Asociación de genes de la cadena mitocondrial respiratoria en el desarrollo de diabetes mellitus tipo 2 y parámetros relacionados

Introducción: la diabetes mellitus tipo 2 (DMT2) es una enfermedad compleja, resultado de la combinación de factores ambientales, genéticos y adquiridos. Se ha convertido en una epidemia global que contribuye significativamente a la morbi-mortalidad prematura. Su heredabilidad es de un 70%; no obstante, los estudios realizados sólo han podido identificar una pequeña proporción de este componente genético. La cadena mitocondrial respiratoria (CMR) es esencial en el metabolismo energético y en la producción de especies reactivas del oxígeno (ROS). Un mal funcionamiento de este sistema biológico parece estar implicado en la DMT2 y otras alteraciones relacionadas (obesidad, hipertensión). Sin embargo, sólo se han estudiado hasta el momento unos pocos genes de los que codifican proteínas de la CMR. Objetivos: estudiar la posible asociación entre genes pertenecientes a la CMR con el riesgo de padecer DMT2, parámetros asociados y otros desórdenes asociados como la obesidad e hipertensión. Metodología: Fase 1: análisis de 96 polimorfismos localizados en 29 genes de la CMR en 3701 individuos (Estudios Pizarra, Segovia y Hortega), mediante la técnica SNPlex. Fase 2: secuenciación de los genes (exones y secuencias intrónicas contiguas) asociados en la fase 1, por metodología Sanger, en 50 controles y 50 casos. Fase 3: estudio de las variantes identificadas en la fase 2, en las muestras incluidas en la Fase 1, mediante secuenciación de nueva generación (NGS). Fase 4: análisis de todos los polimorfismos previamente identificados con DMT2 y parámetros relacionados, en el estudio [email protected], utilizando NGS. Resultados: Se encontraron 17 asociaciones significativas de los polimorfismos analizados en las distintas poblaciones analizadas y para los distintos parámetros relacionados con la DMT2. Cinco polimorfismos pertenecientes a estas asociaciones mostraron un comportamiento similar en la nueva población estudiada, y se han validado sus efectos en el análisis de la población total de este trabajo. Las asociaciones confirmadas al analizar la población conjunta, han sido la asociación de SNPs del gen UQCRB y la glucemia en la población femenina, del gen NDUFS3 y el riesgo de DMT2 en obesos; mientras que en los individuos no obesos, han sido las de los genes NDUFS2 y COX7C con la DMT2 y la del gen NDUFS5 con la PAD. Conclusiones: Hemos encontrado asociaciones relevantes de los genes de la CMR con la DMT2 y parámetros relacionados, como la obesidad y la hipertensión. Estos resultados se han replicado en las diferentes muestras que incluye el presente estudio, lo que confirma la asociación de la CMR con el desarrollo de la DMT2. Se deberán realizar más estudios para verificar estas asociaciones y conocer los mecanismos por los que las diferentes variantes pueden actuar sobre el riesgo de desarrollar DMT2.Introduction: Type 2 diabetes mellitus (T2DM) is a complex disease, a result of combination of environmental, genetic and acquired factors. It has become a global epidemic, which contributs significantly to premature morbidity and mortality. Its heritability is 70%. However, studies have only been able to identify a small proportion of this genetic component. The respiratory mitochondrial chain (CMR) is essential in energy metabolism and in production of reactive oxygen species (ROS). A malfunction of this biological system appears to be involved in T2DM and other related disorders (obesity, hypertension). Only a few genes coding for CMR were studied. Objectives: to study the possible association between genes belonging to the CMR with the risk of suffering DMT2, associated parameters and other associated disorders such as obesity and hypertension. Methodology: Phase 1: analysis of 96 polymorphisms located in 29 CMR genes in 3701 individuals (Pizarra, Segovia and Hortega Studies) using the SNPlex technique. Phase 2: Sequencing of the genes (promotors, exons and contiguous intronic sequences) associated in phase 1, by Sanger methodology, in 50 controls and 50 cases. Phase 3: study of the variants identified in phase 2, in the samples included in Phase 1, through new generation sequencing (NGS). Phase 4: analysis of all previously identified polymorphisms with DMT2 and parameters related, in the study [email protected], using NGS. Results: We found 17 significant associations of the polymorphisms analyzed in the different populations studied, with different parameters related to DMT2. Five polymorphisms belonging to these associations showed similar behavior in the new population, and their effects have been validated in the analysis of the total population of this work. The associations confirmed when analyzing the cohort population, have been the association of SNPs from gene UQCRB and glycemia in the female population; from gene NDUFS3 and the risk of T2DM in obese individuals; whereas in non-obese individuals, the NDUFS2 and COX7C genes have been associated with DMT2 and SNPs of the NDUFS5 gene with the PAD. Conclusions: We found relevant associations of the CMR genes with DMT2 and related parameters, such as obesity and hypertension. These results have been replicated in different samples included in the present study, confirming the association of the CMR with the development of DMT2. Further studies should be carried out to verify these associations and to clarify mechanisms by which the different variants may act on the risk of developing DMT2

