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1.
PLoS One ; 19(5): e0303598, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38768135

RESUMO

Circulating miRNA has recently emerged as important biomolecules with potential clinical values as diagnostic markers for several diseases. However, to be used as such, it is critical to accurately quantify miRNAs in the clinic. Yet, preanalytical factors that can affect an error-free quantification of these miRNAs have not been explored. This study aimed at investigating several of these preanalytical factors that may affect the accurate quantification of miRNA-451a, miRNA-423-5p and miRNA-199a-3p in human blood samples. We initially evaluated levels of these three miRNAs in red blood cells (RBCs), white blood cells (WBCs), platelets, and plasma by droplet digital PCR (ddPCR). Next, we monitored miRNA levels in whole blood or platelet rich plasma (PRP) stored at different temperatures for different time periods by ddPCR. We also investigated the effects of hemolysis on miRNA concentrations in platelet-free plasma (PFP). Our results demonstrate that more than 97% of miRNA-451a and miRNA-423-5p in the blood are localized in RBCs, with only trace amounts present in WBCs, platelets, and plasma. Highest amount of the miRNA-199a-3p is present in platelets. Hemolysis had a significant impact on both miRNA-451a and miRNA-423-5p concentrations in plasma, however miRNA-199a levels remain unaffected. Importantly, PRP stored at room temperature (RT) or 4°C showed a statistically significant decrease in miRNA-451a levels, while the other two miRNAs were increased, at days 1, 2, 3 and 7. PFP at RT caused statistically significant steady decline in miRNA-451a and miRNA-423-5p, observed at 12, 24, 36, 48 and 72 hours. Levels of the miRNA-199a-3p in PFP was stable during first 72 hours at RT. PFP stored at -20°C for 7 days showed declining stability of miRNA-451a over time. However, at -80°C miRNA-451a levels were stable up to 7 days. Together, our data indicate that hemolysis and blood storage at RT, 4°C and -20°C may have significant negative effects on the accuracy of circulating miRNA-451a and miRNA-423-5p quantification.


Assuntos
Eritrócitos , MicroRNAs , Humanos , MicroRNAs/sangue , MicroRNAs/genética , Eritrócitos/metabolismo , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Hemólise , Plaquetas/metabolismo , Leucócitos/metabolismo
2.
Sci Adv ; 10(20): eadl6442, 2024 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-38748787

RESUMO

Early and precise diagnosis of α-synucleinopathies is challenging but critical. In this study, we developed a molecular beacon-based assay to evaluate microRNA-containing extracellular vesicles (EVs) in plasma. We recruited 1203 participants including healthy controls (HCs) and patients with isolated REM sleep behavior disorder (iRBD), α-synucleinopathies, or non-α-synucleinopathies from eight centers across China. Plasma miR-44438-containing EV levels were significantly increased in α-synucleinopathies, including those in the prodromal stage (e.g., iRBD), compared to both non-α-synucleinopathy patients and HCs. However, there are no significant differences between Parkinson's disease (PD) and multiple system atrophy. The miR-44438-containing EV levels negatively correlated with age and the Hoehn and Yahr stage of PD patients, suggesting a potential association with disease progression. Furthermore, a longitudinal analysis over 16.3 months demonstrated a significant decline in miR-44438-containing EV levels in patients with PD. These results highlight the potential of plasma miR-44438-containing EV as a biomarker for early detection and progress monitoring of α-synucleinopathies.


Assuntos
Biomarcadores , MicroRNA Circulante , Vesículas Extracelulares , Doença de Parkinson , Sinucleinopatias , Humanos , Vesículas Extracelulares/metabolismo , Masculino , Biomarcadores/sangue , Feminino , Pessoa de Meia-Idade , MicroRNA Circulante/sangue , Doença de Parkinson/sangue , Doença de Parkinson/diagnóstico , Idoso , Sinucleinopatias/sangue , Sinucleinopatias/diagnóstico , alfa-Sinucleína/sangue , Estudos de Casos e Controles , MicroRNAs/sangue , Atrofia de Múltiplos Sistemas/sangue , Atrofia de Múltiplos Sistemas/diagnóstico
3.
Artigo em Inglês | MEDLINE | ID: mdl-38715982

RESUMO

Purpose: Investigate the efficacy of blood microRNAs (miRNAs) as diagnostic biomarkers for Chronic Obstructive Pulmonary Disease (COPD). Patients and Methods: We conducted a comprehensive search in English and Chinese databases, selecting studies based on predetermined criteria. Diagnostic parameters like summarized sensitivity (SSEN), summarized specificity (SSPE), summarized positive likelihood ratio (SPLR), summarized negative likelihood ratio (SNLR), and diagnostic odds ratio (DOR), and area under the curve (AUC) of the summary receiver operating characteristic (SROC) curves were analyzed using a bivariate model. Each parameter was accompanied by a 95% confidence interval (CI). Results: Eighteen high-quality studies were included. For diagnosing COPD with blood miRNAs, the SSEN was 0.83 (95% CI 0.76-0.89), SSPE 0.76 (95% CI 0.70-0.82), SPLR 3.50 (95% CI 2.66-4.60), SNLR 0.22 (95% CI 0.15-0.33), DOR 15.72 (95% CI 8.58-28.77), and AUC 0.86 (95% CI 0.82-0.88). In acute exacerbations, SSEN was 0.85 (95% CI 0.76-0.91), SSPE 0.80 (95% CI 0.73-0.86), SPLR 4.26 (95% CI 3.05-5.95), SNLR 0.19 (95% CI 0.12-0.30), DOR 22.29 (95% CI 11.47-43.33), and AUC 0.89 (95% CI 0.86-0.91). Conclusion: Blood miRNAs demonstrate significant accuracy in diagnosing COPD, both in general and during acute exacerbations, suggesting their potential as reliable biomarkers.


