RESUMEN

Several studies provide evidence that obesity is a significant risk factor for adverse outcomes in coronavirus disease 2019 (COVID-19). Altered renal function and disturbances in magnesium levels have been reported to play important pathophysiological roles in COVID-19. However, the relationship between obesity, renal function, circulating magnesium levels, and mortality in patients with COVID-19 remains unclear. In this retrospective cohort study, we characterized 390 hospitalized patients with COVID-19 that were categorized according to their body mass index (BMI). Patients were clinically characterized and biochemical parameters, renal function, and electrolyte markers measured upon admission. We found that in patients who died, BMI was associated with reduced estimated glomerular filtration rate (eGFR, Rho: −0.251, p = 0.001) and serum magnesium levels (Rho: −0.308, p < 0.0001). Multiple linear regression analyses showed that death was significantly associated with obesity (p = 0.001). The Cox model for obese patients showed that magnesium levels were associated with increased risk of death (hazard ratio: 0.213, 95% confidence interval: 0.077 to 0.586, p = 0.003). Thus, reduced renal function and lower magnesium levels were associated with increased mortality in obese COVID-19 patients. These results suggest that assessment of kidney function, including magnesium levels, may assist in developing effective treatment strategies to reduce mortality among obese COVID-19 patients.

Asunto(s)

COVID-19 , Insuficiencia Renal , COVID-19/complicaciones , Tasa de Filtración Glomerular/fisiología , Humanos , Riñón/fisiología , Magnesio , Obesidad/complicaciones , Insuficiencia Renal/complicaciones , Estudios Retrospectivos , Factores de Riesgo

RESUMEN

Oxidative stress plays an important role in vascular complications observed in patients with obesity and Type 2 Diabetes (T2D). Xanthine oxidase (XO) breaks down purine nucleotides into uric acid and contributes to the production of reactive oxygen species (ROS). However, the relationship between XO activity and glucose homeostasis in T2D subjects with obesity is unclear. We hypothesized that disordered glucose levels are associated with serum XO activity in overweight women and men with T2D and without hyperuricemia. We studied serum XO activity in women and men with and without T2D. Our results show that serum XO activity was greater in T2D patients with body mass index (BMI) ≥ 25 kg/m2 than in those with BMI < 25 kg/m2 (p < 0.0001). Sex-based comparative analyses of overweight T2D patients showed that serum XO activity correlated with homeostasis model assessment of ß-cell function (HOMA-ß), fasting plasma glucose (FPG), and hemoglobin A1C in overweight T2D women but not in overweight T2D men. In addition, as compared to overweight T2D men, women had higher high-sensitivity C-reactive protein (hs-CRP) levels. However, overweight T2D men had higher XO activity and uric acid levels than women. Our results suggest that XO activity is higher in overweight T2D patients, especially in men, but is more sensitive to disordered glucose levels in overweight women with T2D.

Asunto(s)

Diabetes Mellitus Tipo 2 , Sobrepeso , Glucemia/análisis , Proteína C-Reactiva/metabolismo , Diabetes Mellitus Tipo 2/complicaciones , Femenino , Hemoglobina Glucada/análisis , Humanos , Masculino , Obesidad/complicaciones , Sobrepeso/complicaciones , Nucleótidos de Purina , Especies Reactivas de Oxígeno/metabolismo , Ácido Úrico , Xantina Oxidasa/metabolismo

RESUMEN

Cardiovascular disease (CVD) is a common comorbidity observed in patients with coronavirus disease 2019 (COVID-19), which is associated with increased severity and mortality. However, the effects of biological sex on CVD-associated mortality in patients with COVID-19 are poorly established, particularly among Hispanic/Latin Americans. We examined the association of preexisting CVD with COVID-19 mortality in hospitalized Latin American men and women. This multicenter study included Mexican patients hospitalized with a positive diagnosis of COVID-19. The main outcome was in-hospital mortality. Multivariable regression analyses were used to calculate the adjusted odds ratio with 95% confidence interval for mortality in women and men. Of 81,400 patients with a positive diagnosis for SARS-CoV-2 infection, 28,929 (35.54%) hospitalized patients were evaluated. Of these, 35.41% (10,243) were women. In-hospital death was higher in men than in women. In relation to CVD between the sexes, women had a higher incidence of CVD than men (4.69 vs. 3.93%, P = 0.0023). The adjusted logistic regression analyses showed that CVD was significantly associated with COVID-19 mortality in women but not men. We then stratified by sex according to age <52 and ≥52 yr old. Similar significant association was also found in prespecified analysis in women ≥52 yr old but not in men of similar age. We conclude that CVD's effect on mortality among patients hospitalized with COVID-19 is dependent on biological sex and age in this Latin American cohort. These results suggest that therapeutic strategies for Latin American women with CVD and COVID-19 should include particular attention to their cardiovascular health.NEW & NOTEWORTHY CVD's effect on COVID-19 mortality is dependent on biological sex and age. CVD in women but not men with COVID-19 is associated with significantly unfavorable outcomes.

