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1.
Sci Rep ; 12(1): 20048, 2022 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-36414650

RESUMO

Coronavirus disease-2019 (COVID-19) can be asymptomatic or lead to a wide symptom spectrum, including multi-organ damage and death. Here, we explored the potential of microRNAs in delineating patient condition and predicting clinical outcome. Plasma microRNA profiling of hospitalized COVID-19 patients showed that miR-144-3p was dynamically regulated in response to COVID-19. Thus, we further investigated the biomarker potential of miR-144-3p measured at admission in 179 COVID-19 patients and 29 healthy controls recruited in three centers. In hospitalized patients, circulating miR-144-3p levels discriminated between non-critical and critical illness (AUCmiR-144-3p = 0.71; p = 0.0006), acting also as mortality predictor (AUCmiR-144-3p = 0.67; p = 0.004). In non-hospitalized patients, plasma miR-144-3p levels discriminated mild from moderate disease (AUCmiR-144-3p = 0.67; p = 0.03). Uncontrolled release of pro-inflammatory cytokines can lead to clinical deterioration. Thus, we explored the added value of a miR-144/cytokine combined analysis in the assessment of hospitalized COVID-19 patients. A miR-144-3p/Epidermal Growth Factor (EGF) combined score discriminated between non-critical and critical hospitalized patients (AUCmiR-144-3p/EGF = 0.81; p < 0.0001); moreover, a miR-144-3p/Interleukin-10 (IL-10) score discriminated survivors from nonsurvivors (AUCmiR-144-3p/IL-10 = 0.83; p < 0.0001). In conclusion, circulating miR-144-3p, possibly in combination with IL-10 or EGF, emerges as a noninvasive tool for early risk-based stratification and mortality prediction in COVID-19.


Assuntos
COVID-19 , MicroRNAs , Humanos , Biomarcadores/sangue , COVID-19/diagnóstico , COVID-19/mortalidade , Fator de Crescimento Epidérmico , Interleucina-10 , MicroRNAs/sangue
2.
Zhonghua Yi Xue Za Zhi ; 102(30): 2357-2362, 2022 Aug 16.
Artigo em Chinês | MEDLINE | ID: mdl-35970794

RESUMO

Objective: To investigate the expression of miR-17-5p in the plasma of patients with multiple myeloma (MM) and its role in tumorigenesis and development. Methods: Patients diagnosed with unidentified monoclonal gammopathy of undetermined significance (MGUS) or MM in Cancer Hospital of Zhengzhou University from April 2013 to April 2018 were enrolled, as well as 20 healthy volunteers. Reverse transcription polymerase chain reaction (qRT-PCR) was used to detect the expression levels of miR-17-5p in plasma circulation and bone marrow mononuclear cells. There were 22 cases with newly diagnosed MM (NDMM), 11 cases with complete remission MM (CRMM) and 59 case with recurrent refractory MM (RRMM). The expression levels of miR-17-5p in each group were analyzed. The correlation analysis was used to evaluate the relationship between plasma miR-17-5p and the proportion of serum M protein and bone marrow plasma cells in patients with untreated multiple myeloma. Receiver operating characteristic (ROC) curve was used to evaluate the possibility of plasma miR-17-5p as a molecular marker related to MM diagnosis. After over expression or knockdown of miR-17-5p expression, CCK-8 method was used to detect the effect of miR-17-5p on the proliferation of MM cell line. The effect of miR-17-5p on the proliferation of MM cells was detected in nude mice subcutaneous tumorigenesis experiment. Results: The expression of miR-17-5p in bone marrow mononuclear cells in NDMM and RRMM group were higher than those in healthy volunteers [1.37 (0.47, 4.87), 2.68 (1.02, 5.02) vs 1.00 (1.00, 1.00), all P<0.05], and the expression levels of miR-17-5p in plasma were also higher than those in healthy control group [1.85 (0.92, 3.51), 2.79 (1.22, 5.04) vs 1.00 (1.00, 1.00), all P<0.05]. The expression of miR-17-5p in MM cell lines such as KMS-11, RPMI-8226, H929, MM-1R, U266B1 were higher than that in bone marrow mononuclear cells of healthy control group (3.96±0.68, 1.58±0.32, 3.51±0.55, 5.08±0.76, 3.22±0.75 vs 1.00±0, all P<0.05) ; Plasma miR-17-5p was positively correlated with the ratio of serum M protein and bone marrow plasma cells (r=0.50, P<0.05; r=0.60, P<0.01). ROC curve showed that the specificity was 0.591 and the sensitivity was 0.900 of plasma miR-17-5p as a molecular marker related to diagnosis (area under ROC curve=0.74, cut-off value: 0.491). CCK-8 results showed that over expression of miR-17-5p increased the proliferation of RPMI-8226 and NCI-H929 cell lines at 72 hours compared with the control group (1.37±0.11 vs 1.07±0.09, 2.14±0.09 vs 1.82±0.11, both P<0.05), and low expression of miR-17-5p reduced the proliferation of NCI-H929 and MM-1R cell lines at 72 hours compared with the control group (1.38±0.09 vs 1.83±0.11, 1.45±0.10 vs 1.73±0.09, both P<0.05). The subcutaneous tumorigenesis experiment in nude mice showed that the tumor volume of miR-17-5p over expression group was larger than that of the control group [(1 865±181) vs (1 389±227) mm3, P<0.05], and the tumor volume of miR-17-5p low expression group was smaller than that of the control group [ (1 006±171) vs (1 389±227) mm3, P<0.05]. Conclusion: miR-17-5p may play an oncogene role in MM cell lines as a plasma molecular marker related to the development of MM disease.


