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首页> 外文期刊>The American Journal of Tropical Medicine and Hygiene >Identification and Functional Validation of a Biomarker for the Diagnosis of Miltefosine Relapse during Visceral Leishmaniasis
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Identification and Functional Validation of a Biomarker for the Diagnosis of Miltefosine Relapse during Visceral Leishmaniasis

机译:生物标志物的鉴定和功能验证,用于诊断内脏LeishManiaisis期间Miltefosine复发的诊断

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摘要

Miltefosine is the only orally administrable drug for the treatment of leishmaniasis. But in recent years, a decline in its efficacy points toward the emergence of resistance to this drug. Knowledge of biomarkers for miltefosine resistance may be beneficial for proper selection of treatment regimen. Splenic aspirates were collected and parasites cultured from patients relapsed after initial cure (N = 15) and successfully treated (N = 15) with miltefosine. Differential expression of genes in miltefosine-resistant strains was examined by DNA microarray and validated by real-time reverse transcription polymerase chain reaction and Western blotting. Of 669 upregulated genes, the cysteine protease-like protein of calpain family (GenBank: CBZ34784) was found to be significantly overexpressed in resistant parasite strains and only anti-calpain antibodies showed its presence in the sera of relapse patients through Western blotting. Calpain family cysteine protease-like protein can be useful as a potential biomarker of miltefosine unresponsiveness.
机译:Miltefosine是唯一适用于莱山西亚病的口服药物。但近年来,其疗效点下降到抗抵抗这种药物的抗性。 Knowledge of biomarkers for miltefosine resistance may be beneficial for proper selection of treatment regimen.收集脾吸血物质,并从初始固化(n = 15)后复发的患者培养的寄生虫,并用Miltefosine成功处理(n = 15)。通过DNA微阵列检查耐摩尔小精素抗菌基因的差异表达,并通过实时逆转录聚合酶链反应和蛋白质印迹进行验证。在669个上调基因中,发现钙骨素蛋白质(Genbank:CBZ34784)的半胱氨酸蛋白质样蛋白在抗性寄生虫菌株中显着过表达,并且只有抗钙肽抗体在蛋白质印迹中显示出血清血清中的存在。 CALPAIN家族半胱氨酸蛋白酶样蛋白质可用作Miltefosine的潜在生物标志物无响应。

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