Asunto(s)

COVID-19 , Enfermedades Cardiovasculares , Enfermedades Cardiovasculares/epidemiología , Comorbilidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Factores de Riesgo , SARS-CoV-2

RESUMEN

Patients with type 2 diabetes (T2D) and Latin American subjects in particular are at an increased risk of developing severe COVID-19 and mortality. Altered renal function and lower magnesium levels have been reported to play important roles in the pathophysiology of T2D. The aim of the study was to investigate the relationship between renal function, serum magnesium levels and mortality in T2D patients with COVID-19. In this retrospective study, we characterized 118 T2D and non-diabetic subjects hospitalized with COVID-19. Patients were clinically characterized and electrolyte, renal function and inflammatory markers were evaluated. Patients were grouped according to their estimated glomerular filtration rate (eGFR <60 mL/min per 1.73 m2). T2D patients had lower eGFR and serum magnesium levels when compared to non-diabetics (59.7 ± 32.8 vs. 78.4 ± 33.8 mL/min per 1.73 m2, P = 0.008 and 1.9 ± 0.3 vs. 2.1 ± 0.3 mEq/L, P = 0.012). Survival was worse in T2D patients with eGFR levels less than 60 mL/min per 1.73 m2 as estimated by Kaplan-Meier analyses (log-rank test <0.0001). The Cox model for T2D patients showed that eGFR (HR 0.970, 95% CI 0.949 to 0.991, P = 0.005) and magnesium (HR 8.025, 95% CI 1.226 to 52.512, P = 0.030) were associated with significantly increased risk of death. Reduced eGFR and magnesium levels were associated with increased mortality in our population. These results suggest that early assessment of kidney function, including magnesium levels, may assist in developing effective treatment strategies to reduce morbidity and mortality among Latin American COVID-19 patients with T2D.

Asunto(s)

COVID-19 , Diabetes Mellitus Tipo 2 , Riñón/fisiopatología , Magnesio/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , COVID-19/sangre , COVID-19/complicaciones , COVID-19/diagnóstico , COVID-19/mortalidad , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/sangre , Diabetes Mellitus Tipo 2/complicaciones , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/mortalidad , Nefropatías Diabéticas/sangre , Nefropatías Diabéticas/complicaciones , Nefropatías Diabéticas/diagnóstico , Nefropatías Diabéticas/mortalidad , Femenino , Tasa de Filtración Glomerular/fisiología , Mortalidad Hospitalaria , Humanos , Riñón/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/diagnóstico , Insuficiencia Renal Crónica/mortalidad , Estudios Retrospectivos , SARS-CoV-2/fisiología , Análisis de Supervivencia

RESUMEN

The identification of nested motifs in genomic sequences is a complex computational problem. The detection of these patterns is important to allow the discovery of transposable element (TE) insertions, incomplete reverse transcripts, deletions, and/or mutations. In this study, a de novo strategy for detecting patterns that represent nested motifs was designed based on exhaustive searches for pairs of motifs and combinatorial pattern analysis. These patterns can be grouped into three categories, motifs within other motifs, motifs flanked by other motifs, and motifs of large size. The methodology used in this study, applied to genomic sequences from the plant species Aegilops tauschii and Oryza sativa, revealed that it is possible to identify putative nested TEs by detecting these three types of patterns. The results were validated through BLAST alignments, which revealed the efficacy and usefulness of the new method, which is called Mamushka.

