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新型突变型磷脂酶 D 来自 可作为 BALB/c 小鼠抗蝎毒致死性的高度免疫原。

Novel Mutant Phospholipase D from Acts as A Highly Immunogen in BALB/c Mice Against the Lethality of Scorpion Venom.

机构信息

Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran P.O. Box 14115-111, Iran.

Venom and Biotherapeutics Molecules Lab., Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran P.O. Box 13169-43351, Iran.

出版信息

Molecules. 2020 Apr 4;25(7):1673. doi: 10.3390/molecules25071673.

Abstract

which belongs to the Scorpionidae family, is the deadliest scorpion in Iran. It causes pathological manifestations like dermonecrosis, hemolysis, renal failure, necrotic ulcers, and in some cases, even death. The venom of this scorpion is well-known for its cytotoxic effects in comparison with the other venomous scorpions which show significant neurotoxic effects. Due to the painless nature of the sting of this scorpion, the clinical symptoms occur in victims 24 to 72 h post-sting. In our previous studies during the last decade, we demonstrated that the medical complications are attributable to the presence of phospholipase D (PLD) as a major toxin in the venom. With the purpose of designing and constructing a vaccine against for humans, animal model experiments were performed. To achieve this goal, non-toxic PLD was developed by mutation of two critical catalytic residues-His12 and His48-into alanines and the product was then denominated mut-rPLD1. The in-vivo tests showed that the mice immunized with interval doses of 10 µg of mut-rPLD1, were completely protected against 10× the LD of the venom. In conclusion, this mutant may be an effective vaccine candidate against scorpion envenomation by in future clinical studies.

摘要

它属于蝎科,是伊朗最致命的蝎子。它会导致病理性表现,如皮肤坏死、溶血、肾衰竭、坏死性溃疡,在某些情况下,甚至会导致死亡。与其他表现出明显神经毒性的有毒蝎子相比,这种蝎子的毒液以细胞毒性作用而闻名。由于这种蝎子的蜇刺无痛,受害者在蜇伤后 24 至 72 小时才会出现临床症状。在我们过去十年的研究中,我们证明了医疗并发症是由于毒液中存在磷脂酶 D (PLD) 这一主要毒素所致。为了设计和构建针对 的人类疫苗,我们进行了动物模型实验。为了实现这一目标,我们通过突变两个关键催化残基 His12 和 His48 为丙氨酸,开发了无毒的 PLD,并将产物命名为 mut-rPLD1。体内试验表明,用间隔剂量的 10μg mut-rPLD1 免疫的小鼠完全免受 10 倍毒液 LD 的影响。总之,这种突变体可能是未来临床研究中针对 的蝎子螫伤的有效疫苗候选物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0e04/7180795/d982452d8a1f/molecules-25-01673-g001.jpg

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