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1.
Int J Mol Sci ; 22(19)2021 Sep 26.
Artigo em Inglês | MEDLINE | ID: mdl-34638691

RESUMO

A high incidence of thromboembolic events associated with high mortality has been reported in severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) infections with respiratory failure. The present study characterized post-transcriptional gene regulation by global microRNA (miRNA) expression in relation to activated coagulation and inflammation in 21 critically ill SARS-CoV-2 patients. The cohort consisted of patients with moderate respiratory failure (n = 11) and severe respiratory failure (n = 10) at an acute stage (day 0-3) and in the later course of the disease (>7 days). All patients needed supplemental oxygen and severe patients were defined by the requirement of positive pressure ventilation (intubation). Levels of D-dimers, activated partial thromboplastin time (aPTT), C-reactive protein (CRP), and interleukin (IL)-6 were significantly higher in patients with severe compared with moderate respiratory failure. Concurrently, next generation sequencing (NGS) analysis demonstrated increased dysregulation of miRNA expression with progression of disease severity connected to extreme downregulation of miR-320a, miR-320b and miR-320c. Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis revealed involvement in the Hippo signaling pathway, the transforming growth factor (TGF)-ß signaling pathway and in the regulation of adherens junctions. The expression of all miR-320 family members was significantly correlated with CRP, IL-6, and D-dimer levels. In conclusion, our analysis underlines the importance of thromboembolic processes in patients with respiratory failure and emphasizes miRNA-320s as potential biomarkers for severe progressive SARS-CoV-2 infection.


Assuntos
COVID-19/complicações , COVID-19/genética , MicroRNAs/genética , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/genética , Idoso , Idoso de 80 Anos ou mais , Coagulação Sanguínea , COVID-19/sangue , Progressão da Doença , Regulação para Baixo , Feminino , Humanos , Inflamação/sangue , Inflamação/etiologia , Inflamação/genética , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Insuficiência Respiratória/sangue , SARS-CoV-2/isolamento & purificação , Índice de Gravidade de Doença
2.
Int J Mol Sci ; 22(18)2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34576126

RESUMO

Stress is the physical and psychological tension felt by an individual while adapting to difficult situations. Stress is known to alter the expression of stress hormones and cause neuroinflammation in the brain. In this study, miRNAs in serum-derived neuronal exosomes (nEVs) were analyzed to determine whether differentially expressed miRNAs could be used as biomarkers of acute stress. Specifically, acute severe stress was induced in Sprague-Dawley rats via electric foot-shock treatment. In this acute severe-stress model, time-dependent changes in the expression levels of stress hormones and neuroinflammation-related markers were analyzed. In addition, nEVs were isolated from the serum of control mice and stressed mice at various time points to determine when brain damage was most prominent; this was found to be 7 days after foot shock. Next-generation sequencing was performed to compare neuronal exosomal miRNA at day 7 with the neuronal exosomal miRNA of the control group. From this analysis, 13 upregulated and 11 downregulated miRNAs were detected. These results show that specific miRNAs are differentially expressed in nEVs from an acute severe-stress animal model. Thus, this study provides novel insights into potential stress-related biomarkers.


Assuntos
Exossomos/metabolismo , MicroRNAs/sangue , MicroRNAs/genética , Neurônios/metabolismo , Estresse Psicológico/sangue , Estresse Psicológico/genética , Doença Aguda , Animais , Biomarcadores/sangue , Exossomos/ultraestrutura , Ontologia Genética , Hormônios/metabolismo , Sistema Hipotálamo-Hipofisário/metabolismo , Inflamação/sangue , Inflamação/genética , Inflamação/patologia , Masculino , Ratos Sprague-Dawley
3.
BMC Cancer ; 21(1): 989, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34479528

