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Incretins are a cluster of hormones which are secreted and released into the bloodstream after food intake by gut enteroendocrine cells, reaching to pancreas where produce a potentiating effect on insulin release. The aim of this study was to perform a systematic review of incretins gene expression mediated by nutrients using specific search equations in the PubMed database. The two most relevant incretins are GLP-1 and GIP, which come from proglucagon and proGIP precursor respectively. GLP-1 is mainly synthesized and released by ileum and colon L cells, in contrast to GIP which does it by K cells in duodenum and proximal jejunum. It has been shown that canonical Wnt signalling pathway is closely related to the production of these hormones, since transcription factor TCF7L2 affects proglucagon and proGIP gene expression in L and K enteroendocrine cells. On the other hand, it has been shown that the hexosamine biosynthetic pathway can produce N-linked glycosylation of -catenin, an essential component of canonical Wnt signalling. This process hinders β-catenin phosphorylation and, thereby prevents proteasome degradation. Increasing glucose concentration enhances the hexosamine pathway and thus β-catenin glycosylation. This causes a β-catenin cytoplasmic accumulation allowing entry into nucleus, where it exerts its action by binding to a clump of molecules and transcription factors, allowing to express the target genes, including the incretin hormones. There is also evidence that glucose, through the hexosamine pathway, can induces autocrine activation of Wnt signalling pathway by stimulating secretion of Wnt proteins.Las incretinas son una serie de hormonas que tras una ingesta de alimentos son secretadas y liberadas al torrente sanguíneo por células enteroendocrinas del intestino, llegando al páncreas, donde producen un efecto potenciador en la liberación de insulina. El objetivo de este trabajo ha sido realizar una revisión sistemática de la modulación de la expresión génica de las incretinas mediada por nutrientes utilizando ecuaciones específicas de búsqueda en la base de datos PubMed. Las dos incretinas más relevantes son el péptido análogo al glucagón 1 (GLP-1) y el péptido insulinotrópico dependiente de glucosa (GIP), que provienen de los precursores proglucagón y proGIP, respectivamente. GLP-1 es mayoritariamente sintetizado y secretado por las células L del íleon y del colon, a diferencia de GIP que lo hace por las células K de duodeno y yeyuno proximal. Se ha demostrado que la ruta canónica de señalización Wnt está estrechamente relacionada con la producción de estas hormonas, ya que el factor de transcripción TCF7L2 influye en la expresión génica de proglucagón y proGIP en células enteroendocrinas L y K. Por otra parte, se ha demostrado que la ruta biosintética de las hexosaminas es capaz de glicosilar la β-catenina, componente fundamental de la señalización canónica Wnt, lo que interfiere en la fosforilación de esta proteína, impidiendo así su degradación en el proteasoma. El aumento de la concentración de glucosa incrementa la ruta de las hexosaminas y de esta manera la glicosilación de la β-catenina. Esto produce una acumulación de esta proteína en el citoplasma celular y permite su entrada al núcleo, donde ejerce su acción al unirse a una serie de moléculas y factores de transcripción, permitiendo de este modo que se expresen los genes diana, entre los que se encuentran los de las hormonas incretinas. También hay evidencias de que la glucosa, a través de la ruta de las hexosaminas, es capaz de inducir la activación autocrina de la ruta de señalización Wnt estimulando la secreción de proteínas Wnt.

Introducción: el uso del ácido fólico preconcepcional para la prevención de los defectos del tubo neural (DTN), es una medida de gran impacto en la salud pública. El objetivo de esta revisión es describir el modelo de desarrollo embriológico de los DTN y los mecanismos por los cuales el ácido fólico disminuye su prevalencia. Metodología: se realizó una búsqueda de la literatura en las bases de datos MEDLINE/PubMed, OVID, LILACS y SciELO de las cuales se seleccionaron los artículos que permitieran reconstruir la fisiopatología de la enfermedad, incluyendo la embriología y la presentación clínica y destacando el papel del ácido fólico en la proliferación celular y en el proceso de neurulación. Resultados: se presenta la fisiopatología de los DTN y se describe la relación entre la disminución de la concentración de acido fólico y la neurulación fallida. Conclusiones: el modelo propuesto es útil para entender el desarrollo de los DTN y se resalta el efecto del consumo de ácido fólico sobre la salud materno-fetal.Introduction: using preconceptional folic acid for preventing neural tube defects (NTD) is a recommendation having a great impact on public health. This review was aimed at describing an NTD embryological development model and the mechanisms by which folic acid reduces such malformation’s prevalence. Methodology: a systematic search was made of medical literature related to folic acid deficiency and NTD pathogenesis. A search was done in MEDLINE, using PubMed, OVID, LILACS and SciELO. The selected papers led to modelling the disease’s physiopathology from embryology to clinical presentation, highlighting folic acid’s role in cell proliferation and neurulation. Results: the physiopathological model of NTD is presented as well as the relationship between decreased folic acid concentration and neurulation failure. Conclusions: this model should serve as a means of understanding the disease’s development, highlighting folic acid consumption’s impact on foetal and maternal health.

