Martha Elva Pérez-Andrade

The emerging role of MicroRNAs in the regulation of gene expression by nutrients.

MicroRNAs (miRNAs) are a class of evolutionarily conserved, small non-coding RNAs of 19-24 nucleotides in length that regulate gene expression mostly at the posttranscriptional level. They are known to be involved in the control of different processes such as cell cycling, programmed cell death, cell differentiation, tumor development, metastasis, and sensing of nutrient stress. This review summarizes the evidence regarding the changes in miRNA expression that are caused by diets with a deficiency or augmented intake of nutrients such as amino acids, carbohydrates, fatty acids, vitamins, and phytochemicals. As diet is known to influence the expression of miRNAs, miRNA profiling has the potential to be useful in the assessment of nutritional status in dietary intervention studies. Additionally, as it can change miRNA expression, diet may be used as a therapeutic agent to treat many different diseases. Also, we explored here some ideas on therapeutics based on the manipulation of miRNA expression levels for dietary-derived diseases as well as the putative effect of food-derived miRNAs on host gene expression.

Epidemiología del hipotiroidismo congénito en México

OBJETIVO: Describir las caracteristicas epidemiologicas del hipotiroidismo congenito en recien nacidos en unidades medicas de la Secretaria de Salud de Mexico. MATERIAL Y METODOS: Estudio transversal en el cual se cuantifico tirotropina en 1 379 717 muestras de sangre de recien nacidos (de cordon umbilical o de talon), recolectadas en papel filtro, de enero de 2001 a diciembre de 2002, en unidades medicas de la Secretaria de Salud. Las muestras con tirotropina >15 µUI/ml para sangre de cordon, y > 10 µUI/ml para talon, se consideraron sospechosas, y se notificaron para realizar el perfil tiroideo y gammagrafia. Cuando los resultados fueron positivos, el caso se registro como hipotiroidismo congenito confirmado, y se anotaron los datos clinicos y demograficos en formatos especificos. Se utilizo estadistica descriptiva estandar. RESULTADOS: Se encontro una prevalencia de 4.12 x 10 000 recien nacidos, con predominancia del sexo femenino (66.84%). Se observaron variaciones estatales en la prevalencia, maxima en Quintana Roo (8.13 x 10 000 recien nacidos) y minima en Sinaloa (0.62 X 10 000). Se encontraron 57.46% tiroides ectopicas, 35.91% agenesias tiroideas y 6.63% defectos de la funcion de las hormonas tiroideas. Los principales datos clinicos fueron hernia umbilical (43.73%) e ictericia (41.58%). A 151 (17.12%) sospechosos no se les realizo estudio confirmatorio debido a datos incompletos o falsos en la ficha de identificacion, fallecimiento del recien nacido, renuencia de los padres y cambio de domicilio. CONCLUSIONES: El hipotiroidismo se presento en 1:2 426 recien nacidos, con predominio femenino (2:1), siendo la ectopia tiroidea su forma mas comun, y la hernia umbilical y la ictericia sus datos clinicos prominentes.

Diagnosis of inborn errors of metabolism.

Systematic detection of inborn errors of metabolism (IEM) has usually encountered difficulties in developing countries. We present our experience in a high-risk population in Mexico between 1973 and 1998 with particular reference to the last 10 years, during which time infrastructure and support were considerably improved. Only disorders of intermediary metabolism were sought. The total number of patients studied is not available, but in the last 10 years, patients numbered 5,186. Routine metabolic screening was performed on all patients, with additional tests according to the clinical picture and screening results. The referral criteria have increasingly diversified, one-third being neurological conditions. Of the referrals, 33.8% were from pediatricians (31.1% of whom were at critical medicine departments) and the remainder from specialists. The number of diagnosed patients has increased to 1 per 43.9 patients studied. Amino acid defects have been the most prevalent, the proportion of organic acid and carbohydrate disorders having increased in the last 10 years, associated with improved diagnostic facilities. The most frequently diagnosed diseases were PKU, type 1a glycogen storage, and maple syrup urine disease (MSUD), their frequency apparently varying among different regions of Mexico. Other results of our program include training of specialists and technicians, development of the Latin American Metabolic Information Network, a procedure to locally prepare a special food product low in phenylalanine for the treatment of PKU patients, and extension of approaches for these disorders to the investigation metabolic derangements of infant malnutrition. This work demonstrates that inherited metabolic diseases constitute a significant load in pediatric pathology and that their study can and should be pursued in developing nations.