Interleukin-8 and laryngeal squamous cell carcinoma

Laryngeal squamous cell carcinoma (LSCC) is the second most common neoplasm of the upper aerodigestive tract after cancer of the oral cavity. Over the past two decades, even though patients have benefited greatly from the latest advances in surgical techniques, chemotherapy and radiation therapy, the survival rate of LSCC has not improved significantly. It is reported that changes in the expression of cytokines and growth factors have implications in the malignant transformation of many cancers including head and neck squamous cell carcinoma and, more recently, LSCC. It has been hypothesized that some of these cytokines may be used as additional diagnostic markers in the sera of patients because of their excessive production by the tumor cells. This could be of great value since there are currently no reliable markers to predict either tumor development or relapse. Interleukin-8 (IL-8), a chemokine (C-X-C motif) ligand 8 (CXCL8), is now reported to play an important role in cancer invasion, angiogenesis and metastasis. Recent studies have shown an increased concentration of IL-8 in patients with LSCC and a positive association with lymph node metastasis and T classification. Interleukin-8 levels were not significantly associated with shorter overall survival and cancer progression-free survival. The investigation of the mechanisms of origin, invasion, and metastasis of the cancer is one of the emergent and most promising scientific fields in head and neck cancer, especially in LSCC. Biomarkers such as IL-8 could have a role as a screening test and as a support of the clinical decisions for appropriate therapy and postoperative care in individual patients

A controlled, randomized clinical study to verify the efficacy and safety of a new hypertonic solution (Narlisim) in nasal congestion in adults affected by common cold

Background: Nasal congestion is the main symptom of common cold. Symptomatic treatment with nasal decongestant seems to be the only treatment option. We managed a study to assess the efficacy of Narlisim, a developed nasal spray, on nasal congestions in common cold. Materials and methods: In this study, sixty adult patients with common cold were included. Thirty patients were treated with Narlisim nasal spray, and 30 patients with isotonic nasal spray. The primary outcome was the assessment of the speed of relief of nasal congestion; the secondary outcome was the assessment of nasal congestion and nasal secretion symptoms by a 0–100% rating Visual analog score (VAS) scale on 5 items at baseline and after 5, 10, 15, 20, 25 and 30 minutes from treatment. Results: VAS score progressively reduced for all investigated symptoms in both groups; a statistically significant higher mean reduction at each time point was recorded in the study group compared to controls (p<0.001). Conclusions: Our results suggest that Narlisim may be a promising medical device to control nasal congestion and rhinitis in common cold thanks to its nasal washing, hypertonic city, and low pH and osmo protection properties

Rapid Oxford Nanopore Technologies MinION Sequencing Workflow for Campylobacter jejuni Identification in Broilers on Site-A Proof-of-Concept Study

[EN] Campylobacter is recognised as one of the most important foodborne bacteria, with a worldwide health and socioeconomic impact. This bacterium is one of the most important zoonotic players in poultry, where efficient and fast detection methods are required. Current official culture methods for Campylobacter enumeration in poultry usually include >44 h of culture and >72 h for identification, thus requiring at least five working shifts (ISO/TS 10272-2:2017). Here, we have assembled a portable sequencing kit composed of the Bento Lab and the MinION and developed a workflow for on-site farm use that is able to detect and report the presence of Campylobacter from caecal samples in less than five hours from sampling time, as well as the relationship of Campylobacter with other caecal microbes. Beyond that, our workflow may offer a cost-effective and practical method of microbiologically monitoring poultry at the farm. These results would demonstrate the possibility of carrying out rapid on-site screening to monitor the health status of the poultry farm/flock during the production chain.Laura Lorenzo-Rebenaque was supported by a research grant from the Generalitat Valenciana-Fondo Social Europeo (ACIF/2020/376).Marin, C.; Marco-Jiménez, F.; Martínez-Priego, L.; De Marco-Romero, G.; Soriano-Chirona, V.; Lorenzo-Rebenaque, L.; D Auria, G. (2022). Rapid Oxford Nanopore Technologies MinION Sequencing Workflow for Campylobacter jejuni Identification in Broilers on Site-A Proof-of-Concept Study. Animals. 12(16):1-13. https://doi.org/10.3390/ani12162065113121

Laryngeal tuberculosis in renal transplant recipients: a case report and review of the literature

