Multiple Roles for Cytokines in Atopic Dermatitis: From Pathogenic Mediators to Endotype-Specific Biomarkers to Therapeutic Targets

Atopic dermatitis (AD) is one of the most common chronic inflammatory skin diseases, which generally presents with intense itching and recurrent eczematous lesions. AD affects up to 20% of children and 10% of adults in high-income countries. The prevalence and incidence of AD have increased in recent years. The onset of AD mostly occurs in childhood, although in some cases AD may persist in adult life or even manifest in middle age (adult-onset AD). AD pathophysiology is made of a complex net, in which genetic background, skin barrier dysfunction, innate and adaptive immune responses, as well as itch contribute to disease development, progression, and chronicization. One of the most important features of AD is skin dehydration, which is mainly caused by filaggrin mutations that determine trans-epidermal water loss, pH alterations, and antigen penetration. In accordance with the “outside-inside” theory of AD pathogenesis, in a context of an altered epidermal barrier, antigens encounter epidermal antigen presentation cells (APCs), such as epidermal Langerhans cells and inflammatory epidermal dendritic cells, leading to their maturation and Th-2 cell-mediated inflammation. APCs also bear trimeric high-affinity receptors for immunoglobulin E (IgE), which induce IgE-mediated sensitizations as part of pathogenic mechanisms leading to AD. In this review, we discuss the role of cytokines in the pathogenesis of AD, considering patients with various clinical AD phenotypes. Moreover, we describe the cytokine patterns in patients with AD at different phases of the disease evolution, as well as in relation to different phenotypes/endotypes, including age, race, and intrinsic/extrinsic subtypes. We also discuss the outcomes of current biologics for AD, which corroborate the presence of multiple cytokine axes involved in the background of AD. A deep insight into the correlation between cytokine patterns and the related clinical forms of AD is a crucial step towards increasingly personalized, and therefore more efficient therapy.     

纤维素酶用于改善苎麻织物刺痒感的研究

选用烧碱作为退煮剂,而后用纤维素酶处理,以减轻甚至消除苎麻织物的刺痒感.实验选用四种纤维素酶,通过对比,优选出酸性纤维素酶APL,再通过单因素试验及正交试验,通过测试处理后织物的毛效、白度、断裂强力、强降率、失重率和手感等指标,选出改善苎麻织物刺痒感的最优工艺.并结合柔软剂使织物获得最好的手感.     

IL-31: State of the Art for an Inflammation-Oriented Interleukin

Interleukin 31 belongs to the IL-6 superfamily, and it is an itch mediator already studied in several diseases, comprising atopic dermatitis, allergic pathologies, and onco-hematological conditions. This research aims to assess the role of this cytokine in the pathogenesis of these conditions and its potential therapeutic role. The research has been conducted on articles, excluding reviews and meta-analysis, both on animals and humans. The results showed that IL-31 plays a crucial role in the pathogenesis of systemic skin manifestations, prognosis, and itch severity. Traditional therapies target this interleukin indirectly, but monoclonal antibodies (Mab) directed against it have shown efficacy and safety profiles comparable with biological drugs that are already available. Future perspectives could include the development of new antibodies against IL-31 both for humans and animals, thus adding a new approach to the therapy, which often has proven to be prolonged and specific for each patient.     

用可编程逻辑控制器(PLC)实现电力系统备用电源自投装置

在国内变电站自动化系统中，各继电保护单元一般都由各生产厂家自行研制，功能专一，其扩展性不强。当运行方式改变时，往往不能够灵活地适应，而备用电源自投装置在实际运行时，却要求适应系统灵活多变的运行方式。采用PLC技术，则可较好地解决上述问题、由于PLC可靠性和扩展性较好，支持软件也较丰富，因而增加功能较容易，可适用于未来可能扩展或产品来源较多的变电站自动化系统。文章介绍了一种采用C20系列PLC开发的适应于全分布式变电站自动化系统的备用电源自动投入装置的实例。     

