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Navigating ESKAPE Pathogens: Considerations and Caveats for Animal Infection Models Development. ESKAPE 病原体导航:动物感染模型开发的考虑因素和注意事项。
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-12 Epub Date: 2024-06-12 DOI: 10.1021/acsinfecdis.4c00007
Haojie Yu, Yongchang Xu, Saber Imani, Zhuo Zhao, Saif Ullah, Qingjing Wang

The misuse of antibiotics has led to the global spread of drug-resistant bacteria, especially multi-drug-resistant (MDR) ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species). These opportunistic bacteria pose a significant threat, in particular within hospitals, where they cause nosocomial infections, leading to substantial morbidity and mortality. To comprehensively explore ESKAPE pathogenesis, virulence, host immune response, diagnostics, and therapeutics, researchers increasingly rely on necessitate suitable animal infection models. However, no single model can fully replicate all aspects of infectious diseases. Notably when studying opportunistic pathogens in immunocompetent hosts, rapid clearance by the host immune system can limit the expression of characteristic disease symptoms. In this study, we examine the critical role of animal infection models in understanding ESKAPE pathogens, addressing limitations and research gaps. We discuss applications and highlight key considerations for effective models. Thoughtful decisions on disease replication, parameter monitoring, and data collection are crucial for model reliability. By meticulously replicating human diseases and addressing limitations, researchers maximize the potential of animal infection models. This aids in targeted therapeutic development, bridges knowledge gaps, and helps combat MDR ESKAPE pathogens, safeguarding public health.

抗生素的滥用导致耐药细菌在全球蔓延,尤其是耐多药(MDR)ESKAPE 病原体(粪肠球菌、金黄色葡萄球菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌和肠杆菌)。这些机会性细菌构成了重大威胁,尤其是在医院内,它们会引起院内感染,导致大量的发病率和死亡率。为了全面探索 ESKAPE 的致病机理、毒力、宿主免疫反应、诊断和治疗,研究人员越来越依赖于合适的动物感染模型。然而,没有一种模型能完全复制传染病的所有方面。尤其是在研究免疫功能健全的宿主体内的机会性病原体时,宿主免疫系统的快速清除会限制特征性疾病症状的表达。在本研究中,我们探讨了动物感染模型在了解 ESKAPE 病原体方面的关键作用,并指出了局限性和研究空白。我们讨论了有效模型的应用并强调了关键注意事项。关于疾病复制、参数监测和数据收集的深思熟虑的决定对模型的可靠性至关重要。通过精心复制人类疾病并解决局限性问题,研究人员可以最大限度地发挥动物感染模型的潜力。这有助于进行有针对性的治疗开发,弥补知识差距,并有助于抗击 MDR ESKAPE 病原体,保障公众健康。
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引用次数: 0
Etiopathology, Epidemiology, Diagnosis, and Treatment of Fungal Keratitis. 真菌性角膜炎的病原学、流行病学、诊断和治疗。
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-12 Epub Date: 2024-06-07 DOI: 10.1021/acsinfecdis.4c00203
Amol Chhatrapati Bisen, Sachin Nashik Sanap, Sristi Agrawal, Arpon Biswas, Anjali Mishra, Sarvesh Kumar Verma, Vaishali Singh, Rabi Sankar Bhatta

Fungal keratitis (FK) is a severe ocular condition resulting from corneal infection that is prevalent in tropical countries, particularly in developing regions of Asia and Africa. Factors like corneal lens misuse, inappropriate steroid use, and diagnostic challenges have provoked the epidemic. FK causes significant vision impairment, scarring, and ocular deformities. Accurate pathological diagnosis is crucial for effective therapeutic intervention. Topical antifungal therapy with surface healing medications proves effective in preventing fungal-borne ulcers. Managing FK requires a comprehensive understanding of fungal pathogenesis, guiding formulation strategies and preventive measures to curb global ocular blindness. This review provides in-depth insights into FK, covering etiology, epidemiology, pathogenesis, therapeutic interventions, antifungal resistance, limitations, prevention, and future perspectives on ocular surface disease management.

