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Sufficient vitamin D status is crucial for successful pregnancy and fetal development. The assessment of 25-hydroxyvitamin D (25(OH)D) concentrations is commonly used to evaluate vitamin D status. Our objective was to examine the interrelated biodynamics of maternal and neonatal total, free and bioavailable 25(OH)D in maternal-neonatal dyads at birth and their associations with homeostasis and neonatal birth anthropometry. We analysed a cohort of seventy full-term mother-child pairs. We found positive associations between all neonatal measures of vitamin D status. Maternal forms exhibited a similar pattern of association, except for the bioavailable maternal form. In multivariate analysis, both total and free maternal 25(OH)D concentrations were correlated with all neonatal forms (neonatal total 25(OH)D: 1·29 (95 % CI, 1·12, 1·46) for maternal total 25(OH)D, 10·89 (8·16, 13·63) for maternal free 25(OH)D), (neonatal free 25(OH)D: 0·15 for maternal total 25(OH)D, 1·28 (95 % CI, 0·89, 1·68) for maternal free 25(OH)D) and (0·13 (95 % CI, 0·10, 0·16), 1·06 (95 % CI, 0·68, 1·43) for maternal free 25(OH)D), respectively, with the exclusion of the bioavailable maternal form. We observed no significant interactions within or between groups regarding maternal and neonatal vitamin D parameters and maternal calcium and parathyroid hormone concentrations, and neonatal birth anthropometry. Our study indicates that bioavailable maternal and neonatal 25(OH)D have no significant effects on vitamin D equilibrium, Ca homeostasis and neonatal anthropometry at birth. However, we observed an interaction between maternal and neonatal total and free 25(OH)D concentrations at the maternal-neonatal interface, with no associations observed with other calciotropic or anthropometric outcomes.
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Calcio , Deficiencia de Vitamina D , Vitamina D/análogos & derivados , Embarazo , Recién Nacido , Femenino , Humanos , Calcifediol , Vitaminas , Calcio de la Dieta , Antropometría , Relaciones Madre-HijoRESUMEN
MicroRNAs (miRNAs) are small noncoding RNA molecules that act as major regulators of gene expression at the post-transcriptional level. As the potential applications of miRNAs in the diagnosis and treatment of human diseases have become more evident, many studies of hypertrophic cardiomyopathy (HCM) have focused on the systemic identification and quantification of miRNAs in biofluids and myocardial tissues. HCM is a hereditary cardiomyopathy caused by mutations in genes encoding proteins of the sarcomere. Despite overall improvements in survival, progression to heart failure, stroke, and sudden cardiac death remain prominent features of living with HCM. Several miRNAs have been shown to be promising biomarkers of HCM; however, there are many challenges to ensuring the validity, consistency, and reproducibility of these biomarkers for clinical use. In particular, miRNA testing may be limited by pre-analytical and analytical caveats, making our interpretation of results challenging. Such factors that may affect miRNA testing include sample type selection, hemolysis, platelet activation, and renal dysfunction. Therefore, researchers should be careful when developing appropriate standards for the design of miRNA profiling studies in order to ensure that all results provided are both accurate and reliable. In this review, we discuss the application of miRNAs as biomarkers for HCM.
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Cardiomiopatía Hipertrófica , Enfermedades Cardiovasculares , MicroARN Circulante , MicroARNs , Biomarcadores , Cardiomiopatía Hipertrófica/diagnóstico , Cardiomiopatía Hipertrófica/genética , Humanos , MicroARNs/genética , Reproducibilidad de los ResultadosRESUMEN
INTRODUCTION: Laboratory testing for the SARS-CoV-2 virus and the consequent respiratory coronavirus disease 2019 (COVID-19) is categorized into methods that detect the viral presence and methods that detect antibodies produced in the host as a response to infection. Methods that detect viral presence into the host excretions measure current infection by SARS-CoV-2, whereas the detection of human antibodies exploited against SARS-CoV-2 evaluates the past exposure to the virus. OBJECTIVE: This review provides a comprehensive overview for the use of saliva as a specimen for the detection of SARS-CoV-2, the methods for the salivary diagnostics utilized till very recently, and the arisen considerations for the diagnosis of COVID-19 disease. CONCLUSION: The major advantage of using saliva as a specimen for the detection of SARS-CoV-2 is that saliva collection is a non-invasive method which produces no discomfort to the patient and permits the patients to utilize home self-sampling techniques in order to protect health providers from the exposure to the pathogen. There is an urgent need to increase the active research for the detection of SARS-CoV-2 in the saliva because the non-invasive salivary diagnostics may provide a reliable and cost-effective method suitable for the fast and early detection of COVID-19 infection.
