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A Debreceni Egyetem Bőrgyógyászati Klinikája 2021-ben ünnepelte megalakulásának 100. évfordulóját. A 2021-es esztendő azonban a COVID pandémia miatt nem tette lehetővé számunkra, hogy ezt a jeles évfordulót kellőképpen meg tudjuk ünnepelni, így a Centenárium tiszteletére rendezett ünnepi ülés és egy összefoglaló közlemény 2023 tavaszán került megszervezésre, illetve készült el. Ezen áttekintő közlemény beszámol a Bőrgyógyászati Klinika elmúlt 100 évéről, röviden bemutatja a klinikán végzett betegellátás, oktatás és kutatás fejlődésének fő lépéseit, emléket állít a korábbi munkatársak és vezetők munkásságának, valamint lehetőséget ad az Egyetem minden dolgozójának és az érdeklődő olvasóknak is, hogy betekintést nyerjenek a debreceni bőrgyógyászat orvostörténetileg is érdekes több mint százéves időszakába.

Szodoray Lajos professzor az 1952-1953-as tanévben az önállósuló Debreceni Orvostudományi Egyetemet rektori hatáskörrel bíró dékánként vezette, majd 1954-1955-ben az egyetem tudományos dékánhelyettese, 1961-1964 között pedig tudományos rektorhelyettese volt. Fiatal éveiben céltudatosan készült fel arra a feladatra, melyet később valóban ki is jelölt számára a sors. Megszervezte az ország egyik vezető bőrgyógyászati klinikáját, kialakította az intézetben a széleskörű elméleti alapokra épülő kiváló klinikai betegellátás, a magasszintű oktatói és kutatói munka megfelelő feltételeit. Szodoray Lajos a magyar bőrgyógyászati szakma iskolateremtő alakja, nemzetközi hírű tudós, színes, melegszívű egyéniség volt. Nevéhez fűződik számos bőrgyógyászati kórkép első hazai észlelése és közlése, valamint rendkívüli érdemei voltak a tankönyvírás terén is. A sors a magyar orvostudomány javára hosszú alkotó élettel, páratlan munkabírással, dinamizmussal, egész életen át tartó lankadatlan szorgalommal és kitartással ajándékozta meg. Több évtizedes tanszékvezetői, egyetemi tanári tevékenysége mellett az egyetemen betöltött vezetői tisztségek tették teljessé szakmai életét.

Sebaceous glands drive acne, however, their role in other inflammatory skin diseases remains unclear. To shed light on their potential contribution to disease development, we investigated the spatial transcriptome of sebaceous glands in psoriasis and atopic dermatitis patients across lesional and non-lesional human skin samples. Both atopic dermatitis and psoriasis sebaceous glands expressed genes encoding key proteins for lipid metabolism and transport such as ALOX15B, APOC1, FABP7, FADS1/2, FASN, PPARG , and RARRES1. Also, inflammation-related SAA1 was identified as a common spatially variable gene. In atopic dermatitis, genes mainly related to lipid metabolism (e.g. ACAD8, FADS6 , or EBP) as well as disease-specific genes, i.e., Th2 inflammation-related lipid-regulating HSD3B1 were differentially expressed. On the contrary, in psoriasis, more inflammation-related spatially variable genes (e.g. SERPINF1 , FKBP5 , IFIT1/3, DDX58 ) were identified. Other psoriasis-specific enriched pathways included lipid metabolism (e.g. ACOT4, S1PR3) , keratinization (e.g. LCE5A, KRT5/7/16 ), neutrophil degranulation, and antimicrobial peptides (e.g. LTF, DEFB4A, S100A7-9 ). In conclusion, our results show that sebaceous glands contribute to skin homeostasis with a cell type-specific lipid metabolism, which is influenced by the inflammatory microenvironment. These findings further support that sebaceous glands are not bystanders in inflammatory skin diseases, but can actively and differentially modulate inflammation in a disease-specific manner.

