Keratinization Process Research Articles

Indirect Immunofluorescence Test for Detecting HSV-1, 2 in Patients with Esophageal Cancer: A Pilot Cross-Sectional Survey in Kazakhstan.

To evaluate the detectability of herpes simplex virus type 1 and 2 (HSV-1, 2) antigens in the esophageal mucosa in esophageal cancer. A cross-sectional pilot study with a control group was conducted from December 2022 to May 2023. The patients were divided into two groups: the main group with verified esophageal cancer and the control group without esophageal cancer based on the histological report. Diagnosis using fibroesophagogastroscopy (FEGS), histological analysis, and indirect immunofluorescence reaction (iIFR) was accomplished according to indications at the outpatient center of the endoscopic department of the Multidisciplinary Medical Center, Astana. Descriptive statistics and nonparametric methods were used to analyze the data. A total of 30 patients were recruited in the study, with 15 patients in the main group and 15 patients in the control group. HSV-1 and HSV-2 antigens were detected in the 13 cases (86.7%) during the study of biomaterial from patients with confirmed esophageal cancer in the main group and only in one case (6.8%) in the control group (95% CI 7.35 - 1126.9%, p=0.001). The presence of lymphocytic infiltration was detected in 13 cases (86.7%) in the main group and in 5 cases (33.3%) in the control group (95% CI 2.07 - 81.48%, p = 0.008). The process of keratinization was identified in HSV-1,2 antigens positive cases in the main group in 5 cases (35.7%) G1, in 5 cases (35.7%) G2, and in 3 cases (21.4 %) G3 (95% CI 1.66 - 656.23%, p=0.002). Overall, the local activity of herpesvirus infection to a certain extent influences the malignant potential of tumor cells and the resistance of surrounding healthy tissues. A large-scale study is still needed to confirm these results. The present pilot study provided an overview of a possible method for detecting HSV-1,2 activity in malignant tissue from esophageal cancer.

Changes of epidermal proteins immunolocalization in the corneous layer from embryonic to definitive avian beak

The process of keratinization and cornification in the developing beak has been studied through immunofluorescence and immunogold electron microscopy in chick and zebrafinch embryos. After the curved beak anlagen appears at the tip of the maxillar bone, 5–8 layers of embryonic epidermis are generated from the basal layer of the epidermis. These cells are weakly immunoabeled for IFKs (Intermediate Filament Keratins) and more intensely for scaffoldin, a protein of the EDC (Epidermal Differentiation Complex) involved in the soft keratinization of the embryonic epidermis. Immunolabeling for CBPs (Corneous Beta Proteins) is visible in the transitional embryonic layers that are temporarily generated between the embryonic and definitive beak epidermis. The electron microscope reveals that intermediate layers contain immunolabeled periderm granules for scaffoldin mixed with bundles of corneous material immunolabeled for CBPs. Intense CBPs labeling occurs in the compacting corneous bundles of beta-keratinocytes in the definitive beak while scaffolding labeling disappears. The embryonic epidermis is sloughed before hatching. Sox (Sulfhydryl Oxidase) immunolabeling reveals that the enzyme is almost absent in embryonic layers but is present in transitional and definitive beta-keratinocytes. This indicates the formation of cross-linked disulfide bonds in the definitive corneous layer of the beak. Some calcium precipitation, suggested from von Kossa staining, occurs in the corneous layers only on the 18th day of development in the chick, in preparation for hatching.