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COVID-19 , SARS-CoV-2 , COVID-19/diagnóstico , Humanos , SalivaRESUMEN
Diagnosis of Mycosis Fungoides (MF) may be challenging, due to its polymorphic nature. The use of miRNAs as biomarkers to assist in diagnosis has been investigated, mainly in skin lesion biopsies. The purpose of this study is to evaluate the plasma levels of miR-146a and miR-155 in MF patients and to investigate their association with SNPs of their genes. Plasma miRNAs were quantified by RT-qPCR. Genomic DNA was used for SNPs' genotyping by Sanger sequencing. Plasma levels of miR-146a and miR-155 were significantly higher in patients vs. controls, in early MF patients vs. controls, and in advanced vs. early MF patients. Both miRNAs' levels were significantly higher in stage IIB vs. early-stage patients. miR-155 plasma levels were significantly higher in patients with skin tumors or erythroderma. CC genotype (rs2910164 C>G) was significantly more frequent in healthy controls and associated with lower MF risk and lower miR-146a levels. The AA genotype (rs767649 T>A) was significantly more frequent in patients and correlated with increased MF risk and increased miR-155 levels. The combination of GG+AA was only detected in patients and was correlated with higher MF susceptibility. Increased mir-146a and mir-155 plasma levels in MF is an important finding to establish putative noninvasive biomarkers. The presence of SNPs is closely associated with miRs' expression, and possibly with disease susceptibility.
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MicroARNs , Micosis Fungoide , Neoplasias Cutáneas , Humanos , Biomarcadores , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , MicroARNs/genética , Micosis Fungoide/genética , Polimorfismo de Nucleótido Simple , Neoplasias Cutáneas/genéticaRESUMEN
Exosome selectivity mechanisms underlying exosome-target cell interactions and the specific traits affecting their capability to communicate still remain unclear. Moreover, the capacity of exosomes to efficiently deliver their molecular cargos intracellularly needs precise investigation towards establishing functional exosome-based delivery platforms exploitable in the clinical practice. The current study focuses on: (a) exosome production from normal MRC-5 and Vero cells growing in culture, (b) physicochemical characterization by dynamic light scattering (DLS) and cryo-transmission electron microscopy; (c) cellular uptake studies of rhodamine-labeled exosomes in normal and cancer cells, providing to exosomes either "autologous" or "heterologous" cellular delivery environments; and (d) loading exogenous Alexa Fluor 488-labeled siRNA into exosomes for the assessment of their delivering capacity by immunofluorescence in a panel of recipient cells. The data obtained thus far indicate that MRC-5 and Vero exosomes, indeed exhibit an interesting delivering profile, as promising "bio-shuttles," being pharmacologically exploitable in the context of theranostic applications.
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Sistemas de Liberación de Medicamentos , Exosomas/química , MicroARNs/uso terapéutico , ARN Interferente Pequeño/uso terapéutico , Animales , Comunicación Celular/genética , Línea Celular Tumoral , Chlorocebus aethiops , Microscopía por Crioelectrón , Exosomas/genética , Humanos , MicroARNs/química , ARN Interferente Pequeño/química , Células VeroRESUMEN
BACKGROUND: Alpha-subunit of the interleukin-2 receptor (IL2RA) is involved in the regulation of T-cell function and has been related to autoimmune thyroid disease (AITD). Although the exact mechanisms are not fully understood, promoter methylation might account for differences in gene expression. The aim of this study was to investigate whether there are differences in the percentage of DNA methylation within the IL2RA gene promoter in young patients with AITD. MATERIALS AND METHODS: In a cross-sectional design, the presence of DNA methylation in the IL2RA gene promoter was quantified, by real-time PCR and melting curve analysis, in modified genomic DNA isolated from blood samples of a total of 149 children and adolescents with AITD, including patients with Hashimoto thyroiditis (ΗΤ) (n = 60), Graves' disease (GD) (n = 9), concurrent diagnosis of HT and type 1 diabetes (T1DM + HT) (n = 25), and healthy controls (n = 55). RESULTS: The percentage of DNA methylation in the IL2RA gene promoter was significantly decreased in patients with GD (26.0 ± 4.2%) but not in those with HT (36.3 ± 1.4%) in comparison with controls (41.3 ± 1.5%). CONCLUSIONS: The observed DNA hypomethylation in the IL2RA gene promoter in patients with GD might be related to its increased expression, thus contributing to the etiopathogenesis of GD in childhood and adolescence.
