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Nucleic Acid Therapy for the Skin. 皮肤核酸疗法。
IF 6.5 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-13 DOI: 10.1016/j.jid.2024.07.029
Andreas C Chai,Daniel J Siegwart,Richard C Wang
Advances in sequencing technologies have facilitated the identification of the genes and mechanisms for many inherited skin diseases. Although targeted nucleic acid therapeutics for diseases in other organs have begun to be deployed in patients, the goal of precise therapeutics for skin diseases has not yet been realized. First, we review the current and emerging nucleic acid-based gene-editing and delivery modalities. Next, current and emerging viral and nanoparticle vehicles for the delivery of gene therapies are reviewed. Finally, specific skin diseases that could benefit optimally from nucleic acid therapies are highlighted. By adopting the latest technologies and addressing specific barriers related to skin biology, nucleic acid therapeutics have the potential to revolutionize treatments for patients with skin disease.
测序技术的进步有助于确定许多遗传性皮肤病的基因和发病机制。虽然针对其他器官疾病的核酸靶向疗法已开始在患者身上应用,但针对皮肤病的精确疗法的目标尚未实现。首先,我们回顾了当前和新兴的基于核酸的基因编辑和传递模式。其次,回顾了目前和新兴的病毒和纳米粒子载体用于传递基因疗法。最后,重点介绍了可从核酸疗法中获得最佳疗效的特定皮肤病。通过采用最新技术和解决与皮肤生物学相关的特定障碍,核酸疗法有可能彻底改变皮肤病患者的治疗方法。
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引用次数: 0
Connexin Hemichannel Inhibition and Human Genodermatoses. 附件半通道抑制与人类遗传性皮肤病
IF 6.5 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-11 DOI: 10.1016/j.jid.2024.08.003
Fabio Mammano,Amy S Paller,Thomas W White
Pathogenic variants in genes encoding connexins that cause skin diseases, such as keratitis-ichthyosis-deafness (KID) syndrome and hidrotic ectodermal dysplasia (HED) or Clouston syndrome, display increased hemichannel activity. Mechanistic insights derived from biophysical studies of the variant connexins support the hypothesis that inhibition of the acquired hemichannel activity could alleviate epidermal pathology. Use of pharmacological blockers and engineered mAbs in mouse models of HED and KID confirm that hemichannel inhibition is a promising target for new therapeutic approaches to KID and HED. Insights from this work could apply to other connexin-based genetic skin diseases in which hemichannel activity is elevated.
导致角膜炎-鱼鳞病-聋哑(KID)综合征、潮解性外胚层发育不良(HED)或克鲁斯顿综合征等皮肤病的附件蛋白编码基因中的致病变体显示出更强的半通道活性。通过对变异性连接蛋白的生物物理研究得出的机理观点支持这样的假设,即抑制获得性半通道活性可减轻表皮病变。在 HED 和 KID 小鼠模型中使用药理阻断剂和工程 mAbs 证实,半通道抑制是 KID 和 HED 新疗法的一个有希望的靶点。这项工作的启示可能适用于其他基于附件的遗传性皮肤病,在这些疾病中,半通道活性会升高。
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引用次数: 0
Inhibition of adipocyte-derived fatty-acid-binding protein 4 reduces adipocyte inflammation, improves angiogenesis, and facilitates wound healing in metabolic dysfunctions. 抑制脂肪细胞衍生的脂肪酸结合蛋白4可减少脂肪细胞炎症,改善血管生成,并促进代谢功能障碍患者的伤口愈合。
IF 6.5 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-09-09 DOI: 10.1016/j.jid.2024.08.017
Yen-Wen Wu,Jaw-Wen Chen,Hao-Yuan Tsai,Jih-Hsin Huang,Chia-Chi Chang,Ting-Ting Chang
Dermal white adipose tissue may participate in the wound healing process. Obesity-mediated chronic low-grade inflammation impairs wound healing by suppressing vascularity. Given that fatty-acid-binding protein (FABP) 4 is upregulated in the skin tissue of obese animals, this study aimed to investigate the effects of FABP4 inhibition on wound healing in high-fat-diet (HFD)-induced metabolic dysfunction mice in vivo. The interaction between adipocyte-derived FABP4 and vascular endothelial cell function was also investigated. In HFD-induced metabolic dysfunction mice, FABP4 inhibition increased angiogenesis and facilitated wound healing with reduced wound inflammation. FABP4 inhibition not only attenuated systemic inflammation, decreased body weight, and reduced insulin resistance, but also improved the sizes of adipocytes and hypoxic conditions in dermal white adipose tissue. The in vitro hypoxia was used to induce adipocyte inflammation, and the supernatants from hypoxia-stimulated adipocytes impaired the function and angiogenetic capability of human dermal microvascular endothelial cells. Both of them were improved by FABP4 inhibition. Altogether, FABP4 inhibition reduced systemic and adipocyte inflammation, improved vascular endothelial cell function, and facilitated wound healing in metabolic dysfunctions. Given the complex involvement of wound healing, future studies may be required to validate FABP4 as a potential therapeutic target for wound repair in metabolic dysfunctions.
