Role In Skin Diseases Research Articles

A Comprehensive Review of Dietetic Regimen (Pathya- Apathya) in Skin Disorders

For decades, it was thought that there was no relation between the dermatological conditions or the skin disorders and the diet. But recent studies have made an attempt to explore the relationship between the diet and its role in skin disorders. Ayurvedic system of Medicine also known as the Indian traditional medicine has contributed vastly for the diet and the management of skin disorders. In Ayurveda skin disorders are explained under the name Kustha which are twenty in number and two types as Mahakustha and Kshudra kustha. Since 5000yrs, Ayurveda is serving the society with the objective of curing of the disease and prevention of the same. Ahara has been given the prime importance in Ayurveda and is placed one among the Trayopasthambas or the three pillars of life such as Aaahara (diet), Nidra (sleep) and Brahmacharya (celibacy) In depth of diet for the healthy and also the specific diet for the disorders has been described in Ayurveda and is being practiced by Ayurvedic practitioners since centuries which is witnessed in the latest research studies. The present study has made an attempt to assess both the Modern and Ayurvedic concepts of diet that is presently practiced and their importance in the management of skin disorders.

CASZ1 Is Essential for Skin Epidermal Terminal Differentiation

The barrier function of skin epidermis is crucial for our bodies to interface with the environment. Because epidermis continuously turns over throughout the lifetime, this barrier must be actively maintained by regeneration. Although several transcription factors have been established as essential activators in epidermal differentiation, it is unclear whether additional factors remain to be identified. In this study, we show that CASZ1, a multi zinc-finger transcription factor previously characterized in nonepithelial cell types, shows highest expression in skin epidermis. CASZ1 expression is upregulated during epidermal terminal differentiation. In addition, CASZ1 expression is impaired in several skin disorders with impaired barrier function, such as atopic dermatitis, psoriasis, and squamous cell carcinoma. Using transcriptome profiling coupled with RNA interference, we identified 674 differentially expressed genes with CASZ1 knockdown. Downregulated genes account for 91.2% of these differentially expressed genes and were enriched for barrier function. In organotypic epidermal regeneration, CASZ1 knockdown promoted proliferation and strongly impaired multiple terminal differentiation markers. Mechanistically, we found that CASZ1 upregulation in differentiation requires the action of both the master transcription factor, p63, and the histone acetyltransferase, p300. Taken together, our findings identify CASZ1 as an essential activator of epidermal differentiation, paving the way for future studies understanding of CASZ1 roles in skin disease.

Recent advances in understanding the role of the skin microbiome in the treatment of atopic dermatitis.

The skin is the largest organ in the human body, and histologically consists of the epidermis, dermis and subcutaneous tissue. Humans maintain a cooperative symbiotic relationship with their skin microbiota, a complex community of bacteria, fungi and viruses that live on the surface of the skin, and which act as a barrier to protect the body from the inside and outside. The skin is a 'habitat' and vast 'ecosystem' inhabited by countless microbes; as such, relationships have been forged through millions of years of coevolution. It is not surprising then that microbes are key participants in shaping and maintaining essential physiological processes. In addition to maintaining barrier function, the unique symbiotic microbiota that colonizes the skin increases the immune response and provides protection against pathogenic microbes. This review examines our current understanding of skin microbes in shaping and enhancing the skin barrier, as well as skin microbiome-host interactions and their roles in skin diseases, such as atopic dermatitis (AD). We also report on the current status of AD therapeutic drugs that target the skin microbiome, related research on current therapeutic strategies, and the limitations and future considerations of skin microbiome research. In particular, as a future strategy, we discuss the need for a skin-on-a-chip-based microphysiological system research model amenable to biomimetic in vitro studies and human skin equivalent models, including skin appendages.

Corticotropin-releasing hormone receptor-1 is increased in mast cells in psoriasis and actinic keratosis, but not markedly in keratinocyte skin carcinomas.