RESUMEN

BACKGROUND: Overactivation of the aldosterone and mineralocorticoid receptor (MR) pathway is associated with hyperglycemia and dyslipidemia. Caveolin 1 (cav-1) is involved in glucose/lipid homeostasis and may modulate MR signaling. We investigated the interplay between cav-1 and aldosterone signaling in modulating insulin resistance and dyslipidemia in cav-1-null mice and humans with a prevalent variant in the CAV1 gene. METHODS AND RESULTS: In mouse studies, cav-1 knockout mice exhibited higher levels of homeostatic model assessment of insulin resistance, cholesterol, and resistin and lower ratios of high- to low-density lipoprotein (all P<0.001 versus wild type). Moreover, cav-1 knockout mice displayed hypertriglyceridemia and higher mRNA levels for resistin, retinol binding protein 4, NADPH oxidase 4, and aldose reductase in liver and/or fat tissues. MR blockade with eplerenone significantly decreased glycemia (P<0.01), total cholesterol (P<0.05), resistin (P<0.05), and described enzymes, with no effect on insulin or triglycerides. In the human study, we analyzed the CAV1 gene polymorphism rs926198 in 556 white participants; 58% were minor allele carriers and displayed higher odds of insulin resistance (odds ratio 2.26 [95% CI 1.40-3.64]) and low high-density lipoprotein (odds ratio 1.54 [95% CI 1.01-3.37]). Aldosterone levels correlated with higher homeostatic model assessment of insulin resistance and resistin and lower high-density lipoprotein only in minor allele carriers. CAV1 gene expression quantitative trait loci data revealed lower cav-1 expression in adipose tissues by the rs926198 minor allele. CONCLUSIONS: Our findings in mice and humans suggested that decreased cav-1 expression may activate the effect of aldosterone/MR signaling on several pathways of glycemia, dyslipidemia, and resistin. In contrast, hyperinsulinemia and hypertriglyceridemia are likely mediated by MR-independent mechanisms. Future human studies will elucidate the clinical relevance of MR blockade in patients with genotype-mediated cav-1 deficiency.

Asunto(s)

Caveolina 1/genética , Glucosa/metabolismo , Resistencia a la Insulina/genética , Metabolismo de los Lípidos/genética , Tejido Adiposo/metabolismo , Adolescente , Adulto , Anciano , Aldehído Reductasa/genética , Aldehído Reductasa/metabolismo , Aldosterona/metabolismo , Animales , Glucemia/efectos de los fármacos , Colesterol/metabolismo , Dislipidemias/genética , Dislipidemias/metabolismo , Eplerenona , Femenino , Frecuencia de los Genes , Homeostasis , Humanos , Hipertrigliceridemia/genética , Hipertrigliceridemia/metabolismo , Insulina/metabolismo , Lipoproteínas HDL/metabolismo , Hígado/metabolismo , Masculino , Ratones , Ratones Noqueados , Persona de Mediana Edad , Antagonistas de Receptores de Mineralocorticoides/farmacología , NADPH Oxidasa 4/genética , NADPH Oxidasa 4/metabolismo , Polimorfismo de Nucleótido Simple , ARN Mensajero/metabolismo , Receptores de Mineralocorticoides/metabolismo , Resistina/genética , Resistina/metabolismo , Proteínas Plasmáticas de Unión al Retinol/genética , Proteínas Plasmáticas de Unión al Retinol/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Transducción de Señal , Espironolactona/análogos & derivados , Espironolactona/farmacología , Triglicéridos/metabolismo , Adulto Joven

RESUMEN

BACKGROUND: The number and complexity of repetitive elements varies between species, being in general most represented in those with larger genomes. Combining the flow-sorted chromosome arms approach to genome analysis with second generation DNA sequencing technologies provides a unique opportunity to study the repetitive portion of each chromosome, enabling comparisons among them. Additionally, different sequencing approaches may produce different depth of insight to repeatome content and structure. In this work we analyze and characterize the repetitive sequences of Triticum aestivum cv. Chinese Spring homeologous group 4 chromosome arms, obtained through Roche 454 and Illumina sequencing technologies, hereinafter marked by subscripts 454 and I, respectively. Repetitive sequences were identified with the RepeatMasker software using the interspersed repeat database mips-REdat_v9.0p. The input sequences consisted of our 4DS454 and 4DL454 scaffolds and 4ASI, 4ALI, 4BSI, 4BLI, 4DSI and 4DLI contigs, downloaded from the International Wheat Genome Sequencing Consortium (IWGSC). RESULTS: Repetitive sequences content varied from 55% to 63% for all chromosome arm assemblies except for 4DLI, in which the repeat content was 38%. Transposable elements, small RNA, satellites, simple repeats and low complexity sequences were analyzed. SSR frequency was found one per 24 to 27 kb for all chromosome assemblies except 4DLI, where it was three times higher. Dinucleotides and trinucleotides were the most abundant SSR repeat units. (GA)n/(TC)n was the most abundant SSR except for 4DLI where the most frequently identified SSR was (CCG/CGG)n. Retrotransposons followed by DNA transposons were the most highly represented sequence repeats, mainly composed of CACTA/En-Spm and Gypsy superfamilies, respectively. This whole chromosome sequence analysis allowed identification of three new LTR retrotransposon families belonging to the Copia superfamily, one belonging to the Gypsy superfamily and two TRIM retrotransposon families. Their physical distribution in wheat genome was analyzed by fluorescent in situ hybridization (FISH) and one of them, the Carmen retrotransposon, was found specific for centromeric regions of all wheat chromosomes. CONCLUSION: The presented work is the first deep report of wheat repetitive sequences analyzed at the chromosome arm level, revealing the first insight into the repeatome of T. aestivum chromosomes of homeologous group 4.