真皮白色脂肪组织可能参与伤口愈合过程。肥胖介导的慢性低度炎症会抑制血管,从而损害伤口愈合。鉴于脂肪酸结合蛋白(FABP)4在肥胖动物的皮肤组织中上调,本研究旨在探讨抑制FABP4对高脂饮食(HFD)诱导的代谢功能障碍小鼠体内伤口愈合的影响。研究还探讨了脂肪细胞衍生的 FABP4 与血管内皮细胞功能之间的相互作用。在高密度脂蛋白饮食诱导的代谢功能障碍小鼠中,抑制 FABP4 可增加血管生成,促进伤口愈合,减少伤口发炎。抑制 FABP4 不仅能减轻全身炎症、降低体重和胰岛素抵抗,还能改善脂肪细胞的大小和真皮白色脂肪组织的缺氧状况。体外缺氧诱导脂肪细胞炎症,缺氧刺激脂肪细胞的上清液损害了人真皮微血管内皮细胞的功能和血管生成能力。抑制 FABP4 可改善这两种情况。总之,抑制 FABP4 可减轻全身炎症和脂肪细胞炎症,改善血管内皮细胞功能,促进新陈代谢功能障碍的伤口愈合。鉴于伤口愈合的复杂性,未来的研究可能需要验证 FABP4 作为代谢功能障碍患者伤口修复的潜在治疗靶点。
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引用次数: 0
Reassessing Long-Term Cryopreservation Strategies for Improved Quality, Safety, and Clinical Use of Allogeneic Dermal Progenitor Cells 重新评估长期冷冻保存策略,以提高异体真皮祖细胞的质量、安全性和临床应用。
IF 5.7 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-08-31 DOI: 10.1016/j.jid.2024.06.1285
Marjorie Flahaut , Alexis Laurent , Carla V. Fuenteslópez , Zhanfeng Cui , Hua Ye , Corinne Scaletta , Nathalie Hirt-Burri , Lee Ann Applegate , Viorica Patrulea

In regenerative medicine, ongoing advancements in cell culture techniques, including isolation, expansion, banking, and transport, are crucial for clinical success. Cryopreservation ensures off-the-freezer availability of living cells, enabling long-term storage and transport. Customizing cryopreservation techniques and cryoprotective agents (CPAs) for specific cell types is crucial for cell source quality, sustainability, safety, and therapeutic intervention efficiency. As regenerative medicine progresses, it becomes imperative that the scientific community and industry provide a comprehensive, cell-specific landscape of available and effective cryopreservation techniques, preventing trial-and-error approaches and unlocking the full potential of cell-based therapies. Open-sharing data could lead to safer, more efficient cell therapies and treatments. Two decades of dermal progenitor cell use for burn wound treatment and Good Manufacturing Practice–compliant technology transfers have highlighted the need for further cryopreservation optimization in manufacturing workflows. In this paper, we present experimental data assessing 5 different cryopreservation formulae for long-term storage of clinical-grade FE002 primary progenitor fibroblasts, emphasizing the crucial difference between DMSO-based and DMSO-free CPAs. Our findings suggest that CryoOx, a DMSO-free CPA, is a promising alternative yielding cell viability similar to that of established commercial CPAs. This research highlights the importance of secure, robust, and efficient cryopreservation techniques in cell banking for maximizing quality, ensuring patient safety, and advancing regenerative medicine.