Durante el proceso de transformación de las células normales a células cancerosas, ocurren varias alteraciones genéticas. En este proceso se presenta la pérdida del control de los mecanismos de replicación y reparación del ADN, así como de la segregación del material genético. Aunque las células normales tienen estrategias de defensa contra el desarrollo del cáncer, las células tumorales activan diferentes vías de escape que permiten la progresión de la neoplasia. Avances recientes han permitido enfocar la investigación del cáncer hacia la identificación de algunos de sus factores etiológicos. El estudio del ciclo celular y su regulación han permitido conocer cómo la fidelidad y la integridad de la replicación del genoma son mantenidas por las funciones coordinadas de los puntos de control y de los sistemas de reparación del ADN. El funcionamiento adecuado de estos procesos puede ser alterado por mutaciones genéticas. Estos hallazgos sugieren que los mecanismos moleculares de regulación que participan en la transformación celular pueden ser empleados como sistemas potenciales para instrumentar nuevas terapias contra el desarrollo del cáncer.Several genetic alterations occur during the transformation process from normal to tumor cells, that involve the loss of fidelity of processes as replication, reparation, and segregation of the genomic material. Although normal cells have defense mechanisms against cancer progression, in tumor cells different escape pathways are activated leading to tumor progression. Recent advances have permitted cancer research to focus on the identification of some of its etiological factors. The knowledge of cell cycle reveals a precise mechanism achieved by the coordinated interactions and functions of cyclin-dependent kinases, control checkpoint, and repair pathways. Furthermore, it has been demonstrated that this coordinated function can be abrogated by specific genetic changes. These findings suggest that the molecular mechanisms responsible for cellular transformation may help to identify potential targets to improve cancer therapies.

El estudio de la participación de la variación genética en la predisposición a las enfermedades complejas ha cobrado nuevas dimensiones en la era genómica. Los polimorfismos de un solo nucleótido (SNP) son el tipo de variación más común entre individuos y su vinculación con enfermedades es motivo de investigación intensa. En fecha reciente, el estudio de los SNP que afectan la expresión genética (rSNP) ha suscitado mayor interés, ya que las diferencias de la expresión genética entre un sujeto y otro pueden modificar el fenotipo. El descubrimiento y caracterización funcional de los rSNP y el estudio de su frecuencia alélica representan un nuevo campo en la búsqueda de determinantes genéticos de enfermedades multifactoriales.The genomic era is imparting a new impulse to the study of the role of genetic variation in susceptibility to disease. The most common type of genetic variation between individuals is single nucleotide polymorphisms (SNP). The association of SNPs with susceptibility to disease is the current focus of intense research. Recently, the study of SNPs that alter the regulatory mechanisms of gene expression (rSNP) has emerged as a promising field for understanding disease, since this type of variation can have a profound effect on human traits related to susceptibility to disease. The finding and functional characterization of biologically significant rSNPs is advancing our knowledge of genetic determinants for multifactorial disease.

Apolipoprotein C-III (apoC-III) is a small protein that is predominantly synthesized in the liver and mainly resides at the surface of triglyceride-rich lipoproteins. Its expression is upregulated by glucose and reduced by insulin, with enhanced apoC-III promoting hypertriglyceridemia and inflammation in vascular cells. The protein is also elevated in patients with diabetes, suggesting that enhanced apoC-III levels might contribute to the development of type 2 diabetes mellitus. The present review focuses on the key mechanisms by which apoC-III could promote type 2 diabetes mellitus, including exacerbation of insulin resistance in skeletal muscle, activation of β-cell apoptosis, promotion of weight gain through its effects on white adipose tissue and hypothalamus, and attenuation of the beneficial effects of high-density lipoproteins on glucose metabolism. Therapeutic strategies aimed at reducing apoC-III levels may not only reduce hypertriglyceridemia but also might improve insulin resistance, thus delaying the development of type 2 diabetes mellitus., (Copyright © 2020 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: NRP1 inflammasome is crucial in endothelial dysfunction. Platelets are mandatory for the inflammation that precedes it. Aspirin could inhibit NLRP1 inflammasome in endothelial cells, and clopidogrel could also provoke a reduction in vascular inflammation. A study was carried out on the influence of platelet inflammatory inhibition by P2Y receptor inhibition versus COX enzyme inhibition on the transcription of NLRP1 inflammasome in endothelial cells., Methods: An open-label, prospective, randomised crossover study with two periods of platelet inhibition enrolled 20 healthy volunteers. They received clopidogrel 75mg/day/7days and aspirin 100mg/day/7days. A venous blood sample was collected from all participants before and after this period. Human aortic endothelial cells (HAECs) were exposed for 2h in cultures. NLRP1 gene expression was then analysed in these cultures., Results: HAEC cultures that were exposed to baseline plasma showed higher expression of NLRP1 than HAECs exposed to plasma after one week of aspirin or clopidogrel intake [relative quantification (RQ), 1.077±0.05 vs. 1.002±0.06; OR, 1.8; 95% CI, 1.1-2.9; P<.01 and 1.077±0.05 vs. 1.04±0.03; OR, 1.7; 95% CI, 1.2-2.6; P<.001, respectively]. NLRP1 expression in HAEC cultures exposed to plasma after one week of aspirin or clopidogrel was similar to that observed in control HAECs that was no exposed to human plasma (PBS) [RQ; 1.002±0.06 vs. 1.009±0.03; OR, 0.9; 95% CI, 0.5-1.4; P=.7, and 1.04±0.03 vs. 1.009±0.03; OR, 0.8; 95% CI, 0.3-1.2; P=.5, respectively]. No difference was observed in NLRP1 percentage reduction in HAEC after aspirin or clopidogrel exposure (3.8% vs. 2.8%, P=.3, respectively)., Conclusions: Platelet inhibition by P2Y pathway is similar to COX pathway in NLRP1 expression inhibition in HAECs., (Copyright © 2020 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