RESUMO

BACKGROUND: Gastrointestinal tumors are a leading cause of mortality worldwide. As shown in our previous study, miR-1290 is overexpressed in colorectal cancer (CRC) and promotes tumor progression. We therefore aimed to explore the potential of circulating miR-1290 as a biomarker for gastrointestinal cancer. METHODS: A serum miRNA sequencing analysis was performed. Then, circulating miRNA detection technologies were established. The expression of miR-1290 was analyzed in gastrointestinal tumor cell lines and culture supernatants. Expression levels of circulating miR-1290 in clinical samples were examined. Associations between miR-1290 expression and clinicopathologic characteristics were analyzed. Xenograft models were generated to assess the fluctuation in serum miR-1290 levels during disease progression. RESULTS: Through miRNA sequencing, we identified that miR-1290 was overexpressed in serum samples from patients with CRC. We confirmed that human gastrointestinal tumor cells express and secrete miR-1290. The circulating miR-1290 levels was up-regulated in patients with pancreatic cancer (PC) (p < 0.01), CRC (p < 0.05), and gastric cancer (GC) (p < 0.01). High miR-1290 expression levels were associated with tumor size, lymphatic invasion, vascular invasion, distant metastasis, tumor differentiation and AJCC stage in patients with PC and CRC. The area under the curve (AUC) was 0.8857 in patients with PC, with 60.9% sensitivity and 90.0% specificity. The AUC was 0.7852 in patients with CRC, with 42.0% sensitivity and 90.0% specificity. In patients with GC, the AUC was 0.6576, with 26.0% sensitivity and 90.0% specificity. The in vivo model verified that the circulating miR-1290 level was significantly increased after tumor formation and decreased after drug treatment. CONCLUSIONS: Our findings indicate that circulating miR-1290 is a potential biomarker for gastrointestinal cancer diagnosis and monitoring.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Gastrointestinais/patologia , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Animais , Apoptose , Biomarcadores Tumorais/sangue , Estudos de Casos e Controles , Proliferação de Células , Feminino , Neoplasias Gastrointestinais/sangue , Neoplasias Gastrointestinais/genética , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , MicroRNAs/sangue , Prognóstico , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
4.
Biomed Res Int ; 2021: 6676107, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368354

RESUMO

The present study is aimed at profiling circulating exosome-derived microRNAs (miRNAs/miRs) from patients with dermatomyositis (DM), in particular those complicated with interstitial lung disease (ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody-positive. Fifteen participants were enrolled, including five patients with DM complicated with ILDs prior to treatment with circulating anti-MDA5 antibody-positive status [DM-ILD-MDA5 Ab(+)], five DM patients without ILDs who were negative for 16 detectable myositis-specific antibodies [DM-nonILD-MSA16(-)], and five age- and gender-matched healthy donor controls (HCs). The characteristics of the exosomes extracted by Ribo™ Exosome Isolation Reagent were identified using transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and flow cytometry. Differentially expressed miRNAs, determined by next-generation deep sequencing, were identified through the criteria of ∣log2 fold change | ≥1 and P < 0.01. A total of 38 miRNAs were significantly upregulated in exosomes from patients with DM-ILD-MDA5 Ab(+) compared to those from HC, while 21 miRNAs were significantly downregulated. Compared to exosomes derived from patients with DM-nonILD-MSA16(-), 51 miRNAs were significantly upregulated and 33 miRNAs were significantly downregulated from patients with DM-ILD-MDA5 Ab(+). A total of 73 exosomal miRNAs were significantly differentially expressed between DM-nonILD-MSA16(-) and HC. In particular, two miRNAs, Homo sapiens- (hsa-) miR-4488 and hsa-miR-1228-5p, were common differentially expressed miRNAs among three comparisons. GO and KEGG analyses suggested that several pathways may contribute the pathogenesis of DM-ILD-MDA5 Ab(+) and DM-nonILD-MSA16(-), while PPI network analysis of hsa-miR-4488 and hsa-miR-1228-5p indicated that their predicted target genes, DExD-box helicase 39B and MDM2, may be involved in the mechanisms of DM-ILD-MDA5 Ab(+).


Assuntos
Anticorpos/metabolismo , Dermatomiosite/sangue , Exossomos/genética , Helicase IFIH1 Induzida por Interferon/imunologia , Doenças Pulmonares Intersticiais/sangue , MicroRNAs/sangue , Adulto , Biomarcadores/sangue , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Dermatomiosite/complicações , Dermatomiosite/genética , Exossomos/ultraestrutura , Feminino , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/genética , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Mapas de Interação de Proteínas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
5.
Biomed Res Int ; 2021: 9935671, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34368362

RESUMO

Endovascular repair including percutaneous transluminal angioplasty (PTA) and stent implantation has become the standard approach for the treatment of peripheral arterial disease; however, restenosis is still the main limited complication for the long-term success of the endovascular repair. Endothelial denudation and regeneration, inflammatory response, and neointimal hyperplasia are major pathological processes occurring during in-stent restenosis (ISR). MicroRNAs exhibit great potential in regulating several vascular biological events in different cell types and have been identified as novel therapeutic targets as well as biomarkers for ISR prevention. This review summarized recent experimental and clinical studies on the role of miRNAs in ISR modification, with the aim of unraveling the underlying mechanism and potential therapeutic strategy of ISR.


