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1.
Int J Mol Sci ; 22(11)2021 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-34073737

RESUMO

Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes, affecting between 2 to 38% of pregnancies worldwide, varying considerably depending on diagnostic criteria used and sample population studied. Adverse obstetric outcomes include an increased risk of macrosomia, and higher rates of stillbirth, instrumental delivery, and birth trauma. Metabolomics, which is a platform used to analyse and characterise a large number of metabolites, is increasingly used to explore the pathophysiology of cardiometabolic conditions such as GDM. This review aims to summarise metabolomics studies in GDM (from inception to January 2021) in order to highlight prospective biomarkers for diagnosis, and to better understand the dysfunctional metabolic pathways underlying the condition. We found that the most commonly deranged pathways in GDM include amino acids (glutathione, alanine, valine, and serine), carbohydrates (2-hydroxybutyrate and 1,5-anhydroglucitol), and lipids (phosphatidylcholines and lysophosphatidylcholines). We also highlight the possibility of using certain metabolites as predictive markers for developing GDM, with the use of highly stratified modelling techniques. Limitations for metabolomic research are evaluated, and future directions for the field are suggested to aid in the integration of these findings into clinical practice.


Assuntos
Diabetes Gestacional/metabolismo , Redes e Vias Metabólicas , Metabolômica , Aminoácidos/análise , Biomarcadores/análise , Carboidratos/análise , Diabetes Gestacional/sangue , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/urina , Feminino , Humanos , Lipídeos/análise , Espectrometria de Massas , Gravidez
2.
Nat Commun ; 12(1): 3445, 2021 06 08.
Artigo em Inglês | MEDLINE | ID: mdl-34103512

RESUMO

To fully utilize the advances in omics technologies and achieve a more comprehensive understanding of human diseases, novel computational methods are required for integrative analysis of multiple types of omics data. Here, we present a novel multi-omics integrative method named Multi-Omics Graph cOnvolutional NETworks (MOGONET) for biomedical classification. MOGONET jointly explores omics-specific learning and cross-omics correlation learning for effective multi-omics data classification. We demonstrate that MOGONET outperforms other state-of-the-art supervised multi-omics integrative analysis approaches from different biomedical classification applications using mRNA expression data, DNA methylation data, and microRNA expression data. Furthermore, MOGONET can identify important biomarkers from different omics data types related to the investigated biomedical problems.


Assuntos
Algoritmos , Biomarcadores/análise , Genômica , Doença de Alzheimer/genética , Neoplasias da Mama/genética , Bases de Dados Genéticas , Feminino , Humanos
3.
Medicine (Baltimore) ; 100(21): e25808, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032694

RESUMO

ABSTRACT: MicroRNAs play important roles in gestational diabetes mellitus (GDM), and this study aimed to elucidate the clinical significance of miR-96-5p in diagnosing GDM.There are 123 pregnant women diagnosed with GDM and 123 healthy pregnant women were enrolled as control participants. Placenta and plasma samples from the patients and control participants were collected, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) was performed to determine miR-96-5p expression levels. Moreover, a receiver operating characteristic (ROC) curve was established to evaluate the significance of miR-96-5p in diagnosing GDM. HRT-8/SVneo trophoblasts were cultured under high glucose conditions and treated with miR-96-5p mimics, and cell viability was examined.miR-96-5p levels were significantly decreased in both the placenta and plasma samples of patients with GDM. The ROC curve indicated that miR-96-5p can serve as a diagnostic biomarker for GDM with high sensitivity and specificity. Moreover, miR-96-5p levels were markedly low under high glucose conditions, and the overexpression of miR-96-5p increased the viability, respectively, of trophoblasts in vitro.miR-96-5p may participate in the pathogenesis of GDM by exerting effects on the viability of trophoblasts.


Assuntos
Diabetes Gestacional/diagnóstico , MicroRNAs/análise , Adulto , Biomarcadores/análise , Biomarcadores/metabolismo , Glicemia/análise , Estudos de Casos e Controles , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Meios de Cultura/metabolismo , Diabetes Gestacional/sangue , Diabetes Gestacional/metabolismo , Diabetes Gestacional/patologia , Feminino , Glucose/metabolismo , Teste de Tolerância a Glucose , Humanos , MicroRNAs/agonistas , MicroRNAs/metabolismo , Placenta/patologia , Gravidez , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Trofoblastos
4.
Front Immunol ; 12: 639329, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959123

RESUMO

Background: Infection with the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a wide range of symptoms including gastrointestinal manifestations, and intestinal epithelial cells are a target of the virus. However, it is unknown how the intestinal immune system contributes to systemic immune responses in coronavirus disease 2019 (COVID-19). Methods: We characterized peripheral blood lymphocytes from patients with active COVID-19 and convalescent patients as well as healthy controls by flow cytometry. Results: The frequency and absolute number of circulating memory T and B cells expressing the gut homing integrin α4ß7 integrin was reduced during COVID-19, whether gastrointestinal symptoms were present or not. While total IgA-expressing B cells were increased, gut-imprinted B cells with IgA expression were stable. Conclusion: COVID-19 is associated with a decrease in circulating adaptive immune cells expressing the key gut homing marker α4ß7 suggesting that these cells are preferentially recruited to extra-intestinal tissues independently of α4ß7 or that the systemic immune response against SARS-CoV-2 is at least numerically dominated by extraintestinal, particularly pulmonary, immune cell priming.