真菌性角膜炎(FK)是一种由角膜感染引起的严重眼部疾病,在热带国家,尤其是亚洲和非洲的发展中地区十分流行。角膜塑形镜滥用、类固醇使用不当以及诊断难题等因素引发了这一流行病。FK 会导致严重的视力损伤、疤痕和眼部畸形。准确的病理诊断对于有效的治疗干预至关重要。使用表面愈合药物进行局部抗真菌治疗可有效预防真菌引起的溃疡。治疗 FK 需要全面了解真菌的致病机理,以指导制剂策略和预防措施,从而遏制全球眼盲的发生。本综述深入探讨了 FK 的病因、流行病学、发病机制、治疗干预、抗真菌耐药性、局限性、预防以及眼表疾病管理的未来展望。
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引用次数: 0
Phenotypic Landscape of Immune Cells in Sepsis: Insights from High-Dimensional Mass Cytometry. 败血症中免疫细胞的表型图谱:高维质量细胞计量学的启示
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-12 Epub Date: 2024-06-08 DOI: 10.1021/acsinfecdis.4c00066
Sehee Park, Haribalan Perumalsamy, Zayakhuu Gerelkhuu, Sneha Sunderraj, Yangsoon Lee, Tae Hyun Yoon

Understanding the sepsis-induced immunological response can be facilitated by identifying phenotypic changes in immune cells at the single-cell level. Mass cytometry, a novel multiparametric single-cell analysis technique, offers considerable benefits in characterizing sepsis-induced phenotypic changes in peripheral blood mononuclear cells. Here, we analyzed peripheral blood mononuclear cells from 20 sepsis patients and 10 healthy donors using mass cytometry and employing 23 markers. Both manual gating and automated clustering approaches (PhenoGraph) were used for cell identification, complemented by uniform manifold approximation and projection (UMAP) for dimensionality reduction and visualization. Our study revealed that patients with sepsis exhibited a unique immune cell profile, marked by an increased presence of monocytes, B cells, and dendritic cells, alongside a reduction in natural killer (NK) cells and CD4/CD8 T cells. Notably, significant changes in the distributions of monocytes and B and CD4 T cells were observed. Clustering with PhenoGraph unveiled the subsets of each cell type and identified elevated CCR6 expression in sepsis patients' monocyte subset (PG#5), while further PhenoGraph clustering on manually gated T and B cells discovered sepsis-specific CD4 T cell subsets (CCR4low CD20low CD38low) and B cell subsets (HLA-DRlow CCR7low CCR6high), which could potentially serve as novel diagnostic markers for sepsis.

从单细胞水平识别免疫细胞的表型变化有助于了解败血症诱导的免疫反应。质控细胞术是一种新型的多参数单细胞分析技术,在描述脓毒症诱导的外周血单核细胞表型变化方面有很大的优势。在这里,我们使用质谱仪分析了 20 名败血症患者和 10 名健康捐献者的外周血单核细胞,并采用了 23 种标记物。我们使用手动选通和自动聚类方法(PhenoGraph)进行细胞识别,并辅以均匀流形逼近和投影(UMAP)进行降维和可视化。我们的研究发现,败血症患者表现出独特的免疫细胞特征,其特点是单核细胞、B 细胞和树突状细胞增多,而自然杀伤(NK)细胞和 CD4/CD8 T 细胞减少。值得注意的是,单核细胞、B 细胞和 CD4 T 细胞的分布发生了重大变化。用 PhenoGraph 聚类揭示了每种细胞类型的亚群,并发现脓毒症患者的单核细胞亚群(PG#5)中 CCR6 表达升高,而对人工门控的 T 细胞和 B 细胞进一步用 PhenoGraph 聚类发现了脓毒症特异性 CD4 T 细胞亚群(CCR4 低 CD20 低 CD38 低)和 B 细胞亚群(HLA-DR 低 CCR7 低 CCR6 高),它们有可能成为脓毒症的新型诊断标志物。
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引用次数: 0
Strategic Single-Residue Substitution in the Antimicrobial Peptide Esc(1-21) Confers Activity against Staphylococcus aureus, Including Drug-Resistant and Biofilm Phenotype. 抗菌肽 Esc(1-21) 的策略性单残基置换赋予其对抗金黄色葡萄球菌的活性,包括耐药性和生物膜表型。
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-12 Epub Date: 2024-06-07 DOI: 10.1021/acsinfecdis.4c00130
Maria Rosa Loffredo, Bruno Casciaro, Rosa Bellavita, Cassandra Troiano, Diego Brancaccio, Floriana Cappiello, Francesco Merlino, Stefania Galdiero, Giancarlo Fabrizi, Paolo Grieco, Lorenzo Stella, Alfonso Carotenuto, Maria Luisa Mangoni