Assuntos
Área Sob a Curva , Valor Preditivo dos Testes , Doença Pulmonar Obstrutiva Crônica , Curva ROC , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/genética , Humanos , Razão de Chances , MicroRNAs/sangue , Biomarcadores/sangue , Pessoa de Meia-Idade , Idoso , Marcadores Genéticos , Masculino , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Feminino , Prognóstico , Pulmão/fisiopatologia
4.
Int Ophthalmol ; 44(1): 176, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-38619629

RESUMO

PURPOSE: Conventional diagnosis of primary open angle glaucoma (POAG) needs a combination of ophthalmic examinations. An efficient assay is urgently needed for a timely POAG diagnosis. We aim to explore differential expressions of circulating microRNAs (miRNA) and provide novel miRNA biomarkers for POAG diagnosis. METHODS: A total of 180 POAG patients and 210 age-related cataract (ARC) patients were enrolled. We collected aqueous humor (AH) and plasma samples from the recruited patients. The expressions of candidate miRNAs were measured using quantitative real time polymerase chain reaction. The diagnostic ability of candidate miRNAs was analyzed by receiver operating characteristic curve. RESULTS: The expressions of miR-21-5p and miR-29b-3p were downregulated significantly in AH and plasma of POAG and miR-24-3p expression was significantly increased in AH and plasma of POAG, comparing with those of ARC. A three-miRNA panel was constructed by a binary logistic regression. And the panel could differentiate between POAG and ARC with an area under the curve of 0.8867 (sensitivity = 78.0%, specificity = 83.3%) in aqueous humor and 0.7547 (sensitivity = 73.8%, specificity = 81.2%) in plasma. Next, we verified the three-miRNA panel working as a potential diagnostic biomarker stable and reliable. At last, we identified related function and regulation pathways in vitro. CONCLUSIONS: In conclusion, we built and identified a circulating three-miRNA panel as a potential diagnostic biomarker for POAG. It may be developed into an efficient assay and help improve the POAG diagnosis in the future.


Assuntos
MicroRNA Circulante , Glaucoma de Ângulo Aberto , MicroRNAs , Humanos , Glaucoma de Ângulo Aberto/diagnóstico , Glaucoma de Ângulo Aberto/genética , MicroRNAs/genética , Humor Aquoso , Biomarcadores
5.
Egypt J Immunol ; 31(2): 102-111, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38615267

RESUMO

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers in the world. Two risk factors that cause 80-90% of HCC cases globally are chronic infection with hepatitis B virus (HBV) and hepatitis C virus (HCV). The diagnostic value of circulating microRNAs (miRNAs) in numerous tumors has been described. Our research assessed microRNA-16 (miR-16) as a novel biomarker in patients with HCV-induced HCC. The study included three groups. Group 1 included 55 individuals with cirrhosis caused by liver HCV infection in addition to HCC. Group 2 included 55 individuals with cirrhosis brought on by HCV infection. Group 3 included 55 normal control individuals. Expression of miR-16 in blood was assessed by real-time polymerase chain reaction (RT-PCR). The mean level of miR-16 was significantly different in the three groups, with group 1 having the greatest value (1.098 ± 0.647), followed by group 2 (1.1035 ± 0.8567) and group 3 (control subjects) having the lowest value (0.3842 ± 0.21485). The receiver operating characteristic (ROC) curve analysis showed that miR-16 had a higher diagnostic value at area under the curve (AUC) of 0.935 than alpha-feto protein (AUC of 0.859) to differentiate between HCC and control subjects. MiR-16 has a sensitivity of 81.82 % and a specificity of 69.09%, to distinguish between patients with liver cirrhosis and HCC patients. Our findings illustrated that circulating miR-16 can be proposed as a marker for detection of patients with HCV-induced HCC.


