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一种用于过敏性皮肤病的核酸类药物。

A nucleic acid-based medication for allergic skin diseases.

作者信息

Yokozeki Hiroo

机构信息

Tokyo Medical and Dental University, Graduate School, Department of Dermatology, 113-8519 1-5-45, Yushima, Bunkyo-ku, Tokyo, Japan.

出版信息

J Dermatol Sci. 2014 Aug;75(2):75-81. doi: 10.1016/j.jdermsci.2014.03.003. Epub 2014 Mar 19.

Abstract

Among allergic skin diseases, atopic dermatitis is the most difficult to cure. In the majority of patients, atopic dermatitis can be easily controlled by treatment based on three therapeutic approaches: avoidance of precipitating factors, skin care, and medication. In some adult patients, however, severe atopic dermatitis is refractory to treatment, and no fundamental effective treatment modality has yet been established for such cases. Chronic contact dermatitis without an identified causative hapten is also considered an allergic skin disease that is difficult to cure. Topical nucleic acid-based medications are currently being applied clinically, and an ointment containing nuclear factor-κB decoy oligodeoxynucleotides (hereafter referred to as Decoy) has reached clinical trials. In addition, synthetic double-stranded DNA with high affinity for signal transducers and activators of transcription 6 (STAT6) introduced in vivo as a decoy cis element to bind the transcriptional factor and block the activated gene that contributes to the onset and progression of atopic dermatitis functions as an effective therapeutic agent. We also introduce another STAT1 decoy treatment, cytosine-phosphate-guanine-ODN or STAT6 small interfering RNA therapy, for allergic skin diseases.

摘要

在过敏性皮肤病中,特应性皮炎最难治愈。在大多数患者中,特应性皮炎可通过基于三种治疗方法的治疗轻松得到控制:避免诱发因素、皮肤护理和药物治疗。然而,在一些成年患者中,重度特应性皮炎对治疗具有难治性,且尚未针对此类病例确立根本有效的治疗方式。未明确致病半抗原的慢性接触性皮炎也被视为一种难以治愈的过敏性皮肤病。基于核酸的局部用药目前正在临床应用,一种含有核因子κB诱饵寡脱氧核苷酸(以下简称“诱饵”)的软膏已进入临床试验阶段。此外,对转录信号转导子与激活子6(STAT6)具有高亲和力的合成双链DNA作为诱饵顺式元件引入体内,以结合转录因子并阻断有助于特应性皮炎发病和进展的激活基因,可起到有效的治疗作用。我们还介绍了另一种针对过敏性皮肤病的STAT1诱饵治疗、胞嘧啶-磷酸-鸟嘌呤寡脱氧核苷酸或STAT6小干扰RNA疗法。

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