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1.
J Card Surg ; 2021 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-34494321

RESUMO

PURPOSE: The aim of the study was to identify, determine, and analyze the clinical and surgical outcomes of patients with atrial isomerism (AI) undergoing cardiac surgery. METHODS: A retrospective study was carried out. Patients with diagnosis of AI undergoing cardiac surgery at the National Institute of Cardiology Ignacio Chávez, from January 1, 2010 and March 31, 2020 were included; demographic characteristics and perioperative conditions of the patients were considered. RESULTS: Sixty-five patients were included, with an average age of 6.4 ± 4.9 years, 50.8% males. Thirty-eight (58.5%) had right atrial isomerism (RAI) and 27 (41.5%) had left atrial isomerism (LAI); univentricular physiology (78.5%) predominated. Atrioventricular septal defect (AVSD) in RAI and septal defects in LAI were identified as the main associated defects. The most common surgical procedures performed were modified Blalock-Taussig shunt (MBTS) (27.6%), MBTS with total anomalous pulmonary venous connection (TAPVC) repair (15.3%) and total cavopulmonary connection (TCPC) with an extracardiac conduit fenestrated (10.8%); 100% RAI required a univentricular approach, while in LAI it was 48.1%. Overall survival was 92.3%, with 100% survival in LAI with biventricular physiology and 86.8% in RAI with univentricular physiology. CONCLUSIONS: The survival of our institution is similar to that of other referral centers, where patients with LAI had a better evolution than RAI; in addition, the univentricular approach was required in all with RAI. Patients with AI must undergo a rigorous evaluation to determine an adequate repair strategy, considering univentricular RAI with a high possibility of morbidity and mortality.

3.
J Am Heart Assoc ; : e021765, 2021 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-34558312

RESUMO

Background Patients with single-ventricle physiology who undergo the Fontan procedure are at risk for thrombotic events associated with significant morbidity and mortality. The UNIVERSE Study evaluated the efficacy and safety of a novel liquid rivaroxaban formulation, using a body weight-adjusted dosing regimen, versus acetylsalicylic acid (ASA) in children post-Fontan. Methods and Results The UNIVERSE Study was a randomized, multicenter, 2-part, open-label study of rivaroxaban, in children who had undergone a Fontan procedure, to evaluate its dosing regimen, safety, and efficacy. Part A was the single-arm part of the study that determined the pharmacokinetics/pharmacodynamics and safety of rivaroxaban in 12 participants before proceeding to part B, whereby 100 participants were randomized 2:1 to open-label rivaroxaban versus ASA. The study period was 12 months. A total of 112 participants were enrolled across 35 sites in 10 countries. In part B, for safety outcomes, major bleeding occurred in one participant on rivaroxaban (epistaxis that required transfusion). Clinically relevant nonmajor bleeding occurred in 6% of participants on rivaroxaban versus 9% on ASA. Trivial bleeding occurred in 33% of participants on rivaroxaban versus 35% on ASA. For efficacy outcomes, 1 participant on rivaroxaban in part B had a pulmonary embolism (2% overall event rate); and for ASA, 1 participant had ischemic stroke and 2 had venous thrombosis (9% overall event rate). Conclusions In this study, participants who received rivaroxaban for thromboprophylaxis had a similar safety profile and fewer thrombotic events, albeit not statistically significant, compared with those in the ASA group. Registration URL: https://www.clinicaltrials.gov. Identifier: NCT02846532.