The elevation of blood pressure produces specific organic lesions, including kidney and cardiac damage. On the other hand, cardiovascular disease usually leads to the development of hypertension. Thus, hypertension could be both a cause and a consequence of cardiovascular disease. Previous studies linked the lack of nitric oxide to cardiovascular abnormalities, including hypertension, arteriosclerosis, myocardial infarction, cardiac hypertrophy, diastolic heart failure, and reduced endothelium-derived hyperpolarizing factor responses, with shorter survival. The lack of this gas also leads to renal/cardiac abnormalities. It is widely known that nephrogenic deficiency is a risk factor for kidney disease. Besides, recent evidence suggests that alterations in WT-1, a key nephrogenic factor, could contribute to the development of hypertension. Moreover, some genes involved in the development of hypertension depend on WT-1. This knowledge makes it essential to investigate and understand the mechanisms regulating the expression of these genes during renal/cardiac development, and hypertension. As a consequence, the most in-depth knowledge of the complex aetiopathogenic mechanism responsible for the hypertensive disease will allow us to propose novel therapeutic tools., (Copyright © 2019 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Frizzled-2 plays an important role in maintaining normal hepatic cell functionality. This study aimed to investigate the role of inhibition of Frizzled-2 in protecting rat liver BRL-3A cells from Hypoxia/Reoxygenation (H/R). In vitro H/R hepatic cell model was established by culturing BRL-3A cells under H/R condition. Frizzled-2 siRNA was transfected into BRL-3A cells to inhibit Frizzled-2 signaling. Wnt5a and Frizzled-2 were significantly increased in BRL-3A cells upon H/R treatment. H/R treatment induced cell cytotoxicity, the early apoptosis rate and the intracellular Ca 2+ level in BRL-3A cells while silencing frizzled-2 gene decreased the H/R induced cell cytotoxicity, apoptosis and intracellular Ca 2+ level. In vivo mice study further showed the up-regulation of Frizzled-2/Wnt 5 pathway and cleaved Caspase-3 expression in liver tissues under ischemia and reperfusion injury (IRI). In summary, inhibition of Frizzled-2 by its siRNA may protects BRL-3A cells by attenuating the H/R induced cell cytotoxicity and apoptosis., (Copyright © 2019. Publicado por Elsevier España, S.L.U.)

Background: Non-alcoholic fatty liver disease (NAFLD), a condition that leads to fibrosis, is caused by intake of very high-fat diets (HFDs). However, while the negative impact on the liver of these diets has been an issue of interest, systematic research on the effect of HFDs are lacking., Objective: To characterize the overall impact of HFDs on both molecular and morphological signs of liver remodeling., Methods: A study was conducted on male C57BL/6J mice to assess the effect of 4- and 8-week HFDs (60% kcal from fat) on (i) liver steatosis and fibrosis, and (ii) expression of factors involved in inflammation and angiogenesis., Results: After an 8-week HFD, vascular endothelial growth factor type-2 receptor (VEGF-R2) and fatty acid translocase/trombospondin-1 receptor (CD36) were overexpressed in liver tissue of mice given HFDs. These changes suggest impaired liver angiogenesis and occurred together with (i) increased GPR78-BiP and EIF2α phosphorylation, suggesting endoplasmic reticulum stress, (ii) induction of Col1a1 gene expression, a marker of fibrosis, and (iii) increased CD31 immunolabeling, consistent with active angiogenesis and fibrosis., Conclusion: Our data show that very HFDs promote a rapid inflammatory response, as well as deregulation of angiogenesis, both consistent with development of liver fibrosis., (Copyright © 2019 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction and Objectives: Pulmonary regurgitation (PR) is a frequent complication after repair of congenital heart disease. Lymphocyte expression of adrenoceptors (β1 and β2) and kinases (GRK2, GRK3, and GRK5) reflects the neurohumoral changes that occur in heart failure (HF). The main objective of this study was to describe the gene expression of these molecules in circulating lymphocytes in patients with severe PR., Methods: A prospective study was conducted to analyze lymphocyte expression of these molecules in patients with severe PR and compare it with expression in healthy controls and patients with advanced HF., Results: We studied 35 patients with severe PR, 22 healthy controls, and 13 patients with HF. Multiple comparisons analysis showed that β2-adrenoceptor gene expression levels were higher in the control group than in patients in the PR and HF groups and that expression in the latter 2 groups was similar (748.49 [rank 1703.87] vs 402.80 [rank 1210.81] vs 287.46 [rank 685.69] P = .001). Similar findings were obtained in gene expression of GRK2 (760.89 [rank 1169.46] vs 445.17 [rank 1190.69] vs 284.09 [rank 585.27] P < .001). There were no differences in expression levels of these molecules according to clinical variables in patients with PR., Conclusions: The gene expression pattern of GRK2 and β2-adrenoceptor as molecular markers of cardiac dysfunction was altered in patients with severe PR compared with controls and was similar to expression in patients with advanced HF., (Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Los microRNA (miRNA) son pequeños RNA no codificantes de aproximadamente 17 a 24 nucleótidos de longitud, los cuales se unen complementaria y principalmente en las regiones 3' UTR (región no traducida) de diversos RNA mensajeros (mRNA, messenger RNA). Su función general es regular negativamente la expresión génica a nivel postranscripcional, inhibiendo la traducción. Perfiles de expresión de miRNA alterados han sido identificados en diferentes líquidos, células y tejidos humanos afectados con diversas enfermedades autoinmunes y algunos se han propuestos potencialmente como biomarcadores de diagnóstico, pronóstico, actividad, etcétera, en estas patologías. Adicionalmente, variantes comunes del genoma humano, denominados polimorfismos de un solo nucleótido (SNP, single nucleotide polymorphisms) localizados en genes de miRNA han sido asociados con susceptibilidad, gravedad, y actividad en estas enfermedades. El objetivo de esta revisión es describir la biogénesis de los miRNA, su función, así como los perfiles de expresión y SNP en genes de miRNA asociados con diversas enfermedades autoinmunes, incluyendo tiroiditis autoinmune (tiroiditis de Hashimoto y enfermedad de Graves), lupus eritematoso sistémico, artritis reumatoide y síndrome de Sjögren primario., (Copyright: © 2019 SecretarÍa de Salud.)