Asunto(s)

ADN de Plantas/análisis , Secuencias Repetitivas de Ácidos Nucleicos , Triticum/genética , Cromosomas de las Plantas/genética , Mapeo Físico de Cromosoma , Análisis de Secuencia de ADN/métodos

RESUMEN

BACKGROUND: Type 2 diabetes mellitus (T2DM) is characterized as a disease continuum that is marked by metabolic changes that are present for several years, sometimes well before frank diagnosis of T2DM. Genetic predisposition, ethnicity, geography, alterations in BMI, and lipid profile are considered important markers for the pathogenesis of T2DM through mechanisms that remain unresolved and controversial. The aim of this study was to investigate the relationship between triglycerides (TGs) and ß-cell function, insulin resistance (IR), and insulin sensitivity (IS) in obese first-degree relatives of patients with T2DM (FDR-T2DM) among subjects from central Mexico with normal glucose tolerance (NGT). METHODS: We studied 372 FDR-T2DM subjects (ages,18-65) and determined body mass index (BMI), fasting plasma glucose (FPG), oral glucose tolerance test (OGTT), insulin, and TGs levels. Subjects were categorized based on glycemic control [NGT, prediabetes (PT2DM), or T2DM]. NGT subjects were further categorized by BMI [normal weight (Ob-) or obese (Ob+)] and TGs levels (TG-, <150 mg/dL, or TG+, ≥150 mg/dL). ß-cell function, IR, and IS were determined by the homeostasis model assessment of ß-cell function (HOMA2-ß), homeostasis model assessment of insulin resistance (HOMA2-IR), and Quantitative Insulin Sensitivity Check Index (QUICKI) indices, respectively. RESULTS: The obese subjects with elevated TGs levels had 21%-60% increased ß-cell function when compared to all groups (P<0.05). In addition, this group had insulin levels, IS, and IR similar to PT2DM. Furthermore, only in obese subjects did TGs correlate with ß-cell function (ρ=0.502, P<0.001). CONCLUSION: We characterized FDR-T2DM subjects from central Mexico with NGT and revealed a class of obese subjects with elevated TGs and ß-cell function, which may precede PT2DM.

Asunto(s)

Diabetes Mellitus Tipo 2 , Salud de la Familia , Familia , Células Secretoras de Insulina/fisiología , Obesidad/sangre , Obesidad/fisiopatología , Triglicéridos/sangre , Adolescente , Adulto , Anciano , Índice de Masa Corporal , Estudios Transversales , Diabetes Mellitus Tipo 2/epidemiología , Salud de la Familia/estadística & datos numéricos , Femenino , Humanos , Masculino , México/epidemiología , Persona de Mediana Edad , Obesidad/epidemiología , Estado Prediabético/fisiopatología , Adulto Joven

RESUMEN

Eragrostis curvula includes biotypes reproducing through obligate and facultative apomixis or, rarely, full sexuality. We previously generated a "tetraploid-dihaploid-tetraploid" series of plants consisting of a tetraploid apomictic plant (T), a sexual dihaploid plant (D) and a tetraploid artificial colchiploid (C). Initially, plant C was nearly 100% sexual. However, its capacity to form non-reduced embryo sacs dramatically increased over a four year period (2003-2007) to reach levels of 85-90%. Here, we confirmed high rates of apomixis in plant C, and used AFLPs and MSAPs to characterize the genetic and epigenetic variation observed in this plant in 2007 as compared to 2003. Of the polymorphic sequences, some had no coding potential whereas others were homologous to retrotransposons and/or protein-coding-like sequences. Our results suggest that in this particular plant system increased apomixis expression is concurrent with genetic and epigenetic modifications, possibly involving transposable elements.

