• 文章类型: Journal Article
    特应性皮炎(AD)在临床实践中仍然是一个严峻的挑战。2型炎症是儿童和青少年AD患者中最常见的炎症通路。抗炎药,主要是皮质类固醇(CS)和免疫调节剂是抑制2型炎症的主要治疗方法。然而,AD患者可能需要长期高CS剂量或具有可能显著副作用的药物组合以实现和维持疾病控制。在这方面,生物制剂的出现构成了管理这种情况的突破。Dupilumab是一种针对IL-4受体α亚基(IL-4Rα)的单克隆抗体,拮抗IL-4和IL-13,并被批准用于儿科重度AD。这篇综述介绍并讨论了最近发表的关于dupilumab在儿童和青少年AD中的研究。有令人信服的证据表明dupilumab在治疗AD方面是安全有效的。它可以减少皮肤损伤和相关的瘙痒,减少对额外药物的需求,改善疾病控制和生活质量。然而,彻底的诊断途径是强制性的,特别是考虑到不同的AD表型。理想的合格候选人是患有AD的儿童或青少年,由于严重的临床表现和生活质量受损而需要全身治疗。
    Atopic dermatitis (AD) is still a demanding challenge in clinical practice. Type 2 inflammation is the most common inflammatory pathway in children and adolescents with AD. Anti-inflammatory drugs, mainly corticosteroids (CS) and immunomodulant agents are the primary therapeutic approach to dampening type 2 inflammation. However, AD patients may require long-term high CS doses or drug combinations with possibly significant adverse effects to achieve and maintain disease control. In this regard, the advent of biologics constituted a breakthrough in managing this condition. Dupilumab is a monoclonal antibody directed against the IL-4 receptor α-subunit (IL-4Rα), antagonizing both IL-4 and IL-13 and is approved for pediatric severe AD. This review presents and discusses the most recent published studies on dupilumab in children and adolescents with AD. There is convincing evidence that dupilumab is safe and effective in managing AD. It can reduce skin lesions and associated itching, reduce the need for additional medications, and improve disease control and quality of life. However, a thorough diagnostic pathway is mandatory, especially considering the different AD phenotypes. The ideal eligible candidate is a child or adolescent with AD requiring systemic treatment because of severe clinical manifestations and impaired quality of life.
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  • 文章类型: Journal Article
    特应性皮炎(AD)是一种以瘙痒为特征的慢性炎症性皮肤病,表皮屏障功能障碍,和不平衡的炎症反应。AD病理生理学涉及由T辅助细胞-2驱动的失调的免疫应答。许多因素,包括活性氧(ROS),通过引起细胞损伤和导致皮肤屏障功能障碍的炎症参与AD的发病机理。这篇叙述性综述旨在全面概述天然分子和抗氧化剂化合物的作用,强调其在AD预防和管理中的潜在治疗价值。它们包括维生素D,维生素E,吡哆醇,维生素C,类胡萝卜素,还有褪黑激素.一些研究报告了抗氧化剂水平与AD改善之间的统计学显着关联,然而,抗氧化剂补充剂的结果相互矛盾,尤其是维生素D,没有导致AD的改善。因此,这些膳食营养因子治疗AD的临床疗效需要在临床试验中进一步评估.同时,抗氧化剂可以以个性化的方式纳入AD患者的管理,根据疾病的严重程度量身定制,合并症,和个人需求。
    Atopic dermatitis (AD) is a chronic inflammatory skin disease characterized by itching, epidermal barrier dysfunction, and an unbalanced inflammatory reaction. AD pathophysiology involves a dysregulated immune response driven by T helper-2 cells. Many factors, including reactive oxygen species (ROS), are involved in AD pathogenesis by causing cellular damage and inflammation resulting in skin barrier dysfunction. This narrative review aims to provide a comprehensive overview of the role of natural molecules and antioxidant compounds, highlighting their potential therapeutic value in AD prevention and management. They include vitamin D, vitamin E, pyridoxine, Vitamin C, carotenoids, and melatonin. Some studies report a statistically significant association between antioxidant levels and improvement in AD, however, there are conflicting results in which antioxidant supplementation, especially Vitamin D, did not result in improvement in AD. Therefore, the clinical efficacy of these dietary nutritional factors in the treatment of AD needs to be further evaluated in clinical trials. Meanwhile, antioxidants can be incorporated into the management of AD patients in a personalized manner, tailored to the severity of the disease, comorbidities, and individual needs.