Post-traumatic stress disorder, or PTSD, is a condition that affects a subgroup of individuals that have suffered a previous traumatic event capable of generating changes at a psychological and behavioural level. These changes affect the personal, family, and social environment of those who suffer from this condition. Different genes have been identified as risk markers for development of this disorder. The population heterogeneity and individual differences (genetic and environmental) of each subject have made it difficult to identify valid markers in previous studies. For this reason, studies of Gene x Environment (G×E) have gathered importance in the last two decades, with the aim of identifying of the phenotypes of a particular disease. These studies have included genes such as SLC64A, FKBP5, and ADCYAP1R1, among others. Little is known about the interaction between the genes, pathways, and the molecular and neural circuitry that underlie PTSD. However their identification and association with stimuli and specific environments that stimulate the development of PTSD makes it focus of interest for identify genomic variations in this disorder. In turn, the epigenetic modifications that regulate the expression of genes involved in the hypothalamic-pituitary-adrenal (HPA) axis and the amygdala- hippocampal-medial prefrontal cortex circuits play a role in the identification of biomarkers and endophenotypes in PTSD. In this review, the advances in genetic and epigenetic that have occurred in the genomic era in PTSD are presented., (Copyright © 2016 Asociación Colombiana de Psiquiatría. Publicado por Elsevier España. All rights reserved.)

Introduction: Coenzyme Q is an essential component in the activity of the mitochondrial electron transport chain. Its synthesis involves, at least, a complex of ten different proteins. In this study, an attempt is made to determine the evolution of the expression of the genes involved in coenzyme Q synthesis during mouse ageing., Material and Methods: The messenger RNA (mRNA) of different organs, such as brain, liver, kidney and skeletal muscle from young (8 months), mature (18 months), and old (24 months) mice was extracted by using Trizol and was then analysed by real time PCR (qPCR) using specific primers for all the known components of the coenzyme Q-synthesis complex (COQ genes)., Results: Liver showed the highest age-dependent changes in mRNA levels of the different components of Q-synthesis complex, affecting the extent of the variation as well as the significance of the change. In most of the cases, mRNA levels of the different components were higher in mature animals compared to young and old animals. When mRNAs of young and old animals were compared, only minor reductions of mRNA levels were found. Kidney showed a pattern similar to that found in liver as regards the changes in expression, although with lower increases in mature animals than those observed in the liver. Brain and skeletal muscle showed low variations, with muscle being the tissue with less changes, although a pattern similar to that found in liver and kidney was found, with slight increases in mature animals., Discussion: The results of this study indicate that ageing is an important factor affecting COQ gene expression, but its effect depends on the organ, and that mature animals show higher levels of mRNA than young and old animals. Taken into consideration the importance of coenzyme Q in cell metabolism and ageing, a more detailed study is needed to understand the gene regulation of the coenzyme Q-synthesis mechanisms during ageing., (Copyright © 2017 SEGG. Publicado por Elsevier España, S.L.U. All rights reserved.)