Staphylococcus aureus, a bacterium resistant to multiple drugs, is a significant cause of illness and death worldwide. Antimicrobial peptides (AMPs) provide an excellent potential strategy to cope with this threat. Recently, we characterized a derivative of the frog-skin AMP esculentin-1a, Esc(1-21) (1) that is endowed with potent activity against Gram-negative bacteria but poor efficacy against Gram-positive strains. In this study, three analogues of peptide 1 were designed by replacing Gly8 with α-aminoisobutyric acid (Aib), Pro, and dPro (2-4, respectively). The single substitution Gly8 → Aib8 in peptide 2 makes it active against the planktonic form of Gram-positive bacterial strains, especially Staphylococcus aureus, including multidrug-resistant clinical isolates, with an improved biostability without resulting in cytotoxicity to mammalian cells. Moreover, peptide 2 showed a higher antibiofilm activity than peptide 1 against both reference and clinical isolates of S. aureus. Peptide 2 was also able to induce rapid bacterial killing, suggesting a membrane-perturbing mechanism of action. Structural analysis of the most active peptide 2 evidenced that the improved biological activity of peptide 2 is the consequence of a combination of higher biostability, higher α helical content, and ability to reduce membrane fluidity and to adopt a distorted helix, bent in correspondence of Aib8. Overall, this study has shown how a strategic single amino acid substitution is sufficient to enlarge the spectrum of activity of the original peptide 1, and improve its biological properties for therapeutic purposes, thus paving the way to optimize AMPs for the development of new broad-spectrum anti-infective agents.

金黄色葡萄球菌是一种对多种药物具有抗药性的细菌,是全球疾病和死亡的重要原因。抗菌肽(AMPs)为应对这一威胁提供了一种极好的潜在策略。最近,我们鉴定了一种蛙皮 AMP esculentin-1a 的衍生物 Esc(1-21) (1),它对革兰氏阴性菌具有强效活性,但对革兰氏阳性菌株的疗效较差。本研究设计了肽 1 的三种类似物,分别用 α-氨基异丁酸(Aib)、Pro 和 dPro 取代 Gly8(2-4)。肽 2 中的 Gly8 → Aib8 单个替换使其对革兰氏阳性细菌菌株(尤其是金黄色葡萄球菌,包括耐多药的临床分离菌株)的浮游生物具有活性,并提高了生物稳定性,同时不会对哺乳动物细胞产生细胞毒性。此外,与肽 1 相比,肽 2 对金黄色葡萄球菌参考菌株和临床分离菌株都具有更高的抗生物膜活性。肽 2 还能快速杀灭细菌,这表明它具有膜干扰作用机制。对活性最强的多肽 2 进行的结构分析表明,多肽 2 的生物活性之所以得到提高,是因为它具有更高的生物稳定性、更高的 α 螺旋含量、降低膜流动性的能力以及与 Aib8 相对应的弯曲变形螺旋。总之,这项研究表明,只需战略性地替换一个氨基酸,就足以扩大原始多肽 1 的活性谱,并改善其生物特性以达到治疗目的,从而为优化 AMPs 以开发新的广谱抗感染药物铺平了道路。
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引用次数: 0
3-Position Biaryl Endochin-like Quinolones with Enhanced Antimalarial Performance. 具有更强抗疟性能的 3 位双环内喹啉类喹诺酮。
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-12 Epub Date: 2024-06-11 DOI: 10.1021/acsinfecdis.4c00140
Sovitj Pou, Rolf W Winter, Rozalia A Dodean, Katherine Liebman, Yuexin Li, Michael W Mather, Binod Nepal, Aaron Nilsen, Mason J Handford, Teresa M Riscoe, Sydney Laxson, Payton J Kirtley, Maya Aleshnick, Lev N Zakharov, Jane X Kelly, Martin J Smilkstein, Brandon K Wilder, Sandhya Kortagere, Akhil B Vaidya, P Holland Alday, J Stone Doggett, Michael K Riscoe