5.
Cancers (Basel) ; 13(12)2021 Jun 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208598

RESUMO

Early alterations in cancer include the deregulation of epigenetic events such as changes in DNA methylation and abnormal levels of non-coding (nc)RNAs. Although these changes can be identified in tumors, alternative sources of samples may offer advantages over tissue biopsies. Because tumors shed DNA, RNA, and proteins, biological fluids containing these molecules can accurately reflect alterations found in cancer cells, not only coming from the primary tumor, but also from metastasis and from the tumor microenvironment (TME). Depending on the type of cancer, biological fluids encompass blood, urine, cerebrospinal fluid, and saliva, among others. Such samples are named with the general term "liquid biopsy" (LB). With the advent of ultrasensitive technologies during the last decade, the identification of actionable genetic alterations (i.e., mutations) in LB is a common practice to decide whether or not targeted therapy should be applied. Likewise, the analysis of global or specific epigenetic alterations may also be important as biomarkers for diagnosis, prognosis, and even for cancer drug response. Several commercial kits that assess the DNA promoter methylation of single genes or gene sets are available, with some of them being tested as biomarkers for diagnosis in clinical trials. From the tumors with highest incidence, we can stress the relevance of DNA methylation changes in the following genes found in LB: SHOX2 (for lung cancer); RASSF1A, RARB2, and GSTP1 (for lung, breast, genitourinary and colon cancers); and SEPT9 (for colon cancer). Moreover, multi-cancer high-throughput methylation-based tests are now commercially available. Increased levels of the microRNA miR21 and several miRNA- and long ncRNA-signatures can also be indicative biomarkers in LB. Therefore, epigenetic biomarkers are attractive and may have a clinical value in cancer. Nonetheless, validation, standardization, and demonstration of an added value over the common clinical practice are issues needed to be addressed in the transfer of this knowledge from "bench to bedside".

6.
Nat Commun ; 12(1): 4551, 2021 07 27.
Artigo em Inglês | MEDLINE | ID: mdl-34315879

RESUMO

Cornelia de Lange syndrome (CdLS) is a rare disease affecting multiple organs and systems during development. Mutations in the cohesin loader, NIPBL/Scc2, were first described and are the most frequent in clinically diagnosed CdLS patients. The molecular mechanisms driving CdLS phenotypes are not understood. In addition to its canonical role in sister chromatid cohesion, cohesin is implicated in the spatial organization of the genome. Here, we investigate the transcriptome of CdLS patient-derived primary fibroblasts and observe the downregulation of genes involved in development and system skeletal organization, providing a link to the developmental alterations and limb abnormalities characteristic of CdLS patients. Genome-wide distribution studies demonstrate a global reduction of NIPBL at the NIPBL-associated high GC content regions in CdLS-derived cells. In addition, cohesin accumulates at NIPBL-occupied sites at CpG islands potentially due to reduced cohesin translocation along chromosomes, and fewer cohesin peaks colocalize with CTCF.


Assuntos
Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Síndrome de Cornélia de Lange/genética , Genoma Humano , Transcriptoma/genética , Diferenciação Celular/genética , Cromatina/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Estabilidade Proteica
7.
Int J Mol Sci ; 22(14)2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34298969

RESUMO

Cancer is a complex disease involving alterations of multiple processes, with both genetic and epigenetic features contributing as core factors to the disease. In recent years, it has become evident that non-coding RNAs (ncRNAs), an epigenetic factor, play a key role in the initiation and progression of cancer. MicroRNAs, the most studied non-coding RNAs subtype, are key controllers in a myriad of cellular processes, including proliferation, differentiation, and apoptosis. Furthermore, the expression of miRNAs is controlled, concomitantly, by other epigenetic factors, such as DNA methylation and histone modifications, resulting in aberrant patterns of expression upon the occurrence of cancer. In this sense, aberrant miRNA landscape evaluation has emerged as a promising strategy for cancer management. In this review, we have focused on the regulation (biogenesis, processing, and dysregulation) of miRNAs and their role as modulators of the epigenetic machinery. We have also highlighted their potential clinical value, such as validated diagnostic and prognostic biomarkers, and their relevant role as chromatin modifiers in cancer therapy.


Assuntos
Epigênese Genética , MicroRNAs/genética , Neoplasias/genética , RNA Neoplásico/genética , Pesquisa Médica Translacional , Biomarcadores Tumorais , Neoplasias da Mama/genética , Metilação de DNA , DNA de Neoplasias/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Terapia Genética , Código das Histonas , Humanos , Neoplasias Pulmonares/genética , MicroRNAs/biossíntese , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Neoplasias/metabolismo , Neoplasias/terapia , Neoplasias Ovarianas/genética , Prognóstico , Processamento Pós-Transcricional do RNA , RNA Neoplásico/biossíntese , Neoplasias Gástricas/genética
11.
J Interv Cardiol ; 2021: 5522707, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34007248

