Generation of a quenched phosphonate activity-based probe for labelling the active KLK7 protease

Author(s):  
Evangelos Bisyris ◽  
Eleni Zingkou ◽  
Golfo G Kordopati ◽  
Minos-Timotheos Matsoukas ◽  
Plato A. Magriotis ◽  
...  

Kallikrein 7 (KLK7) is a chymotrypsin-like serine protease with established roles in skin diseases like the rare Netherton syndrome and common atopic dermatitis. Here, a mixed alkyl aryl phosphonate quenched...

2010 ◽  
Vol 2010 ◽  
pp. 1-9 ◽  
Author(s):  
Saveria Pastore ◽  
Liudmila Korkina

The skin is permanently exposed to physical, chemical, and biological aggression by the environment. In addition, acute and chronic inflammatory events taking place in the skin are accompanied by abnormal release of pro-oxidative mediators. In this paper, we will briefly overview the homeostatic systems active in the skin to maintain the redox balance and also to counteract abnormal oxidative stress. We will concentrate on the evidence that a local and/or systemic redox dysregulation accompanies the chronic inflammatory disorder events associated to psoriasis, contact dermatitis, and atopic dermatitis. We will also discuss the fact that several well-established treatments for the therapy of chronic inflammatory skin disorders are based on the application of strong physical or chemical oxidants onto the skin, indicating that, in selected conditions, a further increase of the oxidative imbalance may lead to a beneficial outcome.


Molecules ◽  
2021 ◽  
Vol 26 (15) ◽  
pp. 4409
Author(s):  
Jinjoo Kang ◽  
Soyoung Lee ◽  
Namkyung Kim ◽  
Hima Dhakal ◽  
Taeg-Kyu Kwon ◽  
...  

The extracts of Schisandra chinensis (Turcz.) Baill. (Schisandraceae) have various therapeutic effects, including inflammation and allergy. In this study, gomisin M2 (GM2) was isolated from S. chinensis and its beneficial effects were assessed against atopic dermatitis (AD). We evaluated the therapeutic effects of GM2 on 2,4-dinitrochlorobenzene (DNCB) and Dermatophagoides farinae extract (DFE)-induced AD-like skin lesions with BALB/c mice ears and within the tumor necrosis factor (TNF)-α and interferon (IFN)-γ-stimulated keratinocytes. The oral administration of GM2 resulted in reduced epidermal and dermal thickness, infiltration of tissue eosinophils, mast cells, and helper T cells in AD-like lesions. GM2 suppressed the expression of IL-1β, IL-4, IL-5, IL-6, IL-12a, and TSLP in ear tissue and the expression of IFN-γ, IL-4, and IL-17A in auricular lymph nodes. GM2 also inhibited STAT1 and NF-κB phosphorylation in DNCB/DFE-induced AD-like lesions. The oral administration of GM2 reduced levels of IgE (DFE-specific and total) and IgG2a in the mice sera, as well as protein levels of IL-4, IL-6, and TSLP in ear tissues. In TNF-α/IFN-γ-stimulated keratinocytes, GM2 significantly inhibited IL-1β, IL-6, CXCL8, and CCL22 through the suppression of STAT1 phosphorylation and the nuclear translocation of NF-κB. Taken together, these results indicate that GM2 is a biologically active compound that exhibits inhibitory effects on skin inflammation and suggests that GM2 might serve as a remedy in inflammatory skin diseases, specifically on AD.


2021 ◽  
Vol 22 (4) ◽  
pp. 1553
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Jungmin Jeon ◽  
Yun Hoo Park ◽  
Tae-Cheol Kim ◽  
...  

The SWItch (SWI)3-related gene (SRG3) product, a SWI/Sucrose Non-Fermenting (SNF) chromatin remodeling subunit, plays a critical role in regulating immune responses. We have previously shown that ubiquitous SRG3 overexpression attenuates the progression of Th1/Th17-mediated experimental autoimmune encephalomyelitis. However, it is unclear whether SRG3 overexpression can affect the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD), a Th2-type immune disorder. Thus, to elucidate the effects of SRG3 overexpression in AD development, we bred NC/Nga (NC) mice with transgenic mice where SRG3 expression is driven by the β-actin promoter (SRG3β-actin mice). We found that SRG3β-actin NC mice exhibit increased AD development (e.g., a higher clinical score, immunoglobulin E (IgE) hyperproduction, and an increased number of infiltrated mast cells and basophils in skin lesions) compared with wild-type NC mice. Moreover, the severity of AD pathogenesis in SRG3β-actin NC mice correlated with expansion of interleukin 4 (IL4)-producing basophils and mast cells, and M2 macrophages. Furthermore, this accelerated AD development is strongly associated with Treg cell suppression. Collectively, our results have identified that modulation of SRG3 function can be applied as one of the options to control AD pathogenesis.


Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1392
Author(s):  
Hidaya A. Kader ◽  
Muhammad Azeem ◽  
Suhib A. Jwayed ◽  
Aaesha Al-Shehhi ◽  
Attia Tabassum ◽  
...  

Atopic dermatitis (AD) is one of the most prevalent inflammatory disease among non-fatal skin diseases, affecting up to one fifth of the population in developed countries. AD is characterized by recurrent pruritic and localized eczema with seasonal fluctuations. AD initializes the phenomenon of atopic march, during which infant AD patients are predisposed to progressive secondary allergies such as allergic rhinitis, asthma, and food allergies. The pathophysiology of AD is complex; onset of the disease is caused by several factors, including strong genetic predisposition, disrupted epidermal barrier, and immune dysregulation. AD was initially characterized by defects in the innate immune system and a vigorous skewed adaptive Th2 response to environmental agents; there are compelling evidences that the disorder involves multiple immune pathways. Symptomatic palliative treatment is the only strategy to manage the disease and restore skin integrity. Researchers are trying to more precisely define the contribution of different AD genotypes and elucidate the role of various immune axes. In this review, we have summarized the current knowledge about the roles of innate and adaptive immune responsive cells in AD. In addition, current and novel treatment strategies for the management of AD are comprehensively described, including some ongoing clinical trials and promising therapeutic agents. This information will provide an asset towards identifying personalized targets for better therapeutic outcomes.


Author(s):  
Н.О. Артемьева ◽  
Е.В. Свечникова ◽  
Ю.В. Максимова ◽  
В.Н. Максимов

Атопический дерматит (АД) - это воспалительное заболевание кожи, мультифакториальной или моногенный природы, характеризующееся зудом, хроническим рецидивирующим течением и возрастными особенностями локализации и морфологии очагов поражения. Доля заболевания в структуре кожных болезней в настоящее время составляет от 10 до 30%. Когда процесс приобретает упорное течение с невыраженным эффектом от проводимой терапии и обострениями процесса до 3-4 в год с увеличением их длительности, то становится вялотекущим (торпидным). Торпидное течение АД приводит больного к снижению качества жизни за счёт физического дискомфорта и эмоциональной дезадаптации. Подходы к лечению в теории зависят от механизма развития заболевания. Atopic dermatitis (AD) is an inherited inflammatory disease of skin, multifactor or monogenic nature, characterized by itching, chronic recurrent current and age-specific features of localisation and morphology of lesion centers. The proportion of the disease in the structure of skin diseases is currently between 10 and 30%. When the process acquires a persistent course with an unparalleled effect from the performed therapy and exacerbations of the process up to 3-4 per year with increase of their duration, it becomes sluggish (torpedo) [1, 3]. The torpedo course of AD leads the patient to a decrease in the quality of life due to physical discomfort and emotional disadaptation. Approaches to treatment in theory depend on the mechanism of disease development.


2021 ◽  
Vol 8 ◽  
Author(s):  
Franz J. Legat

Atopic dermatitis (AD) is among the most frequent inflammatory skin diseases in humans, affecting up to 20% of children and 10% of adults in higher income countries. Chronic pruritus is a disease-defining symptom of AD, representing the most burdensome symptom for patients. Severe chronic pruritus causes significant sleep disturbances and impaired quality of life, as well as increased anxiety, depression and suicidal behavior. Until recently, skin care, topical corticosteroids, and calcineurin-inhibitors were primarily used to treat mild to moderate AD, while phototherapy and immunosuppressive agents such as corticosteroids, cyclosporine, and methotrexate were used to treat patients with moderate to severe AD. The potential short- and long-term adverse events associated with these treatments or their insufficient therapeutic efficacy limited their use in controlling pruritus and eczema in AD patients over longer periods of time. As our understanding of AD pathophysiology has improved and new systemic and topical treatments have appeared on the market, targeting specific cytokines, receptors, or their intracellular signaling, a new era in atopic dermatitis and pruritus therapy has begun. This review highlights new developments in AD treatment, placing a specific focus on their anti-pruritic effects.