Assuntos
Linfócitos B/metabolismo , Integrina alfa4/metabolismo , Integrinas/metabolismo , Linfócitos T/metabolismo , Adulto , Linfócitos B/imunologia , Biomarcadores/análise , Feminino , Humanos , Memória Imunológica/imunologia , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Contagem de Linfócitos , Masculino , Pessoa de Meia-Idade , Linfócitos T/imunologia
5.
Medicine (Baltimore) ; 100(21): e26036, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032726

RESUMO

BACKGROUND: As a gynecological disease, endometriosis (EM) seriously endangers the health of women at the age of childbearing and is closely related to long noncoding RNAs (lncRNAs). Current studies have discovered that there are differential expressions of many kinds of lncRNAs in EM. However, whether lncRNAs can be applied as a new marker for the prediction of the recurrence of EM is still controversial. In this study, meta-analysis and bioinformatics analysis were carried out to explore the value of lncRNAs as a predictor of the recurrence of EM and to analyze its biological role. METHODS: PubMed, Embase, and Web of Science databases were searched through computer and the articles published from the self-built database to April 2021 were collected. According to the inclusion and exclusion criteria, the literature was screened, and the quality of the inclusion study was evaluated. Stata 16.0 software was used for meta-analysis. The co-expression genes related to lncRNAs were screened by online tool Co-LncRNA. Then David for Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis were conducted. A competitive endogenous RNA network that may exist in lncRNAs through Starbase was built. RESULTS: The results of this meta-analysis would be submitted to peer-reviewed journals for publication. CONCLUSION: This meta-analysis could provide high-quality evidence support for lncRNAs, so as to predict the recurrence of EM. At the same time, we use bioinformatics technology to predict and analyze its biological effects, which provides a theoretical basis for further experimental verification. ETHICS AND DISSEMINATION: The private information from individuals will not be published. This systematic review also should not damage participants' rights. Ethical approval is not available. The results may be published in a peer-reviewed journal or disseminated in relevant conferences. OSF REGISTRATION NUMBER: DOI 10.17605/OSF.IO/MF3QJ.


Assuntos
Endometriose/diagnóstico , Redes Reguladoras de Genes , RNA Longo não Codificante/análise , Biomarcadores/análise , Biomarcadores/metabolismo , Biologia Computacional , Endometriose/genética , Endometriose/patologia , Endometriose/cirurgia , Endométrio/patologia , Endométrio/cirurgia , Feminino , Humanos , Metanálise como Assunto , RNA Longo não Codificante/metabolismo , Recidiva
6.
Medicine (Baltimore) ; 100(21): e26066, 2021 May 28.
Artigo em Inglês | MEDLINE | ID: mdl-34032735

RESUMO

ABSTRACT: Acute-on-chronic hepatitis B liver failure (ACHBLF) is one severe liver disease with rapid progression and high mortality. Identification of specific markers for the prediction of ACHBLF has important clinical significance. We explored the feasibility of UBE2Q1 gene promoter methylation as an early prediction and prognosis biomarker of ACHBLF.UBE2Q1 promoter methylation frequency was detected in 60 patients with acute-on-chronic hepatitis B pre-liver failure (Pre-ACHBLF), 40 patients with chronic hepatitis B and 20 cases of healthy control (HC). The UBE2Q1 mRNA was detected by quantitative real-time polymerase chain reaction.The methylation frequency of the UBE2Q1 promoter in pre-ACHBLF patients was 38.33%, which was significantly lower than that in chronic hepatitis B patients (60.00%) and HCs (65.00%). The UBE2Q1 mRNA expression in pre-ACHBLF patients with UBE1Q1 non-methylation was significantly higher than that in patients with UBE1Q1 promoter methylation. Further analysis showed that hypomethylation of the UBE2Q1 promoter was positively correlated with total bilirubin and international normalized ratio levels in patients with pre-ACHBLF, but negatively correlated with PTA level. COX multivariate analysis showed that the model for end-stage liver disease score and UBE2Q1 promoter hypomethylation status were potential early warning factors that can predict the progression of pre-ACHBLF to ACHBLF. The sensitivity and specificity of UBE2Q1 promoter methylation status combined with the model for end-stage liver disease score for early diagnosis of ACHBLF were 92.9% and 75.0%, respectively. The area under the receiver-operating characteristic curve was 0.895.The hypomethylation of UBE2Q1 promoter is associated with severity of Pre-ACHBLF, which could serve as a potential prognostic biomarker for pre-ACHBLF.