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Metilación de ADN , Subunidad alfa del Receptor de Interleucina-2/genética , Tiroiditis Autoinmune/genética , Niño , Femenino , Humanos , Masculino , Regiones Promotoras GenéticasRESUMEN
Purpose/Aim of the Study: Osteoprotegerin (OPG) is an α tumor necrosis factor receptor superfamily glucoprotein that acts as a decoy receptor for the receptor activator of nuclear factor kappa B ligand (RANKL), exerting an antiresoptive bone effect. It was recently shown that OPG/RANKL axis is activated during vascular calcification, contributing to atherosclerotic lesions formation. Additionally, OPG levels are charachterized as an independent risk factor for overall vascular mortality in obese adults. We aimed to investigate OPG levels in children/adolescents with obesity and explore possible relations with obesity-related insulin resistance (IR). MATERIAL AND METHODS: A total of 160 participants (85 obese) were enrolled. Participants with obesity underwent an oral glucose tolerance test. IR was evaluated according to the homeostasis model assessment-insulin resistance index. Serum OPG levels were determined. RESULTS: OPG levels did not differ significantly between obese subjects and controls in the total sample (p = 0.133). However, in the adolescents' subgroup, serum OPG levels were significantly increased in obesity (p = 0.019). After stratifying participants according to their IR status, only subjects with both obesity and IR exhibited increased OPG levels compared to controls (p < 0.001). Factor analysis further associated OPG levels variation to insulin levels variation and to IR. CONCLUSIONS: Obese individuals demonstrate increased serum OPG levels during puberty. Obesity per se is not the potent factor for this increase; indeed, IR accompanying obesity seems to exert a fundamental role in OPG upregulation.
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Resistencia a la Insulina , Osteoprotegerina/sangre , Obesidad Infantil/sangre , Adolescente , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
Aerococcus urinae is a microorganism responsible for urinary tract and blood stream infections which are rarely reported in clinical practice. However, it has been proposed that the infrequency of such reports may be partially due to difficulties related to pathogen identification. We present here a case of an elderly male patient with urinary tract infection where A. urinae was initially not identified by a private microbiology laboratory. Our report highlights the need to consider A. urinae as a causative agent of urinary tract infections because if not identified and properly treated it may lead to endocarditis or septicemia.
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Aerococcus/aislamiento & purificación , Infecciones por Bacterias Grampositivas/microbiología , Infecciones Urinarias/microbiología , Aerococcus/efectos de los fármacos , Aerococcus/genética , Anciano de 80 o más Años , Amoxicilina/uso terapéutico , Antibacterianos/uso terapéutico , Bacteriuria/microbiología , Diagnóstico Diferencial , Recuento de Eritrocitos , Infecciones por Bacterias Grampositivas/diagnóstico , Infecciones por Bacterias Grampositivas/tratamiento farmacológico , Humanos , Recuento de Leucocitos , Masculino , Pruebas de Sensibilidad Microbiana , ARN Ribosómico 16S/química , ARN Ribosómico 16S/genética , Infecciones Urinarias/tratamiento farmacológico , Orina/citología , Orina/microbiologíaRESUMEN
The therapeutic potential of cold physical gas plasma operated at atmospheric pressure in oncology has been thoroughly demonstrated in numerous preclinical studies. The cytotoxic effect on malignant cells has been attributed mainly to biologically active plasma-generated compounds, namely, reactive oxygen and nitrogen species. The intracellular accumulation of reactive oxygen and nitrogen species interferes strongly with the antioxidant defense system of malignant cells, activating multiple signaling cascades and inevitably leading to oxidative stress-induced cell death. This study aims to determine whether plasma-induced cancer cell death operates through a universal molecular mechanism that is independent of the cancer cell type. Using whole transcriptome data, we sought to investigate the activation mechanism of plasma-treated samples in patient-derived prostate cell cultures, melanoma, breast, lymphoma, and lung cancer cells. The results from the standardized single-cohort gene expression analysis and parallel multi-cohort meta-analysis strongly indicate that plasma treatment globally induces cancer cell death through immune-mediated mechanisms, such as interleukin signaling, Toll-like receptor cascades, and MyD88 activation leading to pro-inflammatory cytokine release and tumor antigen presentation.
