Seborrheic Keratosis: Is it What it Looks Like? A Case Report with Review of Literature.

Seborrheic Keratosis are common, benign skin tumours usually found in the head neck region of elderly patients in their fifties. Etiopathogenesis and its association with malignant skin tumours such as Malignant Melanoma, Basal cell Carcinoma, remains obscure which highlights the importance of treatment modality offered to such patients. We present a case of 54-year-old male with a lesion mimicking Malignant Melanoma which was diagnosed as Seborrheic Keratosis on histopathologic examination.

Lipid analysis of human primary dermal fibroblasts and epidermal keratinocytes after near-infrared exposure using mass spectrometry imaging.

Photobiomodulation (PBM) therapy is the application of near-infrared (NIR) exposure to injuries or lesions to (among others) improve wound healing, reduce inflammation, and decreases acute and chronic pain. However, the understanding of the molecular mechanism of PBM, more specifically the effects of NIR on skin cells is still lacking behind. Lipids are essential components of cellular membranes that are integral to skin structure and function. This study aims to elucidate the impact of NIR exposure on the skin's lipidome by investigating the molecular effect of NIR exposure on single skin cells. Primary human dermal fibroblasts (NHDFa) and human epidermal keratinocytes (HEKa) were exposed to NIR (850 nm) with a dose of 6.5 J/cm2 for 5 consecutive days between 09.00 and 12.00 am. A workflow utilizing matrix-assisted laser desorption/ionization mass spectrometry imaging combined with liquid chromatography tandem mass spectrometry for lipidomics analysis was performed. This study provides evidence that adequate exposure of NIR influences lipid metabolism in NHDFa, whereas no alterations were found in HEKa. This work lays the groundwork in explaining the beneficial properties on both skin-related effects and systemic health benefits as seen in clinical studies.

Astragaloside IV suppresses the proliferation and inflammatory response of human epidermal keratinocytes and ameliorates imiquimod-induced psoriasis-like skin damage in mice.

The primary pathological features of psoriasis include excessive epidermal keratinocytes and infiltration of inflammatory cells, which are pivotal targets for psoriasis therapy. Astragaloside IV (AS-IV), the principal active compound of astragalus, exhibits anti-inflammatory, antioxidant, and immune-modulatory properties. This study aims to investigate AS-IV's anti--psoriatic effects and underlying mechanisms. Normal human epidermal keratinocytes (NHEKs) were stimulated with a combination of TNF-α, IL-17A, IL-1α, IL-22, and oncostatin M (M5) to replicate psoriatic keratinocyte pathology in vitro. Cell proliferation was assessed using CCK8 and EDU staining. Pro-inflammatory cytokine levels were measured via qRT-PCR. In addition, an imiquimod (IMQ)-induced psoriasis mouse model was utilized. Skin histology changes were evaluated with HE staining, while IL-6 and TNF-α levels in mouse serum were quantified using ELISA. NF-κB pathway protein expression was analyzed by western blotting. The results demonstrated that AS-IV inhibited M5-induced proliferation of NHEKs. AS-IV reduced M5-stimulated IL-1ß, IL-6, IL-8, TNF-α, IL-23, and MCP-1 expression in NHEKs. Moreover, M5-induced phosphorylation of IκBα and p65 was significantly attenuated by AS-IV. Furthermore, AS-IV application ameliorated erythema, scale formation, and epidermal thickening in IMQ-induced psoriasis-like mouse models. AS-IV also decreased IL-6 and TNF-α levels in mouse serum and inhibited IκBα and p65 phosphorylation in skin tissues. However, prostratin treatment reversed these effects. These findings underscore AS-IV's capacity to mitigate M5-induced NHEK proliferation and inflammation. AS-IV shows promise in alleviating IMQ-induced psoriasis-like skin lesions and inflammation by suppressing the NF-κB pathway.

Eruptive Pruritic Papular Porokeratosis (EPPP) Presenting as a Rare Facial Manifestation Associated With COVID-19: A Case Report.

This case report presents a rare instance of Eruptive Pruritic Papular Porokeratosis (EPPP) in a 71-year-old Chinese male, emerging on atypical sites (face, scalp, and ears) following a COVID-19 infection, and explores the potential link between viral infections and EPPP onset. The patient's lesions, characterized by annular brown patches with hyperkeratotic ridges, showed significant improvement following treatment with Baricitinib and Acitretin. This case underscores the need for awareness of unusual presentations of EPPP and suggests the potential efficacy of Janus Kinase (JAK) inhibitors in treatment, prompting further research into the pathophysiological connections between EPPP and viral infections. Adherence to the SCARE 2023 guidelines ensures a comprehensive and transparent case presentation.