ELQ-300 is a potent antimalarial drug with activity against blood, liver, and vector stages of the disease. A prodrug, ELQ-331, exhibits reduced crystallinity and improved in vivo efficacy in preclinical testing, and currently, it is in the developmental pipeline for once-a-week dosing for oral prophylaxis against malaria. Because of the high cost of developing a new drug for human use and the high risk of drug failure, it is prudent to have a back-up plan in place. Here we describe ELQ-596, a member of a new subseries of 3-biaryl-ELQs, with enhanced potency in vitro against multidrug-resistant Plasmodium falciparum parasites. ELQ-598, a prodrug of ELQ-596 with diminished crystallinity, is more effective vs murine malaria than its progenitor ELQ-331 by 4- to 10-fold, suggesting that correspondingly lower doses could be used to protect and cure humans of malaria. With a longer bloodstream half-life in mice compared to its progenitor, ELQ-596 highlights a novel series of next-generation ELQs with the potential for once-monthly dosing for protection against malaria infection. Advances in the preparation of 3-biaryl-ELQs are presented along with preliminary results from experiments to explore key structure-activity relationships for drug potency, selectivity, pharmacokinetics, and safety.

ELQ-300 是一种强效抗疟药物,对血液、肝脏和病媒阶段的疾病具有活性。一种名为 ELQ-331 的原药在临床前测试中显示出较低的结晶度和更好的体内疗效,目前正在开发中,可用于口服预防疟疾的一周一次剂量。由于开发供人类使用的新药成本高昂,而且药物失败的风险也很高,因此谨慎的做法是制定备用计划。我们在此介绍一种新的 3-biaryl-ELQ子系列药物 ELQ-596,它在体外对具有多重耐药性的恶性疟原虫寄生虫具有更强的药效。ELQ-598 是 ELQ-596 的原药,结晶度较低,对小鼠疟疾的疗效是其原药 ELQ-331 的 4 到 10 倍,这表明可以使用相应较低的剂量来保护和治疗人类疟疾。ELQ-596 在小鼠血液中的半衰期比其祖先 ELQ-331 更长,它是新一代 ELQ 的一个新系列,有可能每月用药一次,以防止疟疾感染。本文介绍了制备 3-biaryl-ELQs 的进展,以及探索药物效力、选择性、药代动力学和安全性的关键结构-活性关系的初步实验结果。
{"title":"3-Position Biaryl Endochin-like Quinolones with Enhanced Antimalarial Performance.","authors":"Sovitj Pou, Rolf W Winter, Rozalia A Dodean, Katherine Liebman, Yuexin Li, Michael W Mather, Binod Nepal, Aaron Nilsen, Mason J Handford, Teresa M Riscoe, Sydney Laxson, Payton J Kirtley, Maya Aleshnick, Lev N Zakharov, Jane X Kelly, Martin J Smilkstein, Brandon K Wilder, Sandhya Kortagere, Akhil B Vaidya, P Holland Alday, J Stone Doggett, Michael K Riscoe","doi":"10.1021/acsinfecdis.4c00140","DOIUrl":"10.1021/acsinfecdis.4c00140","url":null,"abstract":"<p><p>ELQ-300 is a potent antimalarial drug with activity against blood, liver, and vector stages of the disease. A prodrug, <b>ELQ-331</b>, exhibits reduced crystallinity and improved in vivo efficacy in preclinical testing, and currently, it is in the developmental pipeline for once-a-week dosing for oral prophylaxis against malaria. Because of the high cost of developing a new drug for human use and the high risk