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MicroRNAs (miRNAs/miRs) are promising prognostic biomarkers in pediatric acute lymphoblastic leukemia (ALL). The present study aimed to identify miRNAs that could serve as prognostic biomarkers or as novel therapeutic targets in ALL. The expression levels of 84 miRNAs were assessed in the bone marrow aspirates of 10 pediatric patients with newly diagnosed ALL at diagnosis and on day 33 of induction of the ALL Intercontinental Berlin-Frankfurt-Münster 2009 protocol, and associations with established prognostic factors were evaluated. The levels at diagnosis of 25 miRNAs were associated with ≥2 prognostic factors. Higher expression levels of let-7c-5p, miR-106b-5p, miR-26a-5p, miR-155-5p, miR-191-5p, miR-30b-5p and miR-31-5p were significantly associated with a good prednisone response. The expression levels of miR-125b-5p, miR-150-5p and miR-99a-5p were significantly higher in standard- or intermediate-risk patients compared with those in high-risk patients (P=0.017, P=0.033 and P=0.017, respectively), as well as in those with a complete response at the end of induction (P=0.044 for all three miRNAs). The change in expression levels between diagnosis and the end of induction differed significantly between risk groups for three miRNAs: miR-206, miR-210 and miR-99a (P=0.033, P=0.047 and P=0.008, respectively), with the post induction levels of miR-206 increased in high-risk patients, whilst miR-210 and miR-99a levels were increased in intermediate/standard risk patients. Therefore, miRNAs that could be integrated into the risk stratification of pediatric ALL after further evaluation in larger patient cohorts were identified.
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Background: Apart from the well-established skeletal effects, vitamin D has been explored as a secretagogue influencing various adipokines, including adiponectin and irisin. Recent evidence suggests that specific forms of 25-Hydroxyvitamin D (25(OHD), such as free and bioavailable 25(OH)D, may provide more accurate measurements of vitamin D status. The relationship between vitamin D status and serum irisin and adiponectin concentrations remains largely unexplored, particularly during pregnancy. Methods: We analyzed data from 67 healthy maternal-neonatal pairs from Northern Greece at birth. Biochemical and hormonal tests were conducted on each maternal-neonatal pair. The vitamin D forms were estimated using validated mathematical models. Subsequently, regression analyses were conducted to determine the association between the vitamin D forms and adipokine levels. Results: Bioavailable maternal 25(OH)D was inversely associated with neonatal irisin concentrations [ß=-73.46 (-140.573 to -6.341), p=0.034]. No other associations were observed between maternal vitamin D status and neonatal adipokine concentrations. Conclusion: In conclusion, maternal bioavailable vitamin D concentrations are inversely associated with neonatal serum irisin concentrations, warranting further studies to evaluate the underlying mechanisms for this finding.
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Adiponectina , Fibronectinas , Vitamina D , Humanos , Fibronectinas/sangre , Femenino , Vitamina D/sangre , Vitamina D/análogos & derivados , Adiponectina/sangre , Grecia , Embarazo , Recién Nacido , Adulto , MasculinoRESUMEN
A well-functioning vascular access is the cornerstone for an optimal hemodialysis treatment and an issue of major importance for the outcome of patients on chronic hemodialysis. Over the last few years reports supporting the aspect that mechanisms involved in vascular access malfunction are genetically controlled have been published. Triggered by two cases reported herein, we present a comprehensive review of the literature on an evolving field of particular significance to patients on hemodialysis.