Assuntos
MicroRNAs , Mieloma Múltiplo , Animais , Biomarcadores/sangue , Carcinogênese , Transformação Celular Neoplásica , Humanos , Camundongos , Camundongos Nus , MicroRNAs/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/patologia , Recidiva Local de Neoplasia , Prognóstico , Sincalida
3.
Dis Markers ; 2022: 7979500, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35928925

RESUMO

Objective: This study was designed to analyze the expression of miR-155 in serum exosomes in children with epilepsy and to explore its diagnostic value. Methods: From March 2020 to March 2021, 43 hospitalized children with epilepsy admitted to the Department of Neurology of the hospital were included, and another 43 gender- and age-matched healthy children were randomly selected as the healthy control group during the same period. Then fasting serum samples of the two groups were collected to extract the exosomes. The morphology of the exosomes was evaluated under a transmission electron microscope, and the expression of specific protein markers on the surface was detected by Western Blot. In addition, the relative expression of miR-155 in serum exosomes in children with epilepsy with different courses of the disease and different degrees of abnormal electroencephalography (EEG) was compared, and the area under the receiver operating characteristic (ROC) curve (ROC-AUC) was used to evaluate the diagnostic value of miR-155. Results: A higher relative expression level of miR-155 in serum exosomes was obtained in the epilepsy group, as compared to the healthy control group (P<0.05), and the relative expression of miR-155 in serum exosomes in children with epilepsy was correlated with the course of the disease and the degree of abnormal EEG (both P<0.05). In addition, the expression of miR-155 in serum exosomes showed high diagnostic efficiency for epilepsy (AUC = 0.813, P<0.05). Conclusion: The expression of miR-155 in serum exosomes in children with epilepsy is up-regulated, and its level is related to the course of the disease and the degree of abnormal EEG, so miR-155 in serum exosomes may be used as a biomarker for the diagnosis and assessment of the severity of epilepsy.


Assuntos
Epilepsia , Exossomos , MicroRNAs , Biomarcadores/sangue , Criança , Epilepsia/diagnóstico , Epilepsia/genética , Exossomos/genética , Humanos , MicroRNAs/sangue , Curva ROC
4.
Mov Disord ; 37(10): 2086-2098, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35962561

RESUMO

BACKGROUND: Isolated rapid eye movement sleep behavior disorder (IRBD) is a well-established clinical risk factor for Lewy body diseases (LBDs), such as Parkinson's disease (PD) and dementia with Lewy bodies (DLB). OBJECTIVE: To elucidate whether serum microRNA (miRNA) deregulation in IRBD can antedate the diagnosis of LBD by performing a longitudinal study in different progression stages of IRBD before and after LBD diagnosis and assessing the predictive performance of differentially expressed miRNAs by machine learning-based modeling. METHODS: Using genome-wide miRNA analysis and real-time quantitative polymerase chain reaction validation, we assessed serum miRNA profiles from patients with IRBD stratified by dopamine transporter (DaT) single-photon emission computed tomography into DaT-negative IRBD (n = 17) and DaT-positive IRBD (n = 21), IRBD phenoconverted into LBD (n = 13), and controls (n = 20). Longitudinally, we followed up the IRBD cohort by studying three time point serum samples over 26 months. RESULTS: We found sustained cross-sectional and longitudinal deregulation of 12 miRNAs across the RBD continuum, including DaT-negative IRBD, DaT-positive IRBD, and LBD phenoconverted IRBD (let-7c-5p, miR-19b-3p, miR-140, miR-22-3p, miR-221-3p, miR-24-3p, miR-25-3p, miR-29c-3p, miR-361-5p, miR-425-5p, miR-4505, and miR-451a) (false discovery rate P < 0.05). Age- and sex-adjusted predictive modeling based on the 12 differentially expressed miRNA biosignatures discriminated IRBD and PD or DLB from controls with an area under the curve of 98% (95% confidence interval: 89-99%). CONCLUSIONS: Besides clinical diagnosis of IRBD or imaging markers such as DaT single-photon emission computed tomography, specific miRNA biosignatures alone hold promise as progression biomarkers for patients with IRBD for predicting PD and DLB clinical outcomes. Further miRNA studies in other PD at-risk populations, such as LRRK2 mutation asymptomatic carriers or hyposmic subjects, are warranted. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.


Assuntos
Doença por Corpos de Lewy , MicroRNAs , Doença de Parkinson , Transtorno do Comportamento do Sono REM , Biomarcadores , Estudos Transversais , Proteínas da Membrana Plasmática de Transporte de Dopamina/genética , Humanos , Corpos de Lewy , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/genética , Estudos Longitudinais , MicroRNAs/sangue , MicroRNAs/genética , Doença de Parkinson/diagnóstico , Doença de Parkinson/genética , Transtorno do Comportamento do Sono REM/diagnóstico , Transtorno do Comportamento do Sono REM/genética
5.
J Immunoassay Immunochem ; 43(6): 648-664, 2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-35915976

RESUMO

Identification of biomarkers is crucial in guiding the treatment decision and improving the future outcomes of DLBCL. The aim of the current study is to detect the biochemical and clinical impacts of miR-150 and miR-21 expression levels in DLBCL. Quantification of serum miR-150 and miR-21 expression levels by real-time PCR after micro-RNA extraction and RT-PCR. At a cutoff point of 2.3 for miR-21, the sensitivity, specificity, positive predictive, and negative predictive values for diagnosis of DLBCL were 98%, 90%, 90.7%, and 97.8%, respectively. At cut-off point (≤19.12) the sensitivity, specificity, the positive predictive and negative predictive values of miR-21 to discriminate stage IV vs stage II DLBCL patients were 68.42%, 80%, 86.7%%,and 57.1%, respectively. Serum miR-150 and serum miR-21 can be used as diagnostic markers for DLBCL patients, but miR-21 is more sensitive than miR-150. Serum miR-21 can be used as prognostic marker for DLBCL patients. It was more sensitive and more specific than miR-150.


