Injury suppresses Ras cell competitive advantage through enhanced wild-type cell proliferation

Healthy skin is a tapestry of wild-type and mutant clones. Although injury can cooperate with Ras mutations to promote tumorigenesis, the consequences in genetically mosaic skin are unknown. Here, we show that wild-type cells prevent oncogenic Ras-induced aberrant growth after injury. Although HrasG12V/+ and KrasG12D/+ cells outcompete wild-type cells in uninjured, mosaic tissue, their competitive advantage is suppressed after injury due to a selective increase in wild-type cell proliferation. EGFR inhibition abolishes the competitive advantage of wild-type cells after injury of HrasG12V/+-mosaic skin. Global loss of the cell cycle inhibitor p21 increases wild-type cell proliferation even without injury, suppressing the competitive advantage of HrasG12V/+ cells. Thus, injury plays an unanticipated role in switching the competitive balance between oncogenic and wild-type cells in genetically mosaic skin.

Expression Patterns of Clock Gene mRNAs and Clock Proteins in Human Psoriatic Skin Samples

Psoriasis is a systemic inflammatory skin disorder that can be associated with sleep disturbance and negatively influence the daily rhythm. The link between the pathomechanism of psoriasis and the circadian rhythm has been suggested by several previous studies. However, there are insufficient data on altered clock mechanisms in psoriasis to prove these theories. Therefore, we investigated the expression of the core clock genes in human psoriatic lesional and non-lesional skin and in human adult low calcium temperature (HaCaT) keratinocytes after stimulation with pro-inflammatory cytokines. Furthermore, we examined the clock proteins in skin biopsies from psoriatic patients by immunohistochemistry. We found that the clock gene transcripts were elevated in psoriatic lesions, especially in non-lesional psoriatic areas, except for rev-erbα, which was consistently downregulated in the psoriatic samples. In addition, the REV-ERBα protein showed a different epidermal distribution in non-lesional skin than in healthy skin. In cytokine-treated HaCaT cells, changes in the amplitude of the bmal1, cry1, rev-erbα and per1 mRNA oscillation were observed, especially after TNFα stimulation. In conclusion, in our study a perturbation of clock gene transcripts was observed in uninvolved and lesional psoriatic areas compared to healthy skin. These alterations may serve as therapeutic targets and facilitate the development of chronotherapeutic strategies in the future.

The defense response of Caenorhabditis elegans to Cutibacterium acnes SK137 via the TIR-1-p38 MAPK signaling pathway

Cutibacterium acnes plays roles in both acne disease and healthy skin ecosystem. We observed that mutations in the tir-1/SARM1 and p38 MAPK cascade genes significantly shortened Caenorhabditis elegans lifespan upon Cutibacterium acnes SK137 infection. Antimicrobial molecules were induced by SK137 in a TIR-1-dependent manner. These results suggest that defense responses against SK137 involve the TIR-1-p38 MAPK pathway in Caenorhabditis elegans.

Comprehensive skin care with cosmetic preparations, dietary supplements and functional food

Diet and consumption of appropriate quality food products are one of the most important elements for good health and condition of the whole organism, including a proper appearance and healthy skin. The condition of the body and the skin is also influenced by additional dietary supplements, synthetic multi-ingredient preparations, especially the ones containing ingredients selected for their beneficial effects on the skin. The aim of the study was to describe the influence of dietary supplementation and the functional food for the condition of the skin, including preparations containing various nutrients and special-purpose food, which can have a beneficial effect on the skin and its healthy appearance. The scope of the work includes a review of literature and sources in the field of dietetics and cosmetology.

Royal Jelly Protects against Epidermal Stress through Upregulation of the NQO1 Expression

Royal jelly (RJ) is secreted by honeybees and has been used as an apitherapy to obtain healthy skin since ancient times. However, the mechanism of the protective effects of RJ against skin aging and skin diseases caused by skin stress and its components have not been clarified. In this study, we attempted to understand the effect of RJ on epidermal function and observed that NAD(P)H quinone dehydrogenase 1 (NQO1) is significantly induced by RJ in keratinocytes. The expression of NQO1 was also increased in the 3D epidermal skin model. NQO1 is involved in antioxidation and detoxification metabolism, and we found that RJ protects against the epidermal stress caused by UVB and menadione through the upregulation of NQO1. We identified 10-hydroxy-2-decenoic acid (10H2DA), a major fatty acid in RJ, as an active compound in this reaction as it induced the expression of NQO1 and protected the skin against oxidative stress. We demonstrated that the protective effect of RJ against epidermal stress is mediated through the upregulation of NQO1 by 10H2DA.