Assuntos
Artérias/metabolismo , Reestenose Coronária/genética , Reestenose Coronária/terapia , Procedimentos Endovasculares , MicroRNAs/metabolismo , Stents , Animais , Artérias/fisiopatologia , Biomarcadores/metabolismo , Reestenose Coronária/sangue , Humanos , MicroRNAs/sangue , MicroRNAs/genética
6.
Nutrients ; 13(7)2021 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-34371836

RESUMO

Cardiometabolic disorders are among the leading causes of mortality in the human population. Dietary polyphenols exert beneficial effects on cardiometabolic health in humans. Molecular mechanisms, however, are not completely understood. Aiming to conduct in-depth integrative bioinformatic analyses to elucidate molecular mechanisms underlying the protective effects of polyphenols on cardiometabolic health, we first conducted a systematic literature search to identify human intervention studies with polyphenols that demonstrate improvement of cardiometabolic risk factors in parallel with significant nutrigenomic effects. Applying the predefined inclusion criteria, we identified 58 differentially expressed genes at mRNA level and 5 miRNAs, analyzed in peripheral blood cells with RT-PCR methods. Subsequent integrative bioinformatic analyses demonstrated that polyphenols modulate genes that are mainly involved in the processes such as inflammation, lipid metabolism, and endothelial function. We also identified 37 transcription factors that are involved in the regulation of polyphenol modulated genes, including RELA/NFKB1, STAT1, JUN, or SIRT1. Integrative bioinformatic analysis of mRNA and miRNA-target pathways demonstrated several common enriched pathways that include MAPK signaling pathway, TNF signaling pathway, PI3K-Akt signaling pathway, focal adhesion, or PPAR signaling pathway. These bioinformatic analyses represent a valuable source of information for the identification of molecular mechanisms underlying the beneficial health effects of polyphenols and potential target genes for future nutrigenetic studies.


Assuntos
Síndrome Metabólica/prevenção & controle , Fenômenos Fisiológicos da Nutrição/genética , Polifenóis/farmacologia , Substâncias Protetoras/farmacologia , Adulto , Fatores de Risco Cardiometabólico , Biologia Computacional , Feminino , Humanos , Masculino , Síndrome Metabólica/genética , MicroRNAs/sangue , Pessoa de Meia-Idade , Nutrigenômica , RNA Mensageiro/sangue , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/genética
7.
Viruses ; 13(8)2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34452458

RESUMO

Cleavage of double-stranded RNA is described as an evolutionary conserved host defense mechanism against viral infection. Small RNAs are the product and triggers of post transcriptional gene silencing events. Up until now, the relevance of this mechanism for SARS-CoV-2-directed immune responses remains elusive. Herein, we used high throughput sequencing to profile the plasma of active and convalescent COVID-19 patients for the presence of small circulating RNAs. The existence of SARS-CoV-2 derived small RNAs in plasma samples of mild and severe COVID-19 cases is described. Clusters of high siRNA abundance were discovered, homologous to the nsp2 3'-end and nsp4 virus sequence. Four virus-derived small RNA sequences have the size of human miRNAs, and a target search revealed candidate genes associated with ageusia and long COVID symptoms. These virus-derived small RNAs were detectable also after recovery from the disease. The additional analysis of circulating human miRNAs revealed differentially abundant miRNAs, discriminating mild from severe cases. A total of 29 miRNAs were reduced or absent in severe cases. Several of these are associated with JAK-STAT response and cytokine storm.


Assuntos
COVID-19/sangue , COVID-19/virologia , Ácidos Nucleicos Livres/sangue , MicroRNAs/sangue , RNA Viral/sangue , SARS-CoV-2/genética , COVID-19/complicações , COVID-19/genética , Feminino , Genoma Viral , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , MicroRNAs/genética , RNA Viral/genética , Índice de Gravidade de Doença , Proteínas não Estruturais Virais/genética
8.
Medicine (Baltimore) ; 100(29): e26627, 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34398018

