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Deficient expression of Suppressor Special AT-rich Binding-1 (SATB1) hampers thymocyte development and results in inept T cell lineages. Recent data implicate dysregulated SATB1 expression in the pathogenesis of mycosis fungoides (MF), the most frequent variant of cutaneous T cell lymphoma (CTCL). Here we report on a disease-stage-associated decrease of SATB1 expression and an inverse expression of STAT5 and SATB1 in situ. Importantly, STAT5 inhibited SATB1 expression through induction of miR-155.
Ixekizumab, a high-affinity monoclonal antibody that selectively targets interleukin-17A, is efficacious for moderate-to-severe plaque psoriasis. We examined relationships between serum ixekizumab concentrations, treatment-emergent anti-drug antibodies (TE-ADA), and efficacy during 60 weeks of treatment in a randomized, controlled, phase 3 study. Steady-state ixekizumab serum trough concentrations were rapidly achieved and associated with high clinical responses at week 12 with a starting dose of 160 mg followed by 80 mg every 2 weeks.
Public health guidance recommends limiting sun-exposure to sub-sunburn levels, but it’s unknown whether these can gain vitamin D (for musculoskeletal health) whilst avoiding epidermal DNA damage (initiates skin cancer). Well-characterised healthy humans of all skin types (I-VI; lightest to darkest skin) were exposed to a low dose-series of solar simulated UVR of 20-80% their individual sunburn threshold dose (minimal erythemal dose, MED). Significant UVR dose-responses were seen for serum 25(OH)D and whole epidermal CPD, with as little as 0.2 MED concurrently producing 25(OH)D and CPD.
Acne051, 240, 312, 336, 383, 421, 447, 505, 532, 556, 566, 578, 600, 675, 833, 854, 880, 899, 914, 941, 970, 992, 1016, 1023, 1029, 1040, 1048, 1061, 1084, 1108, 1279, 1317, 1318, 1321, 1343, 1353
Aasi, Sumaira164, 182, 210
Wound healing is an interactive biological process, involving resident cells as well as distant cells issued from bone barrow. The 3 steps of wound healing, namely inflammation, proliferation and remodeling are finely regulated. Our team has recently shown that a peculiar subpopulation of Microchimeric Fetal Cells (MFCs), transferred from the fetus to the mother during pregnancy, specifically migrated to wounded skin and enhanced skin healing though Ccl2/Ccr2 pathway. Pregnancy is characterized by increased hormonal levels and also a high number of circulating fetal cells.
Keloids represent one extreme of aberrant dermal wound healing and are characterized by fibroblast proliferation, excessive deposition of extracellular matrix and cytokine overexpression. Molecular pathology underlying keloid formation and progression remain unclear. P53 signaling plays a key role in keloid formations. However, the regulatory mechanism for p53 in the keloid pathogenic process remains elusive. Here, we show that expression of TRAF4 was markedly higher in keloid fibroblasts, whereas expression of p53 was decreased.
Over the last 25 years, developments in injectable dermal fillers have revolutionized soft-tissue augmentation, in part due to their lower invasiveness than cosmetic surgeries, but can still be improved upon. Dermal fillers with microspheres (Artefill, Radiesse, Sculptra) can allow new collagen to form, but rely on carriers (bovine collagen and carboxymethylcellulose gel, respectively) that degrade over time generate foreign body reactions. Hyaluronic acid fillers can swell up to three times their size as water diffuses into them and have hydrogel mesh sizes that are sub-micron (Radiesse), making it difficult for new collagen to form within it.
Some chronic wounds fail to heal despite standard therapy. Recently, the armamentarium available to treat chronic wounds has been enriched with the newly discovered functions of beta-blockers (BB). BB are relatively safe and been in use for decades for various indications and therefore represent exciting potential for translation to the bedside. Herein we present clinical outcomes to support existing in vitro evidence for use of BB for wound epithelialization. Three patients were treated with topical timolol maleate 0.5% at a 1 drop/cm2 dose.
Chronic wounds affect over 5 million patients and costing an estimated $20 billion annually, representing a significant burden to patients and the US health care system. Naturally sourced cellular and tissue/growth factor therapies exist to treat chronic wounds but their cost prevents reimbursed use until wounds are chronic, decreasing effectiveness and hindering outcome. Cost-effective, simple treatments are needed that can accelerate healing in acute wounds and prevent development of chronic wounds.
The African spiny mouse (Acomys) can regenerate up to 70% of its skin, including all appendages, after full-thickness skin wounding. This wound-induced hair neogenesis (WIHN) begins from the wound periphery on post-wound day 15 (PWD15), and later in the wound center (PWD21). In contrast, WIHN only occurs in the center of the wound for C57Bl/6 mouse. The spatiotemporal stiffness of the spiny mouse wounds was measured using the atomic force microscopy, which showed a gradual increase from 2.35 kPa (wound center) and 7.87 kPa (wound periphery) on PWD15 to 7.19 kPa and 11.45 kPa on PWD21, respectively.
Epidermolysis bullosa (EB) is a genetic mechanobullous disorder characterized by skin fragility susceptible to blistering with minimal trauma due to malfunction or lack of anchoring proteins within different levels of the basement membrane zone. EB patients often experience chronic wounds due to multiple factors such as prolonged inflammatory phase, infection, nutrition, tissue oxygenation and medications (corticosteroids). BPM315103.0% is a Coenzyme Q10 containing cream that has shown to increase the expression of structural proteins (collagens, plectin, laminins, KRT13, KRT14 and KRT17) in fibroblasts and keratinocytes.
Keloids are pathological scars prone to form in body sites with increased skin tension. Caveolin-1 (CAV1) has been associated with the regulation of cell mechanics, including cell softening and loss of stiffness sensing ability. Although CAV1 is present in low amounts in keloid fibroblasts (KFs), the causal association between CAV1 downregulation and its aberrant responses to mechanical stimuli remain unclear. In this study, atomic force microscopy showed that KFs were softer than normal fibroblasts with a loss of stiffness sensing.
Cysteinyl leukotrienes (CysLTs; LTC4, LTD4, and LTE4) are inflammatory mediators known for their involvement in bronchoconstriction, asthma and allergy, and primarily signal through the receptors CysLT1 and CysLT2. Interestingly, recent studies have found that CysLT receptors are expressed in normal skin, and that CysLT signaling may interfere with wound healing. Furthermore, our preliminary data show that enzymes associated with CysLT synthesis are highly upregulated in burned murine skin compared to healthy skin, while a previous study showed that blister fluids from burn patients contain high LTC4 levels.