Assuntos
Carcinoma Hepatocelular , MicroRNA Circulante , Hepatite C , Neoplasias Hepáticas , MicroRNAs , Humanos , Hepacivirus/genética , Carcinoma Hepatocelular/diagnóstico , Egito , Neoplasias Hepáticas/diagnóstico , Hepatite C/complicações , Cirrose Hepática/diagnóstico , Biomarcadores
6.
Sci Rep ; 14(1): 8603, 2024 04 13.
Artigo em Inglês | MEDLINE | ID: mdl-38615118

RESUMO

Predictive biomarkers of response to immune checkpoint-based therapies (ICI) remain a critically unmet need in the management of advanced renal cell carcinoma (RCC). The complex interplay of the tumour microenvironment (TME) and the circulating immune response has proven to be challenging to decipher. MicroRNAs have gained increasing attention for their role in post-transcriptional gene expression regulation, particularly because they can have immunomodulatory properties. We evaluated the presence of immune-specific extracellular vesicle (EV) microRNAs in the plasma of patients with metastatic RCC (mRCC) prior to initiation of ICI. We found significantly lower levels of microRNA155-3p (miR155) in responders to ICI, when compared to non-responders. This microRNA has unique immunomodulatory properties, thus providing potential biological rationale for our findings. Our results support further work in exploring microRNAs as potential biomarkers of response to immunotherapy.


Assuntos
Carcinoma de Células Renais , MicroRNA Circulante , Neoplasias Renais , MicroRNAs , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/terapia , Neoplasias Renais/genética , Neoplasias Renais/terapia , Imunoterapia , MicroRNAs/genética , Biomarcadores , Microambiente Tumoral/genética
7.
Int J Mol Sci ; 25(8)2024 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-38673876

RESUMO

Schizophrenia is a complex and heterogenous psychiatric disorder. This study aimed to demonstrate the potential of circulating microRNAs (miRNAs) as a clinical biomarker to stratify schizophrenia patients and to enhance understandings of their heterogenous pathophysiology. We measured levels of 179 miRNA and 378 proteins in plasma samples of schizophrenia patients experiencing acute psychosis and obtained their Positive and Negative Syndrome Scale (PANSS) scores. The plasma miRNA profile revealed three subgroups of schizophrenia patients, where one subgroup tended to have higher scores of all the PANSS subscales compared to the other subgroups. The subgroup with high PANSS scores had four distinctively downregulated miRNAs, which enriched 'Immune Response' according to miRNA set enrichment analysis and were reported to negatively regulate IL-1ß, IL-6, and TNFα. The same subgroup had 22 distinctively upregulated proteins, which enriched 'Cytokine-cytokine receptor interaction' according to protein set enrichment analysis, and all the mapped proteins were pro-inflammatory cytokines. Hence, the subgroup is inferred to have comparatively high inflammation within schizophrenia. In conclusion, miRNAs are a potential biomarker that reflects both disease symptoms and molecular pathophysiology, and identify a patient subgroup with high inflammation. These findings provide insights for the precision medicinal strategies for anti-inflammatory treatments in the high-inflammation subgroup of schizophrenia.


Assuntos
Biomarcadores , MicroRNA Circulante , Inflamação , Transtornos Psicóticos , Esquizofrenia , Humanos , Esquizofrenia/sangue , Esquizofrenia/genética , Masculino , Inflamação/sangue , Inflamação/genética , Feminino , Biomarcadores/sangue , Adulto , Transtornos Psicóticos/sangue , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Citocinas/sangue , Pessoa de Meia-Idade , Perfilação da Expressão Gênica , MicroRNAs/sangue , MicroRNAs/genética
8.
Int J Mol Sci ; 25(7)2024 Mar 31.
Artigo em Inglês | MEDLINE | ID: mdl-38612727

RESUMO

Pancreatic cancer remains a formidable malignancy characterized by high mortality rates, primarily attributable to late-stage diagnosis and a dearth of effective therapeutic interventions. The identification of reliable biomarkers holds paramount importance in enhancing early detection, prognostic evaluation, and targeted treatment modalities. Small non-coding RNAs, particularly microRNAs, have emerged as promising candidates for pancreatic cancer biomarkers in recent years. In this review, we delve into the evolving role of cellular and circulating miRNAs, including exosomal miRNAs, in the diagnosis, prognosis, and therapeutic targeting of pancreatic cancer. Drawing upon the latest research advancements in omics data-driven biomarker discovery, we also perform a case study using public datasets and address commonly identified research discrepancies, challenges, and limitations. Lastly, we discuss analytical approaches that integrate multimodal analyses incorporating clinical and molecular features, presenting new insights into identifying robust miRNA-centric biomarkers.


Assuntos
Pesquisa Biomédica , MicroRNA Circulante , MicroRNAs , Neoplasias Pancreáticas , Humanos , MicroRNAs/genética , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/terapia , Pâncreas
9.
Scand J Clin Lab Invest ; 84(2): 133-137, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38597780