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Derivación Arteriovenosa Quirúrgica/efectos adversos , Diálisis Renal/efectos adversos , Anciano , Factor V/genética , Hemo-Oxigenasa 1/genética , Humanos , Interleucina-10/genética , Masculino , Metilenotetrahidrofolato Reductasa (NADPH2)/genética , Persona de Mediana Edad , Peptidil-Dipeptidasa A/genética , Factor de Crecimiento Transformador beta1/genéticaRESUMEN
Nonalcoholic fatty liver disease (NAFLD), the most widespread chronic liver disease worldwide, confers a significant burden on health systems and leads to increased mortality and morbidity through several extrahepatic complications. NAFLD comprises a broad spectrum of liver-related disorders, including steatosis, cirrhosis, and hepatocellular carcinoma. It affects almost 30% of adults in the general population and up to 70% of people with type 2 diabetes (T2DM), sharing common pathogenetic pathways with the latter. In addition, NAFLD is closely related to obesity, which acts in synergy with other predisposing conditions, including alcohol consumption, provoking progressive and insidious liver damage. Among the most potent risk factors for accelerating the progression of NAFLD to fibrosis or cirrhosis, diabetes stands out. Despite the rapid rise in NAFLD rates, identifying the optimal treatment remains a challenge. Interestingly, NAFLD amelioration or remission appears to be associated with a lower risk of T2DM, indicating that liver-centric therapies could reduce the risk of developing T2DM and vice versa. Consequently, assessing NAFLD requires a multidisciplinary approach to identify and manage this multisystemic clinical entity early. With the continuously emerging new evidence, innovative therapeutic strategies are being developed for the treatment of NAFLD, prioritizing a combination of lifestyle changes and glucose-lowering medications. Based on recent evidence, this review scrutinizes all practical and sustainable interventions to achieve a resolution of NAFLD through a multimodal approach.
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OBJECTIVE: Hypertrophic cardiomyopathy (HCM) is a genetic disease of the myocardium that is characterized by phenotypic variability among patients. miR-146a is a small non-coding RNA that is well known for its role in inflammation and myocardial hypertrophy. The aim of this study is to evaluate the role of miR-146a as a candidate genetic factor influencing HCM phenotype. METHODS: In this study, 140 HCM patients and 112 control individuals were genotyped for the rs2910164 single nucleotide polymorphism (SNP) in the MIR146A gene; using this data, the correlation between different genotypes and clinical features of the disease were determined. Additionally, plasma levels of miR-146a-5p were determined in 50 HCM patients and 30 control individuals by using qPCR. RESULTS: The incidence of GC and CC genotypes were significantly lower in HCM patients (odds ratio (OR) = 0.5 [0.3-0.8], p = 0.007). The GC/CC genotypes in the dominant genetic model positively correlated with the presence of left ventricle outflow tract (LVOT) obstruction (OR = 2.3 [1.2-4.7] and p = 0.018), a higher left ventricle mass index (118 ± 47 g/m2 vs 92 ± 42 g/m2 and p = 0.02), and increased left ventricle end-diastolic diameter (4.66 ± 0.64cm vs 4.39 ± 0.7cm and p = 0.026). Atrial fibrillation was significantly higher in patients homozygous for the C allele (OR = 10.6 [2-55], p = 0.003). Interestingly, the plasma levels of miR-146a-5p were significantly increased in HCM patients with LVOT obstruction. CONCLUSION: Our findings indicate that the C allele of the rs2910164 SNP might be under negative selection in HCM patients. Additionally, plasma levels of miR-146a-5p and GC/CC genotypes are indicative of the obstructive phenotype in HCM patients.