在再生医学领域,细胞培养技术(包括分离、扩增、储存和运输)的不断进步对临床成功至关重要。低温保存可确保活细胞在冷藏室外的可用性,实现长期储存和运输。为特定细胞类型定制低温保存技术和低温保护剂(CPA)对于细胞源的质量、可持续性、安全性和治疗干预效率至关重要。随着再生医学的发展,科学界和产业界必须提供全面的、针对特定细胞的可用和有效的低温保存技术,以防止试错方法,充分释放细胞疗法的潜力。开放共享数据可以带来更安全、更高效的细胞疗法和治疗方法。真皮祖细胞用于烧伤创面治疗和符合 "良好生产规范 "的技术转让已有二十年的历史,这凸显了在生产工作流程中进一步低温保存优化的必要性。在本文中,我们提供了实验数据,评估了用于长期储存临床级 FE002 原代成纤维细胞的 5 种不同低温保存配方,强调了基于 DMSO 和不含 DMSO 的 CPA 之间的关键区别。我们的研究结果表明,不含 DMSO 的 CPA CryoOx 是一种很有前途的替代品,其细胞存活率与成熟的商业 CPA 相似。这项研究强调了细胞库中安全、稳健、高效的低温保存技术对于最大限度地提高质量、确保患者安全和促进再生医学发展的重要性。
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引用次数: 0
The Hungry Side of Skin 皮肤饥饿的一面
IF 5.7 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-08-30 DOI: 10.1016/j.jid.2024.04.030
Shivang Parikh , Carmit Levy
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引用次数: 0
Immune Landscape within Cutaneous Lesions of Human Bullous Pemphigoid 人类大疱性类天疱疮皮肤病变中的免疫格局
IF 5.7 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-08-22 DOI: 10.1016/j.jid.2024.04.008
Kalpani de Silva , Jun Yan
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引用次数: 0
Childhood Obesity, Weight Change, and Pediatric Immune-Mediated Skin Diseases 儿童肥胖症、体重变化和小儿免疫性皮肤病。
IF 5.7 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-08-21 DOI: 10.1016/j.jid.2024.01.037
Seong Rae Kim , Seong-Joon Koh , Hyunsun Park

Whether childhood obesity or weight gain leads to the development of pediatric immune-mediated skin diseases remains unclear. We aimed to determine the associations between body mass index or body mass index changes and the development of 3 main immune-mediated skin diseases—alopecia areata, atopic dermatitis (AD), and psoriasis—by analyzing a longitudinal cohort of 2,161,900 Korean children from 2009 to 2020. The findings indicated that children who were obese had a higher risk of pediatric immune-mediated skin diseases than those with normal weight (P for trend < .01). An increase in body mass index was associated with a higher risk of AD, whereas a decrease in body mass index was correlated with a reduced risk of AD. Children who gained weight, transitioning from normal to overweight, exhibited a higher AD risk than those who maintained a normal weight (adjusted hazard ratio = 1.15, 95% confidence interval = 1.11–1.20). However, those who shifted from being overweight to achieving a normal weight (adjusted hazard ratio = 0.87, 95% confidence interval = 0.81–0.94) had a lower AD risk than children who were overweight who maintained their weight. In summary, early childhood obesity may increase the risk of pediatric immune-mediated skin diseases. Weight gain may increase AD risk, whereas weight loss may lower the risk.

儿童肥胖或体重增加是否会导致小儿免疫介导性皮肤病的发生仍不清楚。我们旨在通过分析2009年至2020年期间216.19万名韩国儿童的纵向队列,确定身体质量指数或身体质量指数变化与3种主要免疫介导型皮肤病--斑秃、特应性皮炎(AD)和银屑病--发病之间的关系。研究结果表明,与体重正常的儿童相比,肥胖儿童患小儿免疫介导性皮肤病的风险更高(趋势 P < .01)。体重指数的增加与罹患免疫介导性皮肤病的风险升高有关,而体重指数的降低则与罹患免疫介导性皮肤病的风险降低有关。与保持正常体重的儿童相比,体重增加、从正常体重过渡到超重的儿童患注意力缺失症的风险更高(调整后危险比 = 1.15,95% 置信区间 = 1.11-1.20)。然而,与体重保持正常的超重儿童相比,那些从超重转变为体重正常的儿童(调整后危险比=0.87,95%置信区间=0.81-0.94),其患注意力缺失症的风险较低。总之,儿童早期肥胖可能会增加患小儿免疫介导的皮肤病的风险。体重增加可能会增加AD风险,而体重减轻可能会降低风险。
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引用次数: 0
Editors’ Picks 编辑推荐
IF 5.7 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-08-21 DOI: 10.1016/j.jid.2024.07.002
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引用次数: 0
Clinical Snippets 临床片段
IF 5.7 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-08-21 DOI: 10.1016/j.jid.2024.07.003
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Subscription Information 订阅信息
IF 5.7 2区 医学 Q1 DERMATOLOGY Pub Date : 2024-08-21 DOI: 10.1016/S0022-202X(24)01930-4
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引用次数: 0
期刊
Journal of Investigative Dermatology
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