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降低高迁移率族蛋白B1(HMGB1)水平可改善小鼠角膜炎的预后。

Decreasing HMGB1 levels improves outcome of keratitis in mice.

作者信息

Hazlett Linda D, McClellan Sharon A, Ekanayaka Sandamali A

机构信息

Department of Anatomy and Cell Biology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.

Department of Ophthalmology, Wayne State University, School of Medicine, 540 East Canfield Avenue, Detroit, MI 48201, USA.

出版信息

J Rare Dis Res Treat. 2016;1(1):36-39. Epub 2016 Jul 18.

PMID:29376148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5784448/
Abstract

is a Gram negative bacterium widely dispersed in the environment which can cause acute and chronic infections in humans. According to the Centers for Disease Control and Prevention (CDC), the overall incidence of infections in USA hospitals averages about 0.4% (4/1000 discharges), and the bacterium is the fourth most commonly-isolated nosocomial pathogen accounting for 10.1% of all hospital-acquired infections. keratitis is a severe infection of the eye, progresses rapidly and remains a leading cause of corneal ulcers worldwide. Use of contact lenses is the major risk factor in the USA, while in less industrialized countries, trauma from agricultural accidents are of importance. Animal models of bacterial keratitis are of value in the study of this disease and suggest potential alternative therapeutic targets that are needed urgently due to increasing antibiotic resistance. Recently we have shown success and improved disease outcome after down-regulation of one promising target, high mobility group box1 (HMGB1) using small interfering RNA (siRNA). Testing more clinically relevant approaches are underway to reduce HMGB1 levels in keratitis which may hold promise for its treatment.

摘要

是一种革兰氏阴性菌,广泛分布于环境中,可导致人类急性和慢性感染。根据美国疾病控制与预防中心(CDC)的数据,美国医院感染的总体发病率平均约为0.4%(每1000例出院患者中有4例),该细菌是第四常见的医院获得性病原体,占所有医院感染的10.1%。细菌性角膜炎是一种严重的眼部感染,进展迅速,仍然是全球角膜溃疡的主要原因。在美国,使用隐形眼镜是主要危险因素,而在工业化程度较低的国家,农业事故造成的创伤则很重要。细菌性角膜炎的动物模型在该疾病的研究中具有价值,并提示了由于抗生素耐药性增加而迫切需要的潜在替代治疗靶点。最近我们已经证明,使用小干扰RNA(siRNA)下调一个有前景的靶点——高迁移率族蛋白B1(HMGB1)后取得了成功并改善了疾病结局。正在测试更多临床相关方法以降低细菌性角膜炎中HMGB1的水平,这可能为其治疗带来希望。

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Decreasing HMGB1 levels improves outcome of keratitis in mice.降低高迁移率族蛋白B1(HMGB1)水平可改善小鼠角膜炎的预后。
J Rare Dis Res Treat. 2016;1(1):36-39. Epub 2016 Jul 18.
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Pathogens. 2021 Sep 25;10(10):1235. doi: 10.3390/pathogens10101235.
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High-mobility group box 1: a novel target for treatment of Pseudomonas aeruginosa keratitis.高迁移率族蛋白B1:治疗铜绿假单胞菌角膜炎的新靶点。
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Ann Acad Med Singap. 1995 Nov;24(6):823-9.
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Genetic features of Pseudomonas aeruginosa isolates associated with eye infections referred to Farabi Hospital, Tehran, Iran.与转诊至伊朗德黑兰法拉比医院的眼部感染相关的铜绿假单胞菌分离株的遗传特征。
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引用本文的文献

