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1.
Elife ; 122024 Apr 03.
Article in English | MEDLINE | ID: mdl-38567749

ABSTRACT

Vitamin D possesses immunomodulatory functions and vitamin D deficiency has been associated with the rise in chronic inflammatory diseases, including asthma (Litonjua and Weiss, 2007). Vitamin D supplementation studies do not provide insight into the molecular genetic mechanisms of vitamin D-mediated immunoregulation. Here, we provide evidence for vitamin D regulation of two human chromosomal loci, Chr17q12-21.1 and Chr17q21.2, reliably associated with autoimmune and chronic inflammatory diseases. We demonstrate increased vitamin D receptor (Vdr) expression in mouse lung CD4+ Th2 cells, differential expression of Chr17q12-21.1 and Chr17q21.2 genes in Th2 cells based on vitamin D status and identify the IL-2/Stat5 pathway as a target of vitamin D signaling. Vitamin D deficiency caused severe lung inflammation after allergen challenge in mice that was prevented by long-term prenatal vitamin D supplementation. Mechanistically, vitamin D induced the expression of the Ikzf3-encoded protein Aiolos to suppress IL-2 signaling and ameliorate cytokine production in Th2 cells. These translational findings demonstrate mechanisms for the immune protective effect of vitamin D in allergic lung inflammation with a strong molecular genetic link to the regulation of both Chr17q12-21.1 and Chr17q21.2 genes and suggest further functional studies and interventional strategies for long-term prevention of asthma and other autoimmune disorders.


Subject(s)
Asthma , Pneumonia , Vitamin D Deficiency , Mice , Animals , Humans , Vitamin D/pharmacology , Interleukin-2 , Inflammation , Th2 Cells , Vitamin D Deficiency/metabolism , Vitamins
2.
Am J Ther ; 20(4): 448-58, 2013.
Article in English | MEDLINE | ID: mdl-23838635

ABSTRACT

Sedentarism is considered a risk factor for coronary heart disease and death from any cardiovascular disease. The International Physical Activity Questionnaire (IPAQ) assesses physical activity in metabolic equivalents, using 4 dimensions: occupation, transportation, household activities, and leisure-time physical activity. The purpose of this investigation was to assess physical activity levels in the patients enrolled in the Maracaibo City Metabolic Syndrome Prevalence Study, currently undertaken by the "Dr. Félix Gómez" Endocrine-Metabolic Research Center. Two thousand one hundred eight individuals were recruited and subjected to a standard Medical chart, Graffar scale, and IPAQ long form, applied by trained personnel. Description of the population was done using mean, SD, and coefficient of variation. IPAQ scores were analyzed as medians and distributed by percentiles. From the 2108 individuals, 46.9% were men and 53.1% were women. The most prevalent physical activity was high physical activity with 39.9%, followed by moderate physical activity with 36.9% and low physical activity with 23.2%. Medians for each IPAQ dominion were occupation with 0.00 (0.00-66.00), transportation with 165.00 (0.00-463.00), household activities with 772.50 (0.00-2520.00), and leisure time with 0.00 (0.00-594.00). Using leisure-time scores, a new reclassification was conducted, obtaining 1245 subjects with 0 metabolic equivalents in this dominion. From this new subsample, 43.6% had High physical activity, 56.95% had Moderate physical activity, and 91% had Low physical activity, demonstrating an important overestimation in the former sample results. IPAQ overestimates moderate and vigorous activity in the adult population of the Maracaibo Municipality. Overestimation is mainly located in the household- and gardening-related activity.


Subject(s)
Exercise , Leisure Activities , Motor Activity , Surveys and Questionnaires , Adolescent , Adult , Aged , Cross-Sectional Studies , Female , Humans , Male , Middle Aged , Occupations/statistics & numerical data , Sedentary Behavior , Transportation/statistics & numerical data , Venezuela , Young Adult
3.
Av. diabetol ; 28(6): 123-130, nov.-dic. 2012. ilus, graf, tab
Article in Spanish | IBECS | ID: ibc-108171

ABSTRACT

El síndrome metabólico (SM), es un término empleado en los últimos años para designar un grupo de factores de riesgo que incluyen obesidad visceral, hipertensión arterial, hiperglucemia y dislipidemia aterogénica, los cuales predisponen al individuo a desarrollar enfermedad cardiovascular (ECV) y diabetes mellitus tipo 2 (DM2). La actividad física ha sido parte fundamental para entender el SM y su etiología, ya que el sedentarismo se asocia con ganancia de peso y aumento de grasa visceral, lo cual predispone al individuo a una adipocitopatía proinflamatoria con resistencia insulínica y aparición del fenotipo característico del SM. Los efectos beneficiosos que el ejercicio ejerce sobre el cuerpo humano justifican la evaluación, planificación y aplicación de programas de intervención que disminuyan el riesgo de DM2 y ECV. La siguiente revisión analiza los conceptos, bases moleculares y evidencia clínica del ejercicio como abordaje primordial en los trastornos endocrino-metabólicos