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Cardiomiopatía Hipertrófica , MicroARNs , Cardiomiopatía Hipertrófica/complicaciones , Cardiomiopatía Hipertrófica/genética , Estudios de Casos y Controles , Predisposición Genética a la Enfermedad , Genotipo , Ventrículos Cardíacos , Humanos , MicroARNs/genética , Polimorfismo de Nucleótido SimpleRESUMEN
The insulin (INS) gene is the one of the most important genes involved in the pathogenesis of Type 1 Diabetes (T1D) after the Major Histocompatibility Complex genes. Studies addressing the issue of hyper- or hypo-methylation status of the INS gene promoter have reported inconsistent results. The majority of studies showed hypomethylation; however a few studies have shown hypermethylation at specific cytosine-guanosine (CpG) sites in the promoter region of the INS gene. The aim of the present study was to analyze the methylation status of the promoter region of the INS gene in Greek children and adolescents with T1D. A total of 20 T1D participants (mean diabetes duration of 6.15±4.12 years) and 20 age- and sex-matched controls were enrolled in the present study. DNA was isolated from whole blood samples, modified using sodium bisulfite and analyzed using PCR and electrophoresis. DNA was then pooled with highly reactive supermagnetic beads at similar molar quantities, submitted for library construction and finally sequenced using next-generation sequencing. The methylation profile at 10 CpG sites around the transcription start site (TSS) of the INS promoter was analysed and expressed as the mean ± standard deviation. The overall mean methylation in patients with T1D did not differ compared with the healthy controls. There was a statistically significant difference between the two groups in hypermethylation at position -345 (P=0.02), while a trend (P=0.06) at position -102 was observed. According to the results of the present study, increased methylation in the INS gene promoter at specific CpG sites around the TSS were already present in childhood T1D. These data may possibly serve as a guide towards the identification of a methylation pattern for detection of development of T1D in genetically predisposed children.
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OBJECTIVE: The aim of the present study was to investigate the Th2/Th17 pathway in asthmatic patients and also the relationship to asthma severity and biomarkers of inflammation. METHODS: 90 asthmatic patients, 51 patients with severe, 39 patients with mild asthma and 98 healthy controls were included. Skin prick tests, blood eosinophils, total serum IgE and exhaled FeNO were evaluated. Serum levels of IL-4, IL-5, IL-13, IL-6, IL-17A, IL-23 and TGFß1 were determined by Flow Cytometry using a panel kit (AimPlex Biosciences). The SNP of IL17A (rs17880588) was genotyped using reverse transcriptase polymerase chain reaction (RT-PCR). RESULTS: The genotype of the SNP in IL17A (rs 17880588) was similar among all three groups. Serum levels of IL-4, IL-5, IL-13, IL-6, IL-17A and IL-23 were higher in asthmatics compared to controls (pâ¯<â¯0.05). In addition, IL-17A and IL-4 serum levels were found significantly elevated in patients with allergic asthma (pâ¯<â¯0.05). Furthermore, IL-4, IL-5, IL-13 and IL-23 were found significantly higher in patients with eosinophil cut off values above 300â¯cells/µl (pâ¯<â¯0.05). IL-17A levels were positively correlated with FeNO values in severe asthmatics with eosinophils>400â¯cells/µl. CONCLUSIONS: The above findings suggest the coexistence of Th2/Th17 pathway in severe, eosinophilic and in allergic asthma.
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Asma/sangre , Interleucinas/sangre , Células Th17/metabolismo , Células Th2/metabolismo , Factor de Crecimiento Transformador beta1/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Eosinófilos/metabolismo , Espiración , Femenino , Genotipo , Grecia , Humanos , Inmunoglobulina E/sangre , Interleucinas/genética , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Óxido Nítrico/metabolismo , Polimorfismo de Nucleótido SimpleRESUMEN
Gene promoter methylation is a common epigenetic event, taking place in the early phase of tumorigenesis, which has a great potential as a diagnostic and prognostic cancer biomarker. In this umbrella review, we provide an overview on the association between gene-promoter methylation of protein-coding genes and cancer risk based on currently available meta-analyses data on gene promoter methylation. We searched MEDLINE via PubMed and the Cochrane Database of Systematic Reviews for meta-analyses that examine the association between gene-promoter methylation and cancer, published until January 2019 in English. We used AMSTAR to assess the quality of the included studies and applied a set of pre-specified criteria to evaluate the magnitude of each association. We provide a comprehensive overview of 80 unique combinations between 22 different genes and 18 cancer outcomes, all of which indicated a positive association between promoter hypermethylation and cancer. In total, the 70 meta-analyses produced significant results under a random-effects model with odds ratios that ranged from 1.94 to 26.60, with the summary effect being in favor of the unmethylated group in all cases. Three of the strong evidence associations involve RASSF1 methylation on bladder cancer risk (ORâ¯=â¯18.46; 95% CI: 12.69-26.85; I2â¯=â¯0%), MGMT methylation on NSCLC (ORâ¯=â¯4.25; 95% CI: 2.83-6.38; I2â¯=â¯22.4%) and RARB methylation on prostate cancer (ORâ¯=â¯6.87; 95% CI: 4.68-10.08; I2â¯=â¯0%). Meta-analyses showed a moderate quality, AMSTAR score ranging from 4 to 9 (Mdnâ¯=â¯8; IQR: 7.0 to 8.0). As primary studies and meta-analyses on the subject accumulate, more genetic loci may be found to be highly associated with specific cancer types and hence the biomarker sets will become wider.
