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Abstract：
BACKGROUND: Circulating microRNAs have been implicated in a diverse array of biological and pathological phenomena. Their potential utility as noninvasive biomarkers for screening and diagnosing various diseases has been proposed.
OBJECTIVE: This study aimed to explore the potential role of the miRNAs miR-122 and miR-486 as molecular biomarkers in the pathogenesis of hepatitis C virus (HCV) infection. Thus, miR-122 and miR-486 were detected in the serum of HCV patients and healthy controls. Moreover, the potential correlations of miR-122 and miR-486 with viral complications, such as physical activity, pain, muscle fatigue, and HCV infection, were identified.
METHODS: A total of 150 subjects aged 30 to 66 years were included in this study. The patients were classified as patients with chronic hepatitis C virus (CHC) (n = 110) or healthy controls (n = 40). Real-time polymerase chain reaction (PCR) analyses were performed to determine miR-122 and miR-486 expression. Physical activity (PA), pain score, HCV genotyping, viral overload, aspartate transaminase (AST), alanine transaminase (ALT), lactic acid dehydrogenase (LDH), creatine kinase (CK), and antioxidant status were also estimated by using prevalidated questionnaires, PCR, and spectrophotometric analyses.
RESULTS: Compared with those in normal controls, significant increases in the serum levels of miR-122 and miR-486 were reported in patients with CHC. In physically active CHC patients, there was a significant correlation between the expression of miRNAs and increased alanine transaminase (ALT), aspartate transaminase (AST), fibrosis scores, and inflammation activity, but no association was reported for hepatitis C virus (HCV) RNA or viral load. Additionally, significant decreases in LDH, CK, GSSG, and pain scores and increases in TAC, GSH, and the GSH/GSSG ratio were reported. Moreover, the expression of miR-122 and miR-486 was positively correlated with changes in body mass index (BMI) and liver fibrosis stage, as well as negatively correlated with sex, PA, TAC, GSH, GSSG, and the GSH/GSSG ratio.
CONCLUSIONS: MiR-122 and miR-486 expression levels were strongly correlated with physical activity, pain perception, and muscle fatigue biomarkers in HCV-infected patients. These miRNA levels were associated with elevated AST, ALT, fibrosis scores, LDH, CK, and antioxidant status, thus suggesting their potential as biomarkers for disease severity and oxidative stress. However, no correlation was observed with viral load or HCV-RNA expression, thus implying that these miRNAs may impact disease progression and symptoms through host factors, rather than directly affecting viral replication. In summary, the results demonstrated that molecular studies of miR-22 and miR-468 and their associations with PA, pain, adiposity, sex differences, and muscle fatigue, as well as routine biomarkers, could be useful as prognostic nanoninvasive biomarkers, thus providing novel therapeutic targets for CHC infection.
OBJECTIVE: This study aimed to explore the potential role of the miRNAs miR-122 and miR-486 as molecular biomarkers in the pathogenesis of hepatitis C virus (HCV) infection. Thus, miR-122 and miR-486 were detected in the serum of HCV patients and healthy controls. Moreover, the potential correlations of miR-122 and miR-486 with viral complications, such as physical activity, pain, muscle fatigue, and HCV infection, were identified.
METHODS: A total of 150 subjects aged 30 to 66 years were included in this study. The patients were classified as patients with chronic hepatitis C virus (CHC) (n = 110) or healthy controls (n = 40). Real-time polymerase chain reaction (PCR) analyses were performed to determine miR-122 and miR-486 expression. Physical activity (PA), pain score, HCV genotyping, viral overload, aspartate transaminase (AST), alanine transaminase (ALT), lactic acid dehydrogenase (LDH), creatine kinase (CK), and antioxidant status were also estimated by using prevalidated questionnaires, PCR, and spectrophotometric analyses.
RESULTS: Compared with those in normal controls, significant increases in the serum levels of miR-122 and miR-486 were reported in patients with CHC. In physically active CHC patients, there was a significant correlation between the expression of miRNAs and increased alanine transaminase (ALT), aspartate transaminase (AST), fibrosis scores, and inflammation activity, but no association was reported for hepatitis C virus (HCV) RNA or viral load. Additionally, significant decreases in LDH, CK, GSSG, and pain scores and increases in TAC, GSH, and the GSH/GSSG ratio were reported. Moreover, the expression of miR-122 and miR-486 was positively correlated with changes in body mass index (BMI) and liver fibrosis stage, as well as negatively correlated with sex, PA, TAC, GSH, GSSG, and the GSH/GSSG ratio.
CONCLUSIONS: MiR-122 and miR-486 expression levels were strongly correlated with physical activity, pain perception, and muscle fatigue biomarkers in HCV-infected patients. These miRNA levels were associated with elevated AST, ALT, fibrosis scores, LDH, CK, and antioxidant status, thus suggesting their potential as biomarkers for disease severity and oxidative stress. However, no correlation was observed with viral load or HCV-RNA expression, thus implying that these miRNAs may impact disease progression and symptoms through host factors, rather than directly affecting viral replication. In summary, the results demonstrated that molecular studies of miR-22 and miR-468 and their associations with PA, pain, adiposity, sex differences, and muscle fatigue, as well as routine biomarkers, could be useful as prognostic nanoninvasive biomarkers, thus providing novel therapeutic targets for CHC infection.