Lipid nanoparticles containing labile PEG-lipids transfect primary human skin cells more efficiently in the presence of apoE.

Nucleic acid-based therapeutics encapsulated into lipid nanoparticles (LNPs) can potentially target the root cause of genetic skin diseases. Although nanoparticles are considered impermeable to skin, research and clinical studies have shown that nanoparticles can penetrate into skin with reduced skin barrier function when administered topically. Studies have shown that epidermal keratinocytes express the low-density lipoprotein receptor (LDLR) that mediates endocytosis of apolipoprotein E (apoE)-associated nanoparticles and that dermal fibroblasts express mannose receptors. Here we prepared LNPs designed to exploit these different endocytic pathways for intracellular mRNA delivery to the two most abundant skin cell types, containing: (i) labile PEG-lipids (DMG-PEG2000) prone to dissociate and facilitate apoE-binding to LNPs, enabling apoE-LDLR mediated uptake in keratinocytes, (ii) non-labile PEG-lipids (DSPE-PEG2000) to impose stealth-like properties to LNPs to enable targeting of distant cells, and (iii) mannose-conjugated PEG-lipids (DSPE-PEG2000-Mannose) to target fibroblasts or potentially immune cells containing mannose receptors. All types of LNPs were prepared by vortex mixing and formed monodisperse (PDI âˆ¼ 0.1) LNP samples with sizes of 130 nm (±25%) and high mRNA encapsulation efficiencies (≥90%). The LNP-mediated transfection potency in keratinocytes and fibroblasts was highest for LNPs containing labile PEG-lipids, with the addition of apoE greatly enhancing transfection via LDLR. Coating LNPs with mannose did not improve transfection, and stealth-like LNPs show limited to no transfection. Taken together, our studies suggest using labile PEG-lipids and co-administration of apoE when exploring LNPs for skin delivery.

Evaluation of Cd-induced cytotoxicity in primary human keratinocytes.

An increasing number of studies have investigated the effects of Cd on human health. Cd-induced dermatotoxicity is an important field of research, but numerous studies have focused on the effects of Cd on the human skin. Moreover, most studies have been performed using HaCaT cells but not primary keratinocytes. In this study, we provide the results describing the cytotoxic effects of Cd exposure on primary human epidermal keratinocytes obtained from different donors. The subtoxic concentration of cadmium chloride was determined via MTT assay, and transcriptomic analysis of the cells exposed to this concentration (25 µM) was performed. As in HaCaT cells, Cd exposure resulted in increased ROS levels, cell cycle arrest, and induction of apoptosis. In addition, we report that exposure to Cd affects zinc and copper homeostasis, induces metallothionein expression, and activates various signaling pathways, including Nrf2, NF-kB, TRAIL, and PI3K. Cd induces the secretion of various cytokines (IL-1, IL-6, IL-10, and PGE2) and upregulates the expression of several cytokeratins, such as KRT6B, KRT6C, KRT16, and KRT17. The results provide a better understanding of the mechanisms of cadmium-induced cytotoxicity and its effect on human epidermal skin cells.

Glycyl-tRNA Synthetase Induces Psoriasis-Like Skin by Facilitating Skin Inflammation and Vascular Endothelial Cell Angiogenesis.

Psoriasis is characterized by excessive keratinocyte proliferation and immunocyte infiltration, but the underlying pathogenesis remains unclear. Aminoacyl-tRNA synthetases are universally expressed enzymes that catalyze the first step of protein synthesis. Glycyl-tRNA synthetase (GARS) is a member of the aminoacyl-tRNA synthetase family. In addition to its canonical function, we found that GARS was overexpressed in the serum and skin lesions of patients with psoriasis. Moreover, GARS was highly expressed in human skin keratinocytes, and GARS knockdown in keratinocytes suppressed cell proliferation and promoted apoptosis through NF-κB/MAPK signaling pathway. Moreover, intradermal injection of recombinant GARS protein caused skin thickening, angiogenesis, and IFN/TNF-driven skin inflammation. Intriguingly, the reported functional receptor for GARS, cadherin 6 (CDH6), was specifically expressed in vascular endothelial cells, and we found that keratinocyte-derived GARS promotes inflammation and angiogenesis of vascular endothelial cells through CDH6. In addition, intradermal injection of GARS aggravated the phenotype and angiogenesis in imiquimod-induced psoriasiform dermatitis models, whereas the psoriatic phenotype and angiogenesis were relieved after knockdown of GARS by adeno-associated virus. Taken together, the results of this study identify the critical role of GARS in the pathogenesis of psoriasis and suggest that blocking GARS may be a therapeutic approach for alleviating psoriasis.