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  • 文章类型: Journal Article
    皮肤是身体的重要屏障组织。必须精确控制皮肤中的免疫反应,否则会导致严重的疾病,如牛皮癣,特应性皮炎,或致病性感染。研究证据越来越多地证明了神经支配的重要作用,即,感觉和交感信号,调节皮肤免疫力。值得注意的是,在皮肤病中已经观察到这种神经结构的神经病变,暗示他们直接参与各种病理过程。深入了解皮肤神经病及其免疫调节作用的机制可能有助于揭示治疗干预的新切入点。这里,我们总结了神经性事件和皮肤免疫之间的神经免疫相互作用,强调这一新兴研究前沿的当前知识和未来观点。
    Skin is a vital barrier tissue of the body. Immune responses in the skin must be precisely controlled, which would otherwise cause severe disease conditions such as psoriasis, atopic dermatitis, or pathogenic infection. Research evidence has increasingly demonstrated the essential roles of neural innervations, i.e., sensory and sympathetic signals, in modulating skin immunity. Notably, neuropathic changes of such neural structures have been observed in skin disease conditions, implicating their direct involvement in various pathological processes. An in-depth understanding of the mechanism underlying skin neuropathy and its immunomodulatory effects could help reveal novel entry points for therapeutic interventions. Here, we summarize the neuroimmune interactions between neuropathic events and skin immunity, highlighting the current knowledge and future perspectives of this emerging research frontier.
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  • 文章类型: Journal Article
    长期炎症性皮肤病特应性皮炎的特征是皮肤干燥,瘙痒,和湿疹性病变。在炎症期间,皮肤屏障蛋白受损促进金黄色葡萄球菌在发炎的皮肤中定植,AD患者的临床状况恶化。蛋白质组学分析显示金黄色葡萄球菌细胞外囊泡(EV)中存在几种免疫逃避蛋白和毒力因子,提示这些蛋白质在特应性皮炎的病理生理学中可能发挥作用。这项研究的目的是评估从痤疮梭菌DSM28251(c40)的专利菌株获得的壁片段及其与粘多糖载体(HAc40)的组合在抵消由金黄色葡萄球菌产生的EV的致病潜力中的功效。从对HaCaT角质形成细胞的体外研究获得的结果显示,HAc40和c40处理显著改变金黄色葡萄球菌EV的大小和致病性。具体来说,电动汽车越来越大,潜在地降低它们与靶细胞相互作用的能力并降低细胞毒性。此外,HAc40和C40治疗降低了电动汽车暴露后紧密连接mRNA的过度表达,表明对表皮屏障的功能有保护作用。这些发现证明了Hac40和c40如何减轻金黄色葡萄球菌的有害影响。需要进一步的研究来阐明这种相互作用的确切机制,并探索c40及其粘多糖载体缀合物HAc40在治疗特应性皮炎中的潜在临床效用。
    Long-term inflammatory skin disease atopic dermatitis is characterized by dry skin, itching, and eczematous lesions. During inflammation skin barrier protein impairment promotes S. aureus colonisation in the inflamed skin, worsening AD patient\'s clinical condition. Proteomic analysis revealed the presence of several immune evasion proteins and virulence factors in S. aureus extracellular vesicles (EVs), suggesting a possible role for these proteins in the pathophysiology of atopic dermatitis. The objective of this study is to assess the efficacy of a wall fragment obtained from a patented strain of C. acnes DSM28251 (c40) and its combination with a mucopolysaccharide carrier (HAc40) in counteract the pathogenic potential of EVs produced by S. aureus ATCC 14458. Results obtained from in vitro studies on HaCaT keratinocyte cells showed that HAc40 and c40 treatment significantly altered the size and pathogenicity of S. aureus EVs. Specifically, EVs grew larger, potentially reducing their ability to interact with the target cells and decreasing cytotoxicity. Additionally, the overexpression of the tight junctions mRNA zona occludens 1 (ZO1) and claudin 1 (CLDN1) following EVs exposure was decreased by HAc40 and c40 treatment, indicating a protective effect on the epidermal barrier\'s function. These findings demonstrate how Hac40 and c40 may mitigate the harmful effects of S. aureus EVs. Further investigation is needed to elucidate the exact mechanisms underlying this interaction and explore the potential clinical utility of c40 and its mucopolysaccharide carrier conjugate HAc40 in managing atopic dermatitis.