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HMBG1 as a Driver of Inflammatory and Immune Processes in the Pathogenesis of Ocular Diseases.高迁移率族蛋白B1作为眼部疾病发病机制中炎症和免疫过程的驱动因素
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HMGB1 Antagonist, Box A, Reduces TLR4, RAGE, and Inflammatory Cytokines in the Cornea of P. aeruginosa-Infected Mice.HMGB1拮抗剂A盒可降低铜绿假单胞菌感染小鼠角膜中的TLR4、RAGE和炎性细胞因子水平。
J Ocul Pharmacol Ther. 2018 Nov 8;34(10):659-69. doi: 10.1089/jop.2018.0073.
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Topical Glycyrrhizin Is Therapeutic for Pseudomonas aeruginosa Keratitis.局部甘草酸治疗绿脓杆菌角膜炎有效。
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本文引用的文献

1
Thrombomodulin Protects Against Bacterial Keratitis, Is Anti-Inflammatory, but Not Angiogenic.血栓调节蛋白可预防细菌性角膜炎,具有抗炎作用,但不具有促血管生成作用。
Invest Ophthalmol Vis Sci. 2015 Dec;56(13):8091-100. doi: 10.1167/iovs.15-18393.
2
Thrombomodulin promotes corneal epithelial wound healing.血栓调节蛋白促进角膜上皮伤口愈合。
PLoS One. 2015 Mar 27;10(3):e0122491. doi: 10.1371/journal.pone.0122491. eCollection 2015.
3
High-mobility group box 1: a novel target for treatment of Pseudomonas aeruginosa keratitis.高迁移率族蛋白B1:治疗铜绿假单胞菌角膜炎的新靶点。
J Immunol. 2015 Feb 15;194(4):1776-87. doi: 10.4049/jimmunol.1401684. Epub 2015 Jan 14.
4
Therapeutic face of RNAi: in vivo challenges.RNA干扰的治疗前景:体内挑战
Expert Opin Biol Ther. 2015 Feb;15(2):269-85. doi: 10.1517/14712598.2015.983070. Epub 2014 Nov 15.
5
Anti-HMGB1 neutralizing antibody ameliorates neutrophilic airway inflammation by suppressing dendritic cell-mediated Th17 polarization.抗高迁移率族蛋白 B1 中和抗体通过抑制树突状细胞介导的 Th17 极化缓解中性粒细胞性气道炎症。
Mediators Inflamm. 2014;2014:257930. doi: 10.1155/2014/257930. Epub 2014 May 15.
6
Nanotoxicity: a key obstacle to clinical translation of siRNA-based nanomedicine.纳米毒性:基于小干扰RNA的纳米药物临床转化的关键障碍。
Nanomedicine (Lond). 2014 Feb;9(2):295-312. doi: 10.2217/nnm.13.204.
7
Recombinant lectin-like domain of thrombomodulin suppresses vascular inflammation by reducing leukocyte recruitment via interacting with Lewis Y on endothelial cells.血栓调节蛋白的重组凝集素样结构域通过与内皮细胞上的 Lewis Y 相互作用减少白细胞募集来抑制血管炎症。
Arterioscler Thromb Vasc Biol. 2013 Oct;33(10):2366-73. doi: 10.1161/ATVBAHA.113.301221. Epub 2013 Aug 15.
8
Carbenoxolone blocks endotoxin-induced protein kinase R (PKR) activation and high mobility group box 1 (HMGB1) release.卡波氯铵阻断内毒素诱导的蛋白激酶 R(PKR)激活和高迁移率族蛋白 B1(HMGB1)释放。
Mol Med. 2013 Jul 24;19(1):203-11. doi: 10.2119/molmed.2013.00064.
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HMGB1: The Central Cytokine for All Lymphoid Cells.高迁移率族蛋白 B1:所有淋巴样细胞的核心细胞因子。
Front Immunol. 2013 Mar 20;4:68. doi: 10.3389/fimmu.2013.00068. eCollection 2013.
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Clinical potential of VIP by modified pharmaco-kinetics and delivery mechanisms.通过改良药代动力学和递送机制实现的血管活性肠肽的临床潜力。
Endocr Metab Immune Disord Drug Targets. 2012 Dec;12(4):344-50. doi: 10.2174/187153012803832594.