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Defects in Cockayne syndrome type A (CSA), a gene involved in nucleotide excision repair, cause an autosomal recessive syndrome characterized by growth failure, progressive neurological dysfunction, premature aging, and skin photosensitivity and atrophy. Beyond its role in DNA repair, the CSA protein has additional functions in transcription and oxidative stress response, which are not yet fully elucidated.Here, we investigated the role of CSA protein in primary human keratinocyte senescence. Primary keratinocytes from three CS-A patients displayed premature aging features, namely premature clonal conversion, high steady-state levels of ROS and 8-OH-hydroxyguanine (8-OH-Gua) and senescence-associated secretory phenotype (SASP).
Melanocytes can group together in nevi, commonly thought to form due to intrinsic somatic mutations involving MAPK pathway activation. However, the role of the microenvironment, in particular keratinocytes, in nevogenesis, is rarely studied. Melanocytes proliferate during the hair follicle growth phase and in some basal cell carcinomas, allowing us to construct keratinocyte gene expression clusters correlated with melanocyte activation. We asked whether such correlations are evident in the more subtle context of regulation of melanocyte behaviour in normal skin.
Cutaneous squamous cell cancers (cSCCs) present an under-recognized health issue among NonHispanic Whites (NHWs), one that’s likely to increase as populations age. cSCC risks vary considerably among NHWs, and this heterogeneity indicates the need for risk-stratified screening strategies that are guided by patients’ personal characteristics and clinical histories. Here we describe cSCCscore, a prediction tool that uses patients’ covariates and clinical histories to assign them personal probabilities of developing cSCCs within three years following risk assessment.
Persistent human papillomavirus (HPV) infection is responsible for at least 5% of human malignancies. Most HPV-associated cancers are initiated by the HPV16 genotype, as confirmed by detection of integrated HPV DNA in cells of oral and anogenital epithelial cancers. However, single-cell RNA-sequencing (scRNA-seq) may enable prediction of HPV involvement in carcinogenesis at other sites. We conducted scRNA-seq on keratinocytes from a mouse transgenic for the E7 gene of HPV16, and showed sensitive and specific detection of HPV16-E7 mRNA, predominantly in basal keratinocytes.
Inflammatory acne vulgaris afflicts hundreds of millions of people globally. Propionibacterium acnes (P. acnes), an opportunistic skin bacterium, has been linked to the pathogenesis of acne vulgaris. Our result reveals that a secretory Christie-Atkins-Munch-Peterson (CAMP) factor of P. acnes is up-regulated in anaerobic cultures. Mutation of CAMP factor significantly diminishes the P. acnes colonization and inflammation in mice, demonstrating the essential role of CAMP factor in the cytotoxicity of P.
Atopic dermatitis (AD) is a highly debilitating disease with significant health impacts worldwide. It has been a difficult disease to treat due to the wide spectrum of clinical manifestations. As such, the current clinical management strategies are non-specific. Previous studies have documented that AD disease progression is precipitated by a combination of skin barrier dysfunction, itch and immune dysregulation. However, the precise role played by effector cells and cytokines have not been fully elucidated.
For most scientists, publications are the “currency of the realm.” Professional recognition, career advancement, opportunities, and funding decisions are all influenced by numbers of publications, the perceived impact of the journals in which publications appear, and the extent and nature of individual contributions to each publication. In biomedical sciences, the latter have historically been inferred by readers based on assignments to positions in lists of authors. While never ideal, this convention, which differs among disciplines, has become untenable.
Jones and colleagues explain that transition of hair shaft keratinocytes from actively respiring, nucleated cells to structural cells devoid of nucleus and cytoplasm is key to hair production. Although well described in epidermal keratinocytes, this process is poorly understood in the hair follicle. Their study set out to address this knowledge gap, with the aim of gaining insights into cornification mechanisms within the hair follicle and thereby improving the understanding of normal hair physiology.
In an open-label clinical trial, Jabbari and colleagues demonstrated clinical efficacy of the small molecule JAK1,3 inhibitor tofacitinib in 12 patients with moderate-to-severe alopecia areata (AA), a disease that results from autoimmune attack on the hair follicles with resulting significant hair loss. Tofacitinib, which has previously been approved for treatment of rheumatoid arthritis, halted hair loss and allowed considerable regrowth in 11 of these patients without serious adverse effects. Although the therapy is non-curative, as evidenced by relapse after treatment cessation, tofacitinib is a promising therapy for the treatment of hair loss in AA.
During fetal life, mammals undergo a transition from complete skin regeneration to scarring. Previous work demonstrated that embryonic cells that expressed engrailed 1, termed En1-lineage-past fibroblasts (EPFs), contribute to scarring, while En1-lineage-naïve fibroblasts (ENFs) do not. In order to better map dermal morphogenesis, Jiang and colleagues employed single-cell fate mapping, 3D confocal imaging, and in silico analysis. These endeavors revealed that transplantation of ENFs into adult wounds result in regenerative outcomes, while transplantation of EPFs result in scarring.
Editorial note: Welcome to the Journal of Investigative Dermatology (JID) SnapshotDx Quiz. In this monthly online-only quiz, the first question relates to the clinical image found above, while additional questions concern the findings reported in a JID article that provides new information about that disease entity.
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.
Little is known about tanning addiction in adolescents. Miller et al. found that 7.0% of 11th grade students met addiction criteria. After adjusting for all other comorbidities, the odds of addiction were two times greater for students who reported problem use of marijuana or obsessive-compulsive disorder symptoms. The likelihood of addiction increased with problem substance use and psychological symptoms.
Autophagy, discovered as a starvation-induced cellular recycling pathway, routes protein aggregates, damaged organelles, and pathogens to lysosomes and also supports normal tissue homeostasis. Although prior studies linked autophagy to epidermal differentiation, infection, and carcinogenesis, Wang et al. report upstream regulation of autophagy by microRNAs. Subcutaneous delivery of microRNA mimics and antagonists modulated autophagy in vivo, suggesting a novel potential therapeutic strategy in dermatology.