PHOTODYNAMIC THERAPY IN THE TREATMENT OF ORAL MUCOSAL HYPERKERATOSES: A LITERATURE REVIEW

Relevance: In therapeutic dentistry, oral mucosal diseases considered one of the most difficult areas. Many diseases, including lichen planus (LP), are characterized by a disorder of the keratinization process (hyperkeratosis). OLP is a chronic inflammatory disease of the skin and mucous membranes, characterized by a persistent long course. OLP has various clinical forms, but forms such as erosive-ulcerative and bullous tend to transform into cancer. Although there are currently a large number of treatment options for LP, none of them are completely successful. At the same time, one of the promising treatment methods, which is based on the use of a photosensitizer and light of a certain wavelength, is photodynamic therapy (PDT). The advantages of PDT are low toxicity for normal cells, selectivity of action, and lack of invasiveness. Currently, there are no clear schemes for the use of PDT depending on the nosological form, which determines the relevance of our study. The study aimed to increase the effectiveness of the treatment of oral hyperkeratoses using photodynamic therapy. Methods: An analysis of publications over the past 10 years was carried out in the eLibrary, Pubmed, Google Scholar, CyberLeninka, and Scopus databases using keywords ‘photodynamic therapy’, ‘hyperkeratosis’, ‘oral lichen planus’, ‘laser’, ‘photosensitizer’. The results of both experimental and clinical laboratory studies are included. The review includes 48 sources that present the experience and application of PDT in dental practice based on the results of these studies. Results: Analysis of the world literature made it possible to consider extensively the issue of treating hyperkeratoses of the oral mucosa using PDT. The development and implementation of third-generation photosensitizers obtained by binding to other molecules, including nanoparticles and liposomes, is very promising, thereby increasing the effectiveness of treatment of neoplasms. Conclusion: Thus, PDT shows great potential as a treatment method and can be considered as an important tool in the treatment of oral diseases, both as a primary treatment method and as an adjunctive method.

Reflectance confocal microscopy and clinical evaluation of a product containing Silybum marianum fruit extract in monotherapy for acne vulgaris treatment: A prospective study

AbstractBackgroundAcne is a common pilosebaceous unit chronic inflammatory disease, with a multifactorial pathogenesis. It involves several processes: increased sebum production, alteration of the follicular keratinization process and bacterial colonization by Cutibacterium acnes.ObjectivesTo evaluate the effectiveness of reflectance confocal microscopy (RCM) in evaluating the reduction of mild to severe acne lesions in patients treated with an investigational product containing Silybum marianum fruit extract (SMFE).MethodsSubjects previously examined for counting acne lesions were topically treated in the face, with an investigational product containing SMFE in monotherapy over the course of 60 days (n = 31). They were examined for counting acne lesions. Efficacy and quality of life, tolerability, and safety assessments were performed. The infundibular diameter (ID) measurement of normal and acne skin areas was analyzed using RCM.ResultsThe RCM data statistical analysis allowed us to identify two ID patterns, 300–750 µm, with a reduction of 33.33% (p < 0.05) and 900–1050 µm with 73.16% (p < 0.05) reduction after 60 days. The noninflammatory lesions had a mean variation of −44.51% and −67.82% after 30 and 60 days, respectively (t test: p < 0.05 and p < 0.001 after Bonferroni's correction). The inflammatory lesions had a mean variation of −69.31% and −79.40% after 30 and 60 days (t test: p < 0.05 and p = 0.118 after Bonferroni's correction).ConclusionsThe authors demonstrated the effectiveness of the monotherapy scheme with an investigational product containing SMFE through the statistically significant results obtained by the RCM in acneic and nonacneic skin, in addition to the reduction in the number of noninflammatory at the end of the 60 days of clinical follow‐up. Furthermore, the monotherapy scheme with the investigational product proved safe, with no serious adverse events during the entire clinical study. In summary, the use of RCM proved to be effective in assessing the therapeutic response in patients with moderate to severe acne.

Potential Role of Dietary Salmon Nasal Cartilage Proteoglycan on UVB-Induced Photoaged Skin.