RESUMO

OBJECTIVE: Previous investigations yielded inconsistent results for diagnostic and prognostic predictive values of MicroRNAs (miRNAs) for acute myocardial infarction (AMI). METHODS AND RESULTS: We systematically searched on PubMed and Web of Science for articles explored association of miRNAs and AMI published from January 1989 to March 2019. For diagnostic studies, a summary of sensitivity, specificity, positive likelihood ratios (PLR), negative likelihood ratios (NLR), and diagnostic odds ratio (DOR), which indicated the accuracy of microRNAs in the differentiation of AMI and no AMI, were calculated from the true positive (TP), true negative (TN), false positive (FP), and false negative (FN) of each study. In addition, the summary receive-operating characteristics (SROC) curve was constructed to summarize the TP and FP rates. For follow-up study, we computed hazard ratios (HRs) and 95% confidence intervals (CIs) for individual clinical outcomes. The meta-analysis showed a sensitivity [0.72 (95% CI: 0.61--0.81)] and specificity [0.88 (95% CI: 0.79--0.94)] of miR-1 for AMI. In addition, miR-133 showed a sensitivity [0.73 (95% CI: 0.55--0.85)] and specificity [0.88 (95% CI: 0.74--0.95)] for AMI. Moreover, the present study showed a sensitivity [0.83 (95% CI: 0.74--0.89)] and specificity [0.96 (95% CI: 0.82--0.99)] of miR-208 for AMI. A significant association was found between miR-208 and mortality after AMI (HR 1.09, 95% CI 1.01--1.18). It also indicated a sensitivity [0.84 (95% CI: 0.70--0.92)] and specificity [0.97 (95% CI: 0.87--0.99)] of miR-499 for AMI. CONCLUSIONS: Circulating miR-1, miR-133, miR-208, and miR-499 showed diagnostic values in AMI.


Assuntos
MicroRNAs/análise , Infarto do Miocárdio/sangue , Valor Preditivo dos Testes , Área Sob a Curva , Biomarcadores/análise , Biomarcadores/sangue , Humanos , MicroRNAs/sangue , Infarto do Miocárdio/fisiopatologia , Razão de Chances , Prognóstico , Curva ROC
9.
Eur J Endocrinol ; 185(5): 637-652, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34403358

RESUMO

Objective: Polycystic ovary syndrome (PCOS) is diagnosed based on the clinical signs, but its presentation is heterogeneous and potentially confounded by concurrent conditions, such as obesity and insulin resistance. miRNA have recently emerged as putative pathophysiological and diagnostic factors in PCOS. However, no reliable miRNA-based method for molecular diagnosis of PCOS has been reported. The aim of this study was to develop a tool for accurate diagnosis of PCOS by targeted miRNA profiling of plasma samples, defined on the basis of unbiased biomarker-finding analyses and biostatistical tools. Methods: A case-control PCOS cohort was cross-sectionally studied, including 170 women classified into four groups: non-PCOS/lean, non-PCOS/obese, PCOS/lean, and PCOS/obese women. High-throughput miRNA analyses were performed in plasma, using NanoString technology and a 800 human miRNA panel, followed by targeted quantitative real-timePCR validation. Statistics were applied to define optimal normalization methods, identify deregulated biomarker miRNAs, and build classification algorithms, considering PCOS and obesity as major categories. Results: The geometric mean of circulating hsa-miR-103a-3p, hsa-miR-125a-5p, and hsa-miR-1976, selected among 125 unchanged miRNAs, was defined as optimal reference for internal normalization (named mR3-method). Ten miRNAs were identified and validated after mR3-normalization as differentially expressed across the groups. Multinomial least absolute shrinkage and selection operator regression and decision-tree models were built to reliably discriminate PCOS vs non-PCOS, either in obese or non-obese women, using subsets of these miRNAs as performers. Conclusions: We define herein a robust method for molecular classification of PCOS based on unbiased identification of miRNA biomarkers and decision-tree protocols. This method allows not only reliable diagnosis of non-obese women with PCOS but also discrimination between PCOS and obesity. Capsule: We define a novel protocol, based on plasma miRNA profiling, for molecular diagnosis of PCOS. This tool not only allows proper discrimination of the condition in non-obese women but also permits distinction between PCOS and obesity, which often display overlapping clinical presentations.


Assuntos
Perfilação da Expressão Gênica/métodos , MicroRNAs/sangue , MicroRNAs/genética , Obesidade/etiologia , Obesidade/genética , Síndrome do Ovário Policístico/complicações , Síndrome do Ovário Policístico/genética , Adolescente , Adulto , Algoritmos , Biomarcadores , Estudos de Casos e Controles , Estudos de Coortes , Biologia Computacional , Estudos Transversais , Árvores de Decisões , Feminino , Ensaios de Triagem em Larga Escala , Humanos , Reprodutibilidade dos Testes , Adulto Jovem
10.
Biomolecules ; 11(8)2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34439885