Effects of Schumann resonance on the proliferation and migration of normal human epidermal keratinocytes and the expression of DEFB1 and SIRT1.

BACKGROUND: When the skin is damaged and its barrier function is disrupted, the proliferation and migration of epidermal keratinocytes are vital for repairing the damaged area. The Schumann resonance at 7.8 Hz has been reported to protect rat cardiomyocytes against oxidative stress and inhibit the proliferation of B16 mouse melanoma cells. However, its effect on the skin is unknown. AIMS: In this study, we applied 7.8-Hz electromagnetic waves to normal human epidermal keratinocytes (NHEKs) and investigated its effects on cell proliferation and migration, ß-defensin (DEFB1) and sirtuin 1 (SIRT1) expression. METHODS: We performed cell proliferation assay, cell migrationassay and gene expression analysis of DEFB1 and SIRT1. RESULTS: We found that the application of 7.8-Hz electromagnetic waves caused a 2.8-fold increase in NHEK proliferation, enhanced cell migration, and increased the expression of DEFB1 and SIRT1 by 2.4-fold and 4.9-fold, respectively. CONCLUSIONS: These results suggest that the application of 7.8-Hz electromagnetic waves may contribute to improving the skin barrier function and skin ulcer.

Biology of melanocytes in mammals.

Melanocytes, which originate from the neuroectoderm, are specialized cells responsible for producing pigments and possessing a dendritic morphology. These cells migrate to the epidermis and follicles, contributing to skin and hair pigmentation during embryonic development. The remarkable self-renewal capacity of melanocytes enables them to effectively restore hair and skin pigmentation. The synthesis of melanin to safeguard the skin against damage caused by ultraviolet radiation, as well as the enigmatic immune function of melanocytes, demonstrate their indispensable contributions to maintaining cutaneous homeostasis. The regulation of cutaneous pigmentation involves an intricate network influenced by intrinsic cellular signals within melanocytes and extracellular cues. Therefore, this paper provides a comprehensive review of the role of melanocytes in skin biology. This in-depth analysis could open novel avenues for research aimed at the prevention and treatment of skin disorders.

Skin epidermal keratinocyte p53 induces food uptake upon UV exposure.

Introduction: The first cells affected by UVB exposure are epidermal keratinocytes, and p53, the genome guardian, is activated in these cells when skin is exposed to UVB. UVB exposure induces appetite, but it remains unclear whether p53 in epidermal keratinocytes plays a role in this appetite stimulation. Results: Here we found that food intake was increased following chronic daily UVB exposure in a manner that depends on p53 expression in epidermal keratinocytes. p53 conditional knockout in epidermal keratinocytes reduced food intake in mice upon UVB exposure. Methods: To investigate the effects of p53 activation following UVB exposure, mice behavior was assessed using the staircase, open-field, elevated-plus maze, and conditioned-place preference tests. In addition to effects on appetite, loss of p53 resulted in anxiety-related behaviors with no effect on activity level. Discussion: Since skin p53 induces production of ß-endorphin, our data suggest that UVB-mediated activation of p53 results in an increase in ß-endorphin levels which in turn influences appetite. Our study positions UVB as a central environmental factor in systemic behavior and has implications for the treatment of eating and anxiety-related disorders.

"Input/output cytokines" in epidermal keratinocytes and the involvement in inflammatory skin diseases.

Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases. The purpose of this review is to provide foundation of knowledge on the cytokines which are recognized or produced by epidermal keratinocytes. Since a number of biologics for skin diseases have appeared, it is necessary to fully understand the relationship between epidermal keratinocytes and the cytokines. In this review, the cytokines recognized by epidermal keratinocytes are specifically introduced as "input cytokines", and the produced cytokines as "output cytokines". Furthermore, we also refer to the existence of biologics against those input and output cytokines, and the target skin diseases. These use results demonstrate how important targeted cytokines are in real skin diseases, and enhance our understanding of the cytokines.

Ultraviolet Radiation-Induced Mitochondrial Disturbances Are Attenuated by Metabolites of Melatonin in Human Epidermal Keratinocytes.