New supplements with preventive effects against skin photodamage are receiving increasing attention. This study evaluated the anti-photoaging effects of salmon nasal cartilage proteoglycan (SPG), acting as a functional material for skin health. We administered SPG to in vitro and in vivo models exposed to ultraviolet B (UVB) radiation and assessed its moisturizing and anti-wrinkle effects on dorsal mouse skin and keratinocytes and dermal fibroblasts cell lines. These results showed that SPG restored the levels of filaggrin, involucrin, and AQP3 in the epidermis of UVB-irradiated dorsal skin and keratinocytes, thereby enhancing the keratinization process and water flow. Additionally, SPG treatment increased the levels of hyaluronan and skin ceramide, the major components of intercellular lipids in the epidermis. Furthermore, SPG treatment significantly increased the levels of collagen and procollagen type 1 by down-regulating matrix metalloproteinase 1, which play a crucial role in skin fibroblasts, in both in vitro and in vivo models. In addition, SPG strongly inhibited mitogen-activated protein kinase (MAPKs) signaling, the including extracellular signal-regulated kinase, c-Jun N-terminal kinase (JNK), and p38. These findings suggest that dietary SPG may be an attractive functional food for preventing UVB-induced photoaging. And this SPG product may provide its best benefit when treating several signs of skin photoaging.

Reaction of the oral mucosa to damage and its regeneration during cytostatic therapy

Objective: Experimental study of the damaging effect of cytostatics on the oral mucosa, disruption of the protective mechanisms of the mucous membrane, as well as assessment of the reversibility of these changes.
 Materials and methods: Using histological, morphometric, and quantitative histochemical methods, the mucous membrane of the tongue was studied on 40 mature white outbred mice after intraperitoneal administration of the cytostatic cyclophosphamide (CP) at a dose of 400 mg/kg for 5 days (20 animals). Animals in the control group (20 mice) were injected with isotonic sodium chloride solution at the same frequency. The material was obtained 24 hours and 20 days after the last injection of the drug. The condition of the oral mucosa (OM) on the ventral surface of the tongue was assessed.
 Results: Exposure to CP led to damage to all layers of the mucous membrane: the processes of proliferation and keratinization of the integumentary epithelium were disrupted, and synthetic processes in the epithelial cells of the small mixed salivary glands were disrupted. The number of granulocytes and mast cells decreased, and the relative volume of blood vessels in the connective tissue of the mucous membrane decreased. The changes were reversible.
 Conclusions: Cytostatic therapy leads to damage to the oral mucosa and disruption of its supraepithelial, epithelial and subepithelial protective mechanisms. There is a high degree of regeneration of the mucous membranes after the withdrawal of the cytostatic drug.

Unraveling the molecular mechanisms of cell migration impairment and apoptosis associated with steroid sulfatase deficiency: Implications for X-linked ichthyosis

Steroid sulfatase (STS) deficiency is responsible for X-linked ichthyosis (XLI), a genetic disorder characterized by rough and dry skin caused by excessive keratinization. The impaired keratinization process leads to reduced cell mobility and increased apoptosis, which can cause an excessive buildup of the stratum corneum. In this study, we investigated the mechanisms underlying XLI and found that STS deficiency reduces cell mobility and increases apoptosis in human keratinocyte HaCaT cells. To explore these mechanisms further, RNA-sequencing was conducted on skin tissues from STS transgenic and knockout mice. Our RNA-seq results revealed that STS deficiency plays a critical role in regulating multiple signaling pathways associated with cell mobility and apoptosis, such as Wnt/β signaling and the Hippo signaling pathway. Knockdown of the STS gene using shRNA in HaCaT cells led to an upregulation of E-cadherin expression and suppression of key factors involved in epithelial-mesenchymal transition (EMT), such as N-cadherin and vimentin. Inhibition of EMT involved the Hippo signaling pathway and reduction of HIF-1α. Interestingly, inhibiting STS with shRNA increased mitochondrial respiration levels, as demonstrated by the extracellular flux oxygen consumption rate. Additionally, we observed a significant increase in ROS production in partial STS knockout cells compared to control cells. Our study demonstrated that the excessive generation of ROS caused by STS deficiency induces the expression of Bax and Bak, leading to the release of cytochrome c and subsequent cell death. Consequently, STS deficiency impairs cell mobility and promotes apoptosis, offering insights into the pathophysiological processes and potential therapeutic targets for XLI.

Key Factors in the Complex and Coordinated Network of Skin Keratinization: Their Significance and Involvement in Common Skin Conditions.