Renal allograft recipients are at greater risk of developing tuberculosis than the general population. A woman with a kidney transplant was admitted to the emergency department with high temperature, dysphonia, odynophagia, and asthenia. The final diagnosis was laryngeal tuberculosis. Multidisciplinary collaboration enabled accurate diagnosis and successful treatment. Laryngeal tuberculosis should be considered in renal allograft recipients with hoarseness. A more rapid diagnosis of tuberculosis in renal transplant recipients is desirable when the site involved, such as the larynx, exhibits specific manifestations and the patient exhibits specific symptoms. In these cases, prognosis is excellent, and with adequate treatment, a complete recovery is often achieved

Modelos de Crecimiento de Frutos de Limonero 'Eureka' de la Provincia de Corrientes, Argentina

El objetivo de este trabajo fue modelar el crecimiento de limonero ‘Eureka’ (Citrus limón (L.) Burn f) injertado sobre Limón Rugoso (Citrus jambhiri Lush), desde los 60 días después de plena floración hasta la cosecha, en plantaciones comerciales, de la provincia de Corrientes, Argentina. Para ello se registró el diámetro ecuatorial de frutos desde los 60 días después de plena floración hasta el momento de cosecha en cuatro ambientes de la provincia de Corrientes, Argentina. Para describir el crecimiento se compararon los modelos no lineales de tipo sigmoideo: logístico, Gompertz y monomolecular. Se utilizaron como criterios de selección de los modelos: AIC, BIC y el CME (cuadrado medio del error). La precisión del modelo seleccionado se obtuvo mediante validación cruzada. Los modelos seleccionados para describir el crecimiento de frutos de limonero ‘Eureka’ fueron los modelos monomolecular y logístico, los cuales tuvieron un error de estimación que fue medido en términos del CME con valores menores a 20,03. Los parámetros estimados para los modelos seleccionados resultaron significativos (p &lt; 0,01). De esta manera, productores, y empresas exportadoras citrícolas de la región podrán contar con una herramienta con la que puedan predecir la producción al momento de cosecha y así para prever estrategias de comercialización

The nutrigenetic influence of the interaction between dietary vitamin E and TXN and COMT gene polymorphisms on waist circumference: a case control study

Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND Abdominal obesity (AO) is a common modifiable risk factor for certain non-communicable diseases associated with enhanced oxidative stress (OS). The objective of this work was to investigate whether the interaction between antioxidant vitamin intake and OS-related polymorphisms modulates gene-associated anthropometry in a Spanish population. METHODS A total of 246 subjects with AO, and 492 age and gender matched non-AO subjects were included in the study. Anthropometric, biochemical, and OS parameters, and antioxidant dietary intake data were assessed using validated procedures. DNA from white blood cells was isolated and the genotype of seven polymorphisms from genes involved in OS (pro-oxidant and antioxidant) were analyzed using the SNPlex system. The effects of the c.-793T > C polymorphism on promoter activity and thus thioredoxin (TXN) activity were examined using reporter assays. RESULTS The AO group had higher 8-Oxo-2'-deoxyguanosine levels and took in less vitamin A and vitamin E compared to the non-AO group. Logistic regression analysis revealed that the rs2301241 polymorphism in TXN and rs740603 in catechol-O-methyltransferase (COMT) were associated with waist circumference (WC) and AO. Moreover, these polymorphisms were more strongly associated with variations in WC in subjects with low vitamin E intakes. A promoter assay revealed that the T to C conversion at c.-793 (rs2301241) induced a more than two fold increase in reporter gene expression. CONCLUSIONS WC is associated both with dietary vitamin E intake and genetic variants of TXN and COMT suggesting that existence of a complex nutrigenetic pathway that involves regulation of AO.This work was co-funded with European Funds for Regional Development (FEDER), the Spanish Science and Technology Ministry [SAF2005-02883]; the health research fund from the Carlos III Health Institute [PI070497], CIBER Fisiopatología Obesidad y Nutrición (CIBERobn) [CB06/03], and CIBER de Diabetes y Enfermedades Metabólicas Relacionadas (CIBERDEM). CIBEROB and CIBERDEM are initiatives by the Carlos III Health Institute in Madrid and the Spanish Health Ministry. Funding also came from GRUPOS 03/101, PROMETEO/2009/029 and 2005/027, AMP07/075, and ACOMP/2009/201 from the Valencian Government and European Network of Excellence InGenious HyperCare (EPSS-037093) from the European Commission.Ye

ELOVL6 Genetic Variation Is Related to Insulin Sensitivity: A New Candidate Gene in Energy Metabolism