RESUMO

Background: The resting full-cycle ratio (RFR) is a novel resting index which in contrast to the gold standard (fractional flow reserve (FFR)) does not require maximum hyperemia induction. The objectives of this study were to evaluate the agreement between RFR and FFR with the currently recommended thresholds and to design a hybrid RFR-FFR ischemia detection strategy, allowing a reduction of coronary vasodilator use. Materials and Methods: Patients subjected to invasive physiological study in 9 Spanish centers were prospectively recruited between April 2019 and March 2020. Sensitivity and specificity studies were made to assess diagnostic accuracy between the recommended levels of RFR ≤0.89 and FFR ≤0.80 (primary objective) and to determine the RFR "grey zone" in order to define a hybrid strategy with FFR affording 95% global agreement compared with FFR alone (secondary objective). Results: A total of 380 lesions were evaluated in 311 patients. Significant correlation was observed (R 2 = 0.81; P < 0.001) between the two techniques, with 79% agreement between RFR ≤ 0.89 and FFR ≤ 0.80 (positive predictive value, 68%, and negative predictive value, 80%). The hybrid RFR-FFR strategy, administering only adenosine in the "grey zone" (RFR: 0.86 to 0.92), exhibited an agreement of over 95% with FFR, with high predictive values (positive predictive value, 91%, and negative predictive value, 92%), reducing the need for vasodilators by 58%. Conclusions: Dichotomous agreement between RFR and FFR with the recommended thresholds is significant but limited. The adoption of a hybrid RFR-FFR strategy affords very high agreement, with minimization of vasodilator use.


Assuntos
Adenosina/farmacologia , Angiografia Coronária/métodos , Estenose Coronária , Reserva Fracionada de Fluxo Miocárdico/fisiologia , Hiperemia , Isquemia Miocárdica , Idoso , Circulação Coronária/efeitos dos fármacos , Estenose Coronária/diagnóstico , Estenose Coronária/epidemiologia , Estenose Coronária/fisiopatologia , Correlação de Dados , Relação Dose-Resposta a Droga , Feminino , Humanos , Hiperemia/induzido quimicamente , Hiperemia/fisiopatologia , Masculino , Isquemia Miocárdica/diagnóstico , Isquemia Miocárdica/etiologia , Isquemia Miocárdica/fisiopatologia , Valor Preditivo dos Testes , Sensibilidade e Especificidade , Índice de Gravidade de Doença , Espanha/epidemiologia , Vasodilatadores/farmacologia
13.
Blood Purif ; 50(6): 931-941, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33744901

RESUMO

INTRODUCTION: Acute kidney injury (AKI) is common in coronavirus disease 2019 (COVID-19). It is unknown if hospital-acquired AKI (HA-AKI) and community-acquired AKI (CA-AKI) convey a distinct prognosis. METHODS: The study aim was to evaluate the incidence and risk factors associated with both CA-AKI and HA-AKI. Consecutive patients hospitalized at a reference center for COVID-19 were included in this prospective cohort study. RESULTS: We registered 349 (30%) AKI episodes in 1,170 hospitalized patients, 224 (19%) corresponded to CA-AKI, and 125 (11%) to HA-AKI. Compared to patients with HA-AKI, subjects with CA-AKI were older (61 years [IQR 49-70] vs. 50 years [IQR 43-61]), had more comorbidities (hypertension [44 vs. 26%], CKD [10 vs. 3%]), higher Charlson Comorbidity Index (2 points [IQR 1-4] vs. 1 point [IQR 0-2]), and presented to the emergency department with more severe disease. Mortality rates were not different between CA-AKI and HA-AKI (119 [53%] vs. 63 [50%], p = 0.66). In multivariate analysis, CA-AKI was strongly associated to a history of CKD (OR 4.17, 95% CI 1.53-11.3), hypertension (OR 1.55, 95% CI 1.01-2.36), Charlson Comorbidity Index (OR 1.16, 95% CI 1.02-1.32), and SOFA score (OR 2.19, 95% CI 1.87-2.57). HA-AKI was associated with the requirement for mechanical ventilation (OR 68.2, 95% CI 37.1-126), elevated troponin I (OR 1.95, 95% CI 1.01-3.83), and glucose levels at admission (OR 1.05, 95% CI 1.02-1.08). DISCUSSION/CONCLUSIONS: CA-AKI and HA-AKI portend an adverse prognosis in CO-VID-19. Nevertheless, CA-AKI was associated with a higher comorbidity burden (including CKD and hypertension), while HA-AKI occurred in younger patients by the time severe multiorgan disease developed.


