The cyclization of human salivary Histatin 1 via click chemistry for skin wound healing

IF 4.3 3区 医学 Q1 PHARMACOLOGY & PHARMACY European Journal of Pharmaceutical Sciences Pub Date : 2025-01-01 DOI:10.1016/j.ejps.2024.106978
Xiaoxuan Lei , Yu Yang , Judun Zheng , Liwen Liang , Liuhanghang Cheng , Yunqing Dong , Biying Qiu , Floris J. Bikker , Tymour Forouzanfar , Biao Cheng , Gang Wu , Bin Yang
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Abstract

Acute skin injuries can result in the breakdown of the skin barrier, heightening the risk of infections and complications. Histatin 1 (Hst1) promotes the adhesion, spreading, and migration of various skin-related cells, thus encouraging wound healing. However, Hst1 is extensively degraded upon exposure to wound exudates. Cyclized hst1 (Cyclic-hst1) has a much higher resistance to protease degradation than Hst1, thus increasing its stability and half-life. Herein, we synthesized Cyclic-hst1 via a click reaction and explored its efficacy in wound healing via cellular and animal experiments. Cyclic-hst1, at a 100-fold lower concentration than Hst1, effectively promoted acute skin wound healing. In addition, Cyclic-hst1 had a superior effect to Hst1 in terms of its anti-inflammatory, re-epithelialization, collagen deposition, and angiogenic effects, thus significantly promoting skin wound healing. Consequently, Cyclic-hst1 could represent a favorable treatment to manage acute skin wound healing, providing a promising experimental basis for clinical transformation and application.

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人唾液组蛋白1环化对皮肤创面愈合的影响。
急性皮肤损伤可导致皮肤屏障的破坏,增加感染和并发症的风险。组蛋白1 (Hst1)促进各种皮肤相关细胞的粘附、扩散和迁移,从而促进伤口愈合。然而,Hst1暴露于伤口渗出液后被广泛降解。环化hst1 (Cyclic-hst1)具有比hst1更高的蛋白酶降解抗性,从而提高了其稳定性和半衰期。本研究通过点击反应合成了Cyclic-hst1,并通过细胞和动物实验探讨了其在伤口愈合中的作用。Cyclic-hst1浓度比Hst1低100倍,可有效促进急性皮肤创面愈合。此外,Cyclic-hst1在抗炎、再上皮、胶原沉积、血管生成等方面均优于Hst1,显著促进皮肤创面愈合。因此,Cyclic-hst1可能是治疗急性皮肤创面愈合的良好药物,为临床转化和应用提供了良好的实验基础。
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来源期刊
CiteScore
9.60
自引率
2.20%
发文量
248
审稿时长
50 days
期刊介绍: The journal publishes research articles, review articles and scientific commentaries on all aspects of the pharmaceutical sciences with emphasis on conceptual novelty and scientific quality. The Editors welcome articles in this multidisciplinary field, with a focus on topics relevant for drug discovery and development. More specifically, the Journal publishes reports on medicinal chemistry, pharmacology, drug absorption and metabolism, pharmacokinetics and pharmacodynamics, pharmaceutical and biomedical analysis, drug delivery (including gene delivery), drug targeting, pharmaceutical technology, pharmaceutical biotechnology and clinical drug evaluation. The journal will typically not give priority to manuscripts focusing primarily on organic synthesis, natural products, adaptation of analytical approaches, or discussions pertaining to drug policy making. Scientific commentaries and review articles are generally by invitation only or by consent of the Editors. Proceedings of scientific meetings may be published as special issues or supplements to the Journal.
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