RESUMO

MicroRNA-33b (miR-33b) affected various biological pathways in regulating cholesterol homeostasis which may link to the pathogenesis of atherosclerotic lesions. However, whether this marker is associated with the presence and severity of coronary heart disease (CHD) is undetermined. We aim to explore the diagnostic value of circulating miR-33b level in the presence and severity of CHD. Altogether 320 patients were enrolled, including 240 patients diagnosed with CHD while 80 were classified as controls after CAG examination. Circulating miR-33b level was analyzed in all subjects, the Gensini score was calculated to assess the severity of stenotic lesions. The association between miR-33b and the presence and severity of CHD was analyzed, and the diagnostic potential of miR-33b of CHD was performed by the receiver operating characteristic (ROC) analysis. The CHD group had higher miR-33b levels (p < 0.001), and the miR-33b content significantly elevated following an increasing Gensini score (p for trend < 0.001). After adjustments for potential risk factors, such as several blood lipid markers, miR-33b remained a significant determinant for CHD (p < 0.001). ROC analysis disclosed that the AUC was 0.931. The optimal cutoff value of miR-33b was with a sensitivity of 81.3% and a specificity of 98.7% in differentiating CHD. It can prognosticate that the higher level of miR-33b was linked to increased severity of disease in CHD patients. Thus, the application of this marker might assist in the diagnosis and classification of CHD patients. Nevertheless, additional studies with larger sample sizes will be required to verify these results.


Assuntos
Biomarcadores , Doença das Coronárias , MicroRNAs , Curva ROC , Índice de Gravidade de Doença , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Biomarcadores/sangue , Estudos de Casos e Controles , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Doença das Coronárias/sangue , Doença das Coronárias/genética , Doença das Coronárias/diagnóstico , MicroRNAs/sangue , Fatores de Risco
10.
Head Neck Pathol ; 18(1): 28, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38536520

RESUMO

OBJECTIVES: This study aims to elucidate the expression of circulating exosomal miRNAs miRNA 21, miRNA 184, and miRNA 145 in the studied groups, including patients with (i) leukoplakia; (ii) oral submucous fibrosis; (iii) oral submucous fibrosis with leukoplakia; (iv) oral squamous cell carcinoma; and (v) healthy individuals. STUDY DESIGN: An observational study was conducted among 54 patients who reported to the outpatient department of Saveetha Dental College and Hospitals. The patients were divided into three groups: Group I healthy individuals (n = 18), Group II: case group (leukoplakia, OSMF, and leukoplakia and OSMF) (n = 18), and Group III: OSCC (n = 18). Real-time polymerase chain reaction analysis was carried out to assess the expression profiles of miRNA 21, miRNA 184, and miRNA 145. The statistical analysis was calculated using SPSS software version 23. RESULTS: All three miRNAs showed a statistically significant difference in the one-way ANOVA test between the case group (leukoplakia, OSMF, and leukoplakia and OSMF), healthy group, and OSCC group (p < 0.005). The case group (leukoplakia, OSMF, leukoplakia and OSMF) showed upregulated expression of miRNA 21 and miRNA 184 with threefold change and fourfold change and downregulated expression of miRNA 145 with 1.5-fold change when compared to apparently healthy individuals. CONCLUSION: Plasma circulating exosomal miRNAs miRNA 21, miRNA 145, and miRNA 184 expression could be a novel panel of plasma biomarkers to categorise case group (leukoplakia, OSMF, leukoplakia and OSMF) patients with a high risk of malignant transformation.


Assuntos
Carcinoma de Células Escamosas , MicroRNA Circulante , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Fibrose Oral Submucosa , Humanos , Fibrose Oral Submucosa/patologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/patologia , Leucoplasia
11.
Sci Rep ; 14(1): 7431, 2024 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-38548871

RESUMO

Effective management and control of parasitic infections on farms depends on their early detection. Traditional serological diagnostic methods for Fasciola hepatica infection in livestock are specific and sensitive, but currently the earliest detection of the parasite only occurs at approximately three weeks post-infection. At this timepoint, parasites have already entered the liver and caused the tissue damage and immunopathology that results in reduced body weight and loss in productivity. Here, we investigated whether the differential abundance of micro(mi)miRNAs in sera of F. hepatica-infected sheep has potential as a tool for the early diagnosis of infection. Using miRNA sequencing analysis, we discovered specific profiles of sheep miRNAs at both the pre-hepatic and hepatic infection phases in comparison to non-infected sheep. In addition, six F. hepatica-derived miRNAs were specifically identified in sera from infected sheep. Thus, a panel of differentially expressed miRNAs comprising four sheep (miR-3231-3p; miR133-5p; 3957-5p; 1197-3p) and two parasite miRNAs (miR-124-3p; miR-Novel-11-5p) were selected as potential biomarkers. The expression of these candidates in sera samples from longitudinal sheep infection studies collected between 7 days and 23 weeks was quantified using RT-qPCR and compared to samples from age-matched non-infected sheep. We identified oar-miR-133-5p and oar-miR-3957-5p as promising biomarkers of fasciolosis, detecting infection as early as 7 days. The differential expression of the other selected miRNAs was not sufficient to diagnose infection; however, our analysis found that the most abundant forms of fhe-miR-124-3p in sera were sequence variants (IsomiRs) of the canonical miRNA, highlighting the critical importance of primer design for accurate diagnostic RT-qPCR. Accordingly, this investigative study suggests that certain miRNAs are biomarkers of F. hepatica infection and validates miRNA-based diagnostics for the detection of fasciolosis in sheep.


