Recombinant

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  • 文章类型: Journal Article
    BACKGROUND: Herpes zoster (HZ) incidence is linked to immunosuppression. Patients with psoriasis or psoriatic arthritis (PsA) on systemic therapy might be at an increased risk for HZ.
    OBJECTIVE: To assess HZ risk in patients with psoriasis and PsA by systemic treatment and provide recommendations regarding HZ vaccination.
    METHODS: A systematic literature search was performed for HZ in patients with psoriasis and PsA. HZ vaccination guidelines were reviewed, and the medical board of the National Psoriasis Foundation made consensus recommendations in psoriasis and PsA patients using graded evidence.
    RESULTS: In total, 41 studies met inclusion criteria. Systemic corticosteroids (strong, 1), tofacitinib (strong, 1), and combination therapy with biologic and conventional synthetic disease-modifying antirheumatic drugs (weak, 2a) carry increased HZ risk while monotherapy does not. There is insufficient evidence to determine risk with interleukin 12/23, 17, and 23 inhibitors or apremilast (weak, 2a). Recombinant zoster vaccine is recommended for all psoriasis and PsA patients >50 years old and patients <50 years old on tofacitinib, systemic steroids, or combination systemic treatment. Vaccination of patients <50 years old on other systemic therapies may be considered on a case-by-case basis.
    CONCLUSIONS: There was significant heterogeneity between studies.
    CONCLUSIONS: HZ risk depends on disease severity and treatment class. Recombinant zoster vaccine should be given to all psoriasis and PsA patients >50 years old and younger patients at increased risk.
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  • 文章类型: Journal Article
    三指毒素家族,更确切地说,短链α-神经毒素(也称为I型α-神经毒素)在定义流逝的毒素过程中至关重要,但矛盾的是,它们几乎没有被当前流逝的蛇毒血清中和。这项工作集中在I型神经毒素之间的主要结构同一性上,以创建具有保守特征的共识短链α-神经毒素。考虑到从刺五加菌毒液中报告的十二种毒性最强的短链α-神经毒素的多序列比对,Oxyuranus,Walterinnesia,Naja,Dendroaspis和Micrurus引导我们提出了一种短链共识α-神经毒素,这里叫ScNtx。从头构建合成的ScNtx基因并将其克隆到含有6His-Tag和FXa蛋白水解切割区的表达载体pQE30中。用pQE30/ScNtx载体转染的大肠杆菌折纸细胞以可溶性形式表达重组共有神经毒素,产量为1.5mg/L培养基。60个氨基酸残基ScNtx包含类似于非洲elapids的α-神经毒素的经典结构基序,其3.8µg/小鼠的LD50类似于从elapid毒液报告的毒性最强的短链α-神经毒素。此外,ScNtx也能拮抗肌肉,但不是神经元的,烟碱乙酰胆碱受体(nAChR)。用ScNtx免疫的兔子能够免疫识别整个流逝的毒液中的短链α-神经毒素。I型神经毒素很难从天然来源中分离和纯化;因此,分子如ScNtx的异源表达,带有关键图案和关键氨基酸,是创造共同免疫原以开发具有更广泛功效的具有成本效益的抗蛇毒血清迈出的一步,质量和强大的治疗价值。
    The three-fingered toxin family and more precisely short-chain α-neurotoxins (also known as Type I α-neurotoxins) are crucial in defining the elapid envenomation process, but paradoxically, they are barely neutralized by current elapid snake antivenoms. This work has been focused on the primary structural identity among Type I neurotoxins in order to create a consensus short-chain α-neurotoxin with conserved characteristics. A multiple sequence alignment considering the twelve most toxic short-chain α-neurotoxins reported from the venoms of the elapid genera Acanthophis, Oxyuranus, Walterinnesia, Naja, Dendroaspis and Micrurus led us to propose a short-chain consensus α-neurotoxin, here named ScNtx. The synthetic ScNtx gene was de novo constructed and cloned into the expression vector pQE30 containing a 6His-Tag and an FXa proteolytic cleavage region. Escherichia coli Origami cells transfected with the pQE30/ScNtx vector expressed the recombinant consensus neurotoxin in a soluble form with a yield of 1.5 mg/L of culture medium. The 60-amino acid residue ScNtx contains canonical structural motifs similar to α-neurotoxins from African elapids and its LD50 of 3.8 µg/mice is similar to the most toxic short-chain α-neurotoxins reported from elapid venoms. Furthermore, ScNtx was also able to antagonize muscular, but not neuronal, nicotinic acetylcholine receptors (nAChR). Rabbits immunized with ScNtx were able to immune-recognize short-chain α-neurotoxins within whole elapid venoms. Type I neurotoxins are difficult to isolate and purify from natural sources; therefore, the heterologous expression of molecules such ScNtx, bearing crucial motifs and key amino acids, is a step forward to create common immunogens for developing cost-effective antivenoms with a wider spectrum of efficacy, quality and strong therapeutic value.
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