Corticotropin-releasing hormone receptor-1 (CRH-R1) is expressed in human mast cells, but its role in skin diseases is unknown. By using a sequential double-staining technique, the mast cell expression of CRH-R1 was investigated in biopsies from lesional and non-lesional skin samples of patients with actinic keratosis (AK), basal cell carcinoma (BCC), squamous cell carcinoma (SCC) and psoriasis. Dermal tryptase+ mast cells expressed CRH-R1 immunoreactivity in the non-lesional skin in all patient groups. The CRH-R1 expression was significantly increased in the lesional skin of AK (p = 0.03) and psoriasis (p = 0.02), non-significantly in BCC (p = 0.129), but not increased in SCC. To investigate the regulation of CRH-R1, the LAD2 mast cell line was irradiated with UVB or stimulated with CRH or 1,25-dihydroxyvitamin D3 [1,25-(OH)2 D3 ]. Consequently, UVB at 90 mJ/cm2 (p = 0.041) and 120 mJ/cm2 (p = 0.039) decreased CRH-R1 expression. Instead, CRH at 100 and 1000 nM increased CRH-R1 immunostaining, but did not affect the proliferative response. The treatment with 10 and 100 nM 1,25-(OH)2 D3 led to a noticeable increase in CRH-R1 staining. After irradiating with UVB, the concentration of CRH increased in the conditioned medium, but not in sonicated LAD2 mast cells. In conclusion, the lack of sufficient levels of CRH-R1 in mast cells may be related to diminished antitumoural response in SCC and possibly in BCC.

Alopecia Areata: A Review of the Role of Oxidative Stress, Possible Biomarkers, and Potential Novel Therapeutic Approaches.

Alopecia areata (AA) is a dermatological condition characterized by non-scarring hair loss. Exact etiopathogenesis of AA is still unknown although it is known that several factors contribute to the collapse of the hair-follicle (HF)-immune-privileged (IP) site. Oxidative stress (OS) plays an important role in skin diseases. The aim of this review was to clarify the role of OS in AA pathogenesis and diagnosis, and to discuss potential treatment options. Oxidative-stress markers are altered in serum and skin samples of patients with AA, confirming a general pro-oxidative status in patients with AA. OS induces MHC class I chain-related A (MICA) expression in HF keratinocytes that activates the receptor NKG2D, expressed in NK cells and CD8+ T cytotoxic cells leading to destabilization of the HF immune-privileged site through the production of IFN-γ that stimulates JAK1 and JAK2 pathways. OS also activates the KEAP1-NRF2 pathway, an antioxidant system that contributes to skin homeostasis. In addition, a decrease of ATG5 and LC3B in the hair matrix and an increase in p62 levels indicates a reduction of intrafollicular autophagy during the evolution of AA. Potential biomarkers of OS in AA could be: malondialdehyde (MDA), advanced glycation end-products (AGEs), and ischemic-modified albumin (IMA). JAK inhibitors are the new frontier in treatment of AA and the use of nutraceuticals that modulate the OS balance, in combination with standard treatments, represent promising therapeutic tools.

Life Style Modification, Does it Make a Difference ??

Skin acts as the intermediate between our body & the environment, acting as a shield to perform many complex protective functions [1]. Various life style factors had clinical impact on skin homeostasis and the progress of many dermatological diseases.Life style interventions play important role in skin diseases like psoriasis [2], acne [3], atopic dermatitis, hidradenitis suppurativa, rosacea, vitiligo, skin aging and skin cancer. Although disturbance in life style doesn't cause any of these skin conditions, it can make them worse and exacerbate symptoms.Lifestyle trends and psychosocial disorders have become more important in dermatology , how social media plays a role in affecting beauty trends, body image and self-esteem concerns [4,5].Sexual relationship is a human lifestyle. The quantity and quality of sexual relations, beginning age, different types, freedom or limitations of sex connections has great impact on STD development and spreading [6,7].Unfortunately less attention has been paid to the effect of the environment, stress, nutrition, poor sleep, allergic and infectious agents and sexual performance on the development of many dermatoses and STDs.

Veganism in acne, atopic dermatitis, and psoriasis: Benefits of a plant-based diet.

