Publications by authors named "Gallinat S"

Background: Recent advancements in artificial intelligence have revolutionized dermatological diagnostics. These technologies, particularly machine learning (ML), including deep learning (DL), have shown accuracy equivalent or even superior to human experts in diagnosing skin conditions like melanoma. With the integration of ML, including DL, the development of at home skin analysis devices has become feasible.

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Aging is a complex process characterized by the gradual decline of physiological functions, leading to increased vulnerability to age-related diseases and reduced quality of life. Alterations in DNA methylation (DNAm) patterns have emerged as a fundamental characteristic of aged human skin, closely linked to the development of the well-known skin aging phenotype. These changes have been correlated with dysregulated gene expression and impaired tissue functionality.

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In recent years, reports of non-linear regulations in age- and longevity-associated biological processes have been accumulating. Inspired by methodological advances in precision medicine involving the integrative analysis of multi-omics data, we sought to investigate the potential of multi-omics integration to identify distinct stages in the aging progression from human skin tissue. For this we generated transcriptome and methylome profiling data from suction blister lesions of female subjects between 21 and 76 years, which were integrated using a network fusion approach.

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Article Synopsis
  • cSCC is a common skin cancer that often develops from actinic keratosis (AK), which is caused by UV exposure, but the progression from AK to cSCC is not fully understood.
  • Researchers used Infinium MethylationEPIC BeadChips to study DNA methylation in samples of healthy skin, AK, and cSCC, revealing that AK already exhibits cancer-like methylation patterns similar to cSCC.
  • The study noted that AK and cSCC can be classified into two subclasses based on keratinocyte differentiation, with some samples showing characteristics linked to stem cells while others appear more like healthy skin.
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Background: Aging human skin undergoes significant morphological and functional changes such as wrinkle formation, reduced wound healing capacity, and altered epidermal barrier function. Besides known age-related alterations like DNA-methylation changes, metabolic adaptations have been recently linked to impaired skin function in elder humans. Understanding of these metabolic adaptations in aged skin is of special interest to devise topical treatments that potentially reverse or alleviate age-dependent skin deterioration and the occurrence of skin disorders.

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Integrity of human skin is endangered by exposure to UV irradiation and chemical stressors, which can provoke a toxic production of reactive oxygen species (ROS) and oxidative damage. Since oxidation of proteins and metabolites occurs virtually instantaneously, immediate cellular countermeasures are pivotal to mitigate the negative implications of acute oxidative stress. We investigated the short-term metabolic response in human skin fibroblasts and keratinocytes to H2O2 and UV exposure.

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Changes in the mechanical properties of dermis occur during skin aging or tissue remodeling and affect the activity of resident fibroblasts. With the aim to establish elastic culture substrates that reproduce the variable softness of dermis, we determined Young's elastic modulus E of human dermis at the cell perception level using atomic force microscopy. The E of dermis ranged from 0.

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Background: Periostin is a secreted 90kDa matricellular protein, which is predominantly expressed in collagen-rich tissues. Collagen is the most abundant protein in mammals and has great tensile strength. Recent investigations have shown that periostin influences collagen fibrillogenesis and biomechanical properties of murine connective tissues.

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The common procedures that are used to quantify cyclobutane pyrimidine dimers (CPD) comprise the extraction of cellular DNA followed by the detection of this nucleic acid modification by immunoblotting or electrophoretic methods. Consequently, these approaches provide an averaged damage intensity value of a whole population of cells and are not applicable to studies where a small subgroup such as somatic stem cells are intended to be investigated and the individual cellular damage is of interest. Here, we describe a strategy to isolate epidermal stem cells from minimum human epidermis samples and a subsequent immunocytochemical quantification of cellular CPDs.

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Numerous studies have shown that extracellular matrix (ECM)-based scaffolds are suitable for dermal constructs for the differentiation of various cell types in vitro and for constructive tissue remodeling after implantation in vivo. However, a shortcoming of these ECM materials is its limited elastogenesis. Elastic fibers constitute an essential component of mammalian connective tissue and the presence of elastic fibers is crucial for the proper function of the cardiovascular, pulmonary, and intestinal systems.

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Background: Collagen is the most abundant protein in human skin and is responsible for its resilience. In particular during photoaging, collagen homeostasis is out of balance leading to a continuous loss of intact collagen and to the observed signs of aged skin such as diminished tensile strength and wrinkle development. The process of collagen turnover is very slow and the relevance of cellular uptake of damaged collagen, most likely mediated via Endo180 or integrin α2β1, still remains a matter of investigation.