Assuntos
Linfoma Difuso de Grandes Células B , MicroRNAs , Humanos , Linfoma Difuso de Grandes Células B/diagnóstico , Linfoma Difuso de Grandes Células B/genética , MicroRNAs/sangue , MicroRNAs/genética , Prognóstico , Reação em Cadeia da Polimerase em Tempo Real
6.
Biomed Res Int ; 2022: 3541403, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35993056

RESUMO

The objective of the current study was to look at the levels of blood micro ribonucleic acid- (miR-) 497, carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 24-2, and hepatitis B surface antigen (HBsAg) in patients with colorectal cancer (CRC), as well as the clinical importance of these markers in CRC patients. The serum levels of miR-497, CEA, CA24-2, and HBsAg were compared between 60 patients with CRC (observation group) and another 60 patients with colorectal polyps (control group). The 4 indicators in patients with lymph node metastasis and liver metastasis were compared. The diagnostic effects of 4 detection methods and the combined detection were analyzed, and the influence of 4 indicators on the 5-year cumulative survival rate of patients was discussed. The results showed that the serum levels of miR-497 and HBsAg were lower, and the levels of CEA and CA24-2 were higher in the observation group (P < 0.05). The combined detection had the best diagnostic effect, and CEA alone had the best prediction effect. The serum level of miR-497 was significantly lower in patients with lymphatic metastasis, with the significantly higher levels of CEA and CA24-2 (P < 0.05). The HBsAg level of patients with liver metastases was greatly lower than that of patients without liver metastases (P < 0.05). The 5-year cumulative survival rate of patients with high levels of CEA and CA24-2 was significantly lower than that of patients with low level of CEA. The 5-year cumulative survival rate was lower in patients with low level of HBsAg, but the difference was small. The 5-year cumulative survival rate of patients with elevated serum miR-497 was observably lower. In conclusion, combined detection could diagnose CRC more accurately. Serum miR-497, CEA, and CA24-2 were important in the diagnosis of lymph node metastasis of CRC. HBsAg did a better job of predicting liver metastases in CRC patients. High level of CEA significantly reduced the cumulative survival rate of CRC patients and could predict the long-term survival rate of patients. Serum levels of miR-497, CEA, CA24-2, and HBsAg played a positive role in the diagnosis and evaluation of CRC and could identify lymph node and liver metastases, having a high clinical guidance value.


Assuntos
Antígenos Glicosídicos Associados a Tumores , Antígeno Carcinoembrionário , Neoplasias Colorretais , Antígenos de Superfície da Hepatite B , MicroRNAs , Antígenos Glicosídicos Associados a Tumores/biossíntese , Antígenos Glicosídicos Associados a Tumores/sangue , Antígenos Glicosídicos Associados a Tumores/genética , Biomarcadores Tumorais/genética , Antígeno Carcinoembrionário/biossíntese , Antígeno Carcinoembrionário/sangue , Antígeno Carcinoembrionário/genética , Neoplasias Colorretais/sangue , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Antígenos de Superfície da Hepatite B/biossíntese , Antígenos de Superfície da Hepatite B/sangue , Antígenos de Superfície da Hepatite B/genética , Humanos , Neoplasias Hepáticas/sangue , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Metástase Linfática , MicroRNAs/biossíntese , MicroRNAs/sangue , MicroRNAs/genética , Prognóstico
7.
Iran J Allergy Asthma Immunol ; 21(3): 254-262, 2022 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-35822676

RESUMO

The role of microRNA (miR)200c-3p in regulating ACE2 gene expression in viral and bacterial respiratory diseases has been established. Since ACE2 reduces the acute inflammatory effects in lung diseases and acts as a coronavirus receptor to invade the lung cells, this study investigates the relationship between miR-200c-3p and ACE2 expression in COVID -19 patients. In this study, COVID-19 patients were divided into two groups: mild phase (PCR-positive and mild symptoms) and severe phase (PCR-positive with acute pulmonary symptoms and inflammation). Then, the subjects' demographic, clinical, and paraclinical characteristics were recorded using a prepared checklist. Total RNA was isolated from all samples according to the Trizol kit protocol to evaluate gene expression. Subsequently, the extracted product was analysed for miR-200c expression and ACE2 target gene expression by real-time PCR. The results of the checklist data showed that smoking, cough, and the factors ESR and HCT were statistically significant between the two groups of patients in the mild and acute phases. Also, the mean expression of the miR-200c gene in the mild and acute patients was 1.87±0.70 and 1.87±0.62, respectively, which was not statistically significant. Still, the mean expression of the ACE2 gene, which was 3.96±0.76 and 3.28±0.52 in the mild and acute disease groups, respectively, showed a significant difference between the two groups. This study showed that the expression levels of ACE2 were significantly reduced in people with severe inflammation compared to people with mild inflammation.