of drug failure, it is prudent to have a back-up plan in place. Here we describe <b>ELQ-596</b>, a member of a new subseries of 3-biaryl-ELQs, with enhanced potency in vitro against multidrug-resistant <i>Plasmodium falciparum</i> parasites. <b>ELQ-598</b>, a prodrug of <b>ELQ-596</b> with diminished crystallinity, is more effective vs murine malaria than its progenitor <b>ELQ-331</b> by 4- to 10-fold, suggesting that correspondingly lower doses could be used to protect and cure humans of malaria. With a longer bloodstream half-life in mice compared to its progenitor, <b>ELQ-596</b> highlights a novel series of next-generation ELQs with the potential for once-monthly dosing for protection against malaria infection. Advances in the preparation of 3-biaryl-ELQs are presented along with preliminary results from experiments to explore key structure-activity relationships for drug potency, selectivity, pharmacokinetics, and safety.</p>","PeriodicalId":17,"journal":{"name":"ACS Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":4.0,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141304769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Investigating Penetration and Antimicrobial Activity of Vector-Bicycle Conjugates. 研究载体-自行车共轭物的渗透性和抗菌活性
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-12 Epub Date: 2024-06-12 DOI: 10.1021/acsinfecdis.3c00427
Andreas Hadjicharalambous, Hector Newman, Nick Lewis, Catherine Rowland, Nikolaos Bournakas, Steven J Stanway, Michael Dawson, Michael J Skynner, Paul Beswick

Growing antibiotic resistance is rapidly threatening the efficacy of treatments for Gram-negative infections. Bicycle molecules, constrained bicyclic peptides from diverse libraries generated by bacteriophage display that bind with high affinity to a chosen target are a potential new class of antibiotics. The generally impermeable bacterial outer membrane currently limits the access of peptides to bacteria. The conjugation of membrane active peptides offers an avenue for outer membrane penetration. Here, we investigate which physicochemical properties of a specific membrane active peptide (MAP), derived from ixosin-B, could be tweaked to enhance the penetration of conjugates by generating multiple MAP-Bicycle conjugate variants. We demonstrate that charge and hydrophobicity are important factors, which enhance penetration and, therefore, antimicrobial potency. Interestingly, we show that induction of secondary structure, but not a change in amphipathicity, is vital for effective penetration of the Gram-negative outer membrane. These results offer insights into the ways vectors could be designed to deliver Bicycle molecules (and other cargos) through biological membranes.