The epidermis serves many vital roles, including protecting the body from external influences and healing eventual injuries. It is maintained by an incredibly complex and perfectly coordinated keratinization process. In this process, desquamation is essential for the differentiation of epidermal basal progenitor cells into enucleated corneocytes, which subsequently desquamate through programmed death. Numerous factors control keratinocyte differentiation: epidermal growth factor, transforming growth factor-α, keratinocyte growth factor, interleukins IL-1-β and IL-6, elevated vitamin A levels, and changes in Ca2+ concentration. The backbone of the keratinocyte transformation process from mitotically active basal cells into fully differentiated, enucleated corneocytes is the expression of specific proteins and the creation of a Ca2+ and pH gradient at precise locations within the epidermis. Skin keratinization disorders (histologically characterized predominantly by dyskeratosis, parakeratosis, and hyperkeratosis) may be categorized into three groups: defects in the α-helical rod pattern, defects outside the α-helical rod domain, and disorders of keratin-associated proteins. Understanding the process of keratinization is essential for the pathogenesis of many dermatological diseases because improper desquamation and epidermopoiesis/keratinization (due to genetic mutations of factors or due to immune pathological processes) can lead to various conditions (ichthyoses, palmoplantar keratodermas, psoriasis, pityriasis rubra pilaris, epidermolytic hyperkeratosis, and others).

Early concentrate starter introduction induces rumen epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation

IntroductionRumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively impacts ruminant health and performance. However, we still lack a comprehensive perception of the underlying mechanisms and the predisposing factors for this disorder. ObjectivesHere, we investigated rumen epithelial cell heterogeneity, differentiation trajectories, and cornification to clarify the rumen epithelial keratinization process and discern the key ruminal metabolites contributing to rumen epithelial parakeratosis. MethodsTwenty-four 14-day-old lambs were divided into three groups, including only milk feeding, milk plus alfalfa hay feeding, and milk plus corn-soybean concentrate starter feeding. At 42 days of age, the lambs were slaughtered, and rumen tissues were collected for single-cell RNA-sequencing (scRNA-seq), immunofluorescence, and quantitative real-time PCR (qRT-PCR) analyses. Ruminal fluid samples were collected for metabolomic analyses. Rumen epithelial organoid was used to verify the key ruminal metabolites contributing to parakeratosis. ResultsAs expected, we observed that concentrate starter introduction resulted in rumen epithelial parakeratosis. Moreover, scRNA-seq analysis revealed a developmental impediment in the transition from differentiated keratinocytes to terminally differentiated keratinocytes (TDK) in lambs with concentrate starter introduction. Immunofluorescence and qRT-PCR analyses further verified the location and expression of marker genes of TDK. Metabolomic analysis showed a robust positive correlation between ruminal butyrate levels and rumen epithelial keratinization. More importantly, we successfully established a rumen organoid model capable of facilitating the study of the keratinization process in the rumen epithelia and further confirmed that high dose butyrate indeed contributed to rumen epithelial parakeratosis. ConclusionCollectively, concentrate starter introduction induces ruminal epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation in a neonatal lamb model. These findings enhance our understanding of rumen epithelial keratinization and provide valuable insights for addressing rumen epithelial parakeratosis using early nutritional intervention strategies.