Background Cost-of-illness studies are widely used for healthcare decision-making in chronic conditions. Our aim was to assess the cost-of-illness of adult atopic dermatitis (AD) from the societal perspective in Hungary. Methods We conducted a multicentre, cross-sectional questionnaire survey between February 2018 and January 2021. Data was collected from consecutive AD patients aged ≥ 18 years and their physicians at dermatology departments in Hungary. We calculated direct and indirect costs, including costs for treatments, outpatient visits, hospital admissions, informal care, travel costs and productivity loss. To assess indirect costs, the Work Productivity and Activity Impairment (WPAI) questionnaire was used to collect data, and costs were estimated with the human capital approach. Generalized linear model was used to analyse predictors of total, direct and indirect costs. Results Altogether 218 patients completed the survey (57.8% female) with an average age of 31.3 (SD = 11.7). Patients’ average Dermatology Life Quality Index (DLQI) score was 13.5 (SD = 8.5). According to Eczema Area and Severity Index (EASI) score, 2.3% (n = 5), 21.2% (n = 46), 54.4% (n = 118) and 22.1% (n = 48) had clear, mild, moderate, and severe AD, respectively. We found that the average total, direct medical, direct non-medical and indirect annual costs per patients were €4,331, €1,136, €747, and €2450, respectively, with absenteeism and presenteeism being the main cost drivers, accounting for 24% and 29% of the total cost of AD. A one-year longer disease duration led to, on average, 1.6%, and 4.2% increase in total and direct non-medical costs, respectively. Patients with worse health-related quality of life (higher DLQI score) had significantly higher total, direct medical, direct non-medical costs, and indirect costs. Conclusions Our results indicate a substantial economic burden of AD from a societal perspective, mainly driven by productivity losses.

Takotsubo cardiomyopathy (TTC) is an important complication of subarachnoid hemorrhage (SAH), that may delay surgical or endovascular treatment and may influence patient outcome. This prospective follow-up study intended to collect data on the prevalence, severity, influencing factors and long-term outcome of TTC in patients suffering from non-traumatic SAH. Consecutive patients admitted with the diagnosis of non-traumatic SAH were included. Intitial assessment consisted of cranial CT, Hunt-Hess, Fisher and WFNS scoring, 12-lead ECG, transthoracic echocardiography (TTE), transcranial duplex sonography and collecting laboratory parameters (CK, CK-MB, cardiac troponin T, NT-proBNP and urine metanephrine and normetanephrine). Diagnosis of TTC was based on modified Mayo criteria. TTC patients were dichotomized to mild and severe forms. Follow-up of TTE, Glasgow Outcome Scale assessment, Barthel's and Karnofsky scoring occurred on days 30 and 180. One hundred thirty six patients were included. The incidence of TTC in the entire cohort was 28.7%; of them, 20.6% and 8.1% were mild and severe, respectively. TTC was more frequent in females (30/39; 77%) than in males (9/39; 23%) and was more severe. The occurrence of TTC was related to mFisher scores and WFNS scores. Although the severity of TTC was related to mFisher score, Hunt-Hess score, WFNS score and GCS, multivariate analysis showed the strongest relationship with mFisher scores. Ejection fraction differences between groups were present on day 30, but disappeared by day 180, whereas wall motion score index was still higher in the severe TTC group at day 180. By the end of the follow-up period (180 days), 70 (74.5%) patients survived in the non-TTC, 22 (81.5%) in the mild TTC and 3 (27%) in the severe TTC group (n = 11) (p = 0.002). At day 180, GOS, Barthel, and Karnofsky outcome scores were higher in patients in the control (non-TTC) and the mild TTC groups than in the severe TTC group. Takotsubo cardiomyopathy is a frequent finding in patients with SAH, and severe TTC may be present in 8% of SAH cases. The severity of TTC may be an independent predictor of mortality and outcome at 6 months after disease onset. Therefore, a regular follow-up of ECG and TTE abnormalities is warranted in patients with subrachnoid hemorrhage for early detection of TTC. The study was registered at the Clinical Trials Register under the registration number of NCT02659878 (date of registration: January 21, 2016).

