scholarly journals Current Insights into Immunology and Novel Therapeutics of Atopic Dermatitis

Cells ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1392
Author(s):  
Hidaya A. Kader ◽  
Muhammad Azeem ◽  
Suhib A. Jwayed ◽  
Aaesha Al-Shehhi ◽  
Attia Tabassum ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Developed Countries ◽  
Food Allergies ◽  
Th2 Response ◽  
Therapeutic Outcomes ◽  
Environmental Agents ◽  
Novel Treatment Strategies

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.

scholarly journals The Keratinocyte as a Crucial Cell in the Predisposition, Onset, Progression, Therapy and Study of the Atopic Dermatitis

2021 ◽  
Vol 22 (19) ◽  
pp. 10661
Author(s):  
Pamela Gallegos-Alcalá ◽  
Mariela Jiménez ◽  
Daniel Cervantes-García ◽  
Eva Salinas
Keyword(s):  
Atopic Dermatitis ◽  
Complex Disease ◽  
Skin Diseases ◽  
Current Knowledge ◽  
Immune Dysregulation ◽  
Chronic Inflammatory Disease ◽  
Skin Microbiota ◽  
External Agents ◽  
Chronic Skin ◽  
Inflammatory Molecules

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.

Missing links — epigenetic regulators of the pancreatic cancer–associated inflammation

2021 ◽  
Vol 135 (10) ◽  
pp. 1289-1293
Author(s):  
Gregor Werba ◽  
Tamas A. Gonda
Keyword(s):  
Pancreatic Cancer ◽  
Noncoding Rna ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Therapeutic Interventions ◽  
Ductal Adenocarcinoma ◽  
Gastrointestinal Cancers ◽  
Novel Treatment ◽  
Epigenetic Regulator ◽  
Novel Treatment Strategies

Abstract Pancreatic ductal adenocarcinoma (PDAC) features a hostile tumor microenvironment (TME) that renders it remarkably resistant to most therapeutic interventions. Consequently, survival remains among the poorest compared with other gastrointestinal cancers. Concerted efforts are underway to decipher the complex PDAC TME, break down barriers to efficacious therapies and identify novel treatment strategies. In the recent Clinical Science, Li and colleagues identify the long noncoding RNA KLHDC7B-DT as a crucial epigenetic regulator of IL-6 transcription in PDAC and illustrate its potent influences on the pancreatic TME. In this commentary, we introduce epigenetics in pancreatic cancer and put the findings by Li et al. in context with current knowledge.

scholarly journals PI3K/AKT/mTOR Signaling Regulates the Virus/Host Cell Crosstalk in HPV-Positive Cervical Cancer Cells

2019 ◽  
Vol 20 (9) ◽  
pp. 2188 ◽  
Author(s):  
Felicitas Bossler ◽  
Karin Hoppe-Seyler ◽  
Felix Hoppe-Seyler
Keyword(s):  
Host Cell ◽  
Cancer Cells ◽  
Cell Transformation ◽  
Current Knowledge ◽  
Treatment Strategies ◽  
Mtor Signaling ◽  
Mtorc1 Signaling ◽  
Cervical Cancer Cells ◽  
Novel Treatment Strategies ◽  
Cell Crosstalk

Human papillomavirus (HPV)-induced cancers will remain a significant clinical challenge for decades. Thus, the development of novel treatment strategies is urgently required, which should benefit from improving our understanding of the mechanisms of HPV-induced cell transformation. This should also include analyses of hypoxic tumor cells, which represent a major problem for cancer therapy. Recent evidence indicates that the PI3K/AKT/mTOR network plays a key role for the virus/host cell crosstalk in both normoxic and hypoxic HPV-positive cancer cells. In normoxic cells, the efficacy of the senescence induction upon experimental E6/E7 repression depends on active mTORC1 signaling. Under hypoxia, however, HPV-positive cancer cells can evade senescence due to hypoxic impairment of mTORC1 signaling, albeit the cells strongly downregulate E6/E7. Hypoxic repression of E6/E7 is mediated by the AKT kinase, which is activated under hypoxia by its canonical upstream regulators mTORC2 and PI3K. This review highlights our current knowledge about the oxygen-dependent crosstalk of the PI3K/AKT/mTOR signaling circuit with the HPV oncogenes and the phenotypic state of the host cell. Moreover, since the PI3K/AKT/mTOR pathway is considered to be a promising target for anticancer therapy, we discuss clinical implications for the treatment of HPV-positive cervical and head and neck squamous cell carcinomas.

scholarly journals Clinical manifestations of atopy in children up to two years of age