THE STRUCTURE OF THE ANTERIOR CORNEA EPITHELIUM OF THE SUS SCROFA DOMESTICUS AT THE CRYOPHIXATION

The classic histological picture of the anterior corneal epithelium, known from the results of standard histological techniques and light microscopy of preparations of chemically fixed material, describes the presence of three cell layers: basal - germinative, middle and superficial. On preparations of cryofixed material, another homogeneous layer is identified above the cells of the third layer, which is usually identified as the precorneal tear film, that is, a layer of liquid. Analysis and comparison of known data allows us to identify a scientific problem, which is as follows. The structure of the homogeneous layer has not been previously studied, its structure is unknown, therefore, the identification of the homogeneous layer with the precorneal tear film is not justified. We assume that the histological picture of the anterior epithelium on preparations of chemically fixed material is incomplete, and the homogeneous layer is a structural component of the anterior epithelium. Purpose of the study: the structure of the anterior epithelium and homogeneous layer on preparations of cryofixed material. The material for the study was preparations of the eyes of the domestic pig Sus scrofa domesticus, the research method was light microscopy. As a result of the study, it was established for the first time that the homogeneous layer is a structural component of the anterior corneal epithelium. Between the homogeneous layer and the layer of flat cells of the anterior epithelium, another layer is determined in the form of a microscopically detectable thin strip. Taking into account the established fact, it should be concluded that the anterior epithelium of the cornea consists of five layers. The cells in the layers are in a compacted state, the degree of which increases from the basement membrane to the frontal surface of the epithelium, reaching a maximum at the level of the homogeneous layer. The cells of the surface layer are anucleate, filled with an oxyphilic mass, presumably keratin, which indicates the process of keratinization of epithelial cells. The results of the study confirmed the assumption that the histological picture on preparations of chemically fixed material is incomplete. The identification of a homogeneous layer with the precorneal tear film is unfounded.

Morphologic alterations in the mucosa of the denture site in patients with full removable dentures from acrylic plastics

Relevance. Currently, many new agents have appeared on the market for users of removable dentures to improve adhesion, i.e. fixation and stabilization of dentures. It is important to evaluate the effect of such agents on the denture bed mucosa.Objective. Morphological substantiation of the effectiveness of the use of adhesive cream for fixation of prostheses Asepta Рarodontalu patients with removable dentures made of acrylic plastic.Materials and methods. The study involved 49 patients (12 men and 37 women) of elderly age (62–75 years) who suffered complete loss of teeth on both jaws. All patients were divided into 3 study groups: 1 (control) group, who had previously refused to have full removable acrylic dentures made for them; 2 (comparison) group, patients to whom removable acrylic dentures were made and who did not use any means to improvetheir fixation; 3 (main) group, patients to whom full removable acrylic dentures were made and who during the adaptation period and subsequently for a year used a domestic adhesive cream for fixation; 3 (main) group, patients to whom full removable acrylic dentures were made. In order to solve the realization of the set goal of the study, a number of clinical and histological studies with the use of immunohistochemical method were carried out, outpatient charts of dental patients were analyzed.Results. It was found that dystrophic and chronic inflammatory changes in the soft tissues of the denture bed were most pronounced in the case of using dentures without means to improve their fixation. At use of domestic adhesive cream for fixation of dentures Asepta Рarodontal the process of keratinization of the oral mucous membrane epithelium was minimal, there was no fibrosis of the own lamina of the mucous membrane, scattered infiltration was less expressed than in people not using acrylic dentures or using them without adhesive means, and was represented at the expense of lymphocytes, single neutrophilic granulocytes on the background of single leukostases. The immunohistochemical study showed that T-lymphocytes and mast cells were predominant in the preparations of group 2 patients, and they appeared in the preparations of this group of patients comparatively more than in the 1st control and 3rd main groups of the study, which confirmed the presence of the most pronounced chronic inflammatory infiltration in group 2 patients.Conclusion. The most optimal condition of the denture bed mucosa was observed in patients who used removable acrylic dentures for a year and simultaneously applied an adhesive agent for their fixation (domestic adhesive cream for denture fixation Asepta Рarodontal). It is obviously connected with the protection of the mucous membrane of the prosthetic bed by the adhesive cream from the mechanical impact of a dense acrylic plastic prosthesis, as well as with the reduction of contact with food products aggressive in temperature and structure.

Identifying Key Regulators of Keratinization in Lung Squamous Cell Cancer Using Integrated TCGA Analysis

Keratinization is one of lung squamous cell cancer's (LUSC) hallmark histopathology features. Epithelial cells produce keratin to protect their integrity from external harmful substances. In addition to their roles as cell protectors, recent studies have shown that keratins have important roles in regulating either normal cell or tumor cell functions. The objective of this study is to identify the genes and microRNAs (miRNAs) that act as key regulators of the keratinization process in LUSC. To address this goal, we classified LUSC samples from GDC-TCGA databases based on their keratinization molecular signatures. Then, we performed differential analyses of genes, methylation, and miRNA expression between high keratinization and low keratinization samples. By reconstruction and analysis of the differentially expressed genes (DEGs) network, we found that TP63 and SOX2 were the hub genes that were highly connected to other genes and displayed significant correlations with several keratin genes. Methylation analysis showed that the P63, P73, and P53 DNA-binding motif sites were significantly enriched for differentially methylated probes. We identified SNAI2, GRHL3, TP63, ZNF750, and FOXE1 as the top transcription factors associated with these binding sites. Finally, we identified 12 miRNAs that influence the keratinization process by using miRNA-mRNA correlation analysis.

