Mini-Review: The Contribution of Intermediate Phenotypes to GxE Effects on Disorders of Body Composition in the New OMICS Era

Abstract: Studies of gene-environment (GxE) interactions describe how genetic and environmental factors influence the risk of developing disease. Intermediate (molecular or clinical) phenotypes (IPs) are traits or metabolic biomarkers that mediate the effects of gene-environment influences on risk behaviors. Functional systems genomics discovery offers mechanistic insights into how DNA variations affect IPs in order to detect genetic causality for a given disease. Disorders of body compositionincludeobesity(OB),Type2diabetes(T2D),andosteoporosis(OSTP).Thesepathologies are examples of how a GxE interaction contributes to their development. IPs as surrogates for inherited genotypes play a key role in models of genetic and environmental interactions in health outcomes. Such predictive models may unravel relevant genomic and molecular pathways for preventive and therapeutic interventions for OB, T2D, and OSTP. Annotation strategies for genomes, in contrast to phenomes, are well advanced. They generally do not measure specific aspects of the environment. Therefore, the concepts of deep phenotyping and the exposome generate new avenues to exploit with high-resolution technologies for analyzing this sophisticated phenome. With the successful characterization of phenomes, exposomes, and genomes, environmental and geneticdeterminantsofchronicdiseasescanbeunitedwithmulti-OMICSstudiesthatbetterexamine GxE interactions. Keywords: GxE interactions; intermediate phenotypes; OMICS; diabetes; obesity; osteoporosis; phenome; exposom

Factores de riesgo para enfermedades metabólicas en adolescentes de tres etnias de Chihuahua, México

This study carried out in adolescents of the Mennonite, Tarahumara and Mestizo ethnic groups of the state of Chihuahua, Mexico, aims to make a description of the risk components for metabolic syndrome (MS) that our population has in current life, and that predispose to a large number of metabolic diseases. The following variables were reviewed: age, sex, BMI, waist circumference, fasting glucose, total cholesterol, triglycerides, HDL-C and blood pressure. The variables were compared according to the various criterion to determine the metabolic syndrome: IDF, NCEP-ATP III (Cook and de Ferranti) and WHO. The prevalence of MS in the sample was higher in Tarahumara adolescents (12.65%) compared to mestizos (11.95%) and Mennonites (7.15%), according to the ATP III criterion (De Ferranti). Conclusions. There is a significant statistical difference in the prevalence of MS in adolescents from different ethnic groups in Chihuahua.Este estudio realizado en adolescentes de las etnias Menonita, Tarahumara y Mestiza del estado de Chihuahua, pretende hacer una descripción de los componentes de riesgo para síndrome metabólico (SM) que en la vida actual tiene nuestra población, y que predisponen a un gran número de enfermedades metabólicas. Se revisaron las variables: edad, sexo, IMC, circunferencia de cintura, glucosa en ayunas, colesterol total, triglicéridos, c-HDL y presión arterial. Las variables fueron comparadas de acuerdo con los diversos criterios para determinar el síndrome metabólico: IDF, NCEP-ATP III (Cook y de Ferranti) y OMS. La prevalencia de SM en la muestra fue mayor en adolescentes tarahumaras (12.65%) en comparación con mestizos (11.95%) y menonitas (7.15%), de acuerdo con los criterios de la ATP III (De Ferranti). Conclusiones. Existe una diferencia estadística significante en la prevalencia de SM en adolescentes de los diferentes grupos étnicos de Chihuahua

Establecimiento de una plataforma molecular in vitro para desarrollar oocitos a partir de células madre embrionarias

Las células madre embrionarias (CME) son derivadas de la masa celular interna de blastocitos de mamíferos y debido a su pluripotencia in vitro e in vivo son capaces de generar los 200 tipos celulares identificados en el organismo. El uso de medios selectivos suplementados con determinados factores y la expresión artificial de genes que regulan vías de diferenciación específicas, ha permitido dirigir in vitro la diferenciación de las CME hacia tipos celulares especializados somáticos como células neuronales, cardiacas, etc. Recientes estudios han demostrado que la diferenciación espontánea de las CME, también puede dar origen in vitro a células de tipo germinal que posteriormente se desarrollan hacia células similares a gametos, como son los espermatozoides y óvulos. Lo anterior plantea la interesante idea de generar sistemas in vitro, que permitan dirigir la diferenciación de las CME hacia la formación in vitro de gametos. El desarrollo de estos sistemas tendrá un impacto directo en el entendimiento molecular de la programación genética, que interviene en los procesos de la oogénesis y espermatogénesis, así como el desarrollo de protocolos más eficientes para la clonación animal, clonación terapéutica, fertilización in vitro y transferencia de embriones. En relación a lo anterior, nuestro grupo de trabajo se ha enfocado al estudio de genes denominados ̈maestros ̈, cuya expresión además de darse en etapas muy tempranas de la determinación de la línea germinal, está en relación directa con el correcto desarrollo de las células germinales en los ovarios y testículos, características que los hace candidatos a ser utilizados para dirigir la diferenciación de las CME hacia células de linaje germinal. DOI: https://doi.org/10.54167/tecnociencia.v2i1.6

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic lowgrade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Towards precision medicine: defining and characterizing adipose tissue dysfunction to identify early immunometabolic risk in symptom-free adults from the GEMM family study