RESUMO

The pathogenesis of amyotrophic lateral sclerosis (ALS), a lethal neurodegenerative disease, remains undisclosed. Mutations in ALS related genes have been identified, albeit the majority of cases are unmutated. Clinical pathology of ALS suggests a prion-like cell-to-cell diffusion of the disease possibly mediated by exosomes, small endocytic vesicles involved in the propagation of RNA molecules and proteins. In this pilot study, we focused on exosomal microRNAs (miRNAs), key regulators of many signaling pathways. We analyzed serum-derived exosomes from ALS patients in comparison with healthy donors. Exosomes were obtained by a commercial kit. Purification of miRNAs was performed using spin column chromatography and RNA was reverse transcribed into cDNA. All samples were run on the miRCURY LNATM Universal RT miRNA PCR Serum/Plasma Focus panel. An average of 29 miRNAs were detectable per sample. The supervised analysis did not identify any statistically significant difference among the groups indicating that none of the miRNA of our panel has a strong pathological role in ALS. However, selecting samples with the highest miRNA content, six biological processes shared across miRNAs through the intersection of the GO categories were identified. Our results, combined to those reported in the literature, indicated that further investigation is needed to elucidate the role of exosome-derived miRNA in ALS.


Assuntos
Esclerose Amiotrófica Lateral/sangue , Exossomos/metabolismo , MicroRNAs/sangue , Adulto , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto
11.
Int J Mol Sci ; 22(16)2021 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-34445710

RESUMO

Cancer cachexia displays a complex nature in which systemic inflammation, impaired energy metabolism, loss of muscle and adipose tissues result in unintentional body weight loss. Cachectic patients have a poor prognosis and the presence of cachexia reduces the tolerability of chemo/radio-therapy treatments and it is frequently the primary cause of death in advanced cancer patients. Early detection of this condition could make treatments more effective. However, early diagnostic biomarkers of cachexia are currently lacking. In recent years, although solid biopsy still remains the "gold standard" for diagnosis of cancer, liquid biopsy is gaining increasing interest as a source of easily accessible potential biomarkers. Moreover, the growing interest in circulating microRNAs (miRNAs), has made these molecules attractive for the diagnosis of several diseases, including cancer. Some muscle-derived circulating miRNA might play a pivotal role in the onset/progression of cancer cachexia. This topic is of great interest since circulating miRNAs might be easily detectable by means of liquid biopsies and might allow an early diagnosis of this syndrome. We here summarize the current knowledge on circulating muscular miRNAs involved in muscle atrophy, since they might represent easily accessible and promising biomarkers of cachexia.


Assuntos
Caquexia/diagnóstico , Caquexia/genética , MicroRNAs/genética , Tecido Adiposo/metabolismo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , MicroRNA Circulante/análise , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Metabolismo Energético/fisiologia , Humanos , Inflamação/patologia , Biópsia Líquida/métodos , MicroRNAs/análise , MicroRNAs/sangue , Músculo Esquelético/metabolismo , Atrofia Muscular/patologia , Neoplasias/complicações , Neoplasias/genética , Transdução de Sinais/genética , Perda de Peso/genética
12.
Cells ; 10(7)2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34359957

RESUMO

MicroRNAs are gene expression regulators associated with several human pathologies, including those generated by viral infections. Their role in SARS-CoV-2 infection and COVID-19 has been investigated and reviewed in many informative studies; however, a thorough miRNA outline in SARS-CoV-2-infected pregnant women (SIPW), at both systemic and placental levels, is missing. To fill this gap, blood and placenta biopsies collected at delivery from 15 asymptomatic SIPW were immediately analysed for: miRNA expression (n = 84) (QPCR array), antiviral/immune mRNA target expression (n = 74) (QGene) and cytokine/chemokines production (n = 27) (Multiplex ELISA). By comparing these results with those obtained from six uninfected pregnant women (UPW), we observed that, following SARS-CoV-2 infection, the transcriptomic profile of pregnant women is significantly altered in different anatomical districts, even in the absence of clinical symptoms and vertical transmission. This characteristic combination of miRNA and antiviral/immune factors seems to control both the infection and the dysfunctional immune reaction, thus representing a positive correlate of protection and a potential therapeutic target against SARS-CoV-2.


Assuntos
COVID-19/genética , MicroRNAs/genética , Complicações Infecciosas na Gravidez/genética , Adulto , COVID-19/sangue , COVID-19/diagnóstico , Feminino , Humanos , MicroRNAs/análise , MicroRNAs/sangue , Placenta/metabolismo , Gravidez , Complicações Infecciosas na Gravidez/sangue , Complicações Infecciosas na Gravidez/diagnóstico , SARS-CoV-2/isolamento & purificação , Transcriptoma , Adulto Jovem
13.
Eur J Med Res ; 26(1): 90, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376255