Metabolic syndrome (MS) is a term that has been used in the last decades to define a group of risk factors that include: visceral obesity, arterial hypertension, hyperglycemia and atherogenic dyslipidemia, which predispose the individual to cardiovascular disease (CVD) and type 2 diabetes mellitus (DM2). Physical activity has been a fundamental element to understand MS and its etiology, given the fact that sedentarism is associated with weight gain and increased abdominal fat, which then predisposes the individual to a pro-inflammatory adiposopathy with insulin resistance, and the manifestation of the MS phenotype. The beneficial effects of exercise on the human body are of sufficient merit to evaluate, plan and apply intervention programs that lower the risk for DM2 and CVD. The following review analyzes the concept, molecular basis, and clinical evidence for exercise as a primary tool in endocrine and metabolic disorders


Subject(s)
Humans , Metabolic Diseases/therapy , Motor Activity , Diabetes Mellitus, Type 2/therapy , Risk Factors , Exercise
4.
Transgenic Res ; 12(3): 305-18, 2003 Jun.
Article in English | MEDLINE | ID: mdl-12779119

ABSTRACT

We investigated the effect of the Rb7 matrix attachment region (MAR) on trans-silencing in tobacco plants, comparing the effects of three transgene silencer loci on ten target loci. Two of the silencer loci, C40 and C190, contain complex and rearranged transgene arrays consisting of 35S:GUS or NOS:NPTII containing plasmids. The third silencer locus, V271, was previously characterized as a complex locus containing rearranged 35S:RiN sequences. Each of these silencers can reduce 35S promoter-driven expression at other loci, albeit with varying efficiencies. The presence of MARs at a target locus does not prevent trans-silencing by the V271 silencer. However, four of seven MAR-containing loci were at least partially resistant to silencing by the C40 and C190 loci. One MAR locus was unaffected by C40, our weakest silencer, and three were silenced only when the silencer locus was maternally inherited. Silencing is progressive in the F1 and F2 generations; two days after germination there is little or no difference between seedlings derived from crosses to silencing or control lines, but seedlings containing silencer loci slowly lose expression during subsequent development. These observations are compatible with the hypothesis that a product of the silencer locus must accumulate before unlinked loci can be affected. However, our silencer loci are themselves silenced for GUS transcription, and coding region homology is not required for their effects on target loci. Our results are consistent with a model in which transcriptional silencing is triggered by transcription of sequences during the early stages of embryo or seedling development.


Subject(s)
Gene Silencing , Matrix Attachment Regions/genetics , Nicotiana/genetics , Transcription, Genetic , Inheritance Patterns , Seedlings/genetics , Sequence Homology , Silencer Elements, Transcriptional
5.
Br J Psychiatry ; 155: 79-85, 1989 Jul.
Article in English | MEDLINE | ID: mdl-2605436

ABSTRACT

Ninety-three patients with acute stroke lesions restricted to the right hemisphere were examined for the presence of mood changes. While 46 patients showed no mood changes, 19 were unduly cheerful, 17 had developed major depression, and 11 had developed minor depression. Although there were no significant between-groups differences in other demographic variables, neurological deficits, activities of daily living, cognitive impairment, or quality of social support, patients with major depression had a significantly higher frequency of familial history of psychiatric disorder and lesions of the parietal cortex than patients with either no mood change or major depression following left-hemisphere lesions. On the other hand, undue cheerfulness was significantly associated with lesions of the right frontal operculum. These findings suggest that major depression following right-hemisphere lesions may have a different aetiology and mechanism than major depression following left frontal or basal ganglia lesions.


Subject(s)
Brain Damage, Chronic/diagnosis , Dominance, Cerebral/physiology , Mood Disorders/diagnosis , Neurocognitive Disorders/diagnosis , Activities of Daily Living , Brain/pathology , Cerebral Infarction/diagnosis , Depressive Disorder/diagnosis , Female , Humans , Male , Middle Aged , Mood Disorders/genetics , Neurocognitive Disorders/genetics , Psychiatric Status Rating Scales , Risk Factors , Tomography, X-Ray Computed
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