Trends in stratum corneum research and the management of dry skin conditions

The structure, composition, formation and function of the stratum corneum have been the subject of intense research over the last few decades. As has become apparent, stratum corneum barrier function is not only dependent on one single component but also on its total architecture. Recent developments in understanding lipid composition have led to a new ceramide nomenclature system, a new proposal for a molecular model of the interactions between ceramides, cholesterol and fatty acids, and the demonstration of the presence of crystalline orthorhombic and gel hexagonal lipid phases in the stratum corneum. Linoleate-containing ceramide one, now known as CER EOS, have been shown to be essential for the formation of the 13 nm long periodicity phase (LPP) observed by electron microscopy and X-ray diffraction studies, whereas long-chain fatty acids are important for the formation of the crystalline lipid phases essential for barrier function. The role of the corneocyte envelope, its constituent proteins and its transglutaminase-mediated maturation processes have been shown to be essential for good skin condition. Several proteases may have a role in corneodesmolysis, particularly serine and cathepsin-like enzymes. Novel filaggrin polymorphisms have been identified that may be involved in the expression of a dry skin phenotype. Disturbances in lipid packing states, reduction in ceramide levels (particularly the phytosphingosine-containing ceramides), reductions in the levels of long-chain fatty acids and loss of the LPP largely account for the perturbations in lipid structure that occur in dry skin. The reduced corneodesmolysis that occurs in this xerotic skin disorder is now well accepted and is caused by reductions in the levels and activities of stratum corneum proteases together with elevated levels of corneodesmosomal glycoproteins in the superficial layers of the stratum corneum. Additionally, increased levels of fragile corneocytes are associated with reduced transglutaminase activity and corneocyte envelope cross-linking events. However, in comparison with the advances in our understanding of the textural changes that occur in dry skin, the somatosensory changes are poorly understood and the itching associated with dry skin is still an under-researched area. The unique biosensor role of the stratum corneum essential for a competent natural moisturizing barrier may also have a role to play in the action of anti-ageing technologies by controlling the expression and secretion of epidermal cytokines and growth factors. Technologies to treat the surface textural skin problems, enhance the differentiation process, particularly lipid biosynthesis, and to control the somatosensory problems in dry skin have received much attention in the last decade. This paper will review the state of the art of stratum corneum biology and the trends in the management of dry skin.     

Emerging Role of Transient Receptor Potential Vanilloid 4 (TRPV4) Ion Channel in Acute and Chronic Itch

Itch is a clinical problem that leaves many sufferers insufficiently treated, with over 20 million cases in the United States. This is due to incomplete understanding of its molecular, cellular, and cell-to-cell signaling mechanisms. Transient receptor potential (TRP) ion channels are involved in several sensory modalities including pain, vision, taste, olfaction, hearing, touch, and thermosensation, as well as itch. Relative to the extensive studies on TRPV1 and TRPA1 ion channels in itch modulation, TRPV4 has received relatively little research attention and its mechanisms have remained poorly understood until recently. TRPV4 is expressed in ganglion sensory neurons and a variety of skin cells. Growing evidence in the past few years strongly suggests that TRPV4 in these cells contributes to acute and chronic disease-associated itch. This review focuses on the current experimental evidence involving TRPV4 in itch under pathophysiological conditions and discusses its possible cellular and molecular mechanisms.     

Pathophysiology and Treatment of Pruritus in Elderly

Pruritus is a relatively common symptom that anyone can experience at any point in their life and is more common in the elderly. Pruritus in elderly can be defined as chronic pruritus in a person over 65 years old. The pathophysiology of pruritus in elderly is still unclear, and the quality of life is reduced. Generally, itch can be clinically classified into six types: Itch caused by systemic diseases, itch caused by skin diseases, neuropathic pruritus, psychogenic pruritus, pruritus with multiple factors, and from unknown causes. Senile pruritus can be defined as a chronic pruritus of unknown origin in elderly people. Various neuronal mediators, signaling mechanisms at neuronal terminals, central and peripheral neurotransmission pathways, and neuronal sensitizations are included in the processes causing itch. A variety of therapies are used and several novel drugs are being developed to relieve itch, including systemic and topical treatments.