Melatonin (N-acetyl-5-methoxytryptamine) is recognized as an effective antioxidant produced by the pineal gland, brain and peripheral organs, which also has anti-inflammatory, immunomodulatory, and anti-tumour capacities. Melatonin has been reported as a substance that counteracts ultraviolet radiation B (UVB)-induced intracellular disturbances. Nevertheless, the mechanistic actions of related molecules including its kynurenic derivatives (N1-acetyl-N2-formyl-5-methoxykynurenine (AFMK)), its indolic derivatives (6-hydroxymelatonin (6(OH)MEL) and 5-methoxytryptamine (5-MT)) and its precursor N-acetylserotonin (NAS) are only poorly understood. Herein, we treated human epidermal keratinocytes with UVB and assessed the protective effect of the studied substances in terms of the maintenance of mitochondrial function or their radical scavenging capacity. Our results show that UVB caused the significant elevation of catalase (CAT) and superoxide dismutase (Mn-SOD), the dissipation of mitochondrial transmembrane potential (mtΔΨ), a reduction in ATP synthesis, and the enhanced release of cytochrome c into cytosol, leading subsequently to UVB-mediated activation of the caspases and apoptosis (appearance of sub-G1 population). Our findings, combined with data reported so far, indicate the counteracting and beneficial actions of melatonin and its molecular derivatives against these deleterious changes within mitochondria. Therefore, they define a path to the development of novel strategies delaying mitochondrial aging and promoting the well-being of human skin.

N,N-Dimethylglycine Sodium Salt Exerts Marked Anti-Inflammatory Effects in Various Dermatitis Models and Activates Human Epidermal Keratinocytes by Increasing Proliferation, Migration, and Growth Factor Release.

N,N-dimethylglycine (DMG) is a naturally occurring compound being widely used as an oral supplement to improve growth and physical performance. Thus far, its effects on human skin have not been described in the literature. For the first time, we show that N,N-dimethylglycine sodium salt (DMG-Na) promoted the proliferation of cultured human epidermal HaCaT keratinocytes. Even at high doses, DMG-Na did not compromise the cellular viability of these cells. In a scratch wound-closure assay, DMG-Na augmented the rate of wound closure, demonstrating that it promotes keratinocyte migration. Further, DMG-Na treatment of the cells resulted in the upregulation of the synthesis and release of specific growth factors. Intriguingly, DMG-Na also exerted robust anti-inflammatory and antioxidant effects, as assessed in three different models of human keratinocytes, mimicking microbial and allergic contact dermatitis as well as psoriasis and UVB irradiation-induced solar dermatitis. These results identify DMG-Na as a highly promising novel active compound to promote epidermal proliferation, regeneration, and repair, and to exert protective functions. Further preclinical and clinical studies are under investigation to prove the seminal impact of topically applied DMG-Na on relevant conditions of the skin and its appendages.

Loss of epidermal glucocorticoid receptor protects against whole body metabolic dysfunction upon chronic corticosterone treatment.

OBJECTIVE: Glucocorticoid (GC) excess contributes to the development of metabolic syndrome, defined by visceral obesity, abnormal glucose tolerance, and dyslipidemia. While it is accepted that loss of metabolic control is causative of cutaneous diseases, the systemic effects of epidermal dysfunction have received limited attention. Importantly, independent of GC blood levels, skin synthesis of these hormones can provide tissue-specific variations that may affect global homeostasis. We aimed to assess whether the epidermal-specific loss of the GC receptor (GR) had an impact on the dermal white adipose tissue (dWAT), a specialized fat depot functionally different from other fat pads, as well as on whole body homeostasis. METHODS: GR epidermal KO (GREKO) and control female mice were treated with oral corticosterone (CORT) for 4 weeks, a protocol inducing metabolic dysfunction. Metabolic parameters including body weight, visceral and hepatic fat accumulation, blood glucose and insulin levels, glucose tolerance tests upon fasting, and triglycerides levels, were determined. Systemic alterations of soluble factors with known roles in immunity and inflammation were also assessed by a multiplex antibody array system containing selected cytokines, chemokines, and growth factors. The levels of cutaneous GCs and the profile of skin-secreted factors were determined in tissue explants by ELISA and the multiplex array system. Morphometric studies quantitated changes in dWAT thickness and adipocyte size in both genotypes, basally and at the end of CORT treatment. The expression of adipocyte markers was assessed in purified dermal adipocytes in vehicle and CORT-treated GREKOvs controls. RESULTS: Despite similar circulating levels of GCs, GREKO mice were highly resistant to CORT-induced systemic metabolic anomalies including body weight gain, visceral and hepatic fat, hyperglycemia, insulinemia, and elevated levels of plasma triglycerides, leptin, FGF-21, PAI-1, and CCL11. GREKO mice featured constitutively enhanced levels of cutaneous GCs relative to controls at least partially due to keratinocyte-specific increased expression of the critical steroidogenic enzyme Cyp11b1. Also, the higher ratio of skin-secreted protective vs inflammatory adipokines in GREKOvs controls, correlated with higher capacity of adipogenic conversion in experiments using conditioned media from tissue explants. Following CORT treatment, relative to controls, GREKO mice featured reduced dWAT hyperplasia and adipocyte hypertrophy, with increased Adipoq and decreased Lipocalin 2 expression in purified dermal adipocytes. CONCLUSIONS: Overall data suggest that epidermal GR loss results in paracrine actions on dermal adipocytes as well as endocrine actions on key metabolic tissues that significantly improve the whole body metabolism in a mouse model of metabolic dysfunction.

