Human skin exposed to solar ultraviolet radiation (UVR) results in a dramatic increase in the production of reactive oxygen species (ROS). The sudden increase in ROS shifts the natural balance toward a pro-oxidative state, resulting in oxidative stress. The detrimental effects of oxidative stress occur through multiple mechanisms that involve alterations to proteins and lipids, induction of inflammation, immunosuppression, DNA damage, and activation of signaling pathways that affect gene transcription, cell cycle, proliferation, and apoptosis. All of these alterations promote carcinogenesis and therefore, regulation of ROS levels is critical to the maintenance of normal skin homeostasis. Several botanical products have been found to exhibit potent antioxidant capacity and the ability to counteract UV-induced insults to the skin. These natural products exert their beneficial effects through multiple pathways, including some known to be negatively affected by solar UVR. Aging of the skin is also accelerated by UVR exposure, in particular UVA rays that penetrate deep into the epidermis and the dermis where it causes the degradation of collagen and elastin fibers via oxidative stress and activation of matrix metalloproteinases (MMPs). Because natural compounds are capable of attenuating some of the UV-induced aging effects in the skin, increased attention has been generated in the area of cosmetic sciences. The focus of this review is to cover the most prominent phytoproducts with potential to mitigate the deleterious effects of solar UVR and suitability for use in topical application.

Summary Background Commensal bacteria are a major factor in human health and disease pathogenesis. Interest has recently expanded beyond the gastrointestinal microbiome to include the skin microbiome and its impact on various skin diseases. Objectives Here we present current data reviewing the role of the microbiome in dermatology, considering both the gut and skin microflora. Our objective was to evaluate whether the clinical data support the utility of oral and topical probiotics for certain dermatological diseases. Methods The PubMed and ClinicalTrials.gov databases were searched for basic science, translational research and clinical studies that investigated differences in the cutaneous microbiome and the impact of probiotics in patients with atopic dermatitis, acne vulgaris, psoriasis, chronic wounds, seborrhoeic dermatitis and cutaneous neoplasms. Results Few clinical trials exist that explore the utility of probiotics for the prevention and treatment of dermatological diseases, with the exception of atopic dermatitis. Most studies investigated oral probiotic interventions, and of those utilizing topical probiotics, few included skin commensals. In general, the available clinical trials yielded positive results with improvement of the skin conditions after probiotic intervention. Conclusions Oral and topical probiotics appear to be effective for the treatment of certain inflammatory skin diseases and demonstrate a promising role in wound healing and skin cancer. However, more studies are needed to confirm these results. What's already known about this topic? The microbiome plays a role in human health and disease pathogenesis. Probiotics can manipulate the host microbiome and may confer health benefits for patients. Research to date has already begun to explore the utility of oral and topical probiotics for certain dermatological diseases. What does this study add? This review presents basic science and clinical trial data to support the role of the gut and skin microbiome in dermatology. Current data are reviewed on the use of probiotics in the prevention and treatment of skin diseases, including atopic dermatitis, acne vulgaris, psoriasis, seborrhoeic dermatitis, chronic wounds and cutaneous neoplasms. Future probiotic interventions are proposed.

Vulvovaginal lichen planus (VVLP) is a debilitating disease that causes significant pain and psychological distress. Management is made difficult by the chronic course of the disease and its resistance to treatment. While topical steroids have been accepted as the first-line treatment, they fail to achieve symptomatic control in approximately 40% of patients.Second-line therapies include other topical treatments such as calcineurin inhibitors, systemic therapies including oral steroids, methotrexate, mycophenolate mofetil, biologics, and tacrolimus, and procedural options including surgery and dilation, photodynamic therapy, and ultrasound. This review provides an overview of the current treatments and explores the level of evidence supporting each of them.

Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with formation of a dynamic and optimized niche for tumor cells to grow and evade cell death induced by therapeutic agents. We recently reported that ablation of β-catenin expression in stromal fibroblasts and CAFs disrupted their biological activities in in vitro studies and in an in vivo B16F10 mouse melanoma model. Here, we show that the development of a BRAF-activated PTEN-deficient mouse melanoma was significantly suppressed in vivo after blocking β-catenin signaling in CAFs. Further analysis revealed that expression of phospho-Erk1/2 and phospho-Akt was greatly reduced, effectively abrogating the activating effects and abnormal cell cycle progression induced by Braf and Pten mutations. In addition, the epithelial-mesenchymal transition (EMT)-like process was also suppressed in melanoma cells. Taken together, our data highlight an important crosstalk between CAFs and the RAF-MEK-ERK signaling cascade in BRAF-activated melanoma and may offer a new approach to abrogate host-dependent drug resistance in targeted therapy.

Stem cells are of great interest to the scientific community due to their potential role in regenerative and rejuvenative medicine. However, their role in the aging process and carcinogenesis remains unclear. Because DNA replication in stem cells may contribute to the background mutation rate and thereby to cancer, reducing proliferation and establishing a relatively quiescent stem cell compartment has been hypothesized to limit DNA replication-associated mutagenesis. On the other hand, as the main function of stem cells is to provide daughter cells to build and maintain tissues, the idea of a quiescent stem cell compartment appears counterintuitive. Intriguing observations in mice have led to the idea of separated stem cell compartments that consist of cells with different proliferative activity. Some epithelia of short-lived rodents appear to lack quiescent stem cells. Comparing stem cells of different species and different organs (comparative stem cell biology) may allow us to elucidate the evolutionary pressures such as the balance between cancer and longevity that govern stem cell biology (evolutionary stem cell biology). The oral mucosa and its stem cells are an exciting model system to explore the characteristics of quiescent stem cells that have eluded biologists for decades.

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