Immune Cell Infiltration Analysis Demonstrates Excessive Mast Cell Activation in Psoriasis

Psoriasis represents multiple inflammatory processes and exaggerated physiological responses to epithelial damage by innate and adaptive immune components, thus it is critical to compare the immune cell niche in disease and healthy skin. Here, we inferred the proportions of different immune cell types in psoriatic and healthy skin using the CIBERSORT algorithm with expression profiles as input. As a result, we observed a dramatic change of immune cell profiles in psoriatic skin compared with healthy skin. Interestingly, the resting mast cells is almost eliminated in psoriatic skin. In contrast, the activated mast cells are enriched in psoriatic skin, indicating that mast cells activation may play an important role in psoriasis pathogenesis. In addition, we found that the proportion of the resting mast cells gradually come back to the normal level in lesioned skin upon etanercept treatment, suggesting that mast cells play a critical role in immune cell niche maintenance. Further experiments validated a significant decrease in mast cell population and an excessive mast cell activation in psoriatic skin compared with healthy skin. In conclusion, our integrative analyses of the immune cell profiles and the corresponding marker genes expression provide a better understanding of the inflammation response in psoriasis and important clues for clinical applications.

A REVIEW ON THE ROLE OF VIRECHANA IN VARIOUS SKIN DISEASES

Virechan is one of the Shodhan Chikitsa described in ayurvedic texts. It is mainly advised in the pitta and rakta Pradhan diseases. All skin diseases in ayurveda have been considered under kustha. At present time antibiotics and antifungal medicines are being resistant, so it is becoming difficult day by day to cure such skin diseases, but in Ayurveda, Virechan karma is a very powerful therapy to combat these diseases. Skin is the index of our body. Healthy skin represents a healthy body. Improper usage of foods and drinks along with unhealthy activities mani- fest diseases. Virechan karma is the second therapy in the sequence of panchakarmas, the most widely used pu- rificatory procedure especially for paitika and raktas diseases. It is also useful in the disorders in which pitta is associated with vata or kapha. Ayurveda states that sluggish liver (dysfunction of the liver) associated with doshic imbalance causes skin diseases. There are so many skin diseases that are not curable by other procedures. Accord- ing to Ayurveda Virechan karma is very much beneficial in curing the different obstinate skin diseases as psoria- sis, eczema, acne vulgaris, vitiligo, leukoderma etc. Ayurveda always looks to the root cause so the patient can restore their body to a healthy state and eliminate the symptoms of skin diseases. This article deals with various skin diseases and their treatment by using Virechan therapy. Keywords: Virechan, Shodhanchikitsa, Skin Diseases, Psoriasis, Panchkarma,

Photoplethysmography for demarcation of cutaneous squamous cell carcinoma

A video processing algorithm designed to identify cancer suspicious skin areas is presented here. It is based on video recordings of squamous cell carcinoma in the skin. Squamous cell carcinoma is a common malignancy, normally treated by surgical removal. The surgeon should always balance sufficient tissue removal against unnecessary mutilation, and therefore methods for distinction of cancer boundaries are wanted. Squamous cell carcinoma has angiogenesis and increased blood supply. Remote photoplethysmography is an evolving technique for analysis of signal variations in video recordings in order to extract vital signs such as pulsation. We hypothesize that the remote photoplethysmography signal inside the area of a squamous cell carcinoma is significantly different from the surrounding healthy skin. Based on high speed video recordings of 13 patients with squamous cell carcinoma, we have examined temporal signal differences in cancer areas versus healthy skin areas. A significant difference in temporal signal changes between cancer areas and healthy areas was found. Our video processing algorithm showed promising results encouraging further investigation to clarify how detailed distinctions can be made.