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  • 文章类型: Journal Article
    鉴于过敏性疾病的发生率持续上升,膳食模式的改变被认为是导致这些疾病出现和进展的一个可能因素.目前,人们非常关注利用具有抗过敏特性的天然化合物的饮食疗法的开发。膳食多酚和植物代谢物由于其有据可查的抗炎作用而得到了深入研究,抗氧化剂,和免疫调节特征,使它们成为最突出的天然生物活性化学物质之一。这项研究旨在讨论这些分子可能发挥抗过敏作用的深入机制,即通过它们减少蛋白质过敏性的能力,调节免疫反应,并改变肠道微生物群的组成。然而,需要进一步调查才能充分了解这些影响。本文研究了来自实验和临床研究的现有证据,这些证据支持以下观点:不同的多酚,比如儿茶素,白藜芦醇,姜黄素,槲皮素,和其他人,可以减少过敏性炎症,缓解食物过敏的症状,哮喘,特应性皮炎,和过敏性鼻炎,并防止过敏性免疫反应的进展。总之,膳食多酚和植物代谢物具有显著的抗过敏特性,可用于开发针对过敏性疾病的预防和治疗策略。本文还讨论了多酚研究和广泛使用的制约因素,以及未来研究的潜在途径。
    Given the ongoing rise in the occurrence of allergic disorders, alterations in dietary patterns have been proposed as a possible factor contributing to the emergence and progression of these conditions. Currently, there is a significant focus on the development of dietary therapies that utilize natural compounds possessing anti-allergy properties. Dietary polyphenols and plant metabolites have been intensively researched due to their well-documented anti-inflammatory, antioxidant, and immunomodulatory characteristics, making them one of the most prominent natural bioactive chemicals. This study seeks to discuss the in-depth mechanisms by which these molecules may exert anti-allergic effects, namely through their capacity to diminish the allergenicity of proteins, modulate immune responses, and modify the composition of the gut microbiota. However, further investigation is required to fully understand these effects. This paper examines the existing evidence from experimental and clinical studies that supports the idea that different polyphenols, such as catechins, resveratrol, curcumin, quercetin, and others, can reduce allergic inflammation, relieve symptoms of food allergy, asthma, atopic dermatitis, and allergic rhinitis, and prevent the progression of the allergic immune response. In summary, dietary polyphenols and plant metabolites possess significant anti-allergic properties and can be utilized for developing both preventative and therapeutic strategies for targeting allergic conditions. The paper also discusses the constraints in investigating and broad usage of polyphenols, as well as potential avenues for future research.