Plant-based diets and veganism are receiving increased attention for many reasons. Leading international nutrition organizations have determined that a well-planned and balanced plant-based diet is protective against such chronic diseases as obesity, diabetes, and cardiovascular diseases. Many physicians may be unaware of its potential advantages, especially in the field of dermatology, and for this reason the vegan diet is often discouraged. Although the literature about diet in dermatology is limited, the introduction of foods of plant origin, vitamin B12 supplements, and elimination of animal products may have a protective role in skin diseases. There may be many benefits of a vegan diet for patients with acne, psoriasis, and atopic dermatitis.

Bioactivity of carotenoids and their role in skin disorders: from tradition to application

Bioactivity of carotenoids and their role in skin disorders: from tradition to application

143 Structure of a novel endoplasmic reticulum-desmosome complex and its role in skin disease

Desmosomes are adhesive intercellular junctions that provide strength and integrity to the epidermis and other epithelia. Dysfunction of the endoplasmic reticulum (ER) resident calcium pump, SERCA2, causes Darier’s disease (DD), an epidermal disorder characterized by compromised desmosomal adhesion and abnormal keratinocyte differentiation. However, the mechanism by which ER dysfunction impairs desmosome formation is unclear. Using electron microscopy and live-cell fluorescence imaging, we found that peripheral ER tubules are in close proximity to desmosomes and form mirror image arrangements at desmosomes.

Nickel penetration into stratum corneum in FLG null carriers-A human experimental study.

BackgroundThe filaggrin gene (FLG) plays a role in skin diseases, with the skin barrier function being impaired in FLG null carriers. The role of FLG status in relation to nickel penetration into the skin remains unclear.ObjectivesTo elucidate the association between FLG status and nickel penetration into stratum corneum (SC) in individuals without self‐reported history of nickel allergy.MethodsForty participants (23 FLG wt and 17 FLG null) were exposed to a nickel solution (80 μg/cm2) which was applied onto 2 × 2 cm on their left forearm. After 4 h, the area was tape‐stripped with 10 consecutive tapes. Nickel in each tape was quantified using inductively coupled plasma mass spectrometry.ResultsThe average recovered nickel dose was 35%–48%. A tendency towards lower recovery was seen in FLG null carriers compared to FLG wt carriers, and lower recovery in those with history of skin and/or respiratory symptoms compared to those without such history. This was however not statistically significant.Conclusion FLG null carriers had less nickel recovered by tape strips compared with FLG wt carriers and, compared with individuals without a history of skin and/or respiratory symptoms, indicating higher nickel penetration into SC for FLG null carriers, but further studies are needed.

Thioredoxin-interacting protein regulates keratinocyte differentiation: Implication of its role in psoriasis.

Thioredoxin-interacting protein (TXNIP), also known as Vitamin-D upregulated protein-1 (VDUP-1), interacts with thioredoxin to regulate redox responses and participates in diverse disorders including metabolic, cardiovascular, inflammatory and malignant diseases. Psoriasis is characterized by chronic skin inflammation and an aberrant pattern of keratinocyte differentiation. Clinically, psoriasis is associated with various cardiometabolic comorbidities but studies on TXNIP's biological role in skin disorders are limited. In this study, we investigated TXNIP expression in psoriasis and its regulation in normal human epidermal keratinocytes (NHEKs), and then explored how TXNIP regulated skin keratinocyte differentiation to determine its role in psoriasis pathogenesis. Our immunohistochemical study demonstrated extensive TXNIP expression in the upper and lower epidermis of psoriasis compared to predominant TXNIP expression in the basal layer of normal skin. 1, 25-dihydroxyvitamin D3 suppressed but TGF-α and EGF enhanced TXNIP expression in NHEKs. An inducer of keratinocyte differentiation, phorbol 12-myristate 13-acetate (PMA), also diminished TXNIP expression, which was reversed by PKC-δ knockdown. TXNIP knockdown reduced PMA-induced involucrin and transglutaminse-1 expression, and increased p63 expression in NHEKs but did not significantly affect cell proliferation. H2 O2 -induced ROS production and EGFR phosphorylation decreased in NHEKs with TXNIP knockdown. Furthermore, PMA-induced PKC-δ phosphorylation, TGF-α, and EGF-triggered EGFR phosphorylation were attenuated by TXNIP knockdown. Our results unraveled the regulation and function of TXNIP expression in skin keratinocytes and the cross-regulation between TXNIP and EGFR signaling. These findings imply a role of TXNIP in psoriasis and provide insight into the possible impact of TXNIP regulators on the skin or psoriasis.

