Molecular Insights Into the Effects of PLLA-SCA on Gene Expression and Collagen Synthesis in Human 3D Skin Models Containing Macrophages.

Injectable poly-L-lactic acid (PLLA-SCA) is used for the correction of shallow to deep nasolabial fold contour deficiencies, cheek wrinkles, and other facial wrinkles. In contrast to hyaluronan (HA) fillers, PLLA-SCA has a biostimulatory effect by activating resident fibroblasts to produce collagen, but the mechanisms are not known in detail at the molecular level. Therefore, our aim was to investigate the molecular effects of PLLA-SCA in a comprehensive in vitro study.

Pathological mutations reveal the key role of the cytosolic iRhom2 N-terminus for phosphorylation-independent 14-3-3 interaction and ADAM17 binding, stability, and activity.

The protease ADAM17 plays an important role in inflammation and cancer and is regulated by iRhom2. Mutations in the cytosolic N-terminus of human iRhom2 cause tylosis with oesophageal cancer (TOC). In mice, partial deletion of the N-terminus results in a curly hair phenotype (cub).

Understanding the impact of risankizumab on keratinocyte-derived IL-23A in a novel organotypic 3D skin model containing IL-23A responsive and IL-17A producing γδ-T-cells.

Purpose: To study the effects of the anti-IL-23A antibody risankizumab on the IL-36γ/IL-23A/IL-17A signalling cascade we used a newly developed 3D skin model consisting of primary human keratinocytes, fibroblasts and γδ-T-cells.

Methods: In this study we developed new full-thickness 3D skin models containing normal human epidermal keratinocytes (NHEK), normal human dermal fibroblasts (NHDF) and IL-23A responsive and IL-17A producing γδ-T-cells. The effects of IL-36γ stimulation with and without risankizumab treatment on IL-23A and IL-17A expression were examined at the RNA and protein levels.

Biological effect of laser-assisted scar healing (LASH) on standardized human three-dimensional wound healing skin models using fractional non-ablative 1540 nm Er:Glass or 1550 nm diode lasers.

Purpose: In postoperative wound healing after surgical operations or ablative laser treatments, recent studies suggest the timely use of non-ablative fractional laser treatments with the aim to improve wound healing and prevent pathological scar formation. However, the underlying molecular mechanisms are poorly understood. The aim of this study was to investigate the effects of laser-assisted scar healing (LASH) at the molecular level and to combine it with already established wound healing-promoting local treatments.

Macrophage migration inhibitory factor (MIF) and its homolog D-dopachrome tautomerase (D-DT) are significant promotors of UVB- but not chemically induced non-melanoma skin cancer.

Non-melanoma skin cancer (NMSC) is the most common cancer in Caucasians worldwide. We investigated the pathophysiological role of MIF and its homolog D-DT in UVB- and chemically induced NMSC using Mif, D-dt and Mif/D-dt mice on a hairless SKH1 background. Knockout of both cytokines showed similar attenuating effects on inflammation after acute UVB irradiation and tumor formation during chronic UVB irradiation, without additive protective effects noted in double knockout mice, indicating that both cytokines activate a similar signaling threshold.

Post-Treatment of Micro-Needling with a Dexpanthenol-Containing Ointment Accelerates Epidermal Wound Healing in Human 3D Skin Models.

Purpose: In vitro study on the molecular effects of post-treatment after micro-needling applications with a dexpanthenol-containing ointment (DCO) using 3D skin models.

Patients And Methods: In this in vitro study, full-thickness human 3D skin models were treated with a micro-needling device according to its clinical application. For post-treatment, some of the models were additionally treated with a dexpanthenol-containing ointment (DCO).

ITIH5-Derived Polypeptides Covering the VIT Domain Suppress the Growth of Human Cancer Cells In Vitro.

Oncogenic drivers such as mutated are the preferred targets in modern drug development. However, restoring the lost function of tumor suppressor proteins could also be a valid approach to combatting cancer. ITIH5 has been revealed as a potent metastasis suppressor in both breast and pancreatic cancer.

Establishment of an Intradermal Ear Injection Model of IL-17A and IL-36γ as a Tool to Investigate the Psoriatic Cytokine Network.

Psoriasis is a chronic skin disease affecting 2-3% of the global population. The proinflammatory IL-17A is a key cytokine in psoriasis. Accumulating evidence has revealed that IL-36γ plays also a pathogenic role.

MMP-3 plays a major role in calcium pantothenate-promoted wound healing after fractional ablative laser treatment.

Ablative fractional laser treatment leads to a loss of matrix metalloproteinase-3 (MMP-3) expression; therefore, in the present in vitro study, we addressed the role of MMP-3 and its regulation by calcium pantothenate in wound healing processes at the molecular level. Utilizing confocal laser microscopy, we investigated MMP-3 protein expression in fractional ablative CO laser-irradiated skin models. In addition, we established full-thickness 3D skin models using fibroblasts and keratinocytes with a MMP-3 knockdown that were irradiated with a fractional ablative Er:YAG laser to set superficial injuries with standardized dimensions and minimal thermal damage to the surrounding tissue.

Molecular effects of photon irradiation and subsequent aftercare treatment with dexpanthenol-containing ointment or liquid in 3D models of human skin and non-keratinized oral mucosa.