RESUMO

BACKGROUND: The goal of this study was to investigate the diagnostic value of miR-29c-3p in sepsis and its role in sepsis-induced inflammatory response and cardiac dysfunction. METHODS: Serum level of miR-29c-3p was detected by qRT-PCR. The ROC curve was used to evaluate the diagnostic value of miR-29c-3p for Sepsis. The cecal ligation and puncture method (CLP) was used to establish a rat sepsis model. To assess cardiac function, left ventricular systolic pressure (LVSP), left ventricular end diastolic pressure (LVEDP) and maximum rate of rise/fall of left ventricle pressure (± dp/dtmax) in different experimental groups were detected, and the serum cardiac troponin I (cTnI), creative kinase isoenzyme MB (CK-MB) were measured by ELISA. Meanwhile, TNF-α, IL-1ß, and IL-6 were detected by ELISA to assess the level of inflammatory response in animals. RESULTS: miR-29c-3p level was upregulated in sepsis patients. ROC curve revealed that miR-29c-3p had the ability to distinguish sepsis patients from healthy controls. Cardiac dysfunction and inflammation were observed in sepsis rat, which were characterized by the decrease of LVSP and + dp/dtmax, the increase of LVEDP, - dp/dtmax, cTnI, CK-MB, TNF-α, IL-1ß, IL-6. All effects were reversed by the injection of miR-29c-3p antagomir. Logistics regression analysis manifested miR-29c-3p is an independent factor in the occurrence of cardiac dysfunction in sepsis patients. CONCLUSIONS: miR-29c-3p has potential as a biomarker for the diagnosis of sepsis, and inhibition of miR-29c-3p expression in animal models reduced sepsis-induced cardiac dysfunction and inflammatory response.


Assuntos
Cardiopatias/sangue , MicroRNAs/sangue , Sepse/sangue , Idoso , Animais , Biomarcadores/sangue , Pressão Sanguínea , Citocinas/sangue , Feminino , Cardiopatias/etiologia , Cardiopatias/patologia , Frequência Cardíaca , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Ratos , Ratos Sprague-Dawley , Sepse/complicações , Sepse/patologia , Troponina I/sangue
14.
Nat Commun ; 12(1): 4811, 2021 08 10.
Artigo em Inglês | MEDLINE | ID: mdl-34376648

RESUMO

Circulating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a population-based cohort of adults aged 50-75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498-0.616) for the ERS and 0.622 (0.564-0.681) for the PRS.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias Colorretais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Herança Multifatorial/genética , Polimorfismo de Nucleotídeo Único , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Feminino , Humanos , Modelos Logísticos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real/métodos , Fatores de Risco
15.
Signal Transduct Target Ther ; 6(1): 300, 2021 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-34381015

RESUMO

Elderly people and patients with comorbidities are at higher risk of COVID-19 infection, resulting in severe complications and high mortality. However, the underlying mechanisms are unclear. In this study, we investigate whether miRNAs in serum exosomes can exert antiviral functions and affect the response to COVID-19 in the elderly and people with diabetes. First, we identified four miRNAs (miR-7-5p, miR-24-3p, miR-145-5p and miR-223-3p) through high-throughput sequencing and quantitative real-time PCR analysis, that are remarkably decreased in the elderly and diabetic groups. We further demonstrated that these miRNAs, either in the exosome or in the free form, can directly inhibit S protein expression and SARS-CoV-2 replication. Serum exosomes from young people can inhibit SARS-CoV-2 replication and S protein expression, while the inhibitory effect is markedly decreased in the elderly and diabetic patients. Moreover, three out of the four circulating miRNAs are significantly increased in the serum of healthy volunteers after 8-weeks' continuous physical exercise. Serum exosomes isolated from these volunteers also showed stronger inhibitory effects on S protein expression and SARS-CoV-2 replication. Our study demonstrates for the first time that circulating exosomal miRNAs can directly inhibit SARS-CoV-2 replication and may provide a possible explanation for the difference in response to COVID-19 between young people and the elderly or people with comorbidities.


Assuntos
COVID-19/genética , Diabetes Mellitus/genética , MicroRNAs/genética , Glicoproteína da Espícula de Coronavírus/genética , Adulto , Fatores Etários , Idoso , COVID-19/sangue , COVID-19/patologia , COVID-19/virologia , China , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Estudos de Coortes , Diabetes Mellitus/sangue , Diabetes Mellitus/patologia , Diabetes Mellitus/virologia , Exercício Físico , Exossomos/genética , Exossomos/metabolismo , Exossomos/virologia , Feminino , Regulação da Expressão Gênica , Células HEK293 , Interações Hospedeiro-Patógeno/genética , Humanos , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , SARS-CoV-2/genética , SARS-CoV-2/crescimento & desenvolvimento , SARS-CoV-2/metabolismo , Glicoproteína da Espícula de Coronavírus/sangue , Replicação Viral
16.
Biomolecules ; 11(6)2021 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-34198889