2020 ◽  
pp. 29-32
Author(s):  
L.D. Kaliuzhna ◽  

The article presents modern information on the clinical use and safety of the first-generation H1-antihistamine – dimetindene maleate. Pruritus (itch) mediators act both peripherally (histamine, proteases) and centrally (opioids) and has several mechanisms. Pruritus is the dominant symptom of skin diseases; almost all inflamamatory skin diseases can have associated pruritus. Doctors have focused on the almost one dermatosis with signs of itching – atopic dermatitis. At the same time, the range of diseases, both dermatological and systemic, accompanied by itching, is much wider.


2021 ◽  
Vol 9 (7) ◽  
pp. 1452-1456
Author(s):  
Manish Choudhari ◽  
Nikita Jamadari ◽  
Naresh Jain

Objective - To increase awareness of the psychosocial impact of Kushtha, Visarpa, Mukhadushika, Sheetpitta, Udarda and Kotha in Ayurveda and Acne vulgaris, Urticaria, Various types of fungal infections, Atopic dermatitis, Psoriasis etc. in modern point of view. Quality Of Evidence - A literature review was based on a MEDLINE search (1966 to 2000). Selected articles from the dermatologic and psychiatric literature, as well as other relevant medical journals, were reviewed and used as the basis for discussion of how skin disease affects patients’ lives and of appropriate management. Message - Dermatologic problems hurt patients’ quality of life. skin disease can produce stress, anxiety, anger, depression, low self-esteem, embarrassment, and other psychological, personal, professional and social life problems that affect patients’ lives in ways comparable to arthritis or other disabling illnesses, as well as showing a bidirectional relationship between skin disease and psychological distress. This review focuses on the effects of five common skin diseases seen by family physicians- Acne, Urticaria, Various types of fungal infections, Atopic dermatitis and Psoriasis. Conclusion - How skin disease affects psychosocial well-being is un- derappreciated. Increased understanding of the psychiatric comorbidity associated with skin disease and a biopsy- chosocial approach to management will ultimately improve patients’ lives. Keywords: Skin disease, Psychosocial Impact, Quality of life.


2021 ◽  
Vol 22 (19) ◽  
pp. 10661
Author(s):  
Pamela Gallegos-Alcalá ◽  
Mariela Jiménez ◽  
Daniel Cervantes-García ◽  
Eva Salinas

The keratinocyte (KC) is the main functional and structural component of the epidermis, the most external layer of the skin that is highly specialized in defense against external agents, prevention of leakage of body fluids and retention of internal water within the cells. Altered epidermal barrier and aberrant KC differentiation are involved in the pathophysiology of several skin diseases, such as atopic dermatitis (AD). AD is a chronic inflammatory disease characterized by cutaneous and systemic immune dysregulation and skin microbiota dysbiosis. Nevertheless, the pathological mechanisms of this complex disease remain largely unknown. In this review, we summarize current knowledge about the participation of the KC in different aspects of the AD. We provide an overview of the genetic predisposing and environmental factors, inflammatory molecules and signaling pathways of the KC that participate in the physiopathology of the AD. We also analyze the link among the KC, the microbiota and the inflammatory response underlying acute and chronic skin AD lesions.


Dermatology ◽  
2020 ◽  
Vol 236 (4) ◽  
pp. 324-328 ◽  
Author(s):  
Lynda Grine ◽  
Giulia Tochtermann ◽  
Hilde Lapeere ◽  
Nele Maes ◽  
Günther F.L. Hofbauer ◽  
...  

Background: Psoriasis and atopic dermatitis are chronic skin diseases that greatly affect the quality of life. Both diseases can be triggered or exacerbated by stress. Objective: We aimed to differentiate personality traits between patients with chronic skin conditions and people treated for stress in a pilot study. Methods: Patients participating voluntarily in educational programs in Belgium and Switzerland were recruited to complete personality trait questionnaires, including the Temperament and Character Inventory (TCI) and the Tridimensional Personality Questionnaire (TPQ). A comparison was made with patients treated for work-related stress. Results: A total of 48 and 91 patients suffering from skin diseases and work-related stress, respectively, were included in the study. Based on the questionnaires, we found that dermatology patients were less persistent and impulsive than those with work-related stress. Dermatology patients also exhibited more rigidness and less focus on performance. Finally, patients with work-related stress seem more likely to change in response to health-promoting programs than patients with chronic dermatoses. Conclusion: Patients with chronic skin diseases may perceive and cope with stress differently in comparison to patients with work-related stress due to inherent personality traits. Therefore, stress coping mechanisms may differ among different diseases. More research is needed into the design of educational interventions and the impact of personality traits in disease-specific groups.


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