2011 ◽  
Vol 68 (8) ◽  
pp. 690-695 ◽  
Author(s):  
Nevenka Ilic ◽  
Vesna Velickovic ◽  
Dragoljub Djokic ◽  
Nebojsa Rankovic ◽  
Gordana Kostic ◽  
...  
Keyword(s):  
Allergic Rhinitis ◽  
Atopic Dermatitis ◽  
Clinical Manifestations ◽  
Allergic Diseases ◽  
Developed Countries ◽  
Specific Ige ◽  
Food Allergies ◽  
Atopic Diseases ◽  
Ige Antibodies ◽  
Total Ige

Background/Aim. Atopic diseases such as atopic dermatitis, allergic rhinitis and asthma have had increased prevalence during the past decade and nowadays occur in every third child in developed countries. The aim of the study was to determine frequency and type of atopic diseases at the age of two, as well as the importance the total IgE antibodies concentrations have in diagnosis and prognosis of the disease. Methods. The study involved 175 children up to two years of age. Allergy-like symptoms were found after surveying their parents and pediatric medical records. Using the fluorescence immunossay (FIA) method, total IgE antibodies concentrations and specific IgE antibodies (Phadiatop infant) were determined on an Immunocap 100 Dyagnostic System. Results. One or more allergy-like symptoms accounted for 57.7% of findings in children under the age of two, whilst in 19.4% the existence of IgE-related allergic diseases was found. Atopic diseases usually have clinical manifestations of atopic dermatitis (11.4%), IgE-bound wheezing/asthma (10.8%) and food allergies (7.4%), and to much lesser extent those of allergic rhinitis (3.4%) and urticaria (1.7%). The significantly higher total IgE antibodies concentrations were found in children with allergy-like symptoms (p < 0.0005) (cut-off 15.15 kU/L, sensitivity 76.5% specificity 71.6%). Conclusion. Almost 20% of two-year-old children have any of clinically manifested allergic diseases, with atopic dermatitis and IgE wheeze/asthma being predominant. The higher total IgE antibodies concentration is a good marker for sensitization in children with allergy-like symptoms.

scholarly journals The main aspects of the immunopathogenesis of atopic dermatitis in children

2021 ◽  
pp. 27-34
Author(s):  
Olga Olegovna Pobezhimova ◽  
Alexander Viktorovich Zhestkov
Keyword(s):  
Atopic Dermatitis ◽  
Rural Areas ◽  
Skin Diseases ◽  
Secondary Infection ◽  
Allergic Diseases ◽  
Developed Countries ◽  
Severe Form ◽  
Pathological Process ◽  
The Body ◽  
Social Adaptation

Research objective Atopic dermatitis (AtD) is the earliest and most frequent manifestation of the body’s hypersensitivity reaction to environmental allergens. Often manifested in severe form, affecting the skin, can occur in early infancy, childhood. The disease is genetically determined and is chronic. AtD is one of the most common skin diseases (from 20 to 40% in the structure of skin diseases), which occurs in all countries in people of both sexes. In recent years, there has been an increase in the incidence of AtD throughout the world. The disease is more common in highly developed countries and cities (less commonly in rural areas). AtD significantly reduces the quality of life of children, causing psychological discomfort and disrupting their social adaptation. AtD in children is a risk factor for the «atopic march» — the further sequential development of other allergic diseases: allergic rhinitis, pollinosis, allergic conjunctivitis, bronchial asthma. With a reduced immune response of the body, AtD in children can be complicated by the addition of a secondary infection (bacterial, viral, fungal). Such a high incidence rate, a debut in early childhood, a frequently recurring course of the pathological process, and a tendency towards an increase in the forms of the disease resistant to traditional therapy make the details of the pathogenesis of AtD particularly relevant. One of the main roles in the pathogenesis of AtD belongs to the cells of the immune system. The purpose of this article: to systematize the information available today on the immunopathogenesis of atopic dermatitis.

scholarly journals Evolutionary Emergence of Drug Resistance in Candida Opportunistic Pathogens

Genes ◽  
2018 ◽  
Vol 9 (9) ◽  
pp. 461 ◽  
Author(s):  
Ewa Ksiezopolska ◽  
Toni Gabaldón
Keyword(s):  
Drug Resistance ◽  
Fungal Infections ◽  
Current Knowledge ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Developed Countries ◽  
Antifungal Drugs ◽  
Opportunistic Pathogens ◽  
Evolutionary Mechanisms

Fungal infections, such as candidiasis caused by Candida, pose a problem of growing medical concern. In developed countries, the incidence of Candida infections is increasing due to the higher survival of susceptible populations, such as immunocompromised patients or the elderly. Existing treatment options are limited to few antifungal drug families with efficacies that vary depending on the infecting species. In this context, the emergence and spread of resistant Candida isolates are being increasingly reported. Understanding how resistance can evolve within naturally susceptible species is key to developing novel, more effective treatment strategies. However, in contrast to the situation of antibiotic resistance in bacteria, few studies have focused on the evolutionary mechanisms leading to drug resistance in fungal species. In this review, we will survey and discuss current knowledge on the genetic bases of resistance to antifungal drugs in Candida opportunistic pathogens. We will do so from an evolutionary genomics perspective, focusing on the possible evolutionary paths that may lead to the emergence and selection of the resistant phenotype. Finally, we will discuss the potential of future studies enabled by current developments in sequencing technologies, in vitro evolution approaches, and the analysis of serial clinical isolates.