Assuntos
Insuficiência Hepática Crônica Agudizada/epidemiologia , Hepatite B Crônica/complicações , Enzimas de Conjugação de Ubiquitina/genética , Insuficiência Hepática Crônica Agudizada/sangue , Insuficiência Hepática Crônica Agudizada/diagnóstico , Insuficiência Hepática Crônica Agudizada/genética , Adulto , Bilirrubina/sangue , Biomarcadores/análise , Estudos de Casos e Controles , Metilação de DNA , Estudos de Viabilidade , Voluntários Saudáveis , Hepatite B Crônica/sangue , Humanos , Coeficiente Internacional Normatizado , Testes de Função Hepática , Pessoa de Meia-Idade , Prognóstico , Regiões Promotoras Genéticas/genética , Curva ROC , Medição de Risco/métodos , Fatores de Risco , Índice de Gravidade de Doença
7.
Sci Rep ; 11(1): 9361, 2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33931677

RESUMO

Deterioration is sometimes unexpected in SARS-CoV2 infection. The aim of our study is to establish laboratory predictors of mortality in COVID-19 disease which can help to identify high risk patients. All patients admitted to hospital due to Covid-19 disease were included. Laboratory biomarkers that contributed with significant predictive value for predicting mortality to the clinical model were included. Cut-off points were established, and finally a risk score was built. 893 patients were included. Median age was 68.2 ± 15.2 years. 87(9.7%) were admitted to Intensive Care Unit (ICU) and 72(8.1%) needed mechanical ventilation support. 171(19.1%) patients died. A Covid-19 Lab score ranging from 0 to 30 points was calculated on the basis of a multivariate logistic regression model in order to predict mortality with a weighted score that included haemoglobin, erythrocytes, leukocytes, neutrophils, lymphocytes, creatinine, C-reactive protein, interleukin-6, procalcitonin, lactate dehydrogenase (LDH), and D-dimer. Three groups were established. Low mortality risk group under 12 points, 12 to 18 were included as moderate risk, and high risk group were those with 19 or more points. Low risk group as reference, moderate and high patients showed mortality OR 4.75(CI95% 2.60-8.68) and 23.86(CI 95% 13.61-41.84), respectively. C-statistic was 0-85(0.82-0.88) and Hosmer-Lemeshow p-value 0.63. Covid-19 Lab score can very easily predict mortality in patients at any moment during admission secondary to SARS-CoV2 infection. It is a simple and dynamic score, and it can be very easily replicated. It could help physicians to identify high risk patients to foresee clinical deterioration.


Assuntos
/diagnóstico , Idoso , Biomarcadores/análise , /patologia , Feminino , Hospitalização , Humanos , Masculino , Análise Multivariada , Estudos Retrospectivos , Medição de Risco , Espanha/epidemiologia , Resultado do Tratamento
8.
Artigo em Inglês | MEDLINE | ID: mdl-33947712

RESUMO

OBJECTIVES: Following the disruption of normal paediatric inflammatory bowel disease (IBD) services during the peak of the COVID-19 pandemic, we prospectively audited the first-time use of home faecal calprotectin testing. We aimed to provide an alternative to laboratory tests and to assess the value of home testing as part of our regular services going forward. METHODS: Home test kits as well as accompanying user instructions were made available to our patients with paediatric IBD that required faecal calprotectin test between 17 April and 12 August 2020. Once the user completed the test, results were automatically uploaded to the result portal and clinical staff were alerted. A user feedback questionnaire was sent to users that had completed the home test. RESULTS: Of the 54 patients, 41 (76%) aged between 4.7 and 18.1 years used the home test. A total of 45 home tests were done, one of which produced an invalid result. The decision to modify management was made in 12 (29%) of the patients, while 14 (34%) had no changes made and 15 (37%) required further assessment. Twenty (48.8%) responded to the questionnaire and 85% stated that they preferred the home test to the laboratory testing method. CONCLUSIONS: Home calprotectin tests were useful in guiding clinical management during a time when laboratory testing was less available. They may offer benefits as part of routine paediatric IBD monitoring to help target appointments and reduce unnecessary hospital attendances in the future.


Assuntos
/epidemiologia , Fezes/química , Doenças Inflamatórias Intestinais/terapia , Complexo Antígeno L1 Leucocitário/análise , Pandemias , Testes Imediatos , Adolescente , Biomarcadores/análise , Criança , Pré-Escolar , Testes de Química Clínica/estatística & dados numéricos , Retroalimentação , Feminino , Serviços de Assistência Domiciliar , Humanos , Masculino , Portais do Paciente , Preferência do Paciente/estatística & dados numéricos , Estudos Prospectivos , Kit de Reagentes para Diagnóstico/estatística & dados numéricos , Valores de Referência , Inquéritos e Questionários
9.
BMC Gastroenterol ; 21(1): 197, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33933033