Assuntos
Enzima de Conversão de Angiotensina 2 , COVID-19 , MicroRNAs , Enzima de Conversão de Angiotensina 2/biossíntese , Enzima de Conversão de Angiotensina 2/genética , COVID-19/sangue , COVID-19/enzimologia , COVID-19/genética , Expressão Gênica , Humanos , MicroRNAs/sangue , MicroRNAs/genética
8.
Eur Rev Med Pharmacol Sci ; 26(13): 4638-4653, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35856354

RESUMO

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer. Various microRNAs have been identified to play an important role in PDAC. The study aimed to explore the role of miR-429 in PDAC. PATIENTS AND METHODS: The expression and prognostic value of miR-429 were first analyzed using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Next, miR-429 expression was evaluated in the tissues and serum of 90 patients with PDAC. CCK8, SRB, wound healing and transwell assays were used to determine the effect of miR-429 on the proliferation, invasion, and migration of PDAC cells, respectively. Weighted gene co-expression network analysis (WGCNA), correlation analysis, TargetScan, and miRDB databases were used to screen and identify the target genes of miR-429. RESULTS: The results revealed that the expression of miR-429 was downregulated in PDAC tissues and the serum compared with those in normal tissues and the serum of healthy volunteers, respectively. The decreased expression of miR-429 was significantly associated with shorter overall survival. The overexpression of miR-429 significantly inhibited the proliferation, invasion, and migration of PDAC cells. Potential target genes of miR-429 were identified using WGCNA and bioinformatics analysis, and the results showed that cadherin 11 (CDH11), inositol polyphosphate-4-phosphatase type I (INPP4A), laminin gamma 1 (LAMC1), low density lipoprotein receptor-related protein 1 (LRP1), and quaking (QKI) were potential target genes of miR-429 in PDAC. Lower expression of CDH11 and QKI was associated with a more favorable prognosis in patients with PDAC. The overexpression of miR-429 could inhibit the expression of CDH11 and QKI. A nomogram model, involving miR-429, CDH11, and QKI, was subsequently constructed to determine their ability to accurately predict overall and disease-free survival in patients with PDAC. CONCLUSIONS: Taken together, miR-429 is involved in the development and progress of PDAC. MiR-429 could be recommended as a prognostic biomarker and therapeutic indicator in PDAC diagnosis.


Assuntos
Carcinoma Ductal Pancreático , MicroRNAs , Neoplasias Pancreáticas , Biomarcadores , Carcinoma Ductal Pancreático/sangue , Carcinoma Ductal Pancreático/diagnóstico , Carcinoma Ductal Pancreático/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Genes Supressores de Tumor , Humanos , MicroRNAs/sangue , MicroRNAs/genética , Neoplasias Pancreáticas/sangue , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/genética
9.
J Physiol Pharmacol ; 73(1)2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35793763

RESUMO

To investigate the relationship between plasma microRNA-223 expression and platelet reactivity in patients with acute ischemic stroke (AIS) and to evaluate its predictive value in clopidogrel resistance or high on-treatment platelet reactivity (HTPR). A total of 120 patients with acute ischemic stroke were screened in this study, and 60 patients were included in the acute ischemic stroke group according to the inclusion criteria and platelet reactivity after clopidogrel treatment. control group was 60 non-ischemic stroke patients hospitalized. The levels of phosphorylation of vasodilator-stimulated phosphoprotein (VASP) and adenosine diphosphate-induced platelet aggregation (ADP-PAg) in platelets were detected by flow cytometry. The expression level of plasma microRNA-223 was detected before and after clopidogrel treatment using quantitative real-time polymerase chain reaction (PcR). The AIS group was then divided into the clopidogrel non-HTPR and the clopidogrel HTPR groups based on the relative inhibition rate. We found that: 1) the VASP platelet reactivity index (PRI) was positively correlated with ADP-PAg; 2) before administration, the plasma microRNA-223 expression level and VASP-PRI were higher in the AIS group than in the control group; 3) after administration, the expression level of microRNA-223 was negatively correlated with VASP-PRI; 4) before and after treatment, the plasma microRNA-223 expression level in the clopidogrel HTPR group was lower than in the non-AIS patients; 5) before treatment, there was an interaction between the expression level of microRNA-223 in the plasma and the cYP2c19 loss-of-function (LOF) allele. The study showed that decreased plasma microRNA-223 expression levels in AIS patients indicate an increased risk of clopidogrel HTPR. carrying cYP2c19 LOF alleles may result in the microRNA-223 expression being more distinct. The combined detection of plasma microRNA-223 and cYP2c19 gene polymorphisms may be effective in predicting the occurrence of clopidogrel HTPR in patients with AIS.


Assuntos
AVC Isquêmico , MicroRNAs , Difosfato de Adenosina/farmacologia , Plaquetas/metabolismo , Clopidogrel/farmacologia , Citocromo P-450 CYP2C19/genética , Humanos , AVC Isquêmico/sangue , AVC Isquêmico/genética , AVC Isquêmico/metabolismo , MicroRNAs/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Inibidores da Agregação Plaquetária/farmacologia , Inibidores da Agregação Plaquetária/uso terapêutico , Ticlopidina/farmacologia , Ticlopidina/uso terapêutico
10.
Hematology ; 27(1): 778-784, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35793786