Assuntos
MicroRNA Circulante , Fasciolíase , MicroRNAs , Animais , Ovinos/genética , MicroRNAs/genética , Fasciolíase/diagnóstico , Fasciolíase/genética , Fasciolíase/veterinária , Biomarcadores
12.
Int J Mol Sci ; 25(6)2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38542114

RESUMO

Circulating microRNAs (c-miRNAs) are non-coding RNAs found in different bodily fluids and are highly investigated for their prognostic potential and biological role in cancer. In this narrative review, we provide an update of the last five years' published papers (2018-2023) on PubMed about c-miRNAs in cancer research. We aim to capture the latest research interests in terms of the highly studied cancers and the insights about c-miRNAs. Our analysis revealed that more than 150 papers focusing on c-miRNAs and cancer were published in the last five years. Among these, there was a high prevalence of papers on breast cancer (BC) and lung cancer (LC), which are estimated to be the most diagnosed cancers globally. Thus, we focus on the main evidence and research trends about c-miRNAs in BC and LC. We report evidence of the effectiveness of c-miRNAs in hot topics of cancer research, such as, early detection, therapeutic resistance, recurrence risk and novel detection platform approaches. Moreover, we look at the deregulated c-miRNAs shared among BC and LC papers, focusing on miR-21 and miR-145. Overall, these data clearly indicate that the role of c-miRNAs in cancer is still a hot topic for oncologic research and that blood is the most investigated matrix.


Assuntos
Neoplasias da Mama , MicroRNA Circulante , Neoplasias Pulmonares , MicroRNAs , Humanos , Feminino , MicroRNA Circulante/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Neoplasias da Mama/genética
13.
Int J Mol Sci ; 25(6)2024 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-38542526

RESUMO

The early detection of cognitive decline in Parkinson's disease is important for providing drug therapy and non-pharmacological management. The circulating microRNAs present in plasma are promising biomarkers of PD with dementia (PDD) due to their critical roles in synaptic plasticity and the regulation of neurodegeneration-associated proteins. In this study, we aimed to identify plasma microRNAs that may differentiate PD with or without cognitive impairment. Global microRNA expression was obtained from a discovery set of 123 participants who were divided into four groups, namely normal controls (HC), PD with no dementia (PDND), PD with mild cognitive impairment (PD-MCI), and PDD, using next-generation sequencing. The BOLD selector was used for microRNA candidate selection. Six miRNAs, namely miR-203a-3p, miR-626, miR-662, miR-3182, miR-4274, and miR-4295, were clustered as potential candidates for use in identifying PDND from PD-MCI. Another independent cohort of 120 participants was further recruited in a validation step in order to detect candidate microRNAs via droplet digital PCR (ddPCR), which was used for its high sensitivity in detecting low miRNA concentrations. Our results show that the ratio of miR-203a-3p/miR-16-5p, in which miR-16-5p was used as a reference control miRNA, was significantly increased in PDD compared to that seen in PD-MCI and PDND individually, and was negatively correlated with the MoCA scores (r = -0.237, p = 0.024) in patients with PD. However, there was no significant difference in the ratio of miR-203a-3p/miR-16-5p between HC and PDND, PD-MCI, or PDD individually. The ROC curve of the logistic regression model, factoring in the variables of age, the ratio of miR-203a-3p/miR-16-5p, and the UPDRS III score, demonstrated an AUC of 0.883. Our findings suggest that the ratio of miR-203a-3p/miR-16-5p, used with age and motor score, could be a predictor of dementia among PD patients.


Assuntos
MicroRNA Circulante , Demência , MicroRNAs , Doença de Parkinson , Humanos , Doença de Parkinson/diagnóstico , MicroRNAs/metabolismo , Biomarcadores , Demência/diagnóstico , Demência/genética
14.
Atherosclerosis ; 392: 117502, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38513437

RESUMO

BACKGROUND AND AIMS: Premature atherosclerotic cardiovascular disease (CVD) is a clinic characteristic of familial hypercholesterolemia (FH). Coronary calcium score (CCS) is a highly used imaging modality to evidence atherosclerotic plaque burden. microRNAs (miRNAs) are non-coding RNAs that epigenetically regulate gene expression. Here, we investigated whether CCS associates with a specific miRNA-signature in FH-patients. METHODS: Patients with genetic diagnosis of FH (N = 86) from the nationwide SAFEHEART-cohort were investigated by computed tomography angiography imaging and classified depending on the presence of coronary calcification in FH-CCS (+) and FH-CCS (-) groups by the Agatston score. Differential miRNA profiling was performed in two stages: first by Affymetrix microarray technology (high-throughput differential profiling-studies) and second by RT-PCR using TaqMan-technology (analytical RT-qPCR study) in plasma of the two patient groups. RESULTS: miR-193a-5p, miR-30e-5p and miR-6821-5p levels were significantly higher in FH-CCS (+) compared to FH-CCS (-). miR-6821-5p was the best miRNA to discriminate FH-patients CCS(+), according to receiver operating characteristic (ROC) analysis (AUC: 0.70 ± 0.06, p = 0.006). High miR-6821-5p levels were associated with older age (p = 0.03) and high LDL-burden (p = 0.014) using a ROC-derived cut-off value. However, miR-6821-5p did not correlate with age in either the CCS- or CCS + group. Genes involved in calcification processes were identified by in silico analysis. The relation of cell-calcification and expression levels of miR-6821-5p, BMP2 and SPP1 was validated experimentally in human vascular smooth muscle cell cultures. CONCLUSIONS: Up-regulated levels of miR-6821-5p are found in the plasma of asymptomatic FH-patients with coronary calcified atherosclerotic plaques, as well as in isolated human vascular smooth muscle cells expressing the pro-calcification genes BMP2 and SPP1. These findings highlight the impact of epigenetic regulation on the development of subclinical atherosclerosis.