This study aimed to investigate the molecular effects of radiation and subsequent aftercare treatment with dexpanthenol-containing ointment and liquid on established full-thickness 3D skin models depicting acute radiodermatitis and mucositis. To mimic radiomucositis and radiodermatitis, non-keratinized mucous membrane and normal human skin models were irradiated with 5 Gray. Afterwards, models were treated topically every second day with dexpanthenol-containing ointment or liquid in comparison with placebo and untreated controls.

Long-Term and Clinically Relevant Full-Thickness Human Skin Equivalent for Psoriasis.

Psoriasis is an incurable, immune-mediated inflammatory disease characterized by the hyperproliferation and abnormal differentiation of keratinocytes. To study in depth the pathogenesis of this disease and possible therapy options suitable, pre-clinical models are required. Three-dimensional skin equivalents are a potential alternative to simplistic monolayer cultures and immunologically different animal models.

Biological Effects of Hyaluronic Acid-Based Dermal Fillers and Laser Therapy on Human Skin Models.

Injection of dermal fillers is one of the most frequently performed aesthetic procedures. The aim of the present study was to investigate the biological effects of different stabilized hyaluronan (HA) and poly-l-lactic acid fillers with and without subsequent additional fractional laser co-treatment on skin morphology and gene expression. Intradermal injection resulted in a significant enhancement of epidermal thickness detected by histological analysis.

Bifonazole Exerts Anti-Inflammatory Effects in Human Three-Dimensional Skin Equivalents after UVB or Histamine Challenge.

Background: In addition to its role as a broad-spectrum imidazole antifungal drug, data from animal models as well as human clinical trials also demonstrated an anti-inflammatory efficacy of bifonazole (BFZ). In the histamine wheal test and after UV radiation, BFZ showed antiphlogistic effects that were comparable to those of hydrocortisone. However, the underlying molecular mechanisms of the anti-inflam-matory properties of BFZ are poorly understood.

Novel Human Full-Thickness Three-Dimensional Nonkeratinized Mucous Membrane Model for Pharmacological Studies in Wound Healing.

Introduction: Efforts are increasingly aiming to develop in vitro models that can provide effective alternatives to in vivo experiments. The main aim of this study was the establishment of an in vitro model of the nonkeratinized mucous membrane that can be used as a standardized tool to evaluate biological and therapeutic effects of pharmaceuticals for mucosal wound healing.

Methods: We established a full-thickness in vitro model of the nonkeratinized mucous membrane.

Accelerated wound healing with a dexpanthenol-containing ointment after fractional ablative CO laser resurfacing of photo-damaged skin in a randomized prospective clinical trial.

Laser therapy with an ablative CO laser is a prominent treatment option for photo-damaged skin. The healing process and therefore the success of a laser can be supported by an appropriate postoperative treatment of the laser-treated skin. : The effect of a dexpanthenol-containing ointment with petroleum jelly on wound healing after fractional ablative CO laser therapy of photo-damaged skin.

Comprehensive molecular characterization of microneedling therapy in a human three-dimensional skin model.

Background And Objectives: Microneedling therapy is a widely used technique in dermatology. However, little is known about the underlying molecular effects of this therapy on extracellular matrix remodeling, wound healing, and inflammation. The aim of this study was to examine morphological and molecular changes caused by microneedling treatment in a standardized in vitro full-thickness 3D model of human skin.

Effects of a ceramide-containing water-in-oil ointment on skin barrier function and allergen penetration in an IL-31 treated 3D model of the disrupted skin barrier.

Atopic dermatitis (AD) is a chronically relapsing, pruritic inflammation of the skin with dryness and disturbed skin barrier function. Recently, we established that IL-31 treatment of human 3D skin models resulted in a disrupted skin barrier phenotype resembling AD. In this model, we found that IL-31 interferes with the differentiation of keratinocytes and inhibits the expression of terminal differentiation markers.

ITIH5 mediates epigenetic reprogramming of breast cancer cells.

Background: Extracellular matrix (ECM) is known to maintain epithelial integrity. In carcinogenesis ECM degradation triggers metastasis by controlling migration and differentiation including cancer stem cell (CSC) characteristics. The ECM-modulator inter- α-trypsin inhibitor heavy chain family member five (ITIH5) was recently identified as tumor suppressor potentially involved in impairing breast cancer progression but molecular mechanisms underlying its function are still elusive.

Macrophage migration inhibitory factor protects from nonmelanoma epidermal tumors by regulating the number of antigen-presenting cells in skin.

The response of the skin to harmful environmental agents is shaped decisively by the status of the immune system. Keratinocytes constitutively express and secrete the chemokine-like mediator, macrophage migration inhibitory factor (MIF), more strongly than dermal fibroblasts, thereby creating a MIF gradient in skin. By using global and epidermis-restricted Mif-knockout (Mif and K14-Cre; Mif) mice, we found that MIF both recruits and maintains antigen-presenting cells in the dermis/epidermis.

Inter-α-trypsin inhibitor heavy chain 5 (ITIH5) is overexpressed in inflammatory skin diseases and affects epidermal morphology in constitutive knockout mice and murine 3D skin models.

Inter-α-trypsin inhibitors are protease inhibitors that are thought to be important regulators in various acute-phase processes. They are composed of one light chain (bikunin) and different heavy chains (ITIHs). The only function known so far of ITIHs is the covalent linkage to hyaluronan (HA).