α-Ionone protects against UVB-induced photoaging in epidermal keratinocytes.

Objective: To evaluate whether α-ionone, an aromatic compound mainly found in raspberries, carrots, roasted almonds, fruits, and herbs, inhibits UVB-mediated photoaging and barrier dysfunction in a human epidermal keratinocyte cell line (HaCaT cells). Methods: The anti-photoaging effect of α-ionone was evaluated by detecting the expression of barrier-related genes and matrix metalloproteinases (MMPs) in HaCaT cells. The levels of reactive oxygen species, oxidation product, antioxidant enzyme, and inflammatory factors were further analysed to underline the protective effect of α-ionone on epidermal photoaging. Results: It was found that α-ionone attenuated UVB-induced barrier dysfunction by reversing keratin 1 and filaggrin in HaCaT cells. α-Ionone also reduced the protein amount of MMP-1 and mRNA expression of MMP-1 and MMP-3 in UVB-irradiated HaCaT cells, implying protective effects on extracellular matrix. Furthermore, HaCaT cells exposed to α-ionone showed significant decreases in interleukin (IL)-1ß, IL-6, IL-8, and tumor necrosis factor-α as compared to UVB-irradiated HaCaT cells. α-Ionone treatment significantly inhibited the UVB-induced intracellular reactive oxygen species increase and malondialdehyde accumulation. Therefore, the beneficial effects of α-ionone on inhibiting MMPs secretion and barrier damage may be related to attenuated inflammation and oxidative stress. Conclusion: Our results highlight the protective effects of α-ionone on epidermal photoaging and promote its clinic application as a potential natural anti-photodamage agent in future.

Acceleration of Wound Healing through Amorphous Calcium Carbonate, Stabilized with High-Energy Polyphosphate.

Amorphous calcium carbonate (ACC), precipitated in the presence of inorganic polyphosphate (polyP), has shown promise as a material for bone regeneration due to its morphogenetic and metabolic energy (ATP)-delivering properties. The latter activity of the polyP-stabilized ACC ("ACC∙PP") particles is associated with the enzymatic degradation of polyP, resulting in the transformation of ACC into crystalline polymorphs. In a novel approach, stimulated by these results, it was examined whether "ACC∙PP" also promotes the healing of skin injuries, especially chronic wounds. In in vitro experiments, "ACC∙PP" significantly stimulated the migration of endothelial cells, both in tube formation and scratch assays (by 2- to 3-fold). Support came from ex vivo experiments showing increased cell outgrowth in human skin explants. The transformation of ACC into insoluble calcite was suppressed by protein/serum being present in wound fluid. The results were confirmed in vivo in studies on normal (C57BL/6) and diabetic (db/db) mice. Topical administration of "ACC∙PP" significantly accelerated the rate of re-epithelialization, particularly in delayed healing wounds in diabetic mice (day 7: 1.5-fold; and day 13: 1.9-fold), in parallel with increased formation/maturation of granulation tissue. The results suggest that administration of "ACC∙PP" opens a new strategy to improve ATP-dependent wound healing, particularly in chronic wounds.

Liquiritigenin reverses skin aging by inhibiting UV-induced mitochondrial uncoupling and excessive energy consumption.