RESUMO

BACKGROUND/OBJECTIVE: Bone marrow biopsy, the gold standard for the diagnosis of multiple myeloma (MM), has main limitation of the invasiveness. Here, we explored the diagnostic and prognostic values of circulating miR-1246 in patients with MM. MATERIAL AND METHODS: Ninety MM patients and 30 healthy donors (control group) were recruited in this study. The expression of miR-1246 in the peripheral blood samples was detected using qPCR. The receiver operating characteristic (ROC) curve was used to assess the diagnostic value of miR-1246 in MM. The Kaplan-Meier survival analyze was performed to evaluate the prognostic value of miR-1246. RESULTS: The expression level of serum miR-1246 from newly diagnosed MM patients was significantly higher than that of the control group. Circulating miR-1246 level was decreased after treatment in remission patients, but remained high levels in relapsed patients (P < 0.05). ROC analysis demonstrated that miR-1246 showed a high diagnostic value in MM with an area under the curve (AUC) of 0.952, the sensitivity of 87%, and the specificity of 95% [95% confidence interval (CI) 0.902-1.007; P < 0.001]. Kaplan-Meier analysis showed that the progression-free survival (PFS) (14.0 months vs. 26.5 months, P = 0.045) and overall survival (OS) (20.5 months vs. 55.5 months, P = 0.014) were significantly shorter in patients with high miR-1246 expression as compared with those in patients with miR-1246 low expression. Multiple Cox regression model analysis showed that circulating miR-1246 was an independent prognostic factor for PFS (HR 2.786, 95% CI: 1.420-5.467, P = 0.003) and OS (HR 2.995, 95% CI: 1.166-7.689, P = 0.023) in MM patients. CONCLUSION: This study demonstrates that circulating miR-1246 level is elevated in MM patients, which shows high values in the diagnosis and prognosis prediction in patients with MM.


Assuntos
MicroRNAs , Mieloma Múltiplo , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Humanos , Estimativa de Kaplan-Meier , MicroRNAs/sangue , MicroRNAs/genética , Mieloma Múltiplo/sangue , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/genética , Prognóstico
11.
Cell Mol Biol (Noisy-le-grand) ; 67(5): 293-301, 2022 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-35818240

RESUMO

This study aimed to investigate the expression of miR-221 and miR-145 in papillary thyroid carcinoma, and the effect of miR-221 and miR-145 on the invasion ability of thyroid cancer cells and its mechanism. For this purpose, 120 patients with thyroid nodules were divided into the observation group (PTC) of 43 cases and the control group (benign nodules) of 42 cases according to postoperative pathological diagnosis. Total RNA was extracted from serum samples of all patients, and the expression levels of miRNA-145 and miR-221 were detected by fluorescence quantitative PCR. The expression of two kinds of miRNAs in the groups was compared, and their correlation was analyzed. The results showed that the expression of miRNA-145 in thyroid cancer tissues was lower than that in paired adjacent normal tissues (P < 0.001). The expression of miRNA-221 in thyroid cancer tissues was higher than that in paired adjacent normal tissues (P < 0.001). The proliferation and migration ability of miRNA-145 cells were significantly decreased (P < 0.01). The expression of miRNA-221 was up-regulated, and the proliferation and migration ability of cells was significantly enhanced (P < 0.05). High expression of miRNA-145 can inhibit cell proliferation and migration and promote apoptosis, while high expression of miRNA-221 will promote cell proliferation and migration and enhance the invasion ability of cancer cells. In general, the expression of miRNA-22l in serum of PTC patients is significantly up-regulated, while the expression level of miR-145 is down-regulated, which can be used as effective indicators to judge the biological activity of the tumor, and the combined detection of the two can significantly enhance the diagnostic value of PTC. Upregulation of miR-145 inhibits PTC cell proliferation; arrests cell cycle and promotes apoptosis miR-145 may play an important role as a tumor suppressor gene.


Assuntos
Carcinoma Papilar , MicroRNAs , Neoplasias da Glândula Tireoide , Carcinoma Papilar/diagnóstico , Carcinoma Papilar/genética , Carcinoma Papilar/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/sangue , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Neoplasias da Glândula Tireoide/patologia
12.
Diabetes Res Clin Pract ; 190: 109987, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35820565

RESUMO

AIMS: To investigate whether serum miR-145-5p levels were associated with micro-macrovascular chronic complications in patients with type 1 diabetes (DM1). METHODS: A nested case-control study from the EURODIAB Prospective Complications Study was performed. Cases (n = 289) had one or more complications of diabetes, whereas controls (n = 153) did not have any complication. We measured miR-145-5p levels by qPCR and investigated the association with diabetes complications. RESULTS: Mean miR-145-5p levels were significantly lower in cases with microangiopathy [2.12 (0.86-4.94)] compared to controls [3.15 (1.21-7.36), P < 0.05] even after adjustment for age, gender, and diabetes duration. In logistic regression analysis, miR-145-5p levels in the lowest tertile were associated with an over three-fold increased odds ratio (OR) of albuminuria [3.22 (1.17-8.81)], independently of both demographic and diabetes-related factors. In addition, mir145-5p levels in the lowest tertile were independently and inversely associated with arterial hypertension [1.96 (1.08-3.56)] and hypertension was the mediator of the relationship between miR-145-5p and albuminuria. CONCLUSIONS: In this large cohort of DM1 patients, we found an inverse association between miR-145-5p and albuminuria that was mediated by systemic hypertension.


Assuntos
Diabetes Mellitus Tipo 1 , Hipertensão , MicroRNAs , Albuminúria , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/genética , Humanos , Hipertensão/complicações , MicroRNAs/sangue , Estudos Prospectivos , Fatores de Risco
13.
Mol Cell Probes ; 64: 101831, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35660458

RESUMO

BACKGROUND & OBJECTIVES: Tumor cells have various effects and dominance over other healthy cells. Cancer cells alter the cell program in healthy cells by secreting exosomes containing microRNAs involved in epithelial-mesenchymal transition (EMT). They can migrate to distant organs and establish a pre-metastatic niche. The purpose of this study was to determine the expression of miRNA-21-5p and miRNA-10b-5p, both of which are involved in EMT, in breast cancer-derived exosomes of various grades in order to identify new biomarkers involved in breast cancer progression. METHODS: In this study, a blood sample was taken from 60 patients with grades I, II, or III breast cancer, as well as twenty healthy individuals as a control group. The exosomes were then purified from serum samples, and their relative expression of miRNA-21-5p and miRNA-10b-5p was determined using the real-time PCR method. RESULTS: miRNA-21-5p expression was significantly increased in patients with breast cancer grades I, II, and III compared to the control group (p < 0.01), (p < 0.0001) and (p < 0.0001), respectively, as was miRNA-10b-5p expression in patients with breast cancer grades I, II, and III compared to the control group (p < 0.0001), (p < 0.0001) and (p < 0.0001), respectively. CONCLUSION: Our results show that both microRNAs increase as cells lose their differentiation and become more invasive, which is evidence of cancer progression. Hence, both microRNAs may have the potential to be used alone or in combination with other biomarkers for the diagnosis and prognosis of breast cancer.