Toll-like receptors (TLR) 2 and 4 are active in sebaceous glands and play a central role in the development of acne. Still, there is only limited knowledge on their effect on sebocytes. In this work we performed global gene expression profile analysis with functional clustering of the differentially regulated genes of TLR1/2 (PAM3CSK4)- and TLR4 (lipopolysaccharide [LPS])-activated SZ95 sebocytes. Both TLR1/2- and 4-activation promoted inflammation in a similar manner already at an early time-point (6 hours), regulating genes involved in inflammation, wound healing and chemotaxis reflecting a more complex cytokine and chemokine regulation than previously known. Importantly, lipid metabolism, the primary feature of sebocytes, was affected at the level of gene expression only at a later time point (24 hours) indicating that sebocytes prioritize to exert a pro-inflammatory phenotype when confronted with a danger signal. Supporting the biological relevance of our results, a meta-analysis revealed that the genes showing the strongest up-regulation were also found up-regulated in acne. Of these genes, serum amyloid A 1/2 (SAA1/2) was confirmed to be a suitable protein marker for in vivo activated sebocytes, underlining their immune-competence, which is structurally defined within sebaceous glands of acne and rosacea skin samples. Altogether our findings demonstrate that sebocytes are not only positioned at the end point of inflammation but are actively involved in shaping the inflammatory response with putative diagnostic and therapeutic relevance.

Background Chronic inflammatory diseases including inflammatory bowel disease (IBD; Crohn's disease and ulcerative colitis), psoriasis and rheumatoid arthritis (RA) afflict millions of people worldwide, but their pathogenesis is still not well understood. It is also not well known if distinct changes in gene expression characterize these diseases and if these patterns can discriminate between diseased and control patients and/or stratify the disease. The main focus of our work was the identification of novel markers that overlap among the 3 diseases or discriminate them from each other. Methods Diseased (n = 13, n = 15 and n = 12 in IBD, psoriasis and RA respectively) and healthy patients (n = 18) were recruited based on strict inclusion and exclusion criteria; peripheral blood samples were collected by clinicians (30 ml) in Venous Blood Vacuum Collection Tubes containing EDTA and peripheral blood mononuclear cells were separated by Ficoll gradient centrifugation. RNA was extracted using Trizol reagent. Gene expression data was obtained using TaqMan Low Density Array (TLDA) containing 96 genes that were selected by an algorithm and the statistical analyses were performed in Prism by using non-parametric Mann-Whitney U test (P-values < 0.05). Results Here we show that using a panel of 96 disease associated genes and measuring mRNA expression levels in peripheral blood derived mononuclear cells; we could identify disease-specific gene panels that separate each disease from healthy controls. In addition, a panel of five genes such as ADM, AQP9, CXCL2, IL10 and NAMPT discriminates between all samples from patients with chronic inflammation and healthy controls. We also found genes that stratify the diseases and separate different subtypes or different states of prognosis in each condition. Conclusions These findings and the identification of five universal markers of chronic inflammation suggest that these diseases have a common background in pathomechanism, but still can be separated by peripheral blood gene expression. Importantly, the identified genes can be associated with overlapping biological processes including changed inflammatory response. Gene panels based on such markers can play a major role in the development of personalized medicine, in monitoring disease progression and can lead to the identification of new potential drug targets in chronic inflammation.

Activation of Toll-like receptors (TLR) 1/2 and 4 are central in inducing inflammation in sebocytes by regulating the expression of protein coding mRNAs, however the microRNA (miRNA) profile in response to TLR activation and thus the possible role of miRNAs in modulating sebocyte functions has not been elucidated. In this work we identified miR-146a to have the highest induction in the TLR1/2 and 4 activated SZ95 sebocytes and found that its increased levels led to the down-regulation of IL-8 secretion, decreased the chemoattractant potential and stimulated the proliferation of sebocytes. Assessing the gene expression profile of SZ95 sebocytes treated with a miR-146a inhibitor, the induction of GNG7 was one of the highest, while when cells were treated with a miR-146a mimic, the expression of GNG7 was down-regulated. These findings correlated with our in situ hybridization results, that compared with control, miR-146a showed an increased, while GNG7 a decreased expression in sebaceous glands of acne samples. Further studies revealed, that when inhibiting the levels of GNG7 in SZ95 sebocytes, cells increased their lipid content and decreased their proliferation. Our findings suggest, that miR-146a could be a potential player in acne pathogenesis by regulating inflammation, inducing proliferation and, through the indirect down-regulation of GNG7 , promoting the lipid production of sebocytes.