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  • 文章类型: Journal Article
    过敏性皮炎是一种皮肤疾病,在全球范围内患病率越来越高,与高脂肪和高糖饮食有关。经常食用含蔗糖的饮料可能会增加一些健康问题的风险,包括过敏性疾病,尤其是哮喘,但蔗糖消耗与过敏性皮炎之间的关联研究不足。我们研究了蔗糖溶液摄入对大鼠过敏性接触性皮炎的影响,发现摄入14天后2,4-二硝基氟苯(DNFB)引起的疾病症状和肠道菌群组成的早期恶化。通过肠道微生物群发酵产生的短链脂肪酸的水平在盲肠内容物和粪便中没有受到影响,但在血液中却有所下降;这种作用对于乙酸盐尤其明显。为了恢复血液中的醋酸盐浓度,将三乙酸甘油酯与10%蔗糖溶液混合并喂入大鼠模型。该策略防止了DNFB诱导的症状的早期恶化。肠腔中短链脂肪酸吸收的减少与小肠中短链脂肪酸转运蛋白表达的减少无关;相反,该机制涉及由于钠-葡萄糖转运蛋白1(SGLT1)表达增加导致肠腔中钠浓度降低.
    Allergic dermatitis is a skin disease with growing prevalence worldwide that has been associated with diets high in fats and sugars. Regular consumption of sucrose-containing beverages may increase the risk for several health problems, including allergic diseases and particularly asthma, but the association between sucrose consumption and allergic dermatitis is understudied. We investigated the effects of sucrose solution intake on allergic contact dermatitis in rats and found early exacerbation of 2,4-dinitrofluorobenzene (DNFB)-induced disease symptoms and altered composition of the gut microbiota after 14 d of intake. The levels of short-chain fatty acids-produced by fermentation by the intestinal microbiota-were not affected in the cecal contents and feces but decreased in the blood; this effect was especially notable for acetate. To restore blood acetate concentrations, triacetin was mixed with a 10% sucrose solution and fed to the rat model. This strategy prevented the early exacerbation of DNFB-induced symptoms. The decreased absorption of short-chain fatty acids from the intestinal lumen was not linked to the decreased expression of short-chain fatty acid transporters in the small intestine; instead, the mechanism involves a reduction in the sodium concentration in the intestinal lumen due to increased expression of sodium-glucose transporter 1 (SGLT1).
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  • 文章类型: Journal Article
    大麻含有许多天然成分,具有抗癌等多种作用,抗炎和抗氧化剂。Cheungsam是多种非药物型大麻,在韩国开发,用于纤维(茎)和油(种子)。Cheungsam对皮肤的功效尚不清楚,尽管以前有关于昌沙籽油的研究,没有关于Cheungsam种子壳的研究。在这项研究中,我们通过评估炎症介质的基因和蛋白质表达水平,研究了Cheungsam籽壳乙醇提取物(CSSH)缓解皮肤炎症的潜力。结果表明,CSSH降低了促炎细胞因子(IL-1β,TNF-α/IFN-γ诱导的HaCaT细胞中的IL-6,IL-8,MCP-1和CXCL10)和特应性皮炎相关细胞因子(IL-4,CCL17,MDC和RANTES)。此外,ERK,JNK和p38磷酸化降低,p-p65,p-IκBα,CSSH处理后,NLRP3、caspase-1、p-JAK1和p-STAT6被抑制。CSSH显着增加了皮肤屏障因子聚丝团蛋白和总蛋白的水平。以上结果提示,川崎籽壳乙醇提取物具有调节皮肤炎症机制的作用,可作为一种治疗皮肤炎症疾病的新方法。
    Cannabis contains numerous natural components and has several effects such as anticancer, anti-inflammatory and antioxidant. Cheungsam is a variety of non-drug-type hemp, developed in Korea and is used for fiber (stem) and oil (seed). The efficacy of Cheungsam on skin is not yet known, and although there are previous studies on Cheungsam seed oil, there are no studies on Cheungsam seed husk. In this study, we investigated the potential of Cheungsam seed husk ethanol extract (CSSH) to alleviate skin inflammation through evaluating the gene and protein expression levels of inflammatory mediators. The results showed that CSSH reduced pro-inflammatory cytokines (IL-1β, IL-6, IL-8, MCP-1 and CXCL10) and atopic dermatitis-related cytokines (IL-4, CCL17, MDC and RANTES) in TNF-α/IFN-γ-induced HaCaT cells. Furthermore, ERK, JNK and p38 phosphorylation were decreased and p-p65, p-IκBα, NLRP3, caspase-1, p-JAK1 and p-STAT6 were suppressed after CSSH treatment. CSSH significantly increased the level of the skin barrier factors filaggrin and involucrin. These results suggest that Cheungsam seed husk ethanol extract regulates the mechanism of skin inflammation and can be used as a new treatment for skin inflammatory diseases.