Prevalence of MCPyV, HPyV6, HPyV7 and TSPyV in Actinic Keratosis Biopsy Specimens.

To date, 14 human polyomaviruses (HPyVs) have been identified using high-throughput technologies. Among them, MCPyV, HPyV6, HPyV7 and TSPyV present a skin tropism, but a causal role in skin diseases has been established only for MCPyV as a causative agent of Merkel cell carcinoma (MCC) and TSPyV as an etiological agent of Trichodysplasia Spinulosa (TS). In the search for a possible role for cutaneous HPyVs in the development of skin malignant lesions, we investigated the prevalence of MCPyV, HPyV6, HPyV7 and TSPyV in actinic keratosis (AK), a premalignant skin lesion that has the potential to progress towards a squamous cell carcinoma (SCC). One skin lesion and one non-lesion skin from nine affected individuals were analyzed by qualitative PCR. MCPyV was detected in 9 out of 9 lesion biopsies and 6 out of 8 non-lesion biopsies. HPyV6 was detected only in healthy skin, while HPyV7 and TSPyV were not detected in any skin sample. These findings argue against a possible role of cutaneous HPyVs in AK. However, considering the small sample size analyzed, a definitive conclusion cannot be drawn. Longitudinal studies on large cohorts are warranted.

Autophagy and Skin Diseases.

Autophagy is a highly conserved lysosomal degradation system that involves the creation of autophagosomes, which eventually fuse with lysosomes and breakdown misfolded proteins and damaged organelles with their enzymes. Autophagy is widely known for its function in cellular homeostasis under physiological and pathological settings. Defects in autophagy have been implicated in the pathophysiology of a variety of human diseases. The new line of evidence suggests that autophagy is inextricably linked to skin disorders. This review summarizes the principles behind autophagy and highlights current findings of autophagy’s role in skin disorders and strategies for therapeutic modulation.

The role of a recently discovered peptide—irisin—in physiological and pathological processes

Abstract Irisin, a cleaved fragment of fibronectin type III domain-containing protein 5 (FNDC5), was originally described as a factor stimulating browning of white adipose tissue, produced during physical exercise by skeletal muscles. However, irisin is not only a new and promising biomarker of metabolism; its expression has been found in a wide variety of tissues and organs such as the peripheral nerves, stomach, pancreas, and skin, and recent data also indicate its role in cancer. Numerous studies focus on the protective role of this protein, which could become an important factor in predicting disease risk, disease prognosis, or possible metastases in cancer patients. Possible use of irisin in therapy is also worth considering. The aim of this paper is to systematize knowledge on the role of irisin in patients and to draw attention to its role in skin diseases including acne vulgaris, psoriasis vulgaris, and hidradenitis suppurativa.

M308 GETTING UNDER THE SKIN OF ATOPIC DERMATITIS: CASE SERIES INVESTIGATING DUOX2 AND ATOPIC DERMATITIS

Atopic dermatitis(AD) pathogenesis is complex, multifactorial and inadequately understood. Elucidating AD immune dysregulation can improve diagnosis and management. DUOX2(dual oxidase 2) plays a role in innate immunity and is expressed by multiple cell types, including keratinocytes. Preclinical studies suggest that DUOX2 may play a role in AD. DUOX2 is expressed abundantly in human AD lesions and is critical for house dust mite-induced inflammation in human keratinocytes. To date, loss-of-function DUOX2 variants are associated with congenital hypothyroidism and inflammatory bowel disease(IBD), but its role in skin disease remains unclear.

ABCB1 in dermatology: roles in skin diseases and their treatment.