BACKGROUND: The elongase of long chain fatty acids family 6 (ELOVL6) is an enzyme that specifically catalyzes the elongation of saturated and monounsaturated fatty acids with 12, 14 and 16 carbons. ELOVL6 is expressed in lipogenic tissues and it is regulated by sterol regulatory element binding protein 1 (SREBP-1). OBJECTIVE: We investigated whether ELOVL6 genetic variation is associated with insulin sensitivity in a population from southern Spain. DESIGN: We undertook a prospective, population-based study collecting phenotypic, metabolic, nutritional and genetic information. Measurements were made of weight and height and the body mass index (BMI) was calculated. Insulin resistance was measured by homeostasis model assessment. The type of dietary fat was assessed from samples of cooking oil taken from the participants' kitchens and analyzed by gas chromatography. Five SNPs of the ELOVL6 gene were analyzed by SNPlex. RESULTS: Carriers of the minor alleles of the SNPs rs9997926 and rs6824447 had a lower risk of having high HOMA_IR, whereas carriers of the minor allele rs17041272 had a higher risk of being insulin resistant. An interaction was detected between the rs6824447 polymorphism and the intake of oil in relation with insulin resistance, such that carriers of this minor allele who consumed sunflower oil had lower HOMA_IR than those who did not have this allele (P = 0.001). CONCLUSIONS: Genetic variations in the ELOVL6 gene were associated with insulin sensitivity in this population-based study

The nutrigenetic influence of the interaction between dietary vitamin E and TXN and COMT gene polymorphisms on waist circumference: a case control study

Background: Abdominal obesity (AO) is a common modifiable risk factor for certain non-communicable diseases associated with enhanced oxidative stress (OS). The objective of this work was to investigate whether the interaction between antioxidant vitamin intake and OS-related polymorphisms modulates gene-associated anthropometry in a Spanish population. Methods: A total of 246 subjects with AO, and 492 age and gender matched non-AO subjects were included in the study. Anthropometric, biochemical, and OS parameters, and antioxidant dietary intake data were assessed using validated procedures. DNA from white blood cells was isolated and the genotype of seven polymorphisms from genes involved in OS (pro-oxidant and antioxidant) were analyzed using the SNPlex system. The effects of the c.-793T > C polymorphism on promoter activity and thus thioredoxin (TXN) activity were examined using reporter assays. Results: The AO group had higher 8-Oxo-2′-deoxyguanosine levels and took in less vitamin A and vitamin E compared to the non-AO group. Logistic regression analysis revealed that the rs2301241 polymorphism in TXN and rs740603 in catechol-O-methyltransferase (COMT) were associated with waist circumference (WC) and AO. Moreover, these polymorphisms were more strongly associated with variations in WC in subjects with low vitamin E intakes. A promoter assay revealed that the T to C conversion at c.-793 (rs2301241) induced a more than two fold increase in reporter gene expression. Conclusions: WC is associated both with dietary vitamin E intake and genetic variants of TXN and COMT suggesting that existence of a complex nutrigenetic pathway that involves regulation of AO

The SeqCOVID-Spain consortium: unravelling the dynamics of the COVID-19 first epidemic wave in Spain

Póster presentado a la Applied Bioinformatics and Public Health Microbiology 2021 Virtual Conference, celebrada del 5 al 7 de mayo de 2021.The COVID-19 pandemic has shaken the world since the beginning of 2020. Spain is among the European countries with the highest incidence of the disease during the first pandemic wave. We established a multidisciplinary consortium to monitor and study the evolution of the epidemic, with the aim of contributing to decision making and stopping rapid spreading across the country. We present the results for 2170 sequences from the first wave of the SARS-Cov-2 epidemic in Spain, representing 12% of diagnosed cases until 14th March. This effort allows us to document at least 500 initialintroductions, between early February-March from multiple international sources. Importantly, we document the early raise of two dominant genetic variants in Spain (Spanish Epidemic Clades), named SEC7 and SEC8, likely amplified by superspreading events. In sharp contrast to other non Asian countries those two variants were closely related to the initial variants of SARS-CoV-2 described in Asia and represented 40% of the genome sequences analyzed. The two dominant SECs were widely spread across the country compared to other genetic variants with SEC8 reaching a 60% prevalence just before the lockdown. Employing Bayesian phylodynamic analysis, we inferred a reduction in the effective reproductive number of these two SECs from around 2.5 to below 0.5 after the implementation of strict public-health interventions in mid-March. The effects of lockdown on the genetic variants of the virus are reflected in the general replacement of pre-existing SECs by a new variant at the beginning of the summer season. Our results reveal a significant difference in the genetic makeup of the epidemic in Spain and support the effectiveness of lockdown measures in controlling virus spread even for the most successful genetic variants.This work was funded by the Instituto de Salud Carlos III project COV20/00140, Spanish National Research Council project CSIC-COV19-021, Ministerio de Ciencia PID2019-104477RB-I00 and ERC StG 638553 to IC, and BFU2017-89594R to FGC. MC is supported by Ramón y Cajal program from Ministerio de Ciencia and grants RTI2018-094399-A-I00 and SEJI/2019/011.Peer reviewe