Assuntos
Neoplasias da Mama , Exossomos , MicroRNAs , Neoplasias da Mama/sangue , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Transição Epitelial-Mesenquimal , Exossomos/genética , Exossomos/metabolismo , Feminino , Humanos , MicroRNAs/sangue , Gradação de Tumores
14.
Iran J Immunol ; 19(2): 150-160, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35767888

RESUMO

BACKGROUND: Vitamin D has anti-inflammatory efficacy against ulcerative colitis (UC), however, the mechanism is yet little understood. OBJECTIVE: To investigate the immunomodulatory effects of vitamin D against the UC, and to explore the potential downstream mechanisms. MATERIALS AND METHODS: Serum vitamin D, Interferon-γ (IFN-γ) and Interleukin (IL)-17 levels of the patients with UC were quantified using enzyme-linked immunosorbent assay (ELISA). Long non-coding RNAs (lncRNAs) levels were determined by using quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Peripheral blood mononuclear cells (PBMCs) were collected from healthy control subjects, stimulated with CD4+ T lymphocytes or helper T cells 17(Th17) differentiation conditions, and then exposed to calcitriol (vitamin D active form) or certain lentiviral treatment, followed by subsequent molecular level testing. For in vivo assay, mice were given 3% dextran sulfate sodium (DSS) to induce colitis. RESULTS: Compared with the control group, vitamin D levels in the UCs were statistically lower, and there was a negative correlation between IL-17 and vitamin D in the UCs. The lncRNA OIP5-AS1 could decrease under calcitriol treatment in both CD4+ T cells and Th17 differentiation. The lncRNA OIP5-AS1 was a microRNA (miR)-26a-5p sponge and therefore modulated the Th17 cells and IL-6 expression. The lncRNA OIP5-AS1/miR-26a-5p/IL-6 axis mediated the regulation of calcitriol-induced Th17 differentiation. Calcitriol had therapeutic effects on the UC mouse models by regulating the lncRNA OIP5-AS1 related pathway. CONCLUSION: Vitamin D might have anti-inflammatory potential in the treatment of the UC.


Assuntos
Colite Ulcerativa , Interleucina-6 , MicroRNAs , RNA Longo não Codificante , Células Th17 , Vitamina D , Animais , Calcitriol/farmacologia , Colite Ulcerativa/sangue , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/genética , Colite Ulcerativa/patologia , Humanos , Interleucina-6/sangue , Leucócitos Mononucleares/metabolismo , Camundongos , MicroRNAs/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/sangue , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Células Th17/efeitos dos fármacos , Células Th17/metabolismo , Vitamina D/sangue
15.
Front Endocrinol (Lausanne) ; 13: 814347, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35712251

RESUMO

Objective: To explore differentially expressed miRNAs in type 2 diabetes and their potential cellular functions. Methods: We screened plasma miRNAs by miRNA array analysis and validated them by TaqMan real-time PCR in 113 newly diagnosed, untreated type 2 diabetes cases and 113 healthy controls. Low-abundance plasma proteins encoded by miR-193b-3p target genes were explored in this study population. We further investigated the potential cellular functions of the differentially expressed miRNAs in HepG2 cells. Results: miR-193b-3p was differentially expressed in type 2 diabetes cases compared to healthy controls (fold change = 2.01, P = 0.006). Plasma levels of triosephosphate isomerase (TPI1, a protein involved in the glycolytic pathway) decreased in type 2 diabetes cases (fold change = 1.37, P = 0.002). The effect of miR-193b-3p on TPI1 was verified by transfection of miR-193b-3p into HepG2 cells. miR-193b-3p inhibited the expression of YWHAZ/14-3-3ζ in the PI3K-AKT pathway, subsequently altering the expression of FOXO1 and PCK1. After transfection, cells were incubated in glucose-free medium for another 4 h. Glucose levels in medium from cells with elevated miR-193b-3p levels were significantly higher than those in medium from negative control cells (P = 0.016). In addition, elevated miR-193b-3p reduced glucose uptake by inhibiting insulin receptor (IR) and GLUT2 expression. Conclusion: Plasma miR-193b-3p levels increased in type 2 diabetes cases, and TPI1 levels decreased in both plasma and HepG2 cells with increased miR-193b-3p levels, while extracellular lactate levels did not significantly changed. Moreover, miR-193b-3p may affect glucose metabolism by directly targeting YWHAZ/14-3-3ζ and upregulating the transcription factor FOXO1 downstream of the PI3K-AKT pathway.