RESUMO

BACKGROUND: Fecal biomarkers are considered to be useful surrogate markers for endoscopic activity. Given the mechanisms of fecal biomarkers, we hypothesized that the extent of ulcerative colitis (UC; pancolitis, left-sided colitis, and proctitis) could affect the usefulness of fecal biomarkers for assessing endoscopic and clinical disease activity; however, few studies have evaluated the utility of fecal biomarkers in the disease extent of UC. METHODS: Fecal calprotectin, a fecal immunochemical test for hemoglobin, and fecal lactoferrin were used as fecal biomarkers. UC patients, who underwent colonoscopy within 30 days of the fecal biomarker test, participated in this observational study. Clinical and endoscopic disease activity was assessed using the Lichtiger Index and Mayo endoscopic subscore (MES), respectively. RESULTS: A total of 162 colonoscopies were performed on 133 UC patients. A correlation analysis between each biomarker and the MES for each disease-extent subgroup showed a decreased correlation in the proctitis compared with the other groups. With the exception of proctitis, it was possible to distinguish between MES 0 and MES ≥ 1 with high area-under-the-curve values for fecal calprotectin and fecal lactoferrin. The fecal immunochemical test for hemoglobin was superior at discriminating MES 0 for proctitis. CONCLUSIONS: For the practical application of fecal biomarkers for UC patients, it is necessary to consider disease extent before use. In particular, patients with proctitis exhibit a low correlation between stool biomarkers and endoscopic findings. The usefulness of these biomarkers for endoscopic remission is reduced, except for the fecal immunochemical test for hemoglobin.


Assuntos
Colite Ulcerativa , Biomarcadores/análise , Colite Ulcerativa/diagnóstico , Colonoscopia , Fezes/química , Humanos , Mucosa Intestinal , Complexo Antígeno L1 Leucocitário , Índice de Gravidade de Doença
11.
Health Qual Life Outcomes ; 19(1): 142, 2021 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-33964944

RESUMO

BACKGROUND: Heart failure (HF) is a major and growing medical and economic problem, with high prevalence and incidence rates worldwide. Cardiac Biomarker is emerging as a novel tool for improving management of patients with HF with a reduced left ventricular ejection fraction (HFrEF). METHODS: This is a before and after interventional study, that assesses the impact of a personalized follow-up procedure for HF on patient's outcomes and care associated cost, based on a clinical model of risk stratification and personalized management according to that risk. A total of 192 patients were enrolled and studied before the intervention and again after the intervention. The primary objective was the rate of readmissions, due to a HF. Secondary outcome compared the rate of ED visits and quality of life improvement assessed by the number of patients who had reduced NYHA score. A cost-analysis was also performed on these data. RESULTS: Admission rates significantly decreased by 19.8% after the intervention (from 30.2 to 10.4), the total hospital admissions were reduced by 32 (from 78 to 46) and the total length of stay was reduced by 7 days (from 15 to 9 days). The rate of ED visits was reduced by 44% (from 64 to 20). Thirty-one percent of patients had an improved functional class score after the intervention, whereas only 7.8% got worse. The overall cost saving associated with the intervention was € 72,769 per patient (from € 201,189 to € 128,420) and €139,717.65 for the whole group over 1 year. CONCLUSIONS: A personalized follow-up of HF patients led to important outcome benefits and resulted in cost savings, mainly due to the reduction of patient hospitalization readmissions and a significant reduction of care-associated costs, suggesting that greater attention should be given to this high-risk cohort to minimize the risk of hospitalization readmissions.


Assuntos
Biomarcadores/análise , Custos de Cuidados de Saúde/estatística & dados numéricos , Insuficiência Cardíaca/economia , Insuficiência Cardíaca/terapia , Hospitalização/economia , Qualidade de Vida/psicologia , Função Ventricular Esquerda , Idoso , Doença Crônica/economia , Doença Crônica/terapia , Estudos de Coortes , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Espanha
12.
Viruses ; 13(5)2021 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-33946171

RESUMO

No routine laboratory biomarkers perform well enough in diagnosing COVID-19 in isolation for them to be used as a standalone diagnostic test or to help clinicians prioritize patients for treatment. Instead, other diagnostic tests are needed. The aim of this work was to statistically summarise routine laboratory biomarker measurements in COVID-19-positive and -negative patients to inform future work. A systematic literature review and meta-analysis were performed. The search included names of commonly used, routine laboratory tests in the UK NHS, and focused on research papers reporting laboratory results of patients diagnosed with COVID-19. A random effects meta-analysis of the standardized mean difference between COVID-19-positive and -negative groups was conducted for each biomarker. When comparing reported laboratory biomarker results, we identified decreased white blood cell, neutrophil, lymphocyte, eosinophil, and platelet counts; while lactate dehydrogenase, aspartate aminotransferase, and alanine aminotransferase were elevated in COVID-19-positive compared to COVID-19-negative patients. Differences were identified across a number of routine laboratory biomarkers between COVID-19-positive and -negative patients. Further research is required to identify whether routine laboratory biomarkers can be used in the development of a clinical scoring system to aid with triage of patients.