Asunto(s)

Apomixis/genética , Epigénesis Genética , Eragrostis/genética , Variación Genética , Poliploidía , Análisis del Polimorfismo de Longitud de Fragmentos Amplificados , Elementos Transponibles de ADN , Regulación de la Expresión Génica de las Plantas , Biblioteca de Genes , Genotipo , Polimorfismo Genético

RESUMEN

PURPOSE OF REVIEW: Aldosterone's functions and mechanisms of action are different depending on the tissue and the environmental condition. The mineralocorticoid receptor is present in tissues beyond epithelial cells, including the heart and vessels. Furthermore, aldosterone has direct adverse effects by both genomic and rapid/nongenomic actions not only through a nuclear receptor but also through caveolae-mediated intracellular events. Also, multiple environmental-genetic interactions play an important role in salt-sensitive hypertension (SSH) and aldosterone modulation. These findings have reshaped our vision of aldosterone's role in cardiovascular pathophysiology. This review describes new mediators of aldosterone's mechanisms of action: lysine-specific demethylase 1 (LSD1), caveolin 1 (cav-1) and striatin. RECENT FINDINGS: LSD1, an epigenetic regulator, is involved in the pathogenesis of SSH in both humans and rodents. In addition, cav-1, the main component of caveolae, plays a substantial role in mediating aldosterone pathways of SSH. The mineralocorticoid receptor interacts with cav-1 and is modulated by sodium intake. Finally, striatin, a scaffolding protein, mediates a novel interaction between signalling molecules and mineralocorticoid receptor's rapid effects in the cardiovascular system. SUMMARY: Substantial progress in aldosterone's functions and mechanisms of action should facilitate the study of cardiovascular diseases and the role of sodium intake in aldosterone-induced damage.

Asunto(s)

Aldosterona/metabolismo , Proteínas de Unión a Calmodulina/metabolismo , Enfermedades Cardiovasculares/enzimología , Sistema Cardiovascular/enzimología , Caveolinas/metabolismo , Histona Demetilasas/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/metabolismo , Transducción de Señal , Animales , Enfermedades Cardiovasculares/etiología , Enfermedades Cardiovasculares/genética , Enfermedades Cardiovasculares/fisiopatología , Sistema Cardiovascular/fisiopatología , Epigenómica , Hemodinámica , Humanos , Receptores de Mineralocorticoides/metabolismo , Cloruro de Sodio Dietético/efectos adversos

RESUMEN

BACKGROUND AND AIMS: There is evidence that family history of type 2 diabetes (FHT2D) and single nucleotide polymorphisms (SNP) on the IL-6 gene promoter region are separately associated with the risk of developing type 2 diabetes. However the relationship between adult Mexican subjects with FHT2D and genotypes/haplotypes for IL-6 gene has not been explored. The aim of the present work was to study the prevalence of IL-6 -598G>A-572G>C-174G>C haplotypes among subjects with FHT2D and to determine whether their presence influences the relationship between FHT2D and risk factors for diabetes. METHODS: Two hundred fifty eight nondiabetic subjects participated in this study; 153 with and 105 without FHT2D. Polymerase chain reaction-restriction fragment-length polymorphism (PCR-RFLP) was used for genotyping. Logistic regression analysis was employed to assess the impact of IL-6 haplotypes on FHT2D per se and hyperinsulinemia and insulin resistance as risk factors for diabetes. RESULTS: Subjects with FHT2D showed a higher prevalence of hyperinsulinemia and insulin resistance (IR) than those without FHT2D (14.4 vs. 5.7%, p = 0.029, and 14.2 vs. 7.0% p = 0.050, respectively). Lower prevalence of -598 -572-174 (AGC)-haplotype (19%) in subjects with FHT2D was observed as well as a lower prevalence of hyperinsulinemia and IR among AGC haplotype carriers (12 and 14%, respectively). The relationship between FHT2D and IR was modified by the presence of AGC haplotype (from OR, 2.70; 95% CI, 0.99-7.36; p = 0.050 OR, 30.08; 95% CI, 0.58-1,568.06; p = 0.092). CONCLUSIONS: IL-6 -598/-572/-174 (AGC) haplotype has a low prevalence among first-degree relatives of subjects with type 2 diabetes. Our results suggest that this haplotype is associated with decreased risk of type 2 diabetes in Mexican subjects with FHT2D.

Asunto(s)

Diabetes Mellitus Tipo 2/epidemiología , Diabetes Mellitus Tipo 2/genética , Predisposición Genética a la Enfermedad/genética , Haplotipos , Interleucina-6/genética , Adulto , Anciano , Femenino , Humanos , Resistencia a la Insulina/genética , Masculino , México/epidemiología , Persona de Mediana Edad , Polimorfismo de Longitud del Fragmento de Restricción , Polimorfismo de Nucleótido Simple , Prevalencia , Factores de Riesgo