Assuntos
Diabetes Mellitus Tipo 2 , Glucose , MicroRNAs , Proteínas 14-3-3/metabolismo , Diabetes Mellitus Tipo 2/genética , Glucose/metabolismo , Células Hep G2 , Humanos , MicroRNAs/sangue , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo
16.
Comput Math Methods Med ; 2022: 9430708, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35734774

RESUMO

Objective: To determine the level of expression and clinical importance of serum miR-204 and miR-451 in patients with pulmonary arterial hypertension caused by congenital heart disease (CHD-PAH). Methods: From July 2019 to January 2021, 114 infants with congenital heart disease (CHD) were hospitalized at Qingdao's Fuwai Cardiovascular Hospital. They were grouped into categories: CHD (53 cases) and CHD-PAH (61 cases) based on whether they had pulmonary hypertension (PAH). In addition, 60 healthy children were selected as the control group. All children underwent routine biochemical examination, echocardiography, and pulmonary arterial pressure examination. By using an enzyme-linked immunosorbent assay (ELISA), the levels of brain natriuretic peptide (BNP) and asymmetric dimethylarginine (ADMA) in the blood were measured. Additionally, reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression levels of miR-204 and miR-451 in peripheral blood. The correlation between miR-204, miR-451, BNP, ADMA, and mPAP was investigated using Pearson correlation analysis. Results: Consequently, the TC, BNP, and ADMA serum levels were considerably higher in the CHD and CHD-PAH groups than in the control group (P < 0.05), whereas BNP and ADMA serum levels were significantly higher in the CHD-PAH group than in the CHD group (P < 0.05). According to RT-PCR data, the expression levels of miR-204 and miR-451 in the peripheral blood of children in the CHD and CHD-PAH groups were significantly lower (P < 0.05) when compared to the control group. The expression levels of miR-204 and miR-451 in the peripheral blood of children in the CHD-PAH group were substantially lower (P < 0.05) than in the CHD group. Significantly, the findings of the ROC curve revealed that the area under the curve (AUC) of CHD-PAH diagnosed by miR-204 and miR-451 alone was 0.737 and 0.725, respectively, and the AUC of joint diagnosis was 0.840, which was greater than that of single diagnosis (P < 0.05). Patients with CHD-PAH had lower levels of miR-204 and miR-451 in their blood, and this was found to be associated with BNP, ADMA, and mPAP, analyzed by Pearson correlation. Conclusions: Children with CHD-PAH can be diagnosed based on aberrant expressions of miR-204 and miR-451 in their peripheral blood serum. Moreover, CHD-PAH can be diagnosed if the combination of miR-204 and miR-451 is detected as a biomarker, which has a higher diagnostic value.


Assuntos
Cardiopatias Congênitas , MicroRNAs , Hipertensão Arterial Pulmonar , Cardiopatias Congênitas/complicações , Cardiopatias Congênitas/genética , Humanos , Lactente , MicroRNAs/sangue , MicroRNAs/genética , Hipertensão Arterial Pulmonar/etiologia , Hipertensão Arterial Pulmonar/genética
17.
J Mol Med (Berl) ; 100(7): 1043-1056, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35689099

RESUMO

Unexplained recurrent spontaneous abortion (URSA) is commonly observed, and seriously affects women's reproductive health. Excessive interleukin-6 (IL-6) production has been shown to frequently occur and relate to URSA pathogenesis. In this study, the miRNA expression profile in peripheral blood mononuclear cells (PBMCs) from URSA patients and normal pregnant (NP) women was assessed by miRNA microarray and real-time quantitative reverse-transcription polymerase chain reaction (qPCR). MiRNA target prediction tools and luciferase reporter assay were used to detect direct binding between miRNAs and IL6. Functional study of administering anti-IL-6 neutralizing antibody and miR-374c-5p mimics to an URSA animal model was performed to evaluate embryo resorption rates. In the results, compared with NP women, the expression of IL-6 increased markedly in PBMCs and decidual tissues at both mRNA and protein levels, while miR-374c-5p expression decreased significantly. Prediction software and luciferase reporter assay showed that miR-374c-5p binds with IL6 3'UTR via the complementary bases. Transfection of miR-374c-5p mimics into an in vitro HeLa cell line significantly downregulated the expression of IL-6, while transfection of the miR-374c-5p inhibitor induced an opposite result. In the URSA mouse model, miR-374c-5p overexpression reduced the embryo resorption rate significantly, accompanied with decreased expression of IL-6 in the decidua. To sum up, downregulated miR-374c-5p was involved in the pathogenesis of URSA by enhancing IL-6 expression. Modulation of miR-374c-5p expression may be used to regulate IL-6 production for the treatment of URSA.


Assuntos
Aborto Habitual , Interleucina-6 , MicroRNAs , Aborto Habitual/sangue , Aborto Habitual/genética , Aborto Habitual/metabolismo , Animais , Perda do Embrião , Feminino , Células HeLa , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Leucócitos Mononucleares/metabolismo , Camundongos , MicroRNAs/sangue , MicroRNAs/genética , MicroRNAs/metabolismo , Gravidez
18.
J Clin Lab Anal ; 36(7): e24485, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35614030

RESUMO

PURPOSE: To explore the value of the expression of serum miR-92 and miR-122 combined with lung ultrasound score (LUS) in the prognosis of neonatal acute respiratory distress syndrome (ARDS). PATIENTS AND METHODS: This study involved 148 neonatal ARDS cases from January 2018 to October 2021, of which 77 children were discharged from hospital and 31 died. The children with ARDS were classified according to disease severity based on X-ray examination as mild (n = 69 cases) and severe (n = 39 cases). The expression of serum miR-92 and miR-122 was detected by real-time fluorescence quantitative PCR and the LUS score was recorded. The data were subjected to ROC curve analysis and Pearson correlation analysis. RESULTS: The expression of serum miR-92, miR-122, and LUS score in the patients that died were significantly higher than in those who survived (p < 0.05). These indicators were also significantly higher in the severe disease group compared to the mild disease group (p < 0.05). ROC curve showed that serum miR-92 and miR-122 combined with the LUS score had the largest area under the curve (0.920, 95% CI: 0.860-0.977) for predicting death, with a sensitivity and specificity of 92.0% and 87.0%, respectively. Pearson correlation analysis showed that the expression levels of serum miR-92 and miR-122 were positively correlated with the LUS score (all p < 0.01). CONCLUSIONS: The increased expression of serum miR-92 and miR-122 is related to the severity and prognosis of children with ARDS, combined with the LUS score are of value to predict the prognosis of children with ARDS.