How do the skin barrier and microbiome adapt to the extra-uterine environment after birth? Implications for the clinical practice.

The multiple protective functions of the skin derive from the interactions between epithelial skin and immune cells as well as the commensal microbiota. Developed in the last trimester of intra-uterine life, the skin barrier adapts dynamically after birth. Specific differences in the structure and physiology have been disclosed between infant and adult skin. The stratum corneum of infants is thinner and structured by thicker corneocytes with a more anisotropic surface in comparison to adult skin. Lower levels of the natural moisturizing factor and its constituents, together with the increased protease activity in the epidermis result in dry baby skin and ongoing adaptation of the desquamation to the extra-uterine environment. Infant epidermis is characterized by an accelerated proliferation rate and clinically competent permeability barrier in term neonates, despite the higher baseline values of transepidermal water loss in infants. The skin surface of newborns is less acidic, which could increase susceptibility to diaper and atopic dermatitis. Immediately after birth, skin is colonized by commensal bacteria-a process dependent on the mode of delivery and of major importance for the maturation of the immune system. Skin bacterial diversity and dysbiosis have been related to different pathology such as atopic and seborrheic dermatitis. This paper focuses on the ongoing structural, functional and biochemical adaptation of the human skin barrier after birth. We discuss the interactions on the 'skin barrier/ microbiota/ immune system' axis and their role in the development of competent functional integrity of the epidermal barrier.

Main effects of retinol palmitate on skin structures and the technology of its use in dermatological practice

Vitamin A and its synthetic analogues are used in the treatment of numerous skin diseases. The main genomic effects of the natural form of vitamin A (retinol palmitate) are associated with its active metabolite all-trans-retinoic acid and are compensated by several restrictive mechanisms. Numerous studies have proved that retinol stimulates the proliferation of keratinocytes of the basal layer of the epidermis and endothelial cells, and also activates dermal fibroblasts to synthesize proteins of the extracellular matrix of the dermis. As a result, the thickening the epidermis, increases the mechanical strength of the skin and the hydrating ability of the dermis, angiogenesis increase. The ability of retinol to enhance the adhesion of endothelial cells and leukocytes, regulate the processes of keratinization and sebum secretion was found. Vitamin A is also a powerful antioxidant. Retinol palmitate is used as the main or auxiliary drug for the treatment of a wide range of dermatoses. The principle of application is based on clinical studies and confirmed by existing experimental data. In the treatment, the following algorithm is followed. If retinol palmitate is necessary to improve epithelialization and strengthen the epidermal barrier, medium therapeutic doses should be used. For the treatment of disorders of keratinization processes, depending on the severity of the pathological condition, medium and high therapeutic doses of the drug are used. Violation of the processes of sebum secretion and severe hyperkeratosis respond better to treatment at high therapeutic doses. It should be noted that many skins clinical manifestations mostly regress under the action of vitamin A in doses that do not lead to the appearance of signs of toxicity of the drug.

P107 Decreased epithelial keratinization contributes to defective wound healing in Crohn's disease fistula

