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Human neutrophil peptide-1: a new anti-leishmanial drug candidate

机译:人嗜中性粒细胞肽-1:一种新的抗利什曼肽药物

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Leishmaniasis is a vector borne disease caused by different Leishmania species with different clinical manifestations. Cutaneous leishmaniasis (CL) is endemic and widespread especially among young individuals in Iran. Currently prophylactic or therapeutic vaccines are not available, and in spite of vector control wherever possible, the disease has not been controlled. Although the majority of zoonotic CL cases heal within 6-9 months, anthroponotic cases persist much longer. Both types leave lifelong scars that are the cause of social stigma and much morbidity; particularly important for young girls with lesions on the face or exposed area of the body. The first line drugs (antimonials) are toxic and require repeated painful injections accompanied by considerable side effects. This coupled with the development of drug resistance, recently reported in Iran, indicate the urgent need for development of new therapeutics. Sara Dabirian, Ph.D student at Pasteur Institute of Iran, took advantage of molecules with limited toxicity to stimulate innate immune responses as a new approach to fight against leishmaniasis. Human neutrophil peptide-1 (HNP-1) is one of the most potent defensins with a broad antimicrobial activity. This peptide is naturally found within a granule of human neutrophils, a cell type that has the capacity to both kill Leishmania parasites and serve as an immediate host cell. Using a prokaryotic expression system and an in vitro folding procedure, Dabirian et al. succeeded to cost-efficiently produce substantial amounts of active HNP-1.
机译:利什曼病是由具有不同临床表现的不同利什曼原虫物种引起的媒介传播疾病。皮肤利什曼病(CL)是地方性的,并且普遍存在,尤其是在伊朗的年轻人中。目前尚无预防性或治疗性疫苗,尽管有可能进行病媒控制,但仍未控制该病。尽管大多数人畜共患CL病例在6-9个月内months愈,但人为感染病例持续的时间更长。两种类型都留下终身疤痕,这些疤痕是造成社会耻辱和高发病率的原因。对于面部或身体裸露部位有损伤的年轻女孩尤为重要。一线药物(镇静剂)有毒,需要反复痛苦注射并伴有相当大的副作用。加上最近在伊朗报道的耐药性的发展,表明迫切需要开发新的疗法。伊朗巴斯德研究所(Pasteur Institute of Iran)博士生Sara Dabirian利用毒性有限的分子来刺激先天免疫应答,以此作为对抗利什曼病的新方法。人嗜中性粒细胞肽1(HNP-1)是最有效的防御素之一,具有广泛的抗菌活性。这种肽天然存在于人类嗜中性粒细胞颗粒中,这种细胞具有杀死利什曼原虫寄生虫和直接宿主细胞的能力。使用原核表达系统和体外折叠程序,Dabirian等。成功地以成本效益的方式生产了大量的活性HNP-1。

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