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菲律宾日本血吸虫病患者循环微RNA作为肝纤维化生物标志物的研究

Circulating microRNAs as Biomarkers of Hepatic Fibrosis in Schistosomiasis Japonica Patients in the Philippines.

作者信息

Tabios Ian Kim B, Sato Marcello Otake, Tantengco Ourlad Alzeus Gaddi, Fornillos Raffy Jay C, Kirinoki Masashi, Sato Megumi, Rojo Raniv D, Fontanilla Ian Kendrich C, Chigusa Yuichi, Medina Paul Mark B, Kikuchi Mihoko, Leonardo Lydia R

机构信息

Institute of Biology, College of Science, University of the Philippines Diliman, Quezon City 1101, Philippines.

College of Medicine, University of the Philippines Manila, Ermita, Manilla 1000, Philippines.

出版信息

Diagnostics (Basel). 2022 Aug 5;12(8):1902. doi: 10.3390/diagnostics12081902.

Abstract

Host-derived microRNAs (miRNAs) play important regulatory roles in schistosomiasis-induced hepatic fibrosis. This study analyzed selected serum miRNAs among Filipino schistosomiasis japonica patients with ultrasound (US)-detectable hepatic fibrosis. A prospective cohort study design with convenience sampling was employed from 2017 to 2019. The study sites were eight endemic barangays in Leyte, Philippines. Eligible chronic schistosomiasis patients with varying severities of hepatic fibrosis were enrolled in the cohort and serially examined at 6, 12, and 24 months from baseline. Baseline serum miR-146a-5p, let-7a-5p, miR-150-5p, miR-122-5p, miR-93-5p, and miR200b-3p were measured using RT-qPCR. A total of 136 chronic schistosomiasis patients were included in this prospective cohort study. Approximately, 42.6% had no fibrosis, 22.8% had mild fibrosis, and 34.6% had severe fibrosis at baseline The serum levels of the antifibrotic miR-146a (p < 0.0001), miR-150 (p = 0.0058), and let-7a (p < 0.0001) were significantly lower in patients with hepatic fibrosis while the profibrotic miR-93 (p = 0.0024) was elevated. miR-146a-5p (AUC = 0.90, 95% CI [0.84, 0.96], p < 0.0001) has the most promising potential to differentiate patients with (n = 78) versus without (n = 58) hepatic fibrosis. The baseline level of serum miR-146-5p was significantly different in patients with progressive fibrosis (n = 17) compared to those who never developed fibrosis (n = 30, p < 0.01) or those who had fibrosis reversal (n = 20, p < 0.01) after 24 months. These findings demonstrate the potential utility of serum miRNAs, particularly of miR-146a, as a supplementary tool for assessing hepatic fibrosis in chronic schistosomiasis japonica patients.

摘要

宿主来源的微小RNA(miRNA)在血吸虫病诱导的肝纤维化中发挥着重要的调节作用。本研究分析了菲律宾日本血吸虫病患者中经超声(US)检测出有肝纤维化的部分血清miRNA。采用便利抽样的前瞻性队列研究设计,研究时间为2017年至2019年。研究地点为菲律宾莱特岛的8个流行村。符合条件的不同肝纤维化严重程度的慢性血吸虫病患者被纳入队列,并在基线后的6个月、12个月和24个月进行连续检查。使用RT-qPCR检测基线血清miR-146a-5p、let-7a-5p、miR-150-5p、miR-122-5p、miR-93-5p和miR200b-3p。共有136例慢性血吸虫病患者被纳入这项前瞻性队列研究。基线时,约42.6%的患者无纤维化,22.8%的患者有轻度纤维化,34.6%的患者有重度纤维化。肝纤维化患者中抗纤维化miR-146a(p<0.0001)、miR-150(p = 0.0058)和let-7a(p<0.0001)的血清水平显著降低,而促纤维化miR-93(p = 0.0024)升高。miR-146a-5p(AUC = 0.90,95%CI[0.84,0.96],p<0.0001)在区分有肝纤维化(n = 78)和无肝纤维化(n = 58)患者方面具有最有前景的潜力。与24个月后从未发生纤维化(n = 30,p<0.01)或纤维化逆转(n = 20,p<0.01)的患者相比,进行性纤维化患者(n = 17)的血清miR-146-5p基线水平显著不同。这些发现证明了血清miRNA,特别是miR-146a,作为评估慢性日本血吸虫病患者肝纤维化的补充工具的潜在效用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8c06/9406767/f67cb332d687/diagnostics-12-01902-g001.jpg

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