摘要：
背景：循环microRNAs与多种生物学和病理学现象有关。已经提出了它们作为用于筛查和诊断各种疾病的非侵入性生物标志物的潜在用途。
目的：本研究旨在探讨miRNAsmiR-122和miR-486作为分子标志物在丙型肝炎病毒（HCV）感染发病机制中的潜在作用。因此，在HCV患者和健康对照者血清中检测miR-122和miR-486。此外，miR-122和miR-486与病毒并发症的潜在相关性，比如身体活动，疼痛,肌肉疲劳,和HCV感染，已确定。
方法：本研究共纳入150名30至66岁的受试者。患者分为慢性丙型肝炎病毒（CHC）患者（n=110）或健康对照（n=40）。进行实时聚合酶链反应(PCR)分析以确定miR-122和miR-486表达。身体活动（PA），疼痛评分,HCV基因分型,病毒过载，天冬氨酸转氨酶（AST），丙氨酸转氨酶(ALT),乳酸脱氢酶（LDH），肌酸激酶（CK），和抗氧化剂状态也通过使用预先验证的问卷来估计，PCR,和分光光度分析。
结果：与正常对照组相比，据报道,CHC患者血清miR-122和miR-486水平显著升高.在身体活跃的CHC患者中，miRNAs的表达与丙氨酸转氨酶（ALT）升高之间存在显着相关性，天冬氨酸转氨酶（AST），纤维化评分，和炎症活动，但未报道丙型肝炎病毒(HCV)RNA或病毒载量的相关性.此外,LDH显著下降，CK,GSSG,疼痛评分和TAC的增加，GSH,报告了GSH/GSSG比值。此外，miR-122和miR-486的表达与体重指数(BMI)和肝纤维化分期的变化呈正相关,以及与性别呈负相关，PA,TAC,GSH,GSSG,和GSH/GSSG比值。
结论：MiR-122和miR-486表达水平与体力活动密切相关，疼痛感知，和HCV感染患者的肌肉疲劳生物标志物。这些miRNA水平与AST升高有关,ALT,纤维化评分，LDH,CK,和抗氧化状态，因此表明它们可能作为疾病严重程度和氧化应激的生物标志物。然而,与病毒载量或HCV-RNA表达无相关性,因此暗示这些miRNA可能通过宿主因素影响疾病进展和症状，而不是直接影响病毒复制。总之,结果表明，miR-22和miR-468的分子研究及其与PA的关系，疼痛,肥胖,性别差异,和肌肉疲劳，以及常规生物标志物，可用作预后纳米侵入性生物标志物，从而为CHC感染提供新的治疗靶点。
目的：本研究旨在探讨miRNAsmiR-122和miR-486作为分子标志物在丙型肝炎病毒（HCV）感染发病机制中的潜在作用。因此，在HCV患者和健康对照者血清中检测miR-122和miR-486。此外，miR-122和miR-486与病毒并发症的潜在相关性，比如身体活动，疼痛,肌肉疲劳,和HCV感染，已确定。
方法：本研究共纳入150名30至66岁的受试者。患者分为慢性丙型肝炎病毒（CHC）患者（n=110）或健康对照（n=40）。进行实时聚合酶链反应(PCR)分析以确定miR-122和miR-486表达。身体活动（PA），疼痛评分,HCV基因分型,病毒过载，天冬氨酸转氨酶（AST），丙氨酸转氨酶(ALT),乳酸脱氢酶（LDH），肌酸激酶（CK），和抗氧化剂状态也通过使用预先验证的问卷来估计，PCR,和分光光度分析。
结果：与正常对照组相比，据报道,CHC患者血清miR-122和miR-486水平显著升高.在身体活跃的CHC患者中，miRNAs的表达与丙氨酸转氨酶（ALT）升高之间存在显着相关性，天冬氨酸转氨酶（AST），纤维化评分，和炎症活动，但未报道丙型肝炎病毒(HCV)RNA或病毒载量的相关性.此外,LDH显著下降，CK,GSSG,疼痛评分和TAC的增加，GSH,报告了GSH/GSSG比值。此外，miR-122和miR-486的表达与体重指数(BMI)和肝纤维化分期的变化呈正相关,以及与性别呈负相关，PA,TAC,GSH,GSSG,和GSH/GSSG比值。
结论：MiR-122和miR-486表达水平与体力活动密切相关，疼痛感知，和HCV感染患者的肌肉疲劳生物标志物。这些miRNA水平与AST升高有关,ALT,纤维化评分，LDH,CK,和抗氧化状态，因此表明它们可能作为疾病严重程度和氧化应激的生物标志物。然而,与病毒载量或HCV-RNA表达无相关性,因此暗示这些miRNA可能通过宿主因素影响疾病进展和症状，而不是直接影响病毒复制。总之,结果表明，miR-22和miR-468的分子研究及其与PA的关系，疼痛,肥胖,性别差异,和肌肉疲劳，以及常规生物标志物，可用作预后纳米侵入性生物标志物，从而为CHC感染提供新的治疗靶点。