Abstract Background Up to 30% of Crohn's Disease (CD) patients suffer from perianal fistula creating a high disease burden. Treating CD fistula is challenging compared to cryptoglandular fistula, which have a significantly better wound healing response. Previous studies suggested epithelial to mesenchymal transition as an inducer of fistula formation, as markers were observed in fistula tracts. However, most studies compared CD fistula to normal mucosa, thus disregarding whether any observed difference was in fact a sign of healing (as CD fistula will have more active healing than uninjured mucosa) or a sign of pathology (as healing is not occurring effectively). Therefore, in this study we evaluated CD fistula, as well as both healthy mucosa (no active healing) and cryptoglandular fistula (effective healing) in order to determine the role of differences found. Methods Biopsies from the internal opening (n=20) of perianal fistula of CD patients were collected and compared to two publicly available datasets obtained from un-inflamed rectum (RISK cohort and GSE83245). In addition, curettage material of CD (n=54) and cryptoglandular fistula (n=15) was obtained. Expression profiling was performed using RNASeq. Results Comparing the mucosa at the internal opening of CD fistula to publicly available datasets of healthy rectum, 770 genes were differentially expressed. Pathway analysis revealed upregulation of proliferative and inflammatory processes, consistent with expected immune and wound healing responses. Interestingly, strongest upregulation was seen for processes of cornification and keratinization, including expression of IVL (involucrin) and FLGR2 (fillagrin2), involved in keratinocyte differentiation. To evaluate whether this was contributing to active wound healing or rather to persistent disease, we analyzed the actual tract in CD and cryptoglandular fistula. Strikingly, cornification and keratinization processes were more pronounced in cryptoglandular fistula, suggesting a role in effective healing rather than the persistent pathology seen in CD. Similar data was observed for TGFb, previously detected in CD fistula and thus considered a pathological contributor. While we confirm increased TGFb activity in CD fistula compared to normal mucosa, activity in cryptoglandular fistula tracts was higher than in CD fistula tracts. Again, this would suggest TGFb signaling as part of the wound healing response rather than part of the pathogenic mechanism. Conclusion Perianal fistulas show upregulation of keratinization and cornification pathways compared to healthy mucosa. Comparing CD and cryptoglandular fistula, we saw more cornification in the better healing cryptoglandular fistula, suggesting involvement in effective healing rather than pathology.

Chronicles of A.I. Pospelov Moscow Society of Dermatovenereologists and Cosmetologists (MSDC was founded on October 4, 1891). Bulletin of the MSDC № 1149

On October 18, 2022, the 1149th meeting of the A.I. Pospelov Moscow Society of Dermatovenerologists and Cosmetologists (MSDC) took place. The meeting was held in a face-to-face format. There were 128 participants in total. Accepted as a member of the MSDC 53 people.
 Two clinical cases are presented for discussion: trichoadenoma ― a rare benign follicular tumor consisting of strands of epithelial cells and keratinizing cysts embedded in the sclerotic stroma, and Dariers follicular dyskeratosis ― hereditary dermatosis characterized by the formation of follicular hyperkeratotic vegetative papules on seborrheic areas of the skin caused by a violation of the keratinization process by the type of dyskeratosis.
 Scientific reports were devoted to the analysis of differential diagnosis and therapeutic tactics in BrookeSpiegler syndrome (multiple cylindromes and trichoepitheliomas), the mechanisms of action and effectiveness of zinc pyrithione as a means of controlling colonization of the hairy skin by fungi-commensals of the genus Malassezia, as well as the most urgent problems of modern medicine ― the features of the course of chronic-severe dermatoses after SARS-CoV-2 infection (COVID-19) and an increase in the incidence of mucormycosis, which is a marker of immune breakdown that occurs immediately after COVID-19 infections.

CYTOLOGIC CHARACTERISTIC OF THE CELLULAR COMPOSITION OF THE GUM MUCOUS MEMBRANE IN SCHOOL-AGE CHILDREN.

The aim: To establish the characteristics of the gingival mucosa cellular composition in school-age children. Materials and methods: We made a dental and cytological examination on 150 Ukrainian (Poltava city) children aged 6, 12, and 15 years. Smears were got by scraping from the gum mucosa and stained with a May-Grunwald solution. Cytograms were made by using a Biorex-3 BM-500T microscope with a DCM-900 digital microphotographic attachment. The programs were adapted for these types of studies. We used a magnification of 1000. The t-test for paired samples was used to compare values. The difference was considered statistically significant at P<0.05. Results: The number of superficial epitheliocytes in children aged 12 and 15 was significantly higher than in 6-year-olds but did not differ from each other. Conclusions: The process of physiological keratinization of the cells of the gingival mucosa in schoolchildren is diverse and keratinization occurs both due to the phenomenon of physiological necrosis, namely, apoptosis of surface cells and due to orthokeratosis. From the age of 6, the average number of surface cells in cytograms decreases, while the number of intermediate and dead keratinized cells increases up to 12 years and remains on the previous level in children of 15 years.