Assuntos
Biomarcadores/análise , COVID-19/diagnóstico , Testes Diagnósticos de Rotina , Humanos , Reino Unido/epidemiologia
13.
Medicine (Baltimore) ; 100(20): e25821, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34011045

RESUMO

BACKGROUND: To evaluate the value of interleukin (IL)-27 measured in serum and bronchoalveolar lavage fluid (BALF) for the diagnosis of smear-negative pulmonary tuberculosis (TB). METHODS: This was a prospective study of patients planned to undergo bronchoscopy at Wuxi No.5 People's Hospital between January 2017 and September 2018. The patients were grouped as the TB and control groups. BALF and serum IL-27 were measured by ELISA. Receiver operating characteristic (ROC) curves were used to assess the diagnostic value and calculate the optimal cutoff values. RESULTS: There were 40 patients in the control group and 87 in the TB group. In the TB group, 20 had positive sputum smear results and 67 were negative. The area under the ROC curve (AUC) of BALF IL-27 for pulmonary TB was 0.897 (95% CI: 0.830-0.944) (P < .001). The AUC of serum IL-27 for pulmonary TB was 0.703 (95% CI: 0.616-0.781) (P < .001). In patients with negative sputum smear results, the AUCs of BALF IL-27 and serum IL-27 for pulmonary TB was 0.882 (95% confidence interval [CI]: 0.805-0.936) (P < .001) and 0.679 (95% CI: 0.601-0.782) (P < .001), respectively. CONCLUSIONS: BALF IL-27 can be used for the diagnosis of pulmonary TB, particularly in those with a negative sputum smear result. Serum IL-27 could be an auxiliary method for TB screening.


Assuntos
Líquido da Lavagem Broncoalveolar/química , Interleucina-27/análise , Programas de Rastreamento/métodos , Mycobacterium tuberculosis/isolamento & purificação , Tuberculose Pulmonar/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Biópsia , Broncoscopia , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Estudos de Viabilidade , Feminino , Humanos , Pulmão/microbiologia , Pulmão/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Escarro/microbiologia , Tuberculose Pulmonar/microbiologia , Tuberculose Pulmonar/patologia , Adulto Jovem
14.
Respir Res ; 22(1): 148, 2021 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-33985491

RESUMO

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) has been linked to thrombotic complications and endothelial dysfunction. We assessed the prognostic implications of endothelial activation through measurement of endothelin-I precursor peptide (proET-1), the stable precursor protein of Endothelin-1, in a well-defined cohort of patients hospitalized with COVID-19. METHODS: We measured proET-1 in 74 consecutively admitted adult patients with confirmed COVID-19 and compared its prognostic accuracy to that of patients with community-acquired pneumonia (n = 876) and viral bronchitis (n = 371) from a previous study by means of logistic regression analysis. The primary endpoint was all-cause 30-day mortality. RESULTS: Overall, median admission proET-1 levels were lower in COVID-19 patients compared to those with pneumonia and exacerbated bronchitis, respectively (57.0 pmol/l vs. 113.0 pmol/l vs. 96.0 pmol/l, p < 0.01). Although COVID-19 non-survivors had 1.5-fold higher admission proET-1 levels compared to survivors (81.8 pmol/l [IQR: 76 to 118] vs. 53.6 [IQR: 37 to 69]), no significant association of proET-1 levels and mortality was found in a regression model adjusted for age, gender, creatinine level, diastolic blood pressure as well as cancer and coronary artery disease (adjusted OR 0.1, 95% CI 0.0009 to 14.7). In patients with pneumonia (adjusted OR 25.4, 95% CI 5.1 to 127.4) and exacerbated bronchitis (adjusted OR 120.1, 95% CI 1.9 to 7499) we found significant associations of proET-1 and mortality. CONCLUSIONS: Compared to other types of pulmonary infection, COVID-19 shows only a mild activation of the endothelium as assessed through measurement of proET-1. Therefore, the high mortality associated with COVID-19 may not be attributed to endothelial dysfunction by the surrogate marker proET-1.


Assuntos
/mortalidade , Endotelina-1/análise , Endotélio Vascular/fisiopatologia , Precursores de Proteínas/análise , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/análise , Pressão Sanguínea , Estudos de Coortes , Creatinina/sangue , Determinação de Ponto Final , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Prospectivos , Reprodutibilidade dos Testes , Fatores de Risco , Fatores Sexuais , Análise de Sobrevida
15.
Biomed Res Int ; 2021: 6634417, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33959659