抗生素耐药性的不断增加正迅速威胁着革兰氏阴性菌感染的治疗效果。自行车分子(Bicycle molecules)是从噬菌体展示产生的各种文库中提取的受限双环肽,能与所选靶点高亲和力结合,是一类潜在的新型抗生素。目前,细菌外膜通常是不渗透的,这限制了多肽进入细菌体内。膜活性肽的共轭为外膜渗透提供了一条途径。在此,我们研究了从ixosin-B中提取的特定膜活性肽(MAP)的理化特性,通过生成多种MAP-Bicycle共轭变体来提高共轭物的渗透性。我们证明,电荷和疏水性是重要因素,它们能增强穿透力,从而提高抗菌效力。有趣的是,我们发现二级结构的诱导,而非两亲性的变化,对于有效穿透革兰氏阴性菌外膜至关重要。这些结果为设计载体以通过生物膜递送生物分子(和其他载体)提供了启示。
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引用次数: 0
Celebrating a Decade of Trailblazing Research─Collection of Highly Cited Articles Each Year from ACS Infectious Diseases. 庆祝开拓性研究十年--ACS 感染性疾病杂志每年高被引论文集。
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-12 Epub Date: 2024-06-06 DOI: 10.1021/acsinfecdis.4c00381
Jayanta Haldar
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引用次数: 0
Isobavachalcone Exhibits Potent Antifungal Efficacy by Inhibiting Enolase Activity and Glycolysis in Candida albicans. 异巴伐醌通过抑制白色念珠菌的烯醇化酶活性和糖酵解作用,显示出强大的抗真菌功效。
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-12 DOI: 10.1021/acsinfecdis.4c00399
Hao Wu, Zhe Ji, Xin Huang, Liping Li, Sijin Hang, Jinhua Yu, Hui Lu, Yuanying Jiang

Invasive fungal diseases (IFDs) are becoming increasingly acknowledged as a significant concern linked to heightened rates of morbidity and mortality. Regrettably, the available antifungal therapies for managing IFDs are constrained. Emerging evidence indicates that enolase holds promise as a potential target protein for combating IFDs; however, there is currently a deficiency in antifungal medications specifically targeting enolase. This study establishes that isobavachalcone (IBC) exhibits noteworthy antifungal efficacy both in vitro and in vivo. Moreover, our study has demonstrated that IBC effectively targets Eno1 in Candida albicans (CaEno1), resulting in the suppression of the glycolytic pathway. Additionally, our research has indicated that IBC exhibits a higher affinity for CaEno1 compared to human Eno1 (hEno1), with the presence of isoprenoid in the side chain of IBC playing a crucial role in its ability to inhibit enolase activity. These findings contribute to the comprehension of antifungal approaches that target Eno1, identifying IBC as a potential inhibitor of Eno1 in human pathogenic fungi.

人们日益认识到,侵袭性真菌病(IFDs)是与发病率和死亡率上升相关的一个重大问题。令人遗憾的是,目前用于治疗 IFD 的抗真菌疗法非常有限。新的证据表明,烯醇化酶有望成为抗击 IFDs 的潜在靶蛋白;然而,目前缺乏专门针对烯醇化酶的抗真菌药物。本研究证实,异巴伐醌(IBC)在体外和体内都具有显著的抗真菌功效。此外,我们的研究还证明,IBC 能有效靶向白色念珠菌中的 Eno1(CaEno1),从而抑制糖酵解途径。此外,我们的研究还表明,与人类 Eno1(hEno1)相比,IBC 对 CaEno1 具有更高的亲和力,IBC 侧链中存在的异肾上腺素对其抑制烯醇化酶活性的能力起着至关重要的作用。这些发现有助于理解以 Eno1 为靶标的抗真菌方法,确定 IBC 是人类致病真菌中 Eno1 的潜在抑制剂。
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引用次数: 0
Multifunctional Nanosystem for Dual Anti-Inflammatory and Antibacterial Photodynamic Therapy in Infectious Diabetic Wounds. 用于糖尿病感染性伤口的双重消炎抗菌光动力疗法的多功能纳米系统
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-11 DOI: 10.1021/acsinfecdis.4c00306
Mohammad Sadik Ali, Hima Sree Buddhiraju, Mounika Gubige, Apoorva Basa, Gnaneshwar Gupta K, Bantal Veeresh, Aravind Kumar Rengan