RESUMO

Head and neck squamous cell carcinoma is the sixth most common cancer worldwide, with 890,000 new cases and 450,000 deaths in 2018, and although the survival statistics for some patient groups are improving, there is still an urgent need to find a fast and reliable biomarker that allows early diagnosis. This niche can be filled by microRNA, small single-stranded non-coding RNA molecules, which are expressed in response to specific events in the body. This article presents the potential use of microRNAs in the diagnosis of HNSCC, compares the advances in this field to other diseases, especially other cancers, and discusses the detailed use of miRNA as a biomarker in profiling and predicting the treatment outcome with radiotherapy and immunotherapy. Potential problems and difficulties related to the development of this promising technology, and areas on which future research should be focused in order to overcome these difficulties, were also indicated.


Assuntos
Biomarcadores Tumorais/sangue , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/diagnóstico , MicroRNAs/sangue , Biomarcadores Tumorais/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , MicroRNAs/genética , Oncogenes/fisiologia
17.
Ann Hematol ; 100(10): 2621-2631, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34247256

RESUMO

Currently, acute graft-versus-host disease (aGVHD) diagnosis is based on clinical features and pathological findings. Until now, there is no non-invasive diagnostic test for aGVHD. MicroRNAs may act as promising predictive, diagnostic, or prognostic biomarkers for aGVHD. The purpose of the current study was to validate circulating microRNAs as diagnostic biomarkers to assist clinicians in promptly diagnosing aGVHD, so that treatment can be initiated earlier. In the present study, we evaluated six microRNAs (miR-455-3p, miR-5787, miR-6729-5p, miR-6776-5p, miR-548a-3p, and miR-6732-5p) selected from miRNA array data in 40 aGVHD patients compared to 40 non-GVHD patients with RT-qPCR. Target genes of differentially expressed microRNAs (DEMs) were predicted using Targetscan, miRanda, miRDB, miRWalk, PICTAR5, miRmap, DIANA, and miRTarBase algorithms, and their functions were analyzed using EnrichNet, Metascape, and DIANA-miRPath databases. The expressions of plasma miR-455-3p and miR-5787 were significantly downregulated, whereas miR-548a-3p was significantly upregulated in aGVHD patients compared to non-GVHD patients. Moreover, DEMs showed potentially high diagnostic accuracy for aGVHD. In silico analysis of DEMs provided valuable information on the role of DEMs in GVHD, immune regulation, and inflammatory response. Our study suggested that miR-455-3p, miR-5787, and miR-548a-3p could be used as potential noninvasive biomarkers in the diagnosis of aGVHD in addition to possible therapeutic targets in aGVHD.


Assuntos
Doença Enxerto-Hospedeiro/sangue , MicroRNAs/sangue , Biomarcadores/sangue , Regulação para Baixo , Feminino , Doença Enxerto-Hospedeiro/diagnóstico , Doença Enxerto-Hospedeiro/genética , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Transcriptoma , Regulação para Cima
18.
Biomolecules ; 11(7)2021 06 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209965

RESUMO

Extracellular circulating microRNAs (miRNAs) are currently a focus of interest as non-invasive biomarkers of cardiovascular pathologies, including coronary artery disease (CAD) and acute coronary syndromes (ACS): myocardial infarction with and without ST-segment elevation (STEMI and NSTEMI) and unstable angina (UA). However, the current data for some miRNAs are controversial and inconsistent, probably due to pre-analytical and methodological variances in different studies. In this work, we fulfilled the basic pre-analytical requirements provided for circulating miRNA studies for application to stable CAD and ACS research. We used quantitative PCR to determine the relative plasma levels of eight circulating miRNAs that are potentially associated with atherosclerosis. In a cohort of 136 adult clinic CAD patients and outpatient controls, we found that the plasma levels of miR-21-5p and miR-146a-5p were significantly elevated in ACS patients, and the level of miR-17-5p was decreased in ACS and stable CAD patients compared to both healthy controls and hypertensive patients without CAD. Within the ACS patient group, no differences were found in the plasma levels of these miRNAs between patients with positive and negative troponin, nor were any differences found between STEMI and NSTEMI. Our results indicate that increased plasma levels of miR-146a-5p and miR-21-5p can be considered general ACS circulating biomarkers and that lowered miR-17-5p can be considered a general biomarker of CAD.