BACKGROUND: The accumulation of reactive oxygen species (ROS) generated by UV radiation can lead to lipid, protein, nucleic acid, and organelle damage, one of the core mechanisms mediating skin aging. In the photoaging process, how ROS drives the imbalance of the body's complex repair system to induce senescence-like features is not fully understood. METHODS: We irradiated human epidermal keratinocytes with 12 J/cm2 of UVA to establish an in vitro photoaging model. Then we employed whole-transcriptome sequencing and O2K mitochondrial function assay to reveal the photoprotective mechanisms of liquiritigenin (LQ). DISCUSSION: We found that skin reduces endogenous ROS by promoting mitochondrial oxidative phosphorylation uncoupling in response to UVA-induced damage. However, this also causes excessive consumption and idling of nutrients, leading to the inhibition of cell proliferation, and ultimately accelerating the skin aging process. Here, we demonstrated that LQ can reduce stress in keratinocytes, increase oxidative phosphorylation and ATP production efficiency, and block the massive loss of skin nutrients and net energy stress. Furthermore, LQ can promote collagen synthesis and keratinocyte proliferation through the PI3K-AKT pathway, thereby reversing photoaging. CONCLUSION: This work provides a new skin aging mechanism and solution strategy with high clinical translation value.

The mineralocorticoid receptor modulates timing and location of genomic binding by glucocorticoid receptor in response to synthetic glucocorticoids in keratinocytes.

Glucocorticoids (GCs) exert potent antiproliferative and anti-inflammatory properties, explaining their therapeutic efficacy for skin diseases. GCs act by binding to the GC receptor (GR) and the mineralocorticoid receptor (MR), co-expressed in classical and non-classical targets including keratinocytes. Using knockout mice, we previously demonstrated that GR and MR exert essential nonoverlapping functions in skin homeostasis. These closely related receptors may homo- or heterodimerize to regulate transcription, and theoretically bind identical GC-response elements (GRE). We assessed the contribution of MR to GR genomic binding and the transcriptional response to the synthetic GC dexamethasone (Dex) using control (CO) and MR knockout (MREKO ) keratinocytes. GR chromatin immunoprecipitation (ChIP)-seq identified peaks common and unique to both genotypes upon Dex treatment (1 h). GREs, AP-1, TEAD, and p53 motifs were enriched in CO and MREKO peaks. However, GR genomic binding was 35% reduced in MREKO , with significantly decreased GRE enrichment, and reduced nuclear GR. Surface plasmon resonance determined steady state affinity constants, suggesting preferred dimer formation as MR-MR > GR-MR ~ GR-GR; however, kinetic studies demonstrated that GR-containing dimers had the longest lifetimes. Despite GR-binding differences, RNA-seq identified largely similar subsets of differentially expressed genes in both genotypes upon Dex treatment (3 h). However, time-course experiments showed gene-dependent differences in the magnitude of expression, which correlated with earlier and more pronounced GR binding to GRE sites unique to CO including near Nr3c1. Our data show that endogenous MR has an impact on the kinetics and differential genomic binding of GR, affecting the time-course, specificity, and magnitude of GC transcriptional responses in keratinocytes.

[Genome Editing in Therapy of Genodermatoses].

This review is devoted to the prospects for the use of fundamentally important approaches and methods for the correction and therapy of genodermatoses, a group of inherited skin diseases. The greatest number of methods was applicable for the group of inherited epidermolysis bullosa. Gene replacement using viral and non-viral methods of delivery to cells has been replaced by genome editing using programmable nucleases used both in vitro and in vivo. The focus is on more widely used methods applied in vitro to various cell types. The description of the methods used is classified based on the use of DNA break repair pathways: the canonical non-homologous end-reconnection pathway-cNHEJ, and directed homologous recombination-HDR. The choice of editing strategy depends on the type of mutation causing the disease, the type of mutation inheritance, and the nucleotide environment of the mutation. Animal disease models obtained by genome editing are considered. The experience of developing methods for editing the genome and their application for the treatment of genodermatoses, previously recognized as incurable, is summarized.

Polyphosphate in Chronic Wound Healing: Restoration of Impaired Metabolic Energy State.

Many pathological conditions are characterized by a deficiency of metabolic energy. A prominent example is nonhealing or difficult-to-heal chronic wounds. Because of their unique ability to serve as a source of metabolic energy, inorganic polyphosphates (polyP) offer the opportunity to develop novel strategies to treat such wounds. The basis is the generation of ATP from the polymer through the joint action of two extracellular or plasma membrane-bound enzymes alkaline phosphatase and adenylate kinase, which enable the transfer of energy-rich phosphate from polyP to AMP with the formation of ADP and finally ATP. Building on these findings, it was possible to develop novel regeneratively active materials for wound therapy, which have already been successfully evaluated in first studies on patients.