Assuntos
Doença da Artéria Coronariana , Hiperlipoproteinemia Tipo II , MicroRNAs , Calcificação Vascular , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/genética , Hiperlipoproteinemia Tipo II/complicações , Masculino , Feminino , Pessoa de Meia-Idade , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/diagnóstico por imagem , Calcificação Vascular/sangue , Calcificação Vascular/genética , Calcificação Vascular/diagnóstico por imagem , MicroRNAs/sangue , MicroRNAs/genética , Adulto , Doenças Assintomáticas , Angiografia por Tomografia Computadorizada , MicroRNA Circulante/sangue , MicroRNA Circulante/genética , Angiografia Coronária , Células Cultivadas , Placa Aterosclerótica/sangue , Biomarcadores/sangue , Perfilação da Expressão Gênica , Idoso , Miócitos de Músculo Liso/metabolismo , Vasos Coronários/diagnóstico por imagem , Vasos Coronários/patologia , Curva ROC
15.
Neurologia (Engl Ed) ; 39(2): 147-159, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38460993

RESUMO

BACKGROUND & OBJECTIVE: Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease that seriously affects cognitive ability and has become a key public health problem. Many studies have identified the possibility of peripheral blood microRNA as effective non-invasive biomarkers for AD diagnosis, but the results are inconsistent. Therefore, we carried out this meta-analysis to evaluate the diagnostic accuracy of circulating microRNAs in the diagnosis of AD patients. METHODS: We performed a systematic literature search of the following databases: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure, updated to March 15, 2021. A random effects model was used to pool the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve. Meta-regression and subgroup analysis were performed to explore the sources of heterogeneity, and Deeks' funnel plot was used to assess whether there was publication bias. RESULTS: 62 studies from 18 articles were included in this meta-analysis. The pooled sensitivity was 0.82 (95% CI: 0.78-0.85), specificity was 0.80 (95% CI: 0.76-0.83), PLR was 4. 1 (95% CI: 3.4-4.9), NLR was 0.23 (95% CI: 0.19-0.28), DOR was 18 (95% CI: 13-25) and AUC was 0.88 (95% CI: 0.84-0.90). Subgroup analysis shows that the microRNA clusters of plasma type performed a better diagnostic accuracy of AD patients. In addition, publication bias was not found. CONCLUSIONS: Circulating microRNAs can be used as a promising non-invasive biomarker in AD diagnosis.


Assuntos
Doença de Alzheimer , MicroRNA Circulante , Doenças Neurodegenerativas , Humanos , Doença de Alzheimer/diagnóstico , Biomarcadores , Sensibilidade e Especificidade
16.
Cancer Lett ; 588: 216655, 2024 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-38460724

RESUMO

Cancer remains a major burden globally and the critical role of early diagnosis is self-evident. Although various miRNA-based signatures have been developed in past decades, clinical utilization is limited due to a lack of precise cutoff value. Here, we innovatively developed a signature based on pairwise expression of miRNAs (miRPs) for pan-cancer diagnosis using machine learning approach. We analyzed miRNA spectrum of 15832 patients, who were divided into training, validation, test, and external test sets, with 13 different cancers from 10 cohorts. Five different machine-learning (ML) algorithms (XGBoost, SVM, RandomForest, LASSO, and Logistic) were adopted for signature construction. The best ML algorithm and the optimal number of miRPs included were identified using area under the curve (AUC) and youden index in validation set. The AUC of the best model was compared to previously published 25 signatures. Overall, Random Forest approach including 31 miRPs (31-miRP) was developed, proving highly efficient in cancer diagnosis across different datasets and cancer types (AUC range: 0.980-1.000). Regarding diagnosis of cancers at early stage, 31-miRP also exhibited high capacities, with AUC ranging from 0.961 to 0.998. Moreover, 31-miRP exhibited advantages in differentiating cancers from normal tissues (AUC range: 0.976-0.998) as well as differentiating cancers from corresponding benign lesions. Encouragingly, comparing to previously published 25 different signatures, 31-miRP also demonstrated clear advantages. In conclusion, 31-miRP acts as a powerful model for cancer diagnosis, characterized by high specificity and sensitivity as well as a clear cutoff value, thereby holding potential as a reliable tool for cancer diagnosis at early stage.