RESUMO

Background: MicroRNAs (miRNAs) play an important role in the pathogenesis of chronic thromboembolic pulmonary hypertension (CTEPH). However, the potential correlation between miRNA expression and the severity of CTEPH remains unclear. Our previous study indicated that miRNAs hsa-let-7b-3p, hsa-miR-17-5p, hsa-miR-106b-5p, hsa-miR-3202, hsa-miR-665, and hsa-miR-93-5p are closely involved in CTEPH. This study assessed the associations between the expression levels of these miRNAs and clinical parameters in CTEPH patients. Methods: A total of eight CTEPH patients and eight healthy adults as a reference group were included, and clinical data including total protein (TP), albumin (Alb), lactate dehydrogenase (LDH), hydroxybutyrate dehydrogenase (HBDH), uric acid (UA), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels were collected. Right heart catheterization was conducted to obtain hemodynamic data including cardiac index (CI). The expression levels of let-7b-3p, miR-17-5p, miR-106b-5p, miR-3202, miR-665, and miR-93-5p were measured by quantitative real-time PCR (qPCR). Correlation analysis was applied to estimate the associations between miRNA expression levels and clinical parameters in CTEPH patients. Results: Serum TP and Alb levels were decreased, while LDH, HBDH, and UA levels were increased in CTEPH patients compared with the reference group (P < 0.05). miR-3202 and miR-665 were upregulated, whereas let-7b-3p, miR-17-5p, miR-106b-5p, and miR-93-5p were downregulated in CTEPH patients relative to the reference group (P < 0.05). miR-93-5p expression was positively correlated with NT-proBNP level and negatively correlated with CI (P < 0.05). Moreover, let-7b-3p tended to be positively correlated with mean pulmonary arterial pressure. Conclusions: miR-93-5p expression was associated with the severity of CTEPH and could act as a potential predictor of high-risk CTEPH.


Assuntos
Hipertensão Pulmonar , MicroRNAs , Tromboembolia , Idoso , Biomarcadores/análise , Biomarcadores/metabolismo , Feminino , Humanos , Hipertensão Pulmonar/sangue , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/metabolismo , Masculino , MicroRNAs/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Tromboembolia/sangue , Tromboembolia/genética , Tromboembolia/metabolismo
16.
EBioMedicine ; 67: 103369, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33971404

RESUMO

BACKGROUND: Coronavirus-2 (SARS-CoV-2) infection causes an acute respiratory syndrome accompanied by multi-organ damage that implicates a prothrombotic state leading to widespread microvascular clots. The causes of such coagulation abnormalities are unknown. The receptor tissue factor, also known as CD142, is often associated with cell-released extracellular vesicles (EV). In this study, we aimed to characterize surface antigens profile of circulating EV in COVID-19 patients and their potential implication as procoagulant agents. METHODS: We analyzed serum-derived EV from 67 participants who underwent nasopharyngeal swabs molecular test for suspected SARS-CoV-2 infection (34 positives and 33 negatives) and from 16 healthy controls (HC), as referral. A sub-analysis was performed on subjects who developed pneumonia (n = 28). Serum-derived EV were characterized for their surface antigen profile and tested for their procoagulant activity. A validation experiment was performed pre-treating EV with anti-CD142 antibody or with recombinant FVIIa. Serum TNF-α levels were measured by ELISA. FINDINGS: Profiling of EV antigens revealed a surface marker signature that defines circulating EV in COVID-19. A combination of seven surface molecules (CD49e, CD209, CD86, CD133/1, CD69, CD142, and CD20) clustered COVID (+) versus COVID (-) patients and HC. CD142 showed the highest discriminating performance at both multivariate models and ROC curve analysis. Noteworthy, we found that CD142 exposed onto surface of EV was biologically active. CD142 activity was higher in COVID (+) patients and correlated with TNF-α serum levels. INTERPRETATION: In SARS-CoV-2 infection the systemic inflammatory response results in cell-release of substantial amounts of procoagulant EV that may act as clotting initiation agents, contributing to disease severity. FUNDING: Cardiocentro Ticino Institute, Ente ospedaliero Cantonale, Lugano-Switzerland.


Assuntos
COVID-19/complicações , Vesículas Extracelulares/imunologia , Tromboplastina/metabolismo , Trombose/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos de Superfície/análise , Biomarcadores/análise , COVID-19/sangue , COVID-19/imunologia , Estudos de Casos e Controles , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Nasofaringe/virologia , SARS-CoV-2/isolamento & purificação , Suíça , Trombose/etiologia , Trombose/imunologia , Fator de Necrose Tumoral alfa/sangue
17.
Gene ; 790: 145712, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-33984446