Assuntos
Injúria Renal Aguda/etiologia , COVID-19/complicações , Injúria Renal Aguda/diagnóstico , Adulto , Fatores Etários , Idoso , COVID-19/diagnóstico , Feminino , Hospitalização , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Fatores de Risco , SARS-CoV-2/isolamento & purificação
14.
ACS Omega ; 6(10): 6902-6913, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33748604

RESUMO

As a larger elderly human population is expected worldwide in the next 30 years, the occurrence of aging-associated illnesses will also be increased. The use of prosthetic devices by this population is currently important and will be even more dramatic in the near future. Hence, the design of prosthetic devices able to reduce some of the problems associated with the use of current components, such as stress shielding, reduced mobility, infection, discomfort, etc., becomes relevant. The use of additive manufacturing (AM) and the design fabrication of self-supported cellular structures in the biomedical area have opened up important opportunities for controlling the physical and mechanical properties of hip implants, resulting in specific benefits for the patients. Different studies have reported the development of hip prosthetic designs employing AM, although there are still opportunities for improvement when it comes to customized design and tuning of the physical and mechanical properties of such implants. This work shows the design and manufacture by AM of a personalized stainless-steel partial hip implant using tomography data and self-supported triply periodic minimal surface (TPMS) cell structures; the design considers dimensional criteria established by international standards. By employing tomography data, the external dimensions of the implant were established and the bone density of a specific patient was calculated; the density and mechanical properties in compression of the implant were modulated by employing an internal gyroid-type cell structure. Using such a cell structure, the patient's bone density was emulated; also, the mechanical properties of the implant were fine-tuned in order to make them comparable to those reported for the bone tissue replaced by the prosthesis. The implant design and manufacturing methodology developed in this work considered the clinical condition of a specific patient and can be reproduced and adjusted for different types of bone tissue qualities for specific clinical requirements.

15.
Biophys J ; 120(8): 1443-1453, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33607085

RESUMO

Microchannels can be used to simulate xylem vessels and investigate phytopathogen colonization under controlled conditions. In this work, we explore surface functionalization strategies for polydimethylsiloxane and glass microchannels to study microenvironment colonization by Xylella fastidiosa subsp. pauca cells. We closely monitored cell initial adhesion, growth, and motility inside microfluidic channels as a function of chemical environments that mimic those found in xylem vessels. Carboxymethylcellulose (CMC), a synthetic cellulose, and an adhesin that is overexpressed during early stages of X. fastidiosa biofilm formation, XadA1 protein, were immobilized on the device's internal surfaces. This latter protocol increased bacterial density as compared with CMC. We quantitatively evaluated the different X. fastidiosa attachment affinities to each type of microchannel surface using a mathematical model and experimental observations acquired under constant flow of culture medium. We thus estimate that bacterial cells present ∼4 and 82% better adhesion rates in CMC- and XadA1-functionalized channels, respectively. Furthermore, variable flow experiments show that bacterial adhesion forces against shear stresses approximately doubled in value for the XadA1-functionalized microchannel as compared with the polydimethylsiloxane and glass pristine channels. These results show the viability of functionalized microchannels to mimic xylem vessels and corroborate the important role of chemical environments, and particularly XadA1 adhesin, for early stages of X. fastidiosa biofilm formation, as well as adhesivity modulation along the pathogen life cycle.


Assuntos
Biofilmes , Xylella , Aderência Bacteriana , Adesão Celular , Xilema
16.
BMC Cancer ; 21(1): 16, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402115