Objective: Cerebral vasospasm, one of the main complications of subarachnoid hemorrhage (SAH), is characterized by arterial constriction and mainly occurs from day 4 until the second week after the event. Urotensin-II (U-II) has been described as the most potent vasoconstrictor peptide in mammals. An analysis is made of the serum U-II concentrations and mRNA expression levels of U-II, urotensin related peptide (URP) and urotensin receptor (UT) genes in an experimental murine model of SAH., Design: An experimental study was carried out., Setting: Experimental operating room of the Biomedicine Institute of Seville (IBiS), Virgen del Rocío University Hospital (Seville, Spain)., Participants: 96 Wistar rats: 74 SAH and 22 sham intervention animals., Interventions: Day 1: blood sampling, followed by the percutaneous injection of 100μl saline (sham) or blood (SAH) into the subarachnoid space. Day 5: blood sampling, followed by sacrifice of the animals., Main Variables of Interest: Weight, early mortality, serum U-II levels, mRNA values for U-II, URP and UT., Results: Serum U-II levels increased in the SAH group from day 1 (0.62pg/mL [IQR 0.36-1.08]) to day 5 (0.74pg/mL [IQR 0.39-1.43]) (p<0.05), though not in the sham group (0.56pg/mL [IQR 0.06-0.83] day 1; 0.37pg/mL [IQR 0.23-0.62] day 5; p=0.959). Between-group differences were found on day 5 (p<0.05). The ROC analysis showed that the day 5 serum U-II levels (AUC=0.691), URP mRNA (AUC=0.706) and UT mRNA (AUC=0.713) could discriminate between sham and SAH rats. The normal serum U-II concentration range in rats was 0.56pg/mL (IQR 0.06-0.83)., Conclusion: The urotensinergic system is upregulated on day 5 in an experimental model of SAH., (Copyright © 2016 Elsevier España, S.L.U. y SEMICYUC. All rights reserved.)

MicroRNAs (miRNAs) are a class of small noncoding RNA (20-25 nucleotides) involved in gene regulation. In recent years, miRNAs have emerged as a key epigenetic mechanism in the development and physiology of the cardiovascular system. These molecular species regulate basic functions in virtually all cell types, and are therefore directly associated with the pathophysiology of a large number of cardiovascular diseases. Since their relatively recent discovery in extracellular fluids, miRNAs have been studied as potential biomarkers of disease. A wide array of studies have proposed miRNAs as circulating biomarkers of different cardiovascular pathologies (eg, myocardial infarction, coronary heart disease, and heart failure, among others), which may have superior physicochemical and biochemical properties than the conventional protein indicators currently used in clinical practice. In the present review, we provide a brief introduction to the field of miRNAs, paying special attention to their potential clinical application. This includes their possible role as new diagnostic or prognostic biomarkers in cardiovascular disease., (Copyright © 2017 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Introduction: Lysyl oxidase (LOX) participates in the assembly of collagen and elastin fibres. The impact of vascular LOX over-expression on extracellular matrix (ECM) structure and its contribution to oxidative stress has been analysed., Methods: Studies were conducted on mice over-expressing LOX (Tg), specifically in smooth muscle cells (VSMC). Gene expression was assessed by real-time PCR analysis. Sirius Red staining, H 2 O 2 production and NADPH oxidase activity were analysed in different vascular beds. The size and number of fenestra of the internal elastic lamina were determined by confocal microscopy., Results: LOX activity was up-regulated in VSMC of transgenic mice compared with cells from control animals. At the same time, transgenic cells deposited more organised elastin fibres and their supernatants induced a stronger collagen assembly in in vitro assays. Vascular collagen cross-linking was also higher in Tg mice, which showed a decrease in the size of fenestrae and an enhanced expression of Fibulin-5. Interestingly, higher H 2 O 2 production and NADPH oxidase activity was detected in the vascular wall from transgenic mice. The H 2 O 2 scavenger catalase attenuated the stronger deposition of mature elastin fibres induced by LOX transgenesis., Conclusions: LOX over-expression in VSMC was associated with a change in the structure of collagen and elastin fibres. LOX could constitute a novel source of oxidative stress that might participate in elastin changes and contribute to vascular remodelling., (Copyright © 2017 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

The intervertebral disc (IVD) is noted for its low cell content, and being the largest avascular structure of human body. The low amount of cells in the disc have to adapt to an anaerobic metabolism with low oxygen pressure and acidic pH. Apart from surviving in an adverse microenvironment, they are exposed to a high level of mechanical stress. The biological adaptation of cells to acidosis and hyperosmolarity conditions are regulated by mechanoproteins, which are responsible for converting a mechanical signal into a cellular response, thus modifying its gene expression. Mechanobiology helps us to better understand the pathophysiology of IVD and its potential biological repair., (Copyright © 2016 Sociedad Española de Neurocirugía. Publicado por Elsevier España, S.L.U. All rights reserved.)

Aims: To test the hypothesis that the pattern of gene expression in circulating leukocytes may differ between vascular compartments, depending on the presence or absence of atherosclerosis, we evaluated the regional vascular differences in patterns of inflammatory cell activation., Methods: Patients (n=8) with angiographically-established coronary artery disease (CAD+) and 8 without (CAD-) had blood samples taken from a peripheral vein as well as from left and right coronary arteries. Samples were pooled resulting in 4 CAD+ samples versus 4 CAD- samples and hybridised to a Whole Human Genome Microarray 4×44K., Results: CAD- patients had a similar gene expression profile across the different sites. CAD+ patients had statistically significant different gene expression patterns in venous vs. right and left coronary artery compartments. The expression pattern observed in the right coronary was where the most differences in gene expression were observed in CAD+ vs. CAD- patients. Overall, 1964 genes were differentially expressed between CAD+ and CAD-. Of these, 1052 were less expressed in CAD+ and 912 were more expressed in CAD+. Up to 12 of the 20 most differentially expressed genes appeared to reflect different phases of the atherosclerosis process: endothelial dysfunction, lipid accumulation, and smooth muscle cell proliferation., Conclusions: Gene expression of circulating leukocytes differentiates CAD+ from CAD- patients. Gene expression is significantly different between coronary arteries and the systemic circulation in CAD+ patients, but not in CAD- patients. Gene expression is significantly different between CAD+ and CAD- subjects, and appears to reflect the atherosclerosis process. These intra-individual differences may be an additional feature of established coronary artery disease., (Copyright © 2016 Sociedad Española de Arteriosclerosis. Publicado por Elsevier España, S.L.U. All rights reserved.)