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The terminal differentiation of epidermal keratinocytes requires transcriptional and posttranscriptional regulatory mechanisms. MicroRNAs (miRNAs) are small noncoding RNAs that play key roles during differentiation processes by regulating protein expression at the posttranscriptional level. Several studies have investigated miRNA expression in murine or human skin using northern blotting, microarrays, deep sequencing, or real-time PCR (Andl et al.

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Background: Skin derived precursors (SKP) comprise a subset of specialized dermal cells that can be distinguished from fibroblast by their capacity for spheroidal growth. Recent investigations have shown that hair follicles constitute a niche for this cell type, but their localization and their definite function in non-follicular skin remains largely unknown.

Objective: To identify the dermal niche of non-follicular SKPs and to analyze whether functional aspects correlate with this localization.

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Extracellular skin structures in human skin are impaired during intrinsic and extrinsic aging. Assessment of these dermal changes is conducted by subjective clinical evaluation and histological and molecular analysis. We aimed to develop a new parameter for the noninvasive quantitative determination of dermal skin alterations utilizing the high-resolution three-dimensional multiphoton laser scanning microscopy (MPLSM) technique.

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Background: It has been shown for various organisms that expression of tropoelastin (TE) is high during fetal and neonatal growth and that it is reduced in adulthood by an unknown mechanism.

Objective: To highlight the process of TE mRNA repression in vivo, total RNA from human skin biopsies was analyzed and TE mRNA expression was compared in fetal and adult donors.

Methods: TaqMan Real-Time PCR, Poly(A) tail length assay, immunoblot.

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In dermal photodamage the ratio of the collagen types III to I changes. This makes the investigation of the fibrillar collagen type characteristics interesting for skin research. In this study collagen types were characterized using 5-dimensional multiphoton laser scanning microscopy (5D-IVT) that can be applied in vivo.

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Background:   The dermal extracellular matrix provides stability and structure to the skin. With increasing age, however, its major component collagen is subject to degeneration, resulting in a gradual decline in skin elasticity and progression of wrinkle formation. Previous studies suggest that the reduction in cellular energy contributes to the diminished synthesis of cutaneous collagen during aging.

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Background: The epidermis harbors adult stem cells that reside in the basal layer and ensure the continuous maintenance of tissue homeostasis. Various studies imply that stem cells generally possess specific defense mechanisms against several forms of exogenous stress factors. As sun exposition is the most prevalent impact on human skin, this feature would be of particular importance in terms of sensitivity to UV-induced DNA damage.

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Background/purpose: Collagen is the major structural protein of the skin and its crosslinks are essential for its mechanical stability. In photodamaged skin, a decrease of the mature collagen crosslink histidinohydroxylysino-norleucine was reported. In this study, we investigated the consequences and measurability of the reduced crosslinking.

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Background: The decrease in firmness is a hallmark of skin aging. Accelerated by chronic sun exposure, fundamental changes occur within the dermal extracellular matrix over the years, mainly impairing the collagenous network.

Aims: Based on the qualitative and quantitative assessment of skin firmness, in vitro and in vivo studies were carried out to elucidate the effects of topical folic acid and creatine to counteract this age-dependent reduction in the amount of collagen.

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Here, we report a comprehensive investigation of changes in microRNA (miRNA) expression profiles on human keratinocyte (HK) differentiation in vitro and in vivo. We have monitored expression patterns of 377 miRNAs during calcium-induced differentiation of primary HKs, and have compared these patterns with miRNA expression profiles of epidermal stem cells, transient amplifying cells, and terminally differentiated HKs from human skin. Apart from the previously described miR-203, we found an additional nine miRNAs (miR-23b, miR-95, miR-210, miR-224, miR-26a, miR-200a, miR-27b, miR-328, and miR-376a) that are associated with HK differentiation in vitro and in vivo.

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Precise knowledge of the frequency and localization of epidermal stem cells within skin tissue would further our understanding of their role in maintaining skin homeostasis. As a novel approach we used the recently developed method of multi epitope ligand cartography, applying a set of described putative epidermal stem cell markers. Bioinformatic evaluation of the data led to the identification of several discrete basal keratinocyte populations, but none of them displayed the complete stem cell marker set.

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Epithelial tissues exhibit optimal conditions for studying cellular differentiation since the differentiation status of a single cell can be determined by its distance to the basal membrane. For that reason Laser Capture Microdissection (LCM) may serve as a perfect tool to compare the characteristics of cells that have been collected from different strata of the epithelium. However, as cell boundaries are not visible in untreated tissue sections, samples have to be stained to allow for sufficient structural orientation.

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