Assuntos
MicroRNAs , Síndrome do Desconforto Respiratório , Humanos , Recém-Nascido , Pulmão/diagnóstico por imagem , MicroRNAs/sangue , MicroRNAs/genética , Prognóstico , Curva ROC , Síndrome do Desconforto Respiratório/diagnóstico por imagem , Síndrome do Desconforto Respiratório/genética , Ultrassonografia
19.
Am J Med Sci ; 364(5): 601-611, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35588895

RESUMO

BACKGROUND: Deep venous thrombosis (DVT) is a thrombus formed in the deep venous cavity and can cause a fatal pulmonary embolism. Since circulating miRNAs are used as molecular markers for the early warning and diagnosis of various diseases, such as tumors and cardiovascular diseases, the purpose of the present study was initially to identify differential expression circulating miRNAs in plasma, and then explore potential biomarkers for DVT. METHODS: The plasma of 30 patients with DVT before and after DVT-related endovascular interventions constituted 6 sample pools for miRNA sequencing, and the levels of 22 plasma miRNAs were significantly changed. Then, various bioinformatics tools were utilized to screen out 8 miRNAs with potential DVT diagnostic value. Furthermore, their diagnostic values were evaluated in 120 patients with DVT and 120 healthy individuals. RESULTS: The levels of 22 circulating plasma miRNAs (12 up-regulated, 10 down-regulated) were significantly changed in patients with DVT before and after endovascular interventions, especially miR-125a-5p (up-regulation) and miR-223-3p (down-regulation). The values of area under the ROC curve (AUC) of miR-125a-5p and miR-223-3p were both >0.8, indicating that they were valuable in diagnosing DVT. The combination of miR-125a-5p and miR-223-3p with D-dimer significantly improved the efficiency of diagnosing DVT, (AUC >0.97, the sensitivity and specificity >95%), and was better than those of D-dimer alone. CONCLUSIONS: The levels of miR-125a-5p and miR-223-3p were the most significantly changed in patients with DVT before and after endovascular interventions; together with the classic biomarker D-dimer, they can be used as a potential biomarker for diagnostic and therapeutic process of DVT.


Assuntos
MicroRNAs , Trombose Venosa , Humanos , Biomarcadores/sangue , MicroRNAs/sangue , MicroRNAs/genética , Embolia Pulmonar/etiologia , Curva ROC , Trombose Venosa/sangue , Trombose Venosa/complicações , Trombose Venosa/diagnóstico , Trombose Venosa/genética
20.
Biomolecules ; 12(5)2022 04 19.
Artigo em Inglês | MEDLINE | ID: mdl-35625530

RESUMO

Alopecia areata (AA) is a type of immune-mediated alopecia. Recent studies have suggested microRNAs' (miRNAs) implication in several cellular processes, including epidermal and hair follicle biology. Single nucleotide polymorphisms (SNPs) can modify gene expression levels, which may induce an autoimmune response. This case-control study included 480 participants (240 for each case/control group). MicroRNA-34a gene (MIR-34A) rs2666433A/G variant was genotyped using real-time allelic discrimination polymerase chain reaction (PCR). Additionally, circulatory miR-34a levels were quantified by quantitative reverse transcription PCR (qRT-PCR). On comparing between alopecia and non-alopecia cohorts, a higher frequency of A variant was noted among patients when compared to controls-A allele: 28 versus 18% (p < 0.001); A/A genotype: 9 versus 2%; A/G genotype: 39 versus 32% (p < 0.001). A/A and A/G carriers were more likely to develop alopecia under heterozygote comparison (OR = 1.83, 95% CI = 1.14-2.93), homozygote comparison (OR = 4.19, 95% CI = 1.33-13.1), dominant (OR = 2.0, 95% CI = 1.27-3.15), recessive (OR = 3.36, 95% CI = 1.08-10.48), over-dominant (OR = 1.65, 95% CI = 1.04-32.63), and log additive (OR = 1.91, 95% CI = 1.3-2.82) models. Serum miR-34a expression levels were upregulated in alopecia patients with a median and quartile fold change of 27.3 (1.42-2430). Significantly higher levels were more pronounced in A/A genotype patients (p < 0.01). Patients carrying the heterozygote genotype (rs2666433 * A/G) were two times more likely to develop more severe disease grades. Stratified analysis by sex revealed the same results. A high expression level was associated with concomitant autoimmune comorbidities (p = 0.001), in particular SLE (p = 0.007) and vitiligo (p = 0.049). In conclusion, the MIR34A rs2666433 (A/G) variant is associated with AA risk and severity in the studied population. Furthermore, high miR-34a circulatory levels could play a role in disease pathogenesis.


Assuntos
Alopecia em Áreas , MicroRNAs , Alopecia em Áreas/genética , Estudos de Casos e Controles , Estudos Transversais , Predisposição Genética para Doença , Folículo Piloso , Humanos , MicroRNAs/sangue , MicroRNAs/genética
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