RESUMO

BACKGROUND: Sequential inhibition of the vascular endothelial growth factor (VEGF) pathway with sorafenib could be useful for patients with metastatic renal cell carcinoma (RCC). Our aim was to determine the activity and tolerability of sorafenib as a second-line therapy in advanced RCC initially treated with a different VEGF-tyrosine kinase inhibitor (TKI). METHODS: A prospective observational cohort in Mexico (2012-2019). We included 132 subjects with metastatic RCC and who had progression despite treatment with sunitinib. The primary end-point was time to disease progression as evaluated every 12-16 weeks. RESULTS: The mean age of the cohort was 59 years (interquartile range [IQR] 50-72), 96 (73%) were men, and 48 (36%) had a favorable prognosis according to the IMDC (International Metastatic RCC Database Consortium) prognostic model. The median progression-free survival (PFS) and overall-survival after the introduction of sorafenib treatment was 8.6 months (95% confidence interval [CI]: 6.7-10.5) and 40 months (95% CI: 34.5-45.4) respectively. The median overall survival from RCC diagnosis to death was 71 months (95% CI: 58.2-83.8). On multivariable analyses, age > 65 years was associated with a longer PFS (HR 0.51; 95% CI: 0.31-0.86; p = 0.018). The median PFS in subjects aged > 65 years was longer compared to subjects ≤65 years (14.0 [95% CI: 9.2-18.8] vs. 7.2 months [95% CI: 5.3-9.1]; p = 0.012). Adverse events grade ≥ 3 associated with sorafenib occurred in 38 (29%) patients. CONCLUSION: Sequential inhibition of VEGF with sorafenib as a second-line treatment may benefit patients with metastatic RCC, especially in subjects > 65 years old.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma de Células Renais/tratamento farmacológico , Neoplasias Renais/tratamento farmacológico , Terapia de Salvação , Sunitinibe/uso terapêutico , Idoso , Carcinoma de Células Renais/secundário , Feminino , Seguimentos , Humanos , Neoplasias Renais/patologia , Masculino , México , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Taxa de Sobrevida
17.
J Cardiothorac Vasc Anesth ; 35(6): 1638-1645, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33419684

RESUMO

OBJECTIVES: The aim of this study was to analyze whether right ventricular free wall longitudinal strain (RVFWSL) could be a predictor of low-cardiac-output syndrome (LCOS) after surgical aortic valve replacement (SAVR) in patients with left ventricular ejection fraction ≥40%. DESIGN: Prospective, observational study. SETTING: The study was conducted at a third level university hospital. PARTICIPANTS: The study comprised 75 patients with severe aortic stenosis and LVEF ≥40% who underwent SAVR. The primary outcome was the occurrence of LCOS, and secondary outcomes were in-hospital mortality, hospital stay, or vasoplegic syndrome. INTERVENTIONS: Patients were divided into two groups (LCOS and no LCOS), and RVFWSL was analyzed to determine whether it is a predictor for LCOS. In addition, a receiver operating characteristic curve also was constructed, and the best cutoff value to predict LCOS was found. Furthermore, the reproducibility of RVFWSL measurements was evaluated. MEASUREMENT AND MAIN RESULTS: The incidence of LCOS was 20% in the present study's cohort. After multivariate analysis, cross-clamp time (odds ratio 1.06, 95% confidence interval 1.02-1.11; p = 0.002) and RVFWSL (odds ratio 1.41, 95% confidence interval 1.07-1.87; p = 0.015) were the only predictors of LCOS. However, RVFWSL did not show association with secondary outcomes (p > 0.05 for all). The area under the curve of RVFWSL to predict LCOS was 0.75, and the best cutoff value was -17.3%, with a sensitivity of 86.7% and specificity of 61.7%. CONCLUSIONS: RVFWSL seems to be a predictor of LCOS in patients with severe aortic stenosis and LVEF ≥40% undergoing SAVR. RVFWSL less than -17.3% may identify patients at increased risk for LCOS.


Assuntos
Estenose da Valva Aórtica , Implante de Prótese de Valva Cardíaca , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/diagnóstico por imagem , Estenose da Valva Aórtica/cirurgia , Implante de Prótese de Valva Cardíaca/efeitos adversos , Humanos , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Volume Sistólico , Resultado do Tratamento , Função Ventricular Esquerda
18.
Antioxidants (Basel) ; 10(1)2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33430227

RESUMO

Inflammatory bowel disease (IBD) is a complex multifactorial disorder in which external and environmental factors have a large influence on its onset and development, especially in genetically susceptible individuals. Crohn's disease (CD), one of the two types of IBD, is characterized by transmural inflammation, which is most frequently located in the region of the terminal ileum. Oxidative stress, caused by an overabundance of reactive oxygen species, is present locally and systemically in patients with CD and appears to be associated with the well-described imbalanced immune response and dysbiosis in the disease. Oxidative stress could also underlie some of the environmental risk factors proposed for CD. Although the exact etiopathology of CD remains unknown, the key role of oxidative stress in the pathogenesis of CD is extensively recognized. Epigenetics can provide a link between environmental factors and genetics, and numerous epigenetic changes associated with certain environmental risk factors, microbiota, and inflammation are reported in CD. Further attention needs to be focused on whether these epigenetic changes also have a primary role in the pathogenesis of CD, along with oxidative stress.

