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Hirschberg A.,St Johns Hospital | Kiss M.,University of Szeged | Kadocsa E.,University of Szeged | Polyanka H.,MTA SZTE Dermatological Research Group | And 6 more authors.
European Archives of Oto-Rhino-Laryngology | Year: 2016

Both up- and down-regulation of the Toll-like receptors (TLRs) and antimicrobial peptides (AMPs) of the sinonasal mucosa have already been associated with the pathogenesis of chronic rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyps. The objective of this study was to determine the expression of all known TLR and several AMP genes and some selected proteins in association with allergy, asthma and aspirin intolerance (ASA) in CRS subgroups. RT-PCR was applied to measure the mRNA expressions of 10 TLRs, four defensins, lysozyme, cathelicidin and lactoferrin (LTF) in sinonasal samples from patients with CRSsNP (n = 19), CRSwNP [ASA(−): 17; ASA(+): 7] and in control subjects (n = 12). Protein expressions were detected with immunohistochemistry (n = 10). Statistical analysis was done with the Kruskal-Wallis ANOVA, Mann-Whitney U, and Student t test. TLR2, TLR5, TLR6, TLR7, TLR8, TLR9, β-defensins 1 and 4, cathelicidin and LTF mRNA expressions were significantly (p < 0.05) increased in CRSwNP, whereas only TLR2 and LTF were up-regulated in CRSsNP compared to controls. There was no statistical difference in respect of allergy, aspirin intolerance and smoking between CRSsNP, ASA(−) and ASA(+) CRSwNP patients. TLR2, TLR3, TLR4, LTF, β defensin 2 and lysozyme protein expressions were found to be elevated in macrophages of CRSwNP samples (p < 0.05). Gene expression analysis showed markedly different expressions in CRSwNP (6 out of 10 TLR and 4 out of 7 AMP genes were up-regulated) compared to CRSsNP (1/10, 1/7). The distinct activation of the innate immunity may support the concept that CRSsNP and CRSwNP are different subtypes of CRS. These findings were found to be independent from allergy, asthma, smoking, aspirin intolerance and systemic steroid application. © 2015, Springer-Verlag Berlin Heidelberg.


PubMed | University of Szeged, St Johns Hospital and MTA SZTE Dermatological Research Group
Type: Journal Article | Journal: European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery | Year: 2016

Both up- and down-regulation of the Toll-like receptors (TLRs) and antimicrobial peptides (AMPs) of the sinonasal mucosa have already been associated with the pathogenesis of chronic rhinosinusitis with (CRSwNP) or without (CRSsNP) nasal polyps. The objective of this study was to determine the expression of all known TLR and several AMP genes and some selected proteins in association with allergy, asthma and aspirin intolerance (ASA) in CRS subgroups. RT-PCR was applied to measure the mRNA expressions of 10 TLRs, four defensins, lysozyme, cathelicidin and lactoferrin (LTF) in sinonasal samples from patients with CRSsNP (n=19), CRSwNP [ASA(-): 17; ASA(+): 7] and in control subjects (n=12). Protein expressions were detected with immunohistochemistry (n=10). Statistical analysis was done with the Kruskal-Wallis ANOVA, Mann-Whitney U, and Student t test. TLR2, TLR5, TLR6, TLR7, TLR8, TLR9, -defensins 1 and 4, cathelicidin and LTF mRNA expressions were significantly (p<0.05) increased in CRSwNP, whereas only TLR2 and LTF were up-regulated in CRSsNP compared to controls. There was no statistical difference in respect of allergy, aspirin intolerance and smoking between CRSsNP, ASA(-) and ASA(+) CRSwNP patients. TLR2, TLR3, TLR4, LTF, defensin 2 and lysozyme protein expressions were found to be elevated in macrophages of CRSwNP samples (p<0.05). Gene expression analysis showed markedly different expressions in CRSwNP (6 out of 10 TLR and 4 out of 7 AMP genes were up-regulated) compared to CRSsNP (1/10, 1/7). The distinct activation of the innate immunity may support the concept that CRSsNP and CRSwNP are different subtypes of CRS. These findings were found to be independent from allergy, asthma, smoking, aspirin intolerance and systemic steroid application.


Kemeny L.V.,University of Szeged | Kurgyis Z.,University of Szeged | Buknicz T.,University of Szeged | Groma G.,MTA SZTE Dermatological Research Group | And 6 more authors.
International Journal of Molecular Sciences | Year: 2016

After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells’ nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma-stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments. © 2016 by the authors; licensee MDPI, Basel, Switzerland.


PubMed | Witten/Herdecke University, University of Szeged and MTA SZTE Dermatological Research Group
Type: Journal Article | Journal: International journal of molecular sciences | Year: 2016

After the removal of primary cutaneous melanoma some patients develop local recurrences, even after having histologically tumor-free re-excision. A potential explanation behind this phenomenon is that tumor cells switch their phenotype, making their recognition via standard histopathological assessments extremely difficult. Tumor-stromal cell fusion has been proposed as a potential mechanism for tumor cells to acquire mesenchymal traits; therefore, we hypothesized that melanoma cells could acquire fibroblast- and macrophage-like phenotypes via cell fusion. We show that melanoma cells spontaneously fuse with human dermal fibroblasts and human peripheral blood monocytes in vitro. The hybrid cells nuclei contain chromosomes from both parental cells and are indistinguishable from the parental fibroblasts or macrophages based on their morphology and immunophenotype, as they could lose the melanoma specific MART1 marker, but express the fibroblast marker smooth muscle actin or the macrophage marker CD68. Our results suggest that, by spontaneous cell fusion in vitro, tumor cells can adopt the morphology and immunophenotype of stromal cells while still carrying oncogenic, tumor-derived genetic information. Therefore, melanoma-stromal cell fusion might play a role in missing tumor cells by routine histopathological assessments.


PubMed | University of Szeged, Semmelweis University, MTA SZTE Dermatological Research Group, University of Miskolc and 2 more.
Type: Journal Article | Journal: Human immunology | Year: 2015

Inflammation plays a central role in the pathogenesis of chronic rhinosinusitis (CRS), and TNF is a key pro-inflammatory cytokine in the pathogenesis of this disease. In our previous studies, we showed that the TNFA -308A allele is a genetic predisposition factor in a subgroup of aspirin-sensitive (ASA+) CRS patients suffering from nasal polyps (NP) in the Hungarian population. To determine whether the TNF -308A allele or the presence of a complex, extended ancestral haplotype (8.1AH) located on chromosome 6 is responsible for the previously observed genetic effect, we performed a case-control study for examining the frequency of 8.1AH carriers in controls and in subgroups of CRS patients. Our novel observations demonstrate that the presence of the 8.1AH may be responsible for the development of severe forms of CRS (CRSwNP, ASA+) and strengthen the clinical observation that CRS patients can be classified into clinically and genetically different subgroups.


PubMed | Debrecen University, MTA SZTE Dermatological Research Group and University of Szeged
Type: | Journal: The British journal of dermatology | Year: 2016

From our birth, we are constantly exposed to bacteria, fungi and viruses, some of which are capable of transiently or permanently inhabiting our different body parts as our microbiota. The majority of our microbial interactions occur during and after birth, and several different factors, including age, sex, genetic constitution, environmental conditions and life style, have been suggested to shape the composition of this microbial community. Propionibacterium acnes (P. acnes) is one of the most dominant lipophilic microbes of the postadolescent, sebum-rich human skin