Infectious diabetic wounds present a substantial challenge, characterized by inflammation, infection, and delayed wound healing, leading to elevated morbidity and mortality rates. In this work, we developed a multifunctional lipid nanoemulsion containing quercetin, chlorine e6, and rosemary oil (QCRLNEs) for dual anti-inflammatory and antibacterial photodynamic therapy (APDT) for treating infectious diabetic wounds. The QCRLNEs exhibited spherical morphology with a size of 51 nm with enhanced encapsulation efficiency, skin permeation, and localized delivery at the infected wound site. QCRLNEs with NIR irradiation have shown excellent wound closure and antimicrobial properties in vitro, mitigating the nonselective cytotoxic behavior of PDT. Also, excellent biocompatibility and anti-inflammatory and wound healing responses were observed in zebrafish models. The infected wound healing properties in S. aureus-infected diabetic rat models indicated re-epithelization and collagen deposition with no signs of inflammation. This multifaceted approach using QCRLNEs with NIR irradiation holds great promise for effectively combating oxidative stress and bacterial infections commonly associated with infected diabetic wounds, facilitating enhanced wound healing and improved clinical outcomes.

糖尿病感染性伤口是一个巨大的挑战,其特点是炎症、感染和伤口愈合延迟,导致发病率和死亡率升高。在这项研究中,我们开发了一种含有槲皮素、氯e6和迷迭香油(QCRLNEs)的多功能脂质纳米乳液,用于治疗感染性糖尿病伤口的双重消炎和抗菌光动力疗法(APDT)。QCRLNEs 呈球形,大小为 51 纳米,具有更高的封装效率、皮肤渗透性和在感染伤口部位的局部递送能力。经近红外照射的 QCRLNEs 在体外显示出优异的伤口闭合性和抗菌性,减轻了光动力疗法的非选择性细胞毒性。此外,在斑马鱼模型中也观察到了出色的生物相容性、抗炎和伤口愈合反应。在金黄色葡萄球菌感染的糖尿病大鼠模型中,受感染伤口的愈合特性显示了再上皮化和胶原沉积,且无炎症迹象。这种利用 QCRLNEs 和近红外照射的多层面方法有望有效对抗氧化应激和糖尿病感染性伤口常见的细菌感染,促进伤口愈合,改善临床疗效。
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引用次数: 0
Infection and the Glycome─New Insights into Host Response. 感染与糖粒--宿主反应的新见解。
IF 4 2区 医学 Q2 CHEMISTRY, MEDICINAL Pub Date : 2024-07-11 DOI: 10.1021/acsinfecdis.4c00315
F Ifthiha Mohideen, Lara K Mahal

Glycans play critical roles in the host-pathogen interactions leading to infection. However, we still understand very little about the dynamic nature of glycosylation in response to infection and its function in modulating host immunity. Many of the host proteins involved in immune defense are glycoproteins. Furthermore, the innate immune system recognizes glycans. The glycoform of a protein can impact proteolytic stability, receptor interactions, serum half-life, and other aspects. New, cutting-edge chemical biology tools are shedding light on the interplay between infection and the host glycome. In this review, we highlight new work on the importance of dynamic glycosylation of host proteins in the innate and adaptive immune pathways in response to infection. These include recent findings on altered glycoprofiles of mucins, complement components, and antibodies.

糖基化在导致感染的宿主-病原体相互作用中起着关键作用。然而,我们对糖基化在应对感染时的动态性质及其在调节宿主免疫力方面的功能仍然知之甚少。许多参与免疫防御的宿主蛋白质都是糖蛋白。此外,先天性免疫系统也能识别糖蛋白。蛋白质的糖型会影响蛋白水解稳定性、受体相互作用、血清半衰期和其他方面。新的尖端化学生物学工具正在揭示感染与宿主糖蛋白之间的相互作用。在这篇综述中,我们将重点介绍有关宿主蛋白质动态糖基化在先天性和适应性免疫途径中应对感染的重要性的新研究成果。其中包括最近关于粘蛋白、补体成分和抗体的糖基化改变的发现。
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引用次数: 0
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ACS Infectious Diseases
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