19.
Nephrology (Carlton) ; 26(5): 408-419, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33502071

RESUMO

AIM: Severe hypocalcaemia following parathyroidectomy for secondary or tertiary hyperparathyroidism (SHPT/THPT) is scarcely studied. We aimed to describe and identify risk factors for early and persistent hypocalcaemia after parathyroidectomy. METHODS: Retrospective pair-matched cohort study. We assessed 87 dialysis patients with SHPT (n = 73) or THPT (n = 14) paired with 146 subjects with primary hyperparathyroidism (PHPT) who underwent parathyroidectomy and were followed for 12 months. Early severe hypocalcaemia was defined as a free Ca ≤0.8 mmol/L [3.2 mg/dl] or corrected Ca ≤1.87 mmol/L [7.5 mg/dl] within 48 h. After parathyroidectomy and persistent hypocalcaemia, as an elemental Ca intake >3.0 g/day to achieve corrected Ca >2 mmol/L [8.0 mg/dl]. RESULTS: Early severe hypocalcaemia occurred in 77% (67/87) versus 6.8% (10/146) of subjects with SHPT/THPT and PHPT, respectively (p < .001). In SHPT/THPT cases, persistent hypocalcaemia occurred in 77% (49/64) and 64% (35/54) after 6 and 12 months of parathyroidectomy, respectively. In PHPT cases, persistent hypocalcaemia occurred in 6.8% (10/146) after 4-12 months of parathyroidectomy. Preoperative serum alkaline phosphatase (ALP) was the only risk factor associated to early severe hypocalcaemia (OR 7.3, 95% C.I. 1.7-10.9, p = .006) and persistent hypocalcaemia (OR 7.1, 95% C.I: 2.1-14.2, p = .011). Subjects with persistently low intact parathormone (iPTH) (<5.3 pmol/L [50 ng/ml]), suggestive of adynamic bone disease) showed higher Ca increases and less oral calcium requirements compared to those who progressively increased iPTH after parathyroidectomy. CONCLUSION: Early and persistent hypocalcaemia after parathyroidectomy in severe HPT were a common event associated directly to preoperative ALP levels. Subjects with persistently low postoperative iPTH normalized serum Ca more frequently after 1 year of follow up.

20.
Methods ; 187: 3-12, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32640317

RESUMO

Methylation of CpG dinucleotides plays a crucial role in the regulation of gene expression and therefore in the development of different pathologies. Aberrant methylation has been associated to the majority of the diseases, including cancer, neurodegenerative, cardiovascular and autoimmune disorders. Analysis of DNA methylation patterns is crucial to understand the underlying molecular mechanism of these diseases. Moreover, DNA methylation patterns could be used as biomarker for clinical management, such as diagnosis, prognosis and treatment response. Nowadays, a variety of high throughput methods for DNA methylation have been developed to analyze the methylation status of a high number of CpGs at once or even the whole genome. However, identification of specific methylation patterns at specific loci is essential for validation and also as a tool for diagnosis. In this review, we describe the most commonly used approaches to evaluate specific DNA methylation. There are three main groups of techniques that allow the identification of specific regions that are differentially methylated: bisulfite conversion-based methods, restriction enzyme-based approaches, and affinity enrichment-based assays. In the first group, specific restriction enzymes recognize and cleave unmethylated DNA, leaving methylated sequences intact. Bisulfite conversion methods are the most popular approach to distinguish methylated and unmethylated DNA. Unmethylated cytosines are deaminated to uracil by sodium bisulfite treatment, while the methyl cytosines remain unconverted. In the last group, proteins with methylation binding domains or antibodies against methyl cytosines are used to recognize methylated DNA. In this review, we provide the theoretical basis and the framework of each technique as well as the analysis of their strength and the weaknesses.

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