Assuntos
MicroRNA Circulante/análise , Doença da Artéria Coronariana/genética , MicroRNAs/análise , Síndrome Coronariana Aguda/sangue , Síndrome Coronariana Aguda/genética , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Estudos de Coortes , Doença da Artéria Coronariana/sangue , Feminino , Humanos , Masculino , MicroRNAs/sangue , MicroRNAs/genética , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue
19.
Cancer Sci ; 112(10): 4270-4280, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34270831

RESUMO

Cancer-related microRNAs (miRNAs) are emerging as promising and noninvasive biomarkers for colorectal cancer (CRC). This study aimed to investigate the usefulness of postoperative changes in plasma miR21-5p levels for recurrence and progressive disease (PD) after surgical resection. This study was a prospective study of 103 CRC patients who underwent surgical resection. Self-paired plasma samples collected pre-operation (Pre), 7 days post-operation (POD7), 1 month post-operation (POM1), and 6 months post-operation (POM6) were analyzed. The miRNA levels were evaluated by quantitative reverse transcription PCR. Among the enrolled patients, ten cases (9.7%) of postoperative recurrence and six cases (5.8%) of postoperative PD occurred at POM6. In the recurrence and PD group, plasma miR21-5p levels significantly increased (POM1: P < .01, POM6: P < .01, respectively). The area under the curve (AUC) value for postoperative changes in plasma miR21-5p levels at POM1 and POM6 to discriminate recurrence and PD were 0.675 and 0.715, respectively. Combined analysis with postoperative carcinoembryonic antigen (CEA) level in discriminating recurrence and PD increased AUC values (POM1: 0.715 and POM6: 0.789). Furthermore, multivariate analysis for recurrence and PD after surgical resection showed that postoperative changes in the plasma miR21-5p level at POM1 and POM6 were independent prognostic factors (POM1: P = .03, POM6: P < .01). The postoperative changes in plasma miR21-5p level could be a useful noninvasive biomarker for monitoring and predicting recurrence and PD after surgical resection of CRC patients. Furthermore, plasma miR21-5p can predict recurrence and PD after surgical resection.


Assuntos
Biomarcadores Tumorais/sangue , Neoplasias Colorretais/sangue , MicroRNAs/sangue , Recidiva Local de Neoplasia/sangue , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Antígeno Carcinoembrionário/sangue , Neoplasias Colorretais/genética , Neoplasias Colorretais/cirurgia , Diagnóstico Diferencial , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/cirurgia , Período Pós-Operatório , Estudos Prospectivos , Fatores de Tempo
20.
Cancer Sci ; 112(10): 4257-4269, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34273216

RESUMO

Poor survival of patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC) is partly due to early diagnosis difficulties and the lack of reliable biomarkers for predicting treatment outcomes. In the discovery cohort, plasma-derived extracellular vesicles (EVs) from LA-HNSCC patients (n = 48) and healthy volunteers (n = 12) were used for profiling for microRNA (miRNA) expression by NanoString analysis. Ten EV-associated miRNAs were differentially expressed between LA-HNSCC patients and healthy volunteers. Subsequently, the results were validated in the individual discovery and additional cases (HNSCC, n = 73; control, n = 20) by quantitative RT-PCR. Among 10 EV-miRNAs, four (miR-27b-3p, miR-491-5p, miR-1910-5p, and miR-630) were significantly dysregulated in LA-HNSCC patients (n = 73) compared with healthy volunteers (n = 20). The miRNA prediction models were developed to discriminate HNSCC patients from healthy volunteers. The model using miR-491-5p was selected as a diagnostic biomarker for LA-HNSCC with a sensitivity and specificity of 46.6% and 100%, respectively (P < .001). The dynamic changes of miRNA model score (ΔmiRNAs) were determined using scores pre- and postdefinitive treatment to further investigate the prognostic value of miRNA prediction models. The univariate and multivariate analyses indicated that ΔmiR-491-5p was the most powerful and independent prognostic indicator for overall survival (hazard ratio [HR] 5.66, 95% confidence interval, 1.77-18.01; P = .003) and disease-free survival (HR 2.82, 95% CI, 1.13-7.05; P = .027) of HNSCC patients. In summary, the miR-491-5p prediction model could serve as a blood-based diagnostic marker for LA-HNSCC. Moreover, ΔmiR-491-5p could be a potential monitoring prognostic marker to reflect the survival of HNSCC patients.


Assuntos
Vesículas Extracelulares/genética , Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adulto , Idoso , Análise de Variância , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Intervalos de Confiança , Intervalo Livre de Doença , Feminino , Neoplasias de Cabeça e Pescoço/sangue , Neoplasias de Cabeça e Pescoço/mortalidade , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Análise em Microsséries , Pessoa de Meia-Idade , Prognóstico , Sensibilidade e Especificidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/sangue , Carcinoma de Células Escamosas de Cabeça e Pescoço/mortalidade , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
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