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  • 文章类型: Journal Article
    在狗和猫食物中包含β-葡聚糖对这些动物的健康具有许多有益作用。在这方面,我们正在努力阐明这种营养食品在慢性病患者中的潜力。由于缺乏对该主题的审查,这篇综述文章旨在汇编和讨论迄今为止发现的证据。特应性皮炎,炎症性肠病,和骨关节炎是在狗和猫中具有显著临床相关性的疾病。总的来说,这些慢性病的病理生理学与免疫介导和炎症机制有关.因此,本综述强调了β-葡聚糖的免疫调节和抗炎作用.现有信息似乎表明,β-葡聚糖对狗过敏过程影响的研究表明特应性皮炎病例的临床症状减少。此外,虽然β-葡聚糖显示出作为安全补充剂的希望,特别是骨关节炎,进一步的临床试验势在必行,尤其是在不受控制的环境中。β-葡聚糖作为一种潜在的营养药物出现,为炎症性肠病患者提供免疫益处,尽管需要广泛的研究来确定其最佳起源,分子量,剂量,以及在患有这种疾病的动物中的特定应用。
    The inclusion of beta-glucans in dog and cat food is associated with numerous beneficial effects on the health of these animals. In this regard, there is an effort to elucidate the potential of this nutraceutical in chronic patients. Since there is a lack of a review on the topic, this review article aims to compile and discuss the evidence found to date. Atopic dermatitis, inflammatory bowel disease, and osteoarthritis are diseases of significant clinical relevance in dogs and cats. In general, the pathophysiology of these chronic conditions is related to immune-mediated and inflammatory mechanisms. Therefore, the immunomodulation and anti-inflammatory effects of beta-glucans are highlighted throughout this review. The available information seems to indicate that the studies on beta-glucans\' impact on allergic processes in dogs indicate a reduction in clinical signs in atopic dermatitis cases. Additionally, while beta-glucans show promise as a safe supplement, particularly for osteoarthritis, further clinical trials are imperative, especially in uncontrolled environments. Beta-glucans emerge as a potential nutraceutical offering immune benefits for inflammatory bowel disease patients, although extensive research is required to define its optimal origin, molecular weight, dosage, and specific applications across animals suffering from this disease.
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  • 文章类型: Journal Article
    背景和目的:本研究证明了克罗地亚版本的TOPICOP(局部皮质类固醇恐惧症)问卷的因素结构和可靠性,从而有助于进一步验证和标准化皮肤科患者或其父母的局部皮质恐惧症的测量,直接影响患者或父母的依从性,以及最终的治疗效果。材料和方法:横截面,观察性研究是在斯普利特大学医院中心进行的,皮肤科。这项研究邀请了120名参与者(年龄在12-68岁之间)参加了斯普利特大学医院中心的Atopy学校,在大学医院中心皮肤科门诊检查并诊断为特应性皮炎(AD)或过敏性接触性皮炎(ACD)的患者,以及12岁以下患者的父母或法定代表人。TOPICOP问卷由12个项目组成,评估了局部皮质恐惧症的三个不同组成部分(担忧,信仰,和行为)。受访者在填写四点李克特量表后的10分钟内评估了他们对每个陈述正确性的看法。结果:有效率为94%,产生了113名受访者(109名成人和4名儿童)的样本。因子分析得出了一个可靠性相对较高的共同因素(Cronbachα=0.85,95%CI0.81至0.89)。男性和女性参与者的问卷得分没有差异,在皮肤科患者的父母/法定代表和其他患者之间也是如此。结论:本研究有助于进一步开发合适的测量仪器,其实际应用,因此,更好的识别,决议,和预防局部皮质恐惧症,作为更好的整体医疗保健和治疗慢性皮肤病患者的一部分。
    Background and Objectives: This study demonstrates the factor structure and reliability of the Croatian version of the TOPICOP (Topical Corticosteroid Phobia) questionnaire, thereby contributing to further validation and standardization of the measurement of topical corticophobia with dermatological patients or their parents, which directly affects patient or parent compliance, as well as the final therapeutic effect. Materials and Methods: The cross-sectional, observational study was conducted at the University Hospital Centre Split, Department of Dermatovenerology. The research involved inviting 120 participants (age 12-68) who attended