RESUMO

The aim of this study was to evaluate the relation of Human Leukocyte Antigen-G (HLA-G) 14 bp ins/del (insertion/deletion) polymorphism and soluble HLA-G (sHLA-G) level with rejection in kidney transplant recipients. The study was planned as a case-control study involving two hundred fifty kidney transplant recipients. The case group consisted of 125 (female/male: 56/69) kidney transplant recipients diagnosed with acute (n = 52) and chronic rejection (n = 73). The control group consisted of one hundred twenty-five kidney transplant patients with no acute or chronic rejection matched by gender and age in the case group. The sHLA-G level in the recipient's plasma (at the time of rejection for the case, the same time as the case after the transplant for control) was analyzed by Enzyme-Linked Immunosorbent Assay (ELISA). HLA-G 3' untranslated region (3'UTR) polymorphism of recipient and donor was determined using agarose gel electrophoresis and DNA sequencing method. In our study, it was shown that acute rejection rate increased 1.06 times and chronic rejection rate increased 1.14 times in kidney transplant recipients with low serum sHLA-G levels. The rejection patients with the HLA-G 14 bp del/del genotype had higher sHLA-G levels post-transplantation. The frequency of acute rejection was lower in patients with HLA-G 14 bp del/del polymorphism than those with ins/ins and ins/del polymorphisms. This study proposes that HLA-G 3'UTR polymorphism and sHLA-G level might be useful in prediction of rejection in kidney transplant recipients.


Assuntos
Regiões 3' não Traduzidas , Biomarcadores/análise , Rejeição de Enxerto/diagnóstico , Antígenos HLA-G/genética , Transplante de Rim/efeitos adversos , Polimorfismo Genético , Insuficiência Renal Crônica/cirurgia , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Rejeição de Enxerto/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Insuficiência Renal Crônica/patologia , Adulto Jovem
18.
Lancet HIV ; 8(4): e197-e205, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33794182

RESUMO

BACKGROUND: DNA methylation-based estimators of biological age are reliable biomarkers of the ageing process. We aimed to investigate a range of epigenetic ageing biomarkers in a substudy of the NEAT001/ANRS143 clinical trial, which compared ritonavir-boosted darunavir with either raltegravir or tenofovir disoproxil fumarate and emtricitabine in antiretroviral therapy (ART)-naive adults. METHODS: We analysed frozen whole blood samples from 168 ART-naive participants with HIV from the NEAT001/ANRS143 trial, before ART initiation and after 2 years of ART (84 participants on ritonavir-boosted darunavir with raltegravir and 84 participants on ritonavir-boosted darunavir with tenofovir disoproxil fumarate and emtricitabine). We also included 44 participants without HIV with a similar age and sex distribution. We analysed DNA methylation. Epigenetic age estimators (Horvath's clock, Hannum's clock, GrimAge, and PhenoAge) and estimated leucocyte compositions were generated using Horvath's New Online Methylation Age Calculator and Houseman's method. We calculated epigenetic age acceleration measures for each estimator of epigenetic age. The NEAT001/ANRS143 trial is registered with ClinicalTrials.gov, NCT01066962. FINDINGS: Compared with the HIV-uninfected group, ART-naive participants with HIV showed higher epigenetic age acceleration (EAA) according to all EAA estimators (mean 2·5 years, 95% CI 1·89-3·22 for Horvath-EAA; 1·4 years, 0·74-1·99 for Hannum-EAA; 2·8 years, 1·97-3·68 for GrimAge-EAA; and 7·3 years, 6·40-8·13 for PhenoAge-EAA), with all differences being statistically significant except for Hannum-EAA (Horvath-EAA p=0·0008; Hannum-EAA p=0·059; GrimAge-EAA p=0·0021; and PhenoAge-EAA p<0·0001). Epigenetic ageing was more pronounced in participants who had CD4 counts less than 200 cells per µL (significant for PhenoAge and Hannum's clock, p=0·0015 and p=0·034, respectively) or viral loads over 100 000 copies per mL at baseline (significant for PhenoAge, p=0·017). After 2 years of ART, epigenetic age acceleration was reduced, although PhenoAge and GrimAge remained significantly higher in participants with HIV compared with participants without HIV (mean difference 3·69 years, 95% CI 1·77-5·61; p=0·0002 and 2·2 years, 0·47-3·99; p=0·013, respectively). There were no significant differences in the ART effect on epigenetic ageing between treatment regimens. At baseline, participants with HIV showed dysregulation of DNA methylation-based estimated leucocyte subsets towards more differentiated T-cell phenotypes and proinflammatory leucocytes, which was also partly restored with ART. INTERPRETATION: ART initiation partly reversed epigenetic ageing associated with untreated HIV infection. Further studies are needed to understand the long-term dynamics and clinical relevance of epigenetic ageing biomarkers in people with HIV. FUNDING: NEAT-ID Foundation.


