The relationship between epigenetic age and the hallmarks of aging in human cells.

Epigenetic clocks are mathematically derived age estimators that are based on combinations of methylation values that change with age at specific CpGs in the genome. These clocks are widely used to measure the age of tissues and cells. The discrepancy between epigenetic age (EpiAge), as estimated by these clocks, and chronological age is referred to as EpiAge acceleration.

Post-exposure persistence of nitric oxide upregulation in skin cells irradiated by UV-A.

Evidence suggests that exposure to UV-A radiation can liberate nitric oxide from skin cells eliciting vasodilation in-vivo. However, the duration of nitric oxide release in skin cells after UV exposure is not well studied, with emphasis on UV-B mediated iNOS upregulation. The current study demonstrated persistence of nitric oxide release in a dark reaction after moderate UV-A exposure, peaking around 48 h post exposure; this effect was shown in keratinocytes, fibroblasts and endothelial cells from neonatal donors and keratinocytes from aged donors and confirmed the hypothesis that UV-A exposure appeared to upregulate cNOS alongside iNOS.

Isolation of five different primary cell types from a single sample of human skin.

We have developed a technique to isolate primary keratinocytes, melanocytes, fibroblasts, preadipocytes, and microvascular endothelial cells from an individual sample of human skin. The protocol describes step-by-step instructions for processing, cells isolation, and culture of neonatal foreskin, with adaptation for more demanding adult tissues. The availability of multiple isogenic cell types derived from individual skin samples offers the ability to investigate various areas of biology, in the context of cell-type specificity without potential confounding influence of inter-individual or genetic differences.

Chronic irradiation of human cells reduces histone levels and deregulates gene expression.

Over the past decades, there have been huge advances in understanding cellular responses to ionising radiation (IR) and DNA damage. These studies, however, were mostly executed with cell lines and mice using single or multiple acute doses of radiation. Hence, relatively little is known about how continuous exposure to low dose ionising radiation affects normal cells and organisms, even though our cells are constantly exposed to low levels of radiation.

Epigenetic clock for skin and blood cells applied to Hutchinson Gilford Progeria Syndrome and studies.

DNA methylation (DNAm)-based biomarkers of aging have been developed for many tissues and organs. However, these biomarkers have sub-optimal accuracy in fibroblasts and other cell types used in studies. To address this challenge, we developed a novel and highly robust DNAm age estimator (based on 391 CpGs) for human fibroblasts, keratinocytes, buccal cells, endothelial cells, lymphoblastoid cells, skin, blood, and saliva samples.

Ultraviolet Radiation-Induced Production of Nitric Oxide:A multi-cell and multi-donor analysis.

Increasing evidence regarding positive effects of exposure to sunlight has led to suggestions that current advice may be overly weighted in favour of avoidance. UV-A has been reported to lower blood pressure, possibly through nitric oxide (NO) production in skin. Here, we set out to investigate effects of UV-A and solar-simulated radiation on the potential source of dermal NO, the effective doses and wavelengths, the responsiveness of different human skin cells, the magnitude of inter-individual differences and the potential influence of age.

Serum endocannabinoids and N-acyl ethanolamines and the influence of simulated solar UVR exposure in humans in vivo.

Solar ultraviolet radiation (UVR) exposure of human skin has beneficial and harmful effects on health, including impact on immune function, inflammation and reportedly mood, but these are not fully elucidated. Since the endocannabinoid system is implicated in many activities including mood alteration, our objective was to (i) determine and quantify circulating levels of a wide range of endocannabinoid and N-acyl ethanolamine (NAE) species (ii) evaluate whether these are modulated by cutaneous UVR exposures, as attained through repeated low level summer sunlight exposure. Wearing goggles to prevent eye exposure, 16 healthy volunteers (23-59 y; 10 light skin, phototype II, and 6 dark skin, phototype V) received the same UVR exposures (1.

Excision Margins for Melanoma In Situ on the Head and Neck.

Background: Complete surgical excision of melanoma in situ (MIS) is curative. A 5-mm margin is often taken as the standard primary excision margin despite increasing evidence that this is frequently inadequate for tumor clearance.

Objective: To calculate the proportion of patients requiring >5 mm margin for clearance and to investigate any patient/lesion characteristics necessitating larger margins.

Severe Back Pain in a Young Patient with Pyoderma Gangrenosum and Crohn's Disease Controlled with Anti-tumor Necrosis Factor Therapy: Sterile Osteomyelitis.

Introduction: Inflammatory bowel disease has been associated with a number of cutaneous and systemic neutrophilic disorders, including pyoderma gangrenosum. In 1972, the term chronic multi-focal recurrent osteomyelitis was given to a sterile neutrophilic condition which has been associated with inflammatory bowel disease.

Case Report: We report a case of a 23-year-old man with long-standing severe Crohn's disease which necessitated subtotal colectomy.

Peristomal and generalized bullous pemphigoid in patients with underlying inflammatory bowel disease: is plectin the missing link?

Bullous pemphigoid (BP) is a blistering disorder of the skin and mucosa that may coexist with inflammatory bowel disease (IBD). The authors' experiences with peristomal and generalized BP in five patients (three with ulcerative colitis [UC] post colostomy surgery and two with Crohn's disease [CD] post ileostomy surgery, time since surgery 5 to 20 years) is described. The patients presented with peristomal blisters and erosions, subsequently confirmed as BP by skin biopsy.

Ultraviolet radiation-induced upregulation of antimicrobial proteins in health and disease.

This article reviews recent data on the expression, regulation and activation of antimicrobial peptides (AMP) in human skin, and considers their potential protective and pro-inflammatory roles following upregulation by ultraviolet radiation (UVR). Antimicrobial peptides are small peptides that are key components of the innate immune system, originally identified by their vital role in protecting the body-environment interface from infection. However, it has now become clear that AMP have more extensive actions, including the provision of pivotal links with the adaptive immune system.

Recommended summer sunlight exposure amounts fail to produce sufficient vitamin D status in UK adults of South Asian origin.

Background: The cutaneous synthesis of vitamin D is dependent on UVB from sunlight, but melanin reduces the penetration of UVB and thus contributes to vitamin D insufficiency in individuals with darker skin. The national guidance provided on amounts of sunlight exposure in the United Kingdom is for the light-skinned population, and in the absence of dedicated information, darker-skinned people may attempt to follow this guidance.

Objectives: We determined the relative effect of a simulation of UK recommendations of summer sunlight exposure on the vitamin D status of individuals of South Asian ethnicity compared with that of whites.