High-Throughput Profiling of Caenorhabditis elegans Starvation-Responsive microRNAs

MicroRNAs (miRNAs) are non-coding RNAs of ~22 nucleotides in length that regulate gene expression by interfering with the stability and translation of mRNAs. Their expression is regulated during development, under a wide variety of stress conditions and in several pathological processes. In nature, animals often face feast or famine conditions. We observed that subjecting early L4 larvae from Caenorhabditis elegans to a 12-hr starvation period produced worms that are thinner and shorter than well-fed animals, with a decreased lipid accumulation, diminished progeny, reduced gonad size, and an increased lifespan. Our objective was to identify which of the 302 known miRNAs of C. elegans changed their expression under starvation conditions as compared to well-fed worms by means of deep sequencing in early L4 larvae. Our results indicate that 13 miRNAs (miR-34-3p, the family of miR-35-3p to miR-41-3p, miR-39-5p, miR-41-5p, miR-240-5p, miR-246-3p and miR-4813-5p) were upregulated, while 2 miRNAs (let-7-3p and miR-85-5p) were downregulated in 12-hr starved vs. well-fed early L4 larvae. Some of the predicted targets of the miRNAs that changed their expression in starvation conditions are involved in metabolic or developmental process. In particular, miRNAs of the miR-35 family were upregulated 6–20 fold upon starvation. Additionally, we showed that the expression of gld-1, important in oogenesis, a validated target of miR-35-3p, was downregulated when the expression of miR-35-3p was upregulated. The expression of another reported target, the cell cycle regulator lin-23, was unchanged during starvation. This study represents a starting point for a more comprehensive understanding of the role of miRNAs during starvation in C. elegans.

Apparent higher frequency of phenylketonuria in the Mexican state of Jalisco

The geographic origin of Mexican patients with phenylketonuria (PKU) in Mexico City and in southern California was studied. Compared to patients with other metabolic disorders, patients with PKU were significantly more likely to have originated from the Los Altos region of the state of Jalisco and its environs. The incidence of PKU among mentally retarded students attending special education schools was found to be significantly higher in Jalisco (particularly the Los Altos region) than in the neighboring state of Guanajuato (1.09% vs 0.3%). These results strongly suggest a “population of origin” effect, the mutant allele(s) having been introduced by the Spanish ancestors of the current population. Our findings also support the addition of PKU to the neonatal screening program for this region of Mexico.

Hipertirotropinemia en recién nacidos mexicanos

Vela-Amieva M, Hernandez-Osorio C, Gamboa-Cardiel S, Gonzalez-Contreras CR, Perez-Andrade ME, Ortiz-Cortes J, Aguirre-Velez BE. Hipertirotropinemia en recien nacidos mexicanos. Salud Publica Mex 2003;45:269-275. El texto completo en ingles de este articulo esta disponible en: http://www.insp.mx/salud/index.html Resumen Abstract Objective. To assess the differences in the blood concen- tration levels of the thyroid stimulating hormone and their possible use as an indicator of iodine sufficiency, in a sample of Mexican newborns. Material and Methods. A cross- sectional study was conducted from September 1999 to August 2000, among 25,427 Mexican newborns in the Ministry of Health clinics from 5 states. A total of 8 095 heel-prick and 17 332 umbilical cord blood samples were analyzed. Blood samples were collected in filter paper and processed by enzyme-linked immunosorbent assay. The Mann-Whitney U test and the Kruskal-Wallis test were used for statistical analyses. Results. Hyperthyrotropinemia was found in 9.95% of heel samples and in 24.27% of umbilical cord samples (TSH>5 μUI/ml). Conclusions. The percen- tage of hyperthyrotropinemia observed in this study was higher than that expected in a population with sufficient iodine intake; these findings could be due to poor maternal iodine intake. The English version of this paper is available at: http://www.insp.mx/salud/index.html

Caenorhabditis elegans respond to high-glucose diets through a network of stress-responsive transcription factors

High-glycemic-index diets, as well as a sedentary lifestyle are considered as determinant factors for the development of obesity, type 2 diabetes, and cardiovascular diseases in humans. These diets have been shown to shorten the life span of C. elegans in a manner that is dependent on insulin signaling, but the participation of other signaling pathways have not been addressed. In this study, we have determined that worms fed with high-glucose diets show alterations in glucose content and uptake, triglyceride content, body size, number of eggs laid, egg-laying defects, and signs of oxidative stress and accelerated aging. Additionally, we analyzed the participation of different key regulators of carbohydrate and lipid metabolism, oxidative stress and longevity such as SKN-1/NRF2, HIF-1/HIF1α, SBP-1/SREBP, CRH-1/CREB, CEP-1/p53, and DAF-16/FOXO, in the reduction of lifespan in glucose-fed worms.