Assuntos
MicroRNA Circulante , MicroRNAs , Neoplasias , Humanos , MicroRNA Circulante/genética , Neoplasias/diagnóstico , Neoplasias/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Algoritmos , Diagnóstico Precoce
17.
BMC Cardiovasc Disord ; 24(1): 142, 2024 Mar 05.
Artigo em Inglês | MEDLINE | ID: mdl-38443814

RESUMO

BACKGROUND: MicroRNAs (miRNAs) are important regulatory factors in the normal developmental stages of the heart and kidney. However, it is currently unclear how miRNA is expressed in type 2 cardiorenal syndrome (CRS). This study aimed to detect the differential expression of miRNAs and to clarify the main enrichment pathways of differentially expressed miRNA target genes in type 2 CRS. METHODS: Five cases of healthy control (Group 1), eight of chronic heart failure (CHF, Group 2) and seven of type 2 CRS (Group 3) were enrolled, respectively. Total RNA was extracted from the peripheral blood of each group. To predict the miRNA target genes and biological signalling pathways closely related to type 2 CRS, the Agilent miRNA microarray platform was used for miRNA profiling and bioinformatics analysis of the isolated total RNA samples. RESULTS: After the microarray analysis was done to screen for differentially expressed circulating miRNAs among the three different groups of samples, the target genes and bioinformatic pathways of the differential miRNAs were predicted. A total of 38 differential miRNAs (15 up- and 23 down-regulated) were found in Group 3 compared with Group 1, and a total of 42 differential miRNAs (11 up- and 31 down-regulated) were found in Group 3 compared to Group 2. According to the Gene Ontology (GO) function and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis, the top 10 lists of molecular functions, cellular composition and biological processes, and the top 30 signalling pathways of predicted gene targets of the differentially expressed miRNAs were discriminated among the three groups. CONCLUSION: Between the patients with CHF and type 2 CRS, miRNAs were differentially expressed. Prediction of target genes of differentially expressed miRNAs and the use of GO function and KEGG pathway analysis may reveal the molecular mechanisms of CRS. Circulating miRNAs may contribute to the diagnosis of CRS, and further and larger studies are needed to enhance the robustness of our findings.


Assuntos
Síndrome Cardiorrenal , MicroRNA Circulante , MicroRNAs , Humanos , Síndrome Cardiorrenal/diagnóstico , Síndrome Cardiorrenal/genética , MicroRNAs/genética , Rim , Coração , Biologia Computacional
18.
J Transl Med ; 22(1): 235, 2024 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-38433211

RESUMO

BACKGROUND: Psoriasis is a chronic inflammatory disorder characterized by pathogenic hyperproliferation of keratinocytes and immune dysregulation. Currently, objective evaluation tools reflecting the severity of psoriasis are insufficient. MicroRNAs in extracellular vesicles (EV miRNAs) have been shown to be potential biomarkers for various inflammatory diseases. Our objective was to investigate the possibility of plasma-derived EV miRNAs as a marker for the psoriasis disease severity. METHODS: EVs were extracted from the plasma of 63 patients with psoriasis and 12 with Behçet's disease. We performed next-generation sequencing of the plasma-derived EV miRNAs from the psoriasis patients. Real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to validate the level of EV miRNA expression. In situ hybridization was used to discern the anatomical location of miRNAs. qRT-PCR, western blotting, and cell counting kits (CCKs) were used to investigate IGF-1 signaling in cells transfected with miRNA mimics. RESULTS: We identified 19 differentially expressed EV miRNAs and validated the top three up-and down-regulated EV miRNAs. Among these, miR-625-3p was significantly increased in patients with severe psoriasis in both plasma and skin and most accurately distinguished moderate-to-severe psoriasis from mild-to-moderate psoriasis. It was produced and secreted by keratinocytes upon stimulation. We also observed a significant intensification of IGF-1 signalling and increased cell numbers in the miR-625-3p mimic transfected cells. CONCLUSIONS: We propose keratinocyte-derived EV miR-625-3p as a novel and reliable biomarker for estimating the severity of psoriasis. This biomarker could objectively evaluate the severity of psoriasis in the clinical setting and might serve as a potential therapeutic target. Trial registration None.


Assuntos
MicroRNA Circulante , Vesículas Extracelulares , MicroRNAs , Psoríase , Humanos , MicroRNA Circulante/genética , Fator de Crescimento Insulin-Like I , MicroRNAs/genética , Queratinócitos , Psoríase/genética , Biomarcadores
19.
Neurología (Barc., Ed. impr.) ; 39(2): 147-159, Mar. 2024. ilus, tab, graf
Artigo em Inglês | IBECS | ID: ibc-230869

