en la disposición de los estudiantes hacia el curso y a su desempeño en el mismo. The course MQ-203 Biochemistry for microbiology students was taught between 2006 and 2010 through lectures in which the learning process of the students was assessed exclusively by single-selection tests. During the first term of the year 2011, besides lectures, several cooperative learning activities were implemented in this course, such as assignments in groups, the study and discussion of clinical cases, and the development of a research project in groups. These activities had a weight of 25% in the final grade of the course. In this paper student´s opinion about these changes are analyzed as well as their effect on their performance. Students reported a greater commitment to, both, personal and classmate’s learning process, and exhibit high satisfaction with the development of the course. Furthermore, there was a significant increase in the mean score of the students’ compared to previous years, as well as in the rate of students who approved the course. Thus, the implementation of cooperative activities contributed to a better attitude toward the curse and significantly improved their performance.