the University Hospital Centre Split\'s Atopy School, patients examined in the Dermatology Outpatient Clinic of the University Hospital Centre Split and diagnosed with atopic dermatitis (AD) or allergic contact dermatitis (ACD), and parents or legal representatives of patients younger than 12 years old. The TOPICOP questionnaire consists of 12 items assessing the three different components of topical corticophobia (worries, beliefs, and behaviour). Respondents evaluated their perception of the correctness of each statement within 10 min of filling out the questionnaire on a four-point Likert scale. Results: The response rate was 94%, resulting in a sample of 113 respondents (109 adults and 4 children). Factor analysis yielded one common factor of relatively high reliability (Cronbach α = 0.85, 95% CI 0.81 to 0.89). No differences were found in questionnaire scores between male and female participants, nor between the parents/legal representatives of dermatological patients and other patients. Conclusions: This research contributes to further development of the appropriate measuring instrument, its practical application, and thus, the better recognition, resolution, and prevention of topical corticophobia as part of the better overall healthcare and treatment of chronic dermatological patients.
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  • 文章类型: Journal Article
    PAPLAL,铂(nPt)和钯(nPd)纳米颗粒的混合物,由于其强大的抗氧化活性而被广泛用作外用剂。过敏性接触性皮炎(ACD)是世界范围内最常见的职业性皮肤病之一。然而,氧化应激在ACD中的作用尚不清楚.在本研究中,我们研究了局部PAPLAL治疗对2,4-二硝基氟苯(DNFB)诱导的ACD的保护作用。DNFB处理增加了8-异前列腺素含量;上调Xdh,Nox2和Nox4,促氧化剂基因;和下调的Sod1,抗氧化剂基因,表明耳朵皮肤的氧化损伤。PAPLAL治疗显著降低与炎症细胞因子相关基因下调相关的耳厚度。PAPLAL还显着增加了应激反应相关基因Ahr和Nrf2及其靶基因的表达,但未能改变氧化还原相关基因的表达。此外,Sod1损失使耳朵中的ACD病理恶化。这些结果强烈表明PAPLAL通过其抗氧化活性和AHR和NRF2轴的活化来保护ACD。抗氧化剂PAPLAL可用作靶向氧化应激的ACD的新型局部疗法。
    PAPLAL, a mixture of platinum (nPt) and palladium (nPd) nanoparticles, is widely used as a topical agent because of its strong antioxidant activity. Allergic contact dermatitis (ACD) is one of the most common occupational skin diseases worldwide. However, the role of oxidative stress in ACD remains unclear. In the present study, we investigated the protective effects of topical PAPLAL treatment on 2,4-dinitrofluorobenzene (DNFB)-induced ACD. DNFB treatment increased 8-isoprostane content; upregulated Xdh, Nox2, and Nox4, pro-oxidant genes; and downregulated Sod1, an antioxidant gene, indicating oxidative damage in the ear skin. PAPLAL therapy significantly reduced ear thickness associated with the downregulation of inflammatory cytokine-related genes. PAPLAL also significantly increased the expression of the stress-response-related genes Ahr and Nrf2, as well as their target genes, but failed to alter the expression of redox-related genes. Furthermore, Sod1 loss worsened ACD pathologies in the ear. These results strongly suggest that PAPLAL protects against ACD through its antioxidant activity and activation of the AHR and NRF2 axes. The antioxidant PAPLAL can be used as a novel topical therapy for ACD that targets oxidative stress.
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