Different hemoglobin isoforms are expressed during the embryonic, fetal and postnatal stages. They are formed by combination of polypeptide chains synthesized from the α- and β-globin gene clusters. Based on the fact that the presence of high hemoglobin F levels is beneficial in both sickle cell disease and severe thalassemic syndromes, a revision of the regulation of the β-globin cluster expression is proposed, especially regarding the genes encoding the y-globin chains (HBG1 and HBG2). In this review we describe the current knowledge about transcription factors and epigenetic regulators involved in the switches of the β-globin cluster. It is expected that the consolidation of knowledge in this field will allow finding new therapeutic targets for the treatment of hemoglobinopathies.

Introduction: Asthma is an inflammatory disorder of the airways and the symptoms of asthma could be exacerbated by Mycoplasma pneumoniae infection. Interleukin-2 and interleukin-4 have been implicated in immune and inflammatory reactions. We examined the associations of IL2 and IL4 polymorphisms and expression with the risks of asthma and M. pneumoniae infection in children., Methods: 392 asthmatic children and 849 controls were recruited into the study. Eight polymorphisms in IL2 and IL4 were genotyped with Sequenom MassARRAY platform. M. pneumoniae infection and copy number was determined with fluorescence PCR. IL-2 and IL-4 serum expression levels were determined by using ELISA., Results: We found a significant association of IL2 rs6534349 polymorphism with increased asthma risk (heterozygotes, P=.029; homozygous variants; P=.013) and of IL4 rs2227284 polymorphism with reduced asthma risk (heterozygotes, P=.026; homozygous variants; P=.001). Besides, the association of other polymorphisms, except rs2070874 polymorphism, became apparent when the asthmatic children were grouped according to GINA classification of asthma control and severity. In addition, IL-2 and IL-4 serum expression levels were significantly higher in M. pneumoniae negative (P=.038) and positive (P=.011) subjects respectively. This observation holds true among asthmatic patients (P=.016 for IL-2 and P=.042 for IL-4), but only the IL-4 observation remained correct among non-asthmatic controls (P=.032). We also observed that the rs6534349 GG genotype was significantly associated with increased odds of getting high load M. pneumoniae infection (P=.0376)., Conclusions: IL2 and IL4 could be important biomarkers for estimating the risks of asthma and M. pneumoniae infection in children., (Copyright © 2014 SEPAR. Published by Elsevier Espana. All rights reserved.)

In the pathophysiology of spinal cord injury, the secondary biological processes involving changes in gene expression become more important day a day. Within these changes, the expression of different microRNAs has been involved in some of the pathophysiological processes of spinal cord injury. There are several studies that describe the transient expression of microRNA in spinal cord injury, some of them related to inflammation and apoptosis and others to functional recovery and regeneration. MicroRNA may be a potential target for the treatment of spinal cord injury, modifying the processes of inflammation, oxidation, apoptosis, functional recovery and regeneration. It is necessary to continue the study of microRNAs in spinal cord injury, as well as the identification of their target genes and signaling mechanisms involved in its neurological effects. With this, the ultimate goal is the development of effective and safe therapeutic and diagnostic strategies for patients with spinal cord injury., (Copyright © 2015 Academia Mexicana de Cirugía A.C. Published by Masson Doyma México S.A. All rights reserved.)

Introduction: The microphthalmia -associated transcription factor ( MITF ) regulates the expression of specific genes and its cardiac expression and function is not known., Objectives: To identify the expression of MITF in hearts and isolated cardiomyocytes from Guinea pigs, to describe morphological changes associated with mRNA interference of MITF and to evaluate their relative changes in expression in isolated cardiomyocytes under ischemic preconditioning., Materials and Methods: The cardiac specific isoform, MITF-H, and relative expression level analysis, was determined by semi-quantitative real time PCR, sequencing and Western blotting. Reduction of mRNA-MITF-H was induced by transduction of specific-MITF-shRNAi interference. The cardiac morphological changes, diameter and number of cardiac fibers were evaluated by direct observation and light microscopy., Results: A cDNA fragment of 281 bp was amplified from heart and isolated ventricular cardiac myocytes. Sequence analysis confirmed the identity of the isoform MITF-H, exon 1. The MITF silencing was associated with an increase in cardiac index (heart weight/body weight vs . 5.46 x 10 -3 vs 4.6 x 10 -3 ) and higher diameter of cardiac fibers (50.2±16 µ m vs 38,7±14,7 µ m p<0.05, n=150). In isolated cardiac myocytes under ischemic preconditioning we observed a higher relative expression compared with that measured in myocytes exposed to normoxia and simulated ischemia (eighty and one hundred times, p <0.05, n = 5). Conclusion. The results suggest that MITF-H isoform may be involved in Guinea pig cardiac hypertrophy, response to stress by ischemia and cardiomyocytes survival.