scholarly journals Oxidative Stress in Atopic Dermatitis

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Hongxiu Ji ◽  
Xiao-Kang Li
Keyword(s):  
Oxidative Stress ◽  
Atopic Dermatitis ◽  
Skin Diseases ◽  
Treatment Strategies ◽  
Scientific Progress ◽  
Skin Barrier ◽  
Skin Aging ◽  
Barrier Defect ◽  
Pruritic Skin

Atopic dermatitis (AD) is a chronic pruritic skin disorder affecting many people especially young children. It is a disease caused by the combination of genetic predisposition, immune dysregulation, and skin barrier defect. In recent years, emerging evidence suggests oxidative stress may play an important role in many skin diseases and skin aging, possibly including AD. In this review, we give an update on scientific progress linking oxidative stress to AD and discuss future treatment strategies for better disease control and improved quality of life for AD patients.

scholarly journals Glycomacropeptide Attenuates Inflammation, Pruritus, and Th2 Response Associated with Atopic Dermatitis Induced by 2,4-Dinitrochlorobenzene in Rat

2017 ◽  
Vol 2017 ◽  
pp. 1-11 ◽  
Author(s):  
Fabiola Carolina Muñoz ◽  
Maritza Montserrat Cervantes ◽  
Daniel Cervantes-García ◽  
Mariela Jiménez ◽  
Javier Ventura-Juárez ◽  
...  
Keyword(s):  
Atopic Dermatitis ◽  
Inflammatory Process ◽  
Skin Diseases ◽  
Immunoglobulin E ◽  
Alternative Therapy ◽  
Serum Levels ◽  
Inhibitory Effect ◽  
Industrialized Countries ◽  
Th2 Response ◽  
Common Skin

Atopic dermatitis (AD) is one of the most common skin diseases, whose incidence is increasing in industrialized countries. The epicutaneous application of a hapten, such as 2,4-dinitrochlorobenzene (DNCB), evokes an experimental murine AD-like reaction. Glycomacropeptide (GMP) is a dairy bioactive peptide derived from hydrolysis ofκ-casein by chymosin action. It has anti-inflammatory, prebiotic, and immunomodulatory effects. The present study was aimed to investigate the effect of GMP administration on DNCB-induced AD in rats. The severity of inflammatory process, pruritus, production of cytokines, and total immunoglobulin E (IgE) content were measured, and the histopathological features were analyzed. GMP reduced the intensity of inflammatory process and edema of DNCB-induced dermatitis, with a significant decrease in eosinophils recruitment and mast cells hyperplasia. In addition GMP suppressed the serum levels of total IgE and IL-4, IL-5, and IL-13 expression in AD-lesions. Besides, the levels of IL-10 were significantly increased. Remarkably, GMP administration before AD-induction abolished pruritus in dermatitis-like reactions in the rats. Taken together, these results indicate that GMP has an inhibitory effect on AD by downregulating Th2 dominant immune response, suggesting GMP as a potential effective alternative therapy for the prevention and management of AD.

scholarly journals Possible Role of Leptin in Atopic Dermatitis: A Literature Review

Biomolecules ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 1642
Author(s):  
Carlos Jiménez-Cortegana ◽  
Germán Ortiz-García ◽  
Amalia Serrano ◽  
David Moreno-Ramírez ◽  
Víctor Sánchez-Margalet
Keyword(s):  
Atopic Dermatitis ◽  
Skin Disease ◽  
Skin Diseases ◽  
Allergic Diseases ◽  
Developed Countries ◽  
Low Grade ◽  
New Biomarkers ◽  
Age Range ◽  
High Degree

Atopic dermatitis (AD) is the most frequent chronic inflammatory skin disease, and its incidence has been rapidly increasing in developed countries in the last years. AD presents a high degree of heterogeneity due to biases and confounding factors such as age range, sex, or ethnicity. For those reasons, the search for new biomarkers is crucial. At the same time, obesity, which is a global health problem, has also increased over the years. It has been associated with many pathophysiological states, including skin diseases such as AD, mostly in childhood. Obesity promotes a low grade inflammation driven by many different cytokines and adipokines, including leptin, which has a key role in many other diseases due to its pleiotropic effects. Leptin also has a role in both skin and allergic diseases very related to AD. Thus, this adipokine could have an important role in the pathogenesis of AD, especially in its chronicity. Despite the limited literature available, there is some evidence that leads us to consider leptin as an important adipokine in this skin disease. For this reason, here we have reviewed the role of leptin in the pathophysiology of AD.

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