Adenosine triphosphate–binding cassette subfamily B member 1 (ABCB1), also known as permeability glycoprotein, multidrug-resistant protein 1, or cluster of differentiation 243 (CD243), is a crucial protein for purging foreign substances from cells. The functions of ABCB1 have been investigated extensively for their roles in cancer, stem cells, and drug resistance. Abundant pharmacogenetic studies have been conducted on ABCB1 and its association with treatment responsiveness to various agents, particularly chemotherapeutic and immunomodulatory agents. However, its functions in the skin and implications on dermatotherapeutics are far less reported. In this article, we reviewed the roles of ABCB1 in dermatology. ABCB1 is expressed in the skin and its appendages during drug delivery and transport. It is associated with treatment responsiveness to various agents, including topical steroids, methotrexate, cyclosporine, azathioprine, antihistamines, antifungal agents, colchicine, tacrolimus, ivermectin, tetracycline, retinoid acids, and biologic agents. Moreover, genetic variation in ABCB1 is associated with the pathogenesis of several dermatoses, including psoriasis, atopic dermatitis, melanoma, bullous pemphigoid, Behçet disease, and lichen planus. Further investigation is warranted to elucidate the roles of ABCB1 in dermatology and the possibility of enhancing therapeutic efficacy through ABCB1 manipulation.

Fecal microbiota transplant and dermatologic disorders: A retrospective cohort study assessing the gut microbiome’s role in skin disease

Fecal microbiota transplant and dermatologic disorders: A retrospective cohort study assessing the gut microbiome’s role in skin disease

Variation of biophysical parameters of the skin with age, gender, and lifestyles.

Sweet, spicy or greasy food, staying up late, and using electronic products for a long time are common bad habits nowadays. Their role in skin diseases has been paid much attention. The aim of this study was to investigate whether unhealthy lifestyles would affect the skin sebum content, SC hydration, and pH and how do they affect. A total of 300 volunteers were enrolled, and a multifunctional skin physiology monitor measured the three skin biophysical properties on the forehead and dorsal hand. Lifestyle factors were evaluated by a self-administered questionnaire. Eating oily, sweet, spicy food, and staying up late increased the sebum content of the forehead significantly. Dorsal hand SC hydration was higher in people eating more sweet food and oily food, and forehead SC hydration was higher in people eating more sweet food and go to bed earlier. Eating sweet food could increase pH in both forehead and dorsal hand. The forehead pH decreased in using electronic products over 6hours a day or staying up late. There are significant differences in sebum, hydration, and pH value among different age groups. In males, the pH was lower than females, but the sebum was higher. Sebum content, SC hydration, and pH are affected by unhealthy lifestyles, age, and gender.

The Role of Erythroid Differentiation Regulator 1 (ERDR1) in the Control of Proliferation and Photodynamic Therapy (PDT) Response.

Erythroid differentiation regulator 1 (ERDR1) was newly identified as a secreted protein that plays an essential role in maintaining cell growth homeostasis. ERDR1 enhances apoptosis at high cell densities, leading to the inhibition of cell survival. Exogenous ERDR1 treatment decreases cancer cell proliferation and tumor growth as a result of increased apoptosis via the regulation of apoptosis-related gene expression. Moreover, ERDR1 plays a pivotal role in skin diseases; ERDR1 expression in actinic keratosis (AK) is negatively correlated with the increase in apoptosis. Because of its high specificity and efficiency, photodynamic therapy (PDT) is a common therapy for patients with various skin diseases, including cancer. Many studies indicate that apoptosis is mainly induced by PDT treatment. As an apoptosis inducer, the recovery of the ERDR1 expression after PDT is correlated with good therapeutic outcomes. Here, we review recent findings that highlight the function of ERDR1 in the control of apoptosis. Thus, ERDR1 may have a role in the apoptosis regulation of target cells in the lesions, as the recovery of its expression after PDT is correlated with good therapeutic outcomes.

Janus kinases: dermatological perspective, a review

Janus kinases (JAKs) are a group of nonreceptor intracellular tyrosine kinases that could modify cytokine-mediated signals through the JAK-signal transducer and activator of transcription pathway. This pathway is triggered by cytokines participating in the inflammatory process, innate and adaptive immunological responses, as well as cell growth. Current researches suggest the possible disruption in JAK/signal transducer and activator of transcription pathway in different autoimmune and inflammatory skin diseases, such as psoriasis, vitiligo, atopic dermatitis, and alopecia areata. Various drugs that activate or block this pathway are under study for the assessment of their possible role in skin diseases.