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Bakuchiol is a plant-derived phytochemical that is known to have retinoid-like effects in vitro. Dhaliwal and colleagues report a randomized trial in which 44 healthy participants with a mean age of 47 years applied bakuchiol 0.5% cream or retinol 0.5% cream for 12 weeks. Bakuchiol and retinol both significantly decreased wrinkle surface area and hyperpigmentation, with no statistical difference between the compounds. The retinol users reported more facial skin scaling and stinging. The authors concluded that bakuchiol is comparable with retinol in its ability to improve photoageing and is better tolerated than retinol.
Monitoring immune responses in humans typically involves analysis of blood samples. Important immune reactions usually occur in peripheral tissues, such as the skin, and these sites are often not evaluated. Microneedle patches, comprised of arrays of projections that mechanically pierce the stratum corneum to reach the epidermis and upper dermis, have been engineered not only to deliver drugs and vaccines but also to sample interstitial fluid. To extend the utility of these minimally invasive sampling tools, Mandal and colleagues developed a microneedle-based platform involving a hydrogel layer that swells upon application of the skin to enable sampling of both interstitial fluid and cells from the skin.
To bring evidence-based improvements in medicine and health care delivery to clinical practice, health care providers must know how to interpret clinical research findings and critically evaluate the strength of evidence. This requires an understanding of differences in clinical study designs and the various statistical methods used to identify associations. We aim to provide a foundation for understanding the common measures of association used in epidemiologic studies to quantify relationships between exposures and outcomes, including relative risks, odds ratios, and hazard ratios.
Hematopoietic stem cell transplantation (HCT), which is increasingly used to treat patients with malignant and non-malignant conditions, is associated with increased risk for malignancies, including skin cancers. Data on incidence is incomplete, however, as more recent practices have utilized different donor sources and reduced-intensity conditioning regimens. In a contemporary cohort of 1,974 allogeneic HCT patients, Wu and colleagues found significantly increased incidences of basal cell carcinoma, squamous cell carcinoma, and melanoma.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) Snapshot Dx Quiz. In this monthly online-only quiz, the first question relates to the clinical image found below, while additional questions concern the findings reported in a JID article by Stark et al. (2018) (https://doi.org/10.1016/j.jid.2018.02.012).
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 below, while additional questions concern the findings reported in a JID article by Wang et al. (2018) that provides new information about that disease entity (https://doi:10.1016/j.jid.2018.03.1528).
Most susceptibility loci for complex dermatologic diseases fall within non-coding regions, making assignment of function difficult. Chromosome conformation capture addresses this problem by using the spatial organization of chromatin to identify the genes these loci interact with, often across long distances. Furthermore, as gene regulation is tissue-/cell-dependent, studying relevant cell populations is critical to reveal the molecular mechanisms involved.
Allogeneic hematopoietic stem cell transplantation provides a graft-versus-malignancy effect and long-term remissions in high-risk hematological malignancies. Reduced-intensity conditioning regimens have been developed, transplantation has become safer, and the number of long-term transplantation survivors is expected to rise. Wu et al. (2018) report the increased incidence and risk factors of skin cancer in 1994 transplant recipients followed in the last 25 years.
A new report in this issue of Journal of Investigative Dermatology reveals a role for IL-17 and IFN-gamma, signature cytokines of T-helper 17 and T-helper 1 cells, in immunity to Trichophyton benhamiae (Heinen et al., 2018). While there have been many recent advances in understanding host defenses against common fungi, this work illuminates not only adaptive immunity, but also innate immune responses to dermatophytosis.
The development of novel antiviral compounds is hindered by the lack of model systems that recapitulate the pathophysiology of human infections. Tajpara et al. developed an ex vivo human abdominal skin model of HSV-1 infection to examine host-pathogen interactions and test the efficacy of antiviral compounds. This approach provides a platform for future development and testing of antiviral drugs.
Staphylococcus aureus is a significant bacterial pathogen that may penetrate through the barrier into the epidermis and dermis of the skin. We hypothesized that the S. aureus cell wall product, lipoteichoic acid (LTA), may contribute to the development of inflammation and skin barrier defects; however, the effects of LTA in vivo are not well understood. In this study, we examined the effects induced by intradermal S. aureus LTA. We found that keratinocytes in LTA treated skin were highly proliferative, expressing 10-fold increased levels of Ki67.
Nicotinamide (NAM) is the main precursor of NAD+, a co-enzyme essential for DNA repair, glycolysis and oxidative phosphorylation (OXPHOS). NAM has anti-aging activity on human skin, but the underlying mechanisms of action are unclear. Using 3D organotypic skin models, we show that NAM inhibits differentiation of the upper epidermal layers and maintains proliferation in the basal layer. In 2D culture, NAM reduces the expression of early and late epidermal differentiation markers and increases the proliferative capacity of human primary keratinocytes (HPKs).
Chronic low-grade inflammation can cause several metabolic syndromes. Patients with psoriasis, a chronic immunological skin inflammation, often develop diabetes. However, it is not clear to date how psoriasis leads to, or is correlated with, glucose intolerance. Here, we investigate whether psoriasis itself correlates with hyperglycemia in humans and mice. In patients, severity of psoriasis was correlated with high blood glucose levels and treatment of psoriasis by phototherapy improved insulin secretion.
In melanoma, initiating oncogenic mutations in BRAF or NRAS are detected in premalignant lesions that accumulate additional mutations and genomic instability as the tumour evolves to the metastatic state. Here we investigate evolution of clonal composition and neoantigen landscape in an atypical melanoma displaying recurrent cutaneous lesions over a 6-year period without development of extra-cutaneous metastases. Whole exome sequencing of 4 cutaneous lesions taken over the 6-year period identified a collection of single nucleotide variants (SNVs) and small insertions and deletions (Indels) shared amongst all tumours along with progressive selection of subclones displaying fewer SNVs.
The benign melanocytic nevus is the commonest tumor in humans and rarely transforms into cutaneous melanoma. Elucidation of the nevus genome is required to better understand the molecular steps of progression to melanoma. We performed whole genome sequencing on a series of 14 benign melanocytic nevi, consisting of both congenital and acquired types. All nevi had driver mutations in the MAPK signalling pathway, either BRAF V600E or NRAS Q61R/L. No additional definite driver mutations were identified.
Oral mucosa contains a unique transcriptional network that primes oral wounds for rapid resolution in humans. Our previous work identified genes that were consistently upregulated in the oral mucosa and demonstrated that induction of one of the identified genes, transcription factor SOX2, promoted cutaneous wound healing in mice. In this study, we investigated the molecular and cellular mechanisms by which SOX2 accelerates wound healing in skin. RNA-seq analysis showed that SOX2 induced a proliferative and wound-activated phenotype in skin keratinocytes prior to wounding.