Interactions between macrophages and adipocytes are early molecular factors influencing adipose tissue (AT) dysfunction, resulting in high leptin, low adiponectin circulating levels and low-grade metaflammation, leading to insulin resistance (IR) with increased cardiovascular risk. We report the characterization of AT dysfunction through measurements of the adiponectin/leptin ratio (ALR), the adipo-insulin resistance index (Adipo-IRi), fasting/postprandial (F/P) immunometabolic phenotyping and direct F/P differential gene expression in AT biopsies obtained from symptom-free adults from the GEMM family study. AT dysfunction was evaluated through associations of the ALR with F/P insulin-glucose axis, lipid-lipoprotein metabolism, and inflammatory markers. A relevant pattern of negative associations between decreased ALR and markers of systemic low-grade metaflammation, HOMA, and postprandial cardiovascular risk hyperinsulinemic, triglyceride and GLP-1 curves was found. We also analysed their plasma non-coding microRNAs and shotgun lipidomics profiles finding trends that may reflect a pattern of adipose tissue dysfunction in the fed and fasted state. Direct gene differential expression data showed initial patterns of AT molecular signatures of key immunometabolic genes involved in AT expansion, angiogenic remodelling and immune cell migration. These data reinforce the central, early role of AT dysfunction at the molecular and systemic level in the pathogenesis of IR and immunometabolic disorders

Gluteal Compartment Syndrome following an Iliac Bone Marrow Aspiration

The compartment syndrome is a condition characterized by a raised hydraulic pressure within a closed and non expandable anatomical space. It leads to a vascular insufficiency that becomes critical once the vascular flow cannot return the fluids back to the venous system. This causes a potential irreversible damage of the contents of the compartment, especially within the muscle tissues. Gluteal compartment syndrome (GCS) secondary to hematomas is seldom reported. Here we present a case of a 51-year-old patient with history of a non-Hodgkin lymphoma who underwent a bone marrow aspiration from the posterior iliac crest that had excessive bleeding at the puncture zone. The patient complained of increasing pain, tenderness, and buttock swelling. Intraoperative pressure validation of the gluteal compartment was performed, and a GCS was diagnosed. The patient was treated with a gluteal region fasciotomy. The patient recovered from pain and swelling and was discharged shortly after from the hospital. We believe clotting and hematologic disorders are a primary risk factor in patients who require bone marrow aspirations or biopsies. It is important to improve awareness of GCS in order to achieve early diagnosis, avoid complications, and have a better prognosis

Physical activity, Cardio-Respiratory Fitness, and Metabolic Traits in Rural Mexican Tarahumara

OBJECTIVES: To study the association between physical activity energy expenditure (PAEE) and cardio-respiratory fitness (CRF) with key metabolic traits and anthropometric measures in the Tarahumara of Mexico. METHODS: A cross-sectional study was carried out in five rural communities in Chihuahua, México including 64 adult Tarahumara, mean (SD) age 40.7 (12.9) years. Using a combined accelerometer and heart rate sensor, PAEE was measured over three consecutive days and nights and a sub-maximal step test was carried out in order to (1) calibrate heart rate at the individual level and (2) to estimate CRF. Random blood glucose level and resting blood pressure (BP) were measured with standard anthropometrics. RESULTS: Mean (SD) PAEE was 71.2 (30.3) kJ kg(−1) day(−1) and CRF was 36.6 (6.5) mlO(2) min(−1) kg(−1). Mean (SD) glucose was 127.9 (32.4) mg/dl, with 3.3% having diabetes. Mean (SD) systolic and diastolic BP was 122 (20.8) and 82 (14.8) mm Hg, respectively, with 28.1% having hypertension. Mean body mass index was 27.5 (4.2) kg m(−2), with 71.9% being overweight. Following adjustment for age and sex, weak inverse associations were observed between PAEE and systolic BP (β = −0.20, P = 0.27) and diastolic BP (β = −0.16, P = 0.23); and between CRF and systolic BP (β = −0.51, P = 0.14) and diastolic BP (β = −0.53, P = 0.06). The inverse associations with glucose were also weak and not statistically significant for neither PAEE (β = −0.01, P = 0.63) nor CRF (β = −0.05, P = 0.27). CONCLUSIONS: This study suggests high levels of overweight and hypertension in the Tarahumara, and points to fitness and physical activity as potential intervention targets although findings should be confirmed in larger samples. Am. J. Hum. Biol. 2012. © 2012 Wiley Periodicals, Inc

Impact Evaluation of High Energy Ball Milling Homogenization Process in the Phase Distribution of Hydroxyapatite-Barium Titanate Plasma Spray Biocoating

Air plasma spray technique (APS) is widely used in the biomedical industry for the development of HA-based biocoatings. The present study focuses on the influence of powder homogenization treatment by high-energy ball milling (HEBM) in developing a novel hydroxyapatite-barium titanate (HA/BT) composite coating deposited by APS; in order to compare the impact of the milling process, powders were homogenized by mechanical stirring homogenization (MSH) too. For the two-homogenization process, three weight percent ratios were studied; 10%, 30%, and 50% w/w of BT in the HA matrix. The phase and crystallite size were analyzed by X-ray diffraction patterns (XRD); the BT-phase distribution in the coating was analyzed by backscattered electron image (BSE) with a scanning electron microscope (SEM); the energy-dispersive X-ray spectroscopy (EDS) analysis was used to determinate the Ca/P molar ratio of the coatings, the degree of adhesion (bonding strength) of coatings was determinate by pull-out test according to ASTM C633, and finally the nanomechanical properties was determinate by nanoindentation. In the results, the HEBM powder processing shows better efficiency in phase distribution, being the 30% (w/w) of BT in HA matrix that promotes the best bonding strength performance and failure type conduct (cohesive-type), on the other hand HEBM powder treatment promotes a slightly greater crystal phase stability and crystal shrank conduct against MSH; the HEBM promotes a better behavior in the nanomechanical properties of (i) adhesive strength, (ii) cohesive/adhesive failure-type, (iii) stiffness, (iv) elastic modulus, and (v) hardness properties