RESUMO

Background & objective Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disease that seriously affects cognitive ability and has become a key public health problem. Many studies have identified the possibility of peripheral blood microRNA as effective non-invasive biomarkers for AD diagnosis, but the results are inconsistent. Therefore, we carried out this meta-analysis to evaluate the diagnostic accuracy of circulating microRNAs in the diagnosis of AD patients. Methods We performed a systematic literature search of the following databases: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database and China National Knowledge Infrastructure, updated to March 15, 2021. A random effects model was used to pool the sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio and area under the curve. Meta-regression and subgroup analysis were performed to explore the sources of heterogeneity, and Deeks’ funnel plot was used to assess whether there was publication bias. Results 62 studies from 18 articles were included in this meta-analysis. The pooled sensitivity was 0.82 (95% CI: 0.78–0.85), specificity was 0.80 (95% CI: 0.76–0.83), PLR was 4. 1 (95% CI: 3.4–4.9), NLR was 0.23 (95% CI: 0.19–0.28), DOR was 18 (95% CI: 13–25) and AUC was 0.88 (95% CI: 0.84–0.90). Subgroup analysis shows that the microRNA clusters of plasma type performed a better diagnostic accuracy of AD patients. In addition, publication bias was not found. Conclusions Circulating microRNAs can be used as a promising non-invasive biomarker in AD diagnosis. (AU)


Antecedentes y objetivo La enfermedad de Alzheimer (EA) es una enfermedad neurodegenerativa progresiva e irreversible que afecta gravemente la capacidad cognitiva y se ha convertido en un problema clave de salud pública. Muchos estudios han identificado la posibilidad de que los microARN de sangre periférica sean biomarcadores no invasivos para el diagnóstico de la EA, pero los resultados son inconsistentes. Por lo tanto, llevamos a cabo este metaanálisis para evaluar la precisión diagnóstica de los microARN circulantes en el diagnóstico de pacientes con EA. Métodos Realizamos una búsqueda bibliográfica sistemática de las siguientes bases de datos: PubMed, EMBASE, Web of Science, Cochrane Library, Wanfang database y China National Knowledge Infrastructure, actualizado a 15 de marzo de 2021. Se utilizó un modelo de efectos aleatorios para agrupar la sensibilidad, especificidad, razón de probabilidad positiva, razón de probabilidad negativa, razón de probabilidades de diagnóstico y área bajo la curva. Se realizó una metarregresión y un análisis de subgrupos para explorar las fuentes de heterogeneidad, y se utilizó el gráfico en embudo de Deek's para evaluar si había sesgo de publicación. Resultados En este metaanálisis se incluyeron 62 estudios de 18 artículos. La sensibilidad combinada fue de 0,82 (IC 95%: 0,78-0,85), la especificidad fue de 0,80 (IC 95%: 0,76-0,83), la PLR fue de 4,1 (IC 95%: 3,4-4,9), la NLR fue de 0,23 (IC 95%: 0,19-0,28), la DOR fue de 18 (IC 95%: 13-25) y el AUC fue de 0,88 (IC 95%: 0,84-0,90). El análisis de subgrupos muestra que los microARN clústeres de tipo plasmático tuvieron una mejor precisión diagnóstica de pacientes con EA. Además, no se encontró sesgo de publicación. Conclusión Los microARN circulantes pueden utilizarse como un biomarcador no invasivo prometedor para el diagnóstico de la EA. (AU)


Assuntos
MicroRNA Circulante , Doença de Alzheimer/diagnóstico
20.
Respir Res ; 25(1): 118, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38459594

RESUMO

BACKGROUND: Vitamin D may help to alleviate asthma exacerbation because of its anti-inflammation effect, but the evidence is inconsistent in childhood asthma. MiRNAs are important mediators in asthma pathogenesis and also excellent non-invasive biomarkers. We hypothesized that circulating miRNAs are associated with asthma exacerbation and modified by vitamin D levels. METHODS: We sequenced baseline serum miRNAs from 461 participants in the Childhood Asthma Management Program (CAMP). Logistic regression was used to associate miRNA expression with asthma exacerbation through interaction analysis first and then stratified by vitamin D insufficient and sufficient groups. Microarray from lymphoblastoid B-cells (LCLs) treated by vitamin D or sham of 43 subjects in CAMP were used for validation in vitro. The function of miRNAs was associated with gene modules by weighted gene co-expression network analysis (WGCNA). RESULTS: We identified eleven miRNAs associated with asthma exacerbation with vitamin D effect modification. Of which, five were significant in vitamin D insufficient group and nine were significant in vitamin D sufficient group. Six miRNAs, including hsa-miR-143-3p, hsa-miR-192-5p, hsa-miR-151a-5p, hsa-miR-24-3p, hsa-miR-22-3p and hsa-miR-451a were significantly associated with gene modules of immune-related functions, implying miRNAs may mediate vitamin D effect on asthma exacerbation through immune pathways. In addition, hsa-miR-143-3p and hsa-miR-451a are potential predictors of childhood asthma exacerbation at different vitamin D levels. CONCLUSIONS: miRNAs are potential mediators of asthma exacerbation and their effects are directly impacted by vitamin D levels.


Assuntos
Asma , MicroRNA Circulante , MicroRNAs , Humanos , MicroRNAs/metabolismo , MicroRNA Circulante/genética , Perfilação da Expressão Gênica , Asma/diagnóstico , Asma/genética , Vitamina D
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