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Metilación de ADN , Metilasas de Modificación del ADN/genética , Enzimas Reparadoras del ADN/genética , Neoplasias/genética , Receptores de Ácido Retinoico/genética , Proteínas Supresoras de Tumor/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/genética , Epigénesis Genética , Femenino , Predisposición Genética a la Enfermedad , Humanos , Neoplasias Pulmonares/genética , Masculino , Metaanálisis como Asunto , Oportunidad Relativa , Regiones Promotoras Genéticas , Neoplasias de la Próstata/genética , Neoplasias de la Vejiga Urinaria/genéticaRESUMEN
The emergence and spread of NDM-1-encoding Klebsiella pneumoniae is causing worldwide concern, whereas a second epicenter of their dissemination after the Indian subcontinent is thought to be located in the Balkans. In this study, the complete genome sequencing of an NDM-1-producing ST11 K. pneumoniae isolated in a private laboratory in Greece is presented. The genome sequencing was performed on Illumina MiniSeq. Multilocus Sequence Typing was determined using a BLAST-based approach whereas antimicrobial resistance genes and plasmid replicons were identified by ResFinder and PlasmidFinder respectively. The capsular serotype was determined by the nucleotide sequence of the wzc gene. The Rapid Annotation System Technology server v2.0 was used for genome annotation. The isolate was classified to Sequence Type 11 and to the K24 capsular serotype. Its genome consisted of 5,549,974 bp with a G + C content of 57.26%. The resistome included 16 antibiotic resistance genes, 12 located in plasmids and 4 in the chromosome. The whole genome sequence of the isolate has been deposited at GenBank to serve as future reference in the study of the epidemiology and antibiotic resistance mechanisms of carbapenemase-producing Enterobacteriaceae.
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Proteínas Bacterianas/genética , ADN Bacteriano/genética , Infecciones por Klebsiella/microbiología , Klebsiella pneumoniae/genética , beta-Lactamasas/genética , Antibacterianos/uso terapéutico , Farmacorresistencia Bacteriana Múltiple/genética , Femenino , Genotipo , Grecia , Humanos , Infecciones por Klebsiella/tratamiento farmacológico , Klebsiella pneumoniae/efectos de los fármacos , Pruebas de Sensibilidad Microbiana/métodos , Persona de Mediana Edad , Tipificación de Secuencias Multilocus/métodos , Plásmidos/genética , Análisis de Secuencia de ADN/métodos , Secuenciación Completa del Genoma/métodosRESUMEN
BACKGROUND: Type 1 diabetes (T1D) has been associated with a higher fracture risk due to alterations in bone structure and metabolism. On the other hand, the important role of the RANKL/OPG/RANK signaling axis in bone physiology is well established. The aim of this study was to evaluate the levels of receptor activator of nuclear factor kappa-B ligand (RANKL), receptor activator of nuclear factor kappa-B (RANK) and plasma osteoprotegerin (OPG) levels, in T1D youngsters and to investigate factors that could influence the OPG/RANK/RANKL signaling axis such as 25-hydroxy vitamin D [25(OH) D], parathormone (PTH) and age. METHODS: Serum RANKL, RANK, 25(OH) D, PTH levels and plasma OPG levels, were measured in 71 youngsters with T1D and 50 healthy controls matched for age and gender. RESULTS: Plasma OPG levels were significantly lower (p = 0.025) in T1D patients compared to controls. Serum RANKL levels were significantly higher (p = 0.037), while no differences were observed in serum RANK levels (p = 0.946) between the two groups. Serum 25(OH) D levels found significantly decreased (p < 0.001) while serum PTH levels were significantly elevated (p < 0.001) in T1D patients than in controls. CONCLUSIONS: Our results demonstrated that OPG and RANKL may be promising biomarkers for T1D patients. However, their circulating levels were associated with several factors including PTH, 25(OH) D and therefore, may represent an integrative biomarker for a variety of endocrine signaling disturbances observed in T1D.