Introduction and Objectives: Circulating microRNAs (miRNA) are involved in the posttranscriptional regulation of genes associated with lipid metabolism (miRNA-33) and vascular function and angiogenesis (miRNA-126). The objective of this exploratory study was to measure plasma levels of miRNA-33 and miRNA-126 in patients with plaque psoriasis and evaluate their association with clinical parameters., Material and Methods: We studied 11 patients with plaque psoriasis. The median Psoriasis Area Severity Index (PASI) was 13 (interquartile range [IQR], 9-14) and body surface area involvement was 12 (IQR, 11-15). Eleven healthy controls matched for age and sex were also included. We analyzed cardiovascular risk factors and subclinical carotid atheromatosis. Plasma miRNAs were evaluated using quantitative real-time polymerase chain reaction., Results: Carotid intima-media thickness was greater in patients (0.57mm; IQR, 0.54-0.61; n=11) than in controls (0.50mm; IQR, 0.48-0.54; data available for 9 controls) (P=.0055, Mann-Whitney). Expression of miRNA-33 in patients (5.34; IQR, 3.12-7.96; n=11) was significantly higher than in controls (2.33; IQR, 1.71-2.84; only detected in 7 of 11 controls) (P=.0049, Wilcoxon signed rank). No differences in miRNA-126 levels were observed between patients and controls. In patients (n=11), we observed a positive correlation between miRNA-33 and insulin levels (r=0.7289, P=.0109) and a negative correlation between miRNA-126 and carotid intima-media thickness (r=-0.6181, P=.0426)., Conclusion: In psoriasis patients plasma levels of lipid and glucose metabolism-related miRNA-33 are increased and correlated with insulin. The study of circulating miRNA-33 in psoriasis may provide new insights about the associated systemic inflammatory abnormalities., (Copyright © 2013 Elsevier España, S.L. and AEDV. All rights reserved.)

Introduction: Previous studies have shown that the loss of NOR-1 function modulates the activation of vascular smooth muscle cells (VSMC). In this study we use a mouse that over-expresses human NOR-1 in VSMC to analyze the effect of a gain of NOR-1 function on the activation of VSMC and in the hyperplasia of the intima induced by hemodynamic stress., Methods: To generate the transgenic animal the human NOR-1 cDNA was placed under the control of the SM22α promoter. The expression of NOR-1 was analyzed by real time PCR, Western blot, immunohistochemistry and immunocitochemistry, and NOR-1 functionality was evaluated by luciferase activity assays. The incorporation of tritiated thymidine was determined as a cell proliferation index. The left carotid artery was ligated, and cross-sections were subjected to morphometric and immunostaining analysis., Results: The transgenic mouse exhibited significant levels of human NOR-1 in aorta and carotid arteries. In aortic VSMC from transgenic mice an increase in the transcriptional activity of ciclin D2 was detected, as well as higher proliferative rates and increased levels of the marker Myh10. In these animals, carotid artery ligation induced a greater neointimal formation and a higher stenotic grade than in wild-type animals, in accordance with the labelling detected for Myh10 and phosphorylated Histone H3., Conclusions: These results reinforce the role of NOR-1 in VSMC proliferation and in vascular remodelling, and allow us to propose this model as a useful tool to study the involvement of NOR-1 in vascular function and in vascular diseases such as atherosclerosis and restenosis., (Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.)

Background: Cryotherapy is a no invasive technique that uses intense cold to freeze and destroy cancer tissues. There are no descriptions of its effects over the expression of vascular endothelial growth factor and pigment epithelium-derived factor., Methods: Experimental study in cryogenic spot were applied in the right sclera of twelve pigs for ten minutes. Other 3 pigs were used as normal controls. Animals were sacrificed at 7, 14 and 21 and the tissues of choriodes and retina were dissected in areas of approximately 1 cm2 surrounding cryogenic spots. Expression levels of vascular endothelial growth factor and pigment epithelium-derived factor were determined analyzed using polymerase chain reaction coupled to reverse-transcription., Results: Vascular endothelial growth factor was significantly downregulated (24%, p< 0.05) seven days post-treatment meanwhile pigment epithelium-derived factor levels increased 44.8% (p< 0.05) as compared to normal controls (untreated). Both vascular endothelial growth factor and pigment epithelium-derived factor levels remain the same until day 14 but returned to basal expression at day 21., Discussion: This work expose the relation of cryotherapy with the expression of two factors related to angiogenesis. RESULTS showed significant changes on the expression of vascular endothelial growth factor and pigment epithelium-derived factor illustrating that both proteins are regulated in response to cryogenic treatment in relatively short periods (21 days).

