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Chronic wounds represent a major and rising health and economic burden worldwide. There is a continued search towards more effective wound therapy. We found significantly reduced microRNA-132 (miR-132) expression in human diabetic ulcers compared to normal skin wounds, and also in skin wounds of leptin receptor-deficient (db/db) diabetic mice compared to wild-type mice. Local replenishment of miR-132 in the wounds of db/db mice accelerated wound closure effectively, which was accompanied by increased proliferation of wound-edge keratinocytes and reduced inflammation.
Several studies have suggested that Wnts might contribute to skin fibrosis in systemic sclerosis (SSc) by affecting the differentiation of pluripotent dermal cells. We tested C-82, a therapeutic that inhibits canonical Wnt signaling by blocking the interaction of cAMP Response Element-Binding Protein with β-Catenin and inhibiting Wnt-activated genes. We utilized previously unreported trial design, formulating C-82 for topical application and conducting a placebo controlled, double-blinded clinical trial in which patients with diffuse cutaneous SSc were treated with C-82 or placebo on opposite forearms.
Although psoriasis has been associated with obesity, there are few prospective studies with objective measures. We prospectively examined the effect of body mass index (BMI), waist circumference, waist-hip ratio (WHR) and 10-years weight change on the risk of developing psoriasis among 33,734 people in the population-based HUNT Study, Norway. During follow-up, 369 incident psoriasis cases occurred. Relative risk (RR) of psoriasis was estimated from Cox regression. One standard deviation (SD) higher BMI, waist circumference and WHR gave RRs of 1.22 (95% confidence interval (CI) 1.11-1.34), 1.26 (95% CI 1.15-1.39), and 1.18 (95% CI 1.07-1.31), respectively.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx Quiz— In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image above, while additional questions concern the findings reported in a JID article that provides new information about that disease entity.
Patients with psoriasis are often treated with topical glucocorticoids (GCs), supporting the idea that local depletion of GCs in psoriatic skin contributes to disease pathogenesis. Although de novo GC synthesis occurs in skin, the relevance of these steroids has previously been overlooked as the hypothalamic-pituitary-adrenal axis provides the majority of GCs. Hannen and colleagues found that localized GC production was nearly absent in psoriasis skin due to decreased synthesis and increased steroid sulfation.
The authors of this multicentre European study explain that electrochemotherapy (ECT) is regarded as an effective local treatment for cutaneous metastasis. Treatment involves the administration of chemotherapeutic drugs followed by delivery of electrical pulses to the tumour. The aim of this study was to investigate the effectiveness of ECT in cutaneous metastases of melanoma and to identify factors that affect (beneficially or adversely) the outcome. ECT consisted of intratumoral or intravenous injection of bleomycin, followed by application of electric pulses under local or general anaesthesia.
The interactions between melanocytes and hair progenitor cells and the source of the hair pigmentation regulator stem cell factor (SCF) have remained unclear. Recently, Liao and colleagues discovered that cells that express KROX20, a zinc finger transcription factor, in the hair follicle (HF) identify a sublineage of HF cells that give rise to the hair shaft. These hair shaft progenitor cells provide SCF for maintenance of mature melanocytes in the upper HF matrix, enabling hair pigmentation. Ablation of Scf in these Krox20 lineage cells results in complete absence of hair pigmentation.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Cells to Surgery Quiz— In this monthly online-only quiz, the first question (“What is your diagnosis?”) relates to the clinical image above, while additional questions concern the findings reported in a JID article that provides new information about that disease entity.
On 19 June 1937, the Society for Investigative Dermatology (SID) was founded, and its formation was announced in the first issue of the Journal of Investigative Dermatology (JID). In that announcement, the newly elected officers and directors stated that the goals of this new organization were to focus on investigative work in contrast to “purely clinical reports” and to bring together “….all the numerous types of investigative work dealing with the skin.” They also stated that the new SID would focus on “…numerous types of investigative work dealing with the skin, its functions and reactions, both physiologic and pathologic.” Finally, they recognized that this work was being done by both dermatologists and nondermatologists, and they sought to bring all of these individuals and their work together.
Psoriasis has been associated with an increase in myocardial infarctions. Several registries have shown reductions in major adverse cardiovascular events in psoriasis patients and rheumatoid arthritis patients treated with tumor necrosis factor-α antagonists. Many assume that the reduction in cardiovascular events can be attributed to the anti-inflammatory effect of tumor necrosis factor blockers, but a 52-week study conducted by Bissonnette and coworkers failed to show a reduction in cardiovascular inflammation in psoriasis patients treated with adalimumab.
Dusingize et al. used a prospective observational cohort study to demonstrate a decreased risk of basal cell carcinoma and an increased risk of squamous cell carcinoma among smokers. This association disappeared after stratifying for skin screening visits, demonstrating the important role of detection bias. In the absence of randomized clinical trials, well-designed and critically analyzed observational studies can provide similarly valuable evidence.
Extracellular matrix deposition is required for wound healing. Studies by Sato et al. reveal a role for parathyroid hormone 2 receptor (PTH2R) in extracellular matrix production in wounds. Deficiencies in PTH2R or its ligand tuberoinfundibular peptide of 39 residues (TIP39) delayed repair, and TIP39 treatment accelerated healing. TIP39-PTH2R signaling induced decorin expression, which may explain the beneficial effects of PTH2R signaling on healing. These studies identify a novel role for PTH2R signaling in extracellular matrix production.
Big data is a term used for any collection of datasets whose size and complexity exceeds the capabilities of traditional data processing applications. Big data repositories, including those for molecular, clinical, and epidemiology data, offer unprecedented research opportunities to help guide scientific advancement. Advantages of big data can include ease and low cost of collection, ability to approach prospectively and retrospectively, utility for hypothesis generation in addition to hypothesis testing, and the promise of precision medicine.
Hannen et al. report that cutaneous glucocorticoidogenesis and expression of glucocorticoid receptors are inhibited in psoriatic skin. These findings substantiate the previous concept that deficient feedback of local proopiomelanocortin and glucocorticoids on cutaneous immunity contributes to inflammatory and autoimmune dermatoses. Restoration of efficient endogenous glucocorticoid signaling represents a realistic goal in treating psoriasis.
The effect of ultraviolet radiation (UVR) on human basal cell carcinoma (BCC) epidemiology is complex - the incidence rises until approximately 30,000 hours of lifetime sunlight exposure and then plateaus. We hypothesize that UVR has opposing effects on BCC carcinogenesis – stimulatory via mutagenesis, etc. and inhibitory via production of hedgehog-inhibiting vitamin D3 (D3). We find that UVR exposure of ionizing radiation (IR)-treated Ptch1+/- mice accelerates BCC carcinogenesis in male mice, in which UVR does not produce D3.
Interleukin-36 (IL-36) family members are highly expressed in hyperproliferative keratinocytes and play an important role in the pathogenesis of skin diseases such as psoriasis. However, whether and how IL-36 cytokines are induced to promote wound healing remains unknown. Here we demonstrated that skin injury increased the expression of IL-36γ to promote wound healing. Mechanistically, the expression of IL-36γ was induced by RNAs from damaged cells via the activation of Toll-like receptor 3 (TLR3) and TIR-domain-containing adapter-inducing interferon-β (TRIF) followed by the induction of a zinc finger protein SLUG to abrogate the inhibitory effect of vitamin D receptor (VDR) on the promoter of IL-36γ gene.