Ихтиоздың сирек кездесетін клиникалық түрі - бір жақтық ихтиозформалы эритродермия: Клиникалық жағдай

Congenital ichthyosis is one of the hereditary dermatoses that develop due to a violation of the keratinization process. The clinical manifestation of ichthyosis is characterized by dryness of the skin during physical examination and scaling of different degrees of clarity. Congenital ichthyosis can be classified as one of the most difficult and urgent problems in the field of dermatology and pediatrics due to the fact that the pathogenesis of this pathology is not fully studied, its persistent course, and the difficulty of achieving positive treatment results.In addition, despite many common features, types of ichthyosis are distinguished based on clinical and histological appearance: simple ichthyosis, recessive X-doubled ichthyosis, classic lamellar ichthyosis, bullous and non-bullous congenital ichthyosiform erythroderma. In all these types of ichthyosis, there is a violation of cellular kinetics and their physiological exfoliation process, resulting in excessive keratinization of the skin in the primary manifestation. During ichthyosis, there is a violation of the barrier function of the skin, loss of water between the epidermis and inability of the skin to retain moisture. In this article, we have shared a patient with these symptoms who was diagnosed with unilateral ichthyosiform erythroderma, one of the rare forms of ichthyosis encountered in our practice. This article is informative for general practitioners, neonatologists, pediatricians, dermatovenerologists and geneticists.

Oral Lichen Planus and Oral Squamous Cell Carcinoma share key oncogenic signatures

To investigate similarities in the gene profile of Oral Lichen Planus and Oral Squamous Cell Carcinoma that may justify a carcinogenic potential, we analyzed the gene expression signatures of Oral Lichen Planus and Oral Squamous Cell Carcinoma in early and advanced stages. Based on gene expression data from public databases, we used a bioinformatics approach to compare expression profiles, estimate immune infiltrate composition, identify differentially and co-expressed genes, and propose putative therapeutic targets and associated drugs. Our results revealed gene expression patterns related to processes of keratinization, keratinocyte differentiation, cell proliferation and immune response in common between Oral Lichen Planus and early and advanced Oral Squamous Cell Carcinoma, with the cornified envelope formation and antigen processing cross-presentation pathways in common between Oral Lichen Planus and early Oral Squamous Cell Carcinoma. Together, these results reveal that key tumor suppressors and oncogenes such as PI3, SPRR1B and KRT17, as well as genes associated with different immune processes such as CXCL13, HIF1A and IL1B are dysregulated in OLP.

Aquaporins Are One of the Critical Factors in the Disruption of the Skin Barrier in Inflammatory Skin Diseases.

The skin is the largest organ of the human body, serving as an effective mechanical barrier between the internal milieu and the external environment. The skin is widely considered the first-line defence of the body, with an essential function in rejecting pathogens and preventing mechanical, chemical, and physical damages. Keratinocytes are the predominant cells of the outer skin layer, the epidermis, which acts as a mechanical and water-permeability barrier. The epidermis is a permanently renewed tissue where undifferentiated keratinocytes located at the basal layer proliferate and migrate to the overlying layers. During this migration process, keratinocytes undertake a differentiation program known as keratinization process. Dysregulation of this differentiation process can result in a series of skin disorders. In this context, aquaporins (AQPs), a family of membrane channel proteins allowing the movement of water and small neutral solutes, are emerging as important players in skin physiology and skin diseases. Here, we review the role of AQPs in skin keratinization, hydration, keratinocytes proliferation, water retention, barrier repair, wound healing, and immune response activation. We also discuss the dysregulated involvement of AQPs in some common inflammatory dermatological diseases characterised by skin barrier disruption.