Epidermal growth factor (EGF) acts as a paracrine and autocrine mediator of cell proliferation and differentiation in various types of epithelial cells, such as sebocytes, which produce the lipid-rich sebum to moisturize the skin. However, sebum lipids via direct contact and by penetrating through the epidermis may have regulatory roles on epidermal and dermal cells as well. As EGF receptor (EGFR) is expressed throughout the proliferating and the lipid-producing layers of sebaceous glands (SGs) in healthy and acne-involved skin, we investigated the effect of EGF on SZ95 sebocytes and how it may alter the changes induced by palmitic acid (PA), a major sebum component with bioactive roles. We found that EGF is not only a potent stimulator of sebocyte proliferation, but also induces the secretion of interleukin (IL)6 and down-regulates the expression of genes involved in steroid and retinoid metabolism. Importantly, when applied in combination with PA, the PA-induced lipid accumulation was decreased and the cells secreted increased IL6 levels. Functional clustering of the differentially regulated genes in SZ95 sebocytes treated with EGF, PA or co-treated with EGF+PA further confirmed that EGF may be a potent inducer of hyperproliferative/inflammatory pathways (IL1 signaling), an effect being more pronounced in the presence of PA. However, while a group of inflammatory genes was up-regulated significantly in EGF+PA co-treated sebocytes, PA treatment in the absence of EGF, regulated genes only related to cell homeostasis. Meta-analysis of the gene expression profiles of whole acne tissue samples and EGF- and EGF+PA -treated SZ95 sebocytes showed that the EGF+PA co-activation of sebocytes may also have implications in disease. Altogether, our results reveal that PA-induced lipid accumulation and inflammation can be modulated by EGF in sebocytes, which also highlights the need for system biological approaches to better understand sebaceous (immuno)biology.

The interaction between the nervous and immune systems is crucial for maintaining homeostasis and can influence disease progression in inflammatory skin diseases, such as atopic dermatitis (AD). Sensory neurons in the skin can secrete neuropeptides that modulate immune cell activity, including Langerhans cells (LCs), one of the primary antigen-presenting cells in the epidermis. In our study we investigated the effects of neuropeptides on the differentiation of monocyte-derived LCs (moLCs), specifically the neuropeptides with the most profound effect, i.e. atrial- and B-type natriuretic peptides (ANP and BNP, respectively). RNA sequencing and RT-qPCR were used to analyze neuropeptide receptor expression in moLCs and immature dendritic cells (iDCs), and the most translationally relevant, natriuretic peptide receptor A (NPR1) was validated on the protein level using western blotting. Cell surface markers of moLCs were assessed using flow cytometry, and NPR1 functionality was confirmed through intracellular cGMP assays. Confocal microscopy was used to confirm the expression of NPR1 in healthy and AD skin. RNA-Seq analysis was also employed to characterize the phenotypic changes in moLCs differentiated in the presence of BNP. NPR1 expression was significantly higher in moLCs compared to iDCs, and treatment with ANP and BNP enhanced moLC differentiation, increasing CD207, CD1a, and HLA-DQ expression, while other tested neuropeptides (calcitonin gene-related peptide [CGRP], neurotensin) had no significant effect. NPR1 was functionally active, as evidenced by increased intracellular cGMP levels upon ligand binding. Confocal microscopy revealed NPR1 expression on LC cell bodies in both healthy and AD skin, with reduced intensity in AD. RNA-Seq analysis of BNP-treated moLCs indicated a shift toward a migratory LC phenotype, marked by upregulation of genes associated with cell motility (e.g., CCR7, LAMP3). These findings demonstrate that NPR1 activation promotes a migratory LC phenotype, highlighting the role of neuropeptides in shaping cutaneous immune responses. The reduced number of LCs in AD skin suggests a potential link between neuropeptide signaling and disease pathology.