Introduction: Profilins are small ubiquitous proteins of 12-19 kDa involved in actin dynamics. These proteins are found in all eukaryotic organisms studied to date. Profilins have aminoacid sequences and tridimensional structure highly conserved. Allergy patients to pollen frequently have symptoms of allergy when ingestion of plant-derived foods like fruits, vegetables, seeds, among others. This phenomenon is known as latex-pollen-fruit allergy and it's the main cause of oral allergy syndrome (OAS) which is attributed to the cross-reactivity. Allergens shared between different sources theses are called panallergens for example are profilins which representing at least 20% of all pollen allergic patients. This cross-reactivity is results from the high amino acid sequence identity of profilin from plants, which is between 70% and 85%, this may explain the exacerbation symptoms of allergic patients to profilins from plants., Objective: We described some characteristics which show us the important participation of the profilins in the sensitization of people allergic, especially to plants, fruits and pollen., Methods: We looked research aminoacid sequences of all allergenic profilins reported to date and these were analyzed., Conclusions: Profilins are important allergens that are underrated in clinical practice and contribute to cross-reactivity in sensitized individuals by profilins from other sources.

The aim of this work is to present basic information on the lipoprotein physiology. The protein fraction of lipoproteins consists of several apolipoproteins and enzymes whose functions are lipid transport and metabolism. Classification of lipoproteins is based on their density. Chylomicrons, VLDL, IDL, LDL and HDL can be isolated by ultracentrifugation. Both chylomicrons- and VLDL-triglycerides are transported from the intestine and liver, respectively, to the peripheral tissues. The metabolism of VLDL originates IDL and LDL. LDL is the main transporter of cholesterol to extrahepatic tissues. HDL mobilizes cholesterol from peripheral tissues to the liver where it is secreted to bile as free cholesterol or bile salts, a process termed reverse cholesterol transport. Lipoprotein metabolism can be regulated by nuclear receptors that regulate the expression of genes involved in triglyceride and apolipoprotein metabolism., (Copyright © 2013 Elsevier España, S.L. y SEA. All rights reserved.)

Introduction: The well-known drug resistance mechanisms to pentavalent antimony have been widely described in strains of the Leishmania subgenus, but little is known about the mechanisms of resistance and the proteins associated with it in strains of the Viannia subgenus such as Leishmania panamensis., Objective: Differentially expressed proteins were identified between pentavalent antimonial sensitive and resistant L. panamensis (UA140) strains, and the role of these proteins was analyzed as possible resistance mechanisms., Materials and Methods: The protein lysates of pentavalent antimony sensitive and resistant strains were separated by two-dimensional gel electrophoresis,and the protein patterns compared. The proteins identified as overexpressed were separated and analyzed using MALDI-TOF/TOF (Matrix Assisted Laser Desorption Ionization/Time of Flight). The level of mRNA expression of five of these proteins was quantified using real-time PCR., Results: On the 2-dimensional gels, 532 ± 39 protein spots were identified for the sensitive strains, and 541 ± 43 spots for the resistant strains. Ten spots were overexpressed in the resistant strain and identified as heat shock protein (Hsp60 mitochondrial, Hsp70 cytosolic and mitochondrial), disulfide isomerase, cysteine protease, enolase, elongation factor 5-alpha, the proteasome alpha-5 subunit and two hypothetical proteins named as Sp(2) and Sp(25)., Conclusion: This is the first proteomic study conducted with a L. panamensis resistant strain where several proteins were identified and related with the parasite resistance mechanism to pentavalent antimony. This opens the way for future studies aimed at modulating the drug resistance or at evaluating these proteins as therapeutic targets.

Background: Mammals have limited epithelial regeneration capacity. The K6b-E6/E7 mice model has been described as useful for the study of epithelial regeneration. The objective of this study is to compare the expression of E6/E7 oncogenes with those of cell proliferation and apoptosis during epithelization. The hypothesis of this study is that alterations in cell proliferation and apoptosis in K6b-E6/E7 mice will only occur during epithelization., Methods: Deep 2 mm punches were performed in the middle of transgenic and control mice's ears. A biopsy was collected from the epithelization zone 72 hours and 2 weeks post-injury. Assays for cell proliferation and apoptosis were carried out by immunohistochemistry and TUNEL techniques, respectively. RT-PCR in situ was performed to compare E6/E7 expressions in the areas studied., Results: Transgenic strain K6b-E6/E7 presented more proliferative cells and less apoptotic cells in epithelizated zones. This effect was limited to suprabasal stratum only, and correlates with E6/E7 oncogenes expression. Two weeks post-injury, cell proliferation and apoptosis were similar in both samples as the E6/E7 expression went down., Conclusion: K6b-E6/E7 mouse model is useful for epithelial regeneration. Its mechanisms should be considered for the treatment of deep wounds.

MicroRNAs (miRNAs) are small non-coding RNA molecules that negatively regulate gene expression. They actively participate in the modulation of important cell physiological processes and are involved in the pathogenesis of lung diseases such as lung cancer, pulmonary fibrosis, asthma and chronic obstructive pulmonary disease. A better understanding of the role that miRNAs play in these diseases could lead to the development of new diagnostic and therapeutic tools. In this review, we discuss the role of some miRNAs in different lung diseases as well as the possible future of these discoveries in clinical applications., (Copyright © 2012 SEPAR. Published by Elsevier Espana. All rights reserved.)