PARP-1 Expression Influences Cancer Stem Cell Phenotype in Colorectal Cancer Depending on p53.

Poly(ADP-ribose) polymerase-1 (PARP-1) is a protein involved in multiple physiological processes. Elevated PARP-1 expression has been found in several tumours, being associated with stemness and tumorigenesis. In colorectal cancer (CRC), some controversy among studies has been described. In this study, we analysed the expression of PARP-1 and cancer stem cell (CSC) markers in CRC patients with different p53 status. In addition, we used an in vitro model to evaluate the influence of PARP-1 in CSC phenotype regarding p53. In CRC patients, PARP-1 expression correlated with the differentiation grade, but this association was only maintained for tumours harbouring wild-type p53. Additionally, in those tumours, PARP-1 and CSC markers were positively correlated. In mutated p53 tumours, no associations were found, but PARP-1 was an independent factor for survival. According to our in vitro model, PARP-1 regulates CSC phenotype depending on p53 status. PARP-1 overexpression in a wild type p53 context increases CSC markers and sphere forming ability. By contrast, those features were reduced in mutated p53 cells. These results could implicate that patients with elevated PARP-1 expression and wild type p53 could benefit from PARP-1 inhibition therapies, meanwhile it could have adverse effects for those carrying mutated p53 tumours.

Functional polymorphisms in BDNF and COMT genes are associated with objective differences in arithmetical functioning in a sample of young adults.

BACKGROUND: Understanding the molecular genetics of complex human behaviors and functions remains a substantial challenge for the neurosciences. Previous studies have shown a genetic basis for individual differences in mathematical functioning; however, the specific genes remain to be completely identified. In the present study, we explored the possibility that 2 functional polymorphisms in candidate genes could be associated with differences in arithmetical performance. METHODS: A computerized test to analyze performance in basic arithmetical calculations (additions and subtractions) was applied to 168 healthy young Colombian participants using the PEBL (Psychology Experiment Building Language) battery. DNA samples were genotyped for 2 functional SNPs in candidate genes: brain-derived neurotrophic factor (BDNF)-Val66Met and catechol-O-methyltransferase (COMT)-Val158Met. RESULTS: We found significant differences for arithmetical processing scores between genotypes. For BDNF, Val/Val subjects had a worse performance (p value: 0.025) and for COMT, Val/Val carriers had a better performance (p value: 0.006). A multivariate model, including both BDNF and COMT genes, accounted for 7.1% of the variance in math processing scores. DISCUSSION: To our knowledge, this is the first study finding associations of polymorphisms in BDNF and COMT genes with quantitative measures of numerical aptitude in healthy young participants. A future study of other genes involved in neural plasticity could be helpful to identify genetic correlates of arithmetical functioning, which will be important for the understanding of normal human behaviors and related neuropsychiatric disorders.

Narrow Leafed Lupin (Lupinus angustifolius L.) ß-Conglutin Seed Proteins as a New Natural Cytotoxic Agents against Breast Cancer Cells.

Breast cancer (BC) is the most widespread tumor in women and the second type of most common cancer worldwide. Despite all the technical and medical advances in existing therapies, between 30 and 50% of patients with BC will develop metastasis, which contributes to the failure of existing treatments. This situation urges the need to find more effective prevention and treatment strategies like the use of plant-based nutraceutical compounds. In this context, we purified three Narrow Leafed Lupin (NLL) ß-conglutins isoforms using affinity-chromatography and evaluated their effectiveness in terms of viability, proliferation, apoptosis, stemness properties, and mechanism of action on both BC cell lines and a healthy one. NLL ß-conglutins proteins have very promising effects at the molecular level on BC cells at very low concentrations, emerging as a potential natural cytotoxic agent and preserving the viability of healthy cells. These proteins could act through a dual mechanism involving tumorigenic and stemness-related genes such as SIRT1 and FoxO1, depending on the state of p53. More studies must be carried out to completely understand the underlying mechanisms of action of these nutraceutical compounds in BC in vitro and in vivo, and their potential use for the inhibition of other cancer cell types.

Prevalencia y determinantes de automedicación con antibióticos en una comuna de Santiago de Cali, Colombia / Prevalence and determinants of self-medication with antibiotics in a community of Santiago de Cali in Colombia

Introducción: la automedicación con antibióticos en gran medida se realiza de manera irracional y esta a su vez puede ocasionar más adelante resistencia microbiana. Objetivo: establecer la prevalencia y los determinantes de la automedicación de la población que adquiere antibióticos. Métodos: estudio de corte transversal en el que se encuestaron personas que acababan de adquirir antibióticos en droguerías de la Comuna 5 de Santiago de Cali, Colombia. Se consideró como automedicado el usuario que solicitaba antibióticos, sin que estos fuesen recomendados por un médico. Se calculó el tamaño de muestra (140) con el empleo del software Epidat versión 4.0. Para seleccionar las personas a encuestar se realizó un muestro aleatorio simple. Se realizó una regresión logística múltiple entre automedicación y las demás variables, empleando el software Stata versión 10. Resultados: de las personas encuestadas, se encontró que la amoxicilina (31 por ciento) fue el antibiótico más adquirido; las tabletas (71 por ciento), la forma farmacéutica más común; las afecciones del tracto respiratorio (26 por ciento), el motivo de consulta mayoritariamente; y el vendedor de la droguería (49 por ciento), la persona que más aconsejó el uso de lo referido. La prevalencia de automedicación fue del 7 por ciento. Se encontró que la oportunidad de automedicarse entre quienes adquieren amoxicilina fue de 2,4 veces mayor, comparado con quienes adquieren otro antibiótico (p< 0,05). La oportunidad de adquirir amoxicilina entre quienes son aconsejados por el vendedor de la droguería resultó 2,7 veces mayor, comparado con quienes fueron aconsejados por otra persona; 3,0 veces mayor si es hombre y 3,1 veces mayor si el motivo de consulta es respiratorio comparado con otros motivos. Conclusiones: los resultados identifican como causa principal de automedicación con amoxicilina, el consejo del vendedor de la droguería para el tratamiento de afecciones respiratorias(AU)

Introduction: self-medication with antibiotics is performed in a quite irrational way and this in turn can lead to microbial resistance in the future Objective: to establish the prevalence and the determinants of self-medication of the population that purchases antibiotics Methods: a cross-sectional study of the surveys to people who had just purchased antibiotics in drugstores located in community 5 of Santiago de Cali, Colombia. The user was considered as self-medicated if he/she asked for antibiotics although they were not prescribed by a physician. The sample size was estimated at 140 by using Epidat software version 4.0. The selection of the people to be interviewed required a simple random sampling. A multiple logistic regression between self-medication and other variables was applied by using Stata software version 10. Results: in the surveyed group, it was found that Amoxicillin was the most purchased antibiotic (31 percent); the most common dosage form was tablets (71 percent); the respiratory tract diseases (26 percent) were the most common reasons for doctor's appointment and the drugstore seller (49 percent) was the one who mainly advised the use of the antibiotics. The prevalence of self-medication was 7 percent. It was also observed that the possibility of self-medication among the people who purchase Amoxicillin is 2.4 times higher than that of those who buy another antibiotic (p< 0.05). The opportunity of purchasing Amoxicillin in those people who are advised by the drugstore seller is 2.7 times higher than that of those who are advised by another person, 3.0 times higher for men and 3.1 times higher if the reason for going to the doctor's is a respiratory disease in comparison to other reasons. Conclusions: the results identify the drugstore seller's advice as the main cause of self-medication with amoxicillin to treat respiratory illnesses(AU)