Assuntos
Envelhecimento/efeitos dos fármacos , Fármacos Anti-HIV/uso terapêutico , Epigênese Genética/efeitos dos fármacos , Infecções por HIV/tratamento farmacológico , Adulto , Envelhecimento/genética , Biomarcadores/análise , Contagem de Linfócito CD4 , Metilação de DNA , Quimioterapia Combinada , Feminino , Infecções por HIV/genética , Infecções por HIV/patologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Carga Viral
19.
JAMA Netw Open ; 4(4): e215493, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33847753

RESUMO

Importance: Claims that spinal manipulative therapy (SMT) can improve immune function have increased substantially during the COVID-19 pandemic and may have contributed to the rapid spread of both accurate and inaccurate information (referred to as an infodemic by the World Health Organization). Objective: To identify, appraise, and synthesize the scientific literature on the efficacy and effectiveness of SMT in preventing the development of infectious disease or improving disease-specific outcomes in patients with infectious disease and to examine the association between SMT and selected immunological, endocrine, and other physiological biomarkers. Evidence Review: A literature search of MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, the Index to Chiropractic Literature, the Cochrane Central Register of Controlled Trials, and Embase was conducted from inception to April 15, 2020. Randomized clinical trials and cohort studies were included. Eligible studies were critically appraised, and evidence with high and acceptable quality was synthesized using the Synthesis Without Meta-Analysis guideline. Findings: A total of 2593 records were retrieved; after exclusions, 50 full-text articles were screened, and 16 articles reporting the findings of 13 studies comprising 795 participants were critically appraised. The literature search found no clinical studies that investigated the efficacy or effectiveness of SMT in preventing the development of infectious disease or improving disease-specific outcomes among patients with infectious disease. Eight articles reporting the results of 6 high- and acceptable-quality RCTs comprising 529 participants investigated the effect of SMT on biomarkers. Spinal manipulative therapy was not associated with changes in lymphocyte levels or physiological markers among patients with low back pain or participants who were asymptomatic compared with sham manipulation, a lecture series, and venipuncture control groups. Spinal manipulative therapy was associated with short-term changes in selected immunological biomarkers among asymptomatic participants compared with sham manipulation, a lecture series, and venipuncture control groups. Conclusions and Relevance: In this systematic review of 13 studies, no clinical evidence was found to support or refute claims that SMT was efficacious or effective in changing immune system outcomes. Although there were limited preliminary data from basic scientific studies suggesting that SMT may be associated with short-term changes in immunological and endocrine biomarkers, the clinical relevance of these findings is unknown. Given the lack of evidence that SMT is associated with the prevention of infectious diseases or improvements in immune function, further studies should be completed before claims of efficacy or effectiveness are made.


Assuntos
/terapia , Doenças Transmissíveis/terapia , Manipulação Quiroprática/métodos , Manipulação da Coluna/métodos , Modalidades de Fisioterapia , Biomarcadores/análise , Doenças Transmissíveis/imunologia , Humanos , Sistema Imunitário/fisiopatologia , Sistema Imunitário/virologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
20.
PLoS One ; 16(4): e0248602, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33793566

RESUMO

BACKGROUND: SARS-CoV-2 is a rapidly spreading coronavirus responsible for the Covid-19 pandemic, which is characterized by severe respiratory infection. Many factors have been identified as risk factors for SARS-CoV-2, with much early attention being paid to body mass index (BMI), which is a well-known cardiometabolic risk factor. OBJECTIVE: This study seeks to examine the impact of additional baseline cardiometabolic risk factors including high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), Apolipoprotein A-I (ApoA-I), Apolipoprotein B (ApoB), triglycerides, hemoglobin A1c (HbA1c) and diabetes on the odds of testing positive for SARS-CoV-2 in UK Biobank (UKB) study participants. METHODS: We examined the effect of BMI, lipid profiles, diabetes and alcohol intake on the odds of testing positive for SARS-Cov-2 among 9,005 UKB participants tested for SARS-CoV-2 from March 16 through July 14, 2020. Odds ratios and 95% confidence intervals were computed using logistic regression adjusted for age, sex and ancestry. RESULTS: Higher BMI, Type II diabetes and HbA1c were associated with increased SARS-CoV-2 odds (p < 0.05) while HDL-C and ApoA-I were associated with decreased odds (p < 0.001). Though the effect of BMI, Type II diabetes and HbA1c were eliminated when HDL-C was controlled, the effect of HDL-C remained significant when BMI was controlled for. LDL-C, ApoB and triglyceride levels were not found to be significantly associated with increased odds. CONCLUSION: Elevated HDL-C and ApoA-I levels were associated with reduced odds of testing positive for SARS-CoV-2, while higher BMI, type II diabetes and HbA1c were associated with increased odds. The effects of BMI, type II diabetes and HbA1c levels were no longer significant after controlling for HDL-C, suggesting that these effects may be mediated in part through regulation of HDL-C levels. In summary, our study suggests that baseline HDL-C level may be useful for stratifying SARS-CoV-2 infection risk and corroborates the emerging picture that HDL-C may confer protection against sepsis in general and SARS-CoV-2 in particular.


Assuntos
/epidemiologia , Diabetes Mellitus Tipo 2/epidemiologia , Idoso , Apolipoproteína A-I/análise , Apolipoproteína B-100/análise , Bancos de Espécimes Biológicos , Biomarcadores/análise , Índice de Massa Corporal , HDL-Colesterol/análise , LDL-Colesterol/análise , Feminino , Hemoglobina A Glicada/análise , Humanos , Masculino , Pessoa de Meia-Idade , Triglicerídeos/análise , Reino Unido
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