Overexpression of miR-25 Downregulates the Expression of ROBO2 in Idiopathic Intellectual Disability.

Idiopathic intellectual disability (IID) encompasses the cases of intellectual disability (ID) without a known cause and represents approximately 50% of all cases. Neural progenitor cells (NPCs) from the olfactory neuroepithelium (NEO) contain the same information as the cells found in the brain, but they are more accessible. Some miRNAs have been identified and associated with ID of known etiology. However, in idiopathic ID, the effect of miRNAs is poorly understood. The aim of this study was to determine the miRNAs regulating the expression of mRNAs that may be involved in development of IID. Expression profiles were obtained using NPC-NEO cells from IID patients and healthy controls by microarray. A total of 796 miRNAs and 28,869 mRNAs were analyzed. Several miRNAs were overexpressed in the IID patients compared to controls. miR-25 had the greatest expression. In silico analysis showed that ROBO2 was the target for miR-25, with the highest specificity and being the most down-regulated. In vitro assay showed an increase of miR-25 expression induced a decrease in ROBO2 expression. In neurodevelopment, ROBO2 plays a crucial role in episodic learning and memory, so its down-regulation, caused by miR-25, could have a fundamental role in the intellectual disability that, until now, has been considered idiopathic.

Restorative effects of (+)-epicatechin in a rodent model of aging induced muscle atrophy: underlying mechanisms.

Sarcopenia is a progressive and generalized age-related skeletal muscle (SkM) disorder characterized by the accelerated loss of muscle mass (atrophy) and function. SkM atrophy is associated with increased incidence of falls, functional decline, frailty and mortality. In its early stage, SkM atrophy is associated with increased pro-inflammatory cytokine levels and proteasome-mediated protein degradation. These processes also link to the activation of atrophy associated factors and signaling pathways for which, there is a lack of approved pharmacotherapies. The objective of this study, was to characterize the capacity of the flavanol (+)-epicatechin (+Epi) to favorably modulate SkM mass and function in a rat model of aging induced sarcopenia and profile candidate mechanisms. Using 23 month old male Sprague-Dawley rats, an 8 weeks oral administration of the +Epi (1 mg per kg per day in water by gavage) was implemented while control rats only received water. SkM strength (grip), treadmill endurance, muscle mass, myofiber area, creatine kinase, lactate dehydrogenase, troponin, α-actin, tumor necrosis factor (TNF)-α and atrophy related endpoints (follistatin, myostatin, NFκB, MuRF 1, atrogin 1) were quantified in plasma and/or gastrocnemius. We also evaluated effects on insulin growth factor (IGF)-1 levels and downstream signaling (AKT/mTORC1). Treatment of aged rats with +Epi, led to significant increases in front paw grip strength, treadmill time and SkM mass vs. controls as well as beneficial changes in makers of myofiber integrity. Treatment significantly reversed adverse changes in plasma and/or SkM TNF-α, IGF-1, atrophy and protein synthesis related endpoints vs. controls. In conclusion, +Epi has the capacity to reverse sarcopenia associated detrimental changes in regulatory pathways leading to improved SkM mass and function. Given these results and its recognized safety and tolerance profile, +Epi warrants consideration for clinical trials.

Cardiovascular risk factors in a Mexican middle-class urban population: The Lindavista Study. Baseline data / Factores de riesgo cardiovascular en mexicanos de clase media: el estudio Lindavista. Datos basales

Introduction and objective: The aim of this communication is to describe the cardiovascular risk factors affecting a Mexican urban middle-class population. Methods: A convenience sample of 2602 middle class urban subjects composed the cohort of the Lindavista Study, a prospective study aimed to determine if conventional cardiovascular risks factors have the same prognosis impact as in other populations. For the baseline data, several measurements were done: obesity indexes, smoking, blood pressure, fasting serum glucose, total cholesterol, HDL-c, LDL-c and triglycerides. This paper presents the basal values of this population, which represents a sample of the Mexican growing urban middle-class. Results: The mean age in the sample was 50 years; 59% were females. Around 50% of the entire group were overweighed, while around 24% were obese. 32% smoked; 32% were hypertensive with a 20% rate of controlled pressure. 6% had diabetes, and 14% had impaired fasting glucose; 66% had total cholesterol ≥ 200mg/dL; 62% showed HDL-c levels <40mg/dL; 52% triglycerides > 150 mg/dL, and 34% levels of LDL-c ≥ 160 mg/dL. Half of the population studied had the metabolic syndrome. Conclusion: These data show a population with a high-risk profile, secondary to the agglomeration of several cardiovascular risk factors.

Introducción y objetivo: el objetivo de este comunicado es describir los factores de riesgo cardiovascular en la población urbana mexicana de clase media. Métodos: La cohorte del estudio Lindavista se compone de una muestra por conveniencia de 2,602 sujetos de clase media. El estudio es prospectivo y tiene como finalidad determinar si los factores de riesgo cardiovascular tienen el mismo factor pronóstico que en otras poblaciones. Para los datos basales, se hicieron varias determinaciones: índices de obesidad, consumo de tabaco, presión arterial, glucosa, colesterol total, c-HDL, c-LDL y triglicéridos en ayuno. Resultados: La media de edad fue de 50 años; el 59% fueron mujeres. Aproximadamente el 50% de la muestra presentó sobrepeso, mientras que el 24% eran obesos. El 32% fumaban, el 32% eran hipertensos con una tasa de control del 20%. El 6% tenían diabetes y el 14% resistencia a la insulina. El 66% tuvieron colesterol total ≥ 200 mg/dl; el 62% mostraron bajos niveles de c-HDL, el 52% triglicéridos > 150 mg/dl, y el 34% niveles de c-LDL ≥ 160 mg/dl. La mitad de la muestra tenía síndrome metabólico. Conclusión: Los datos revelan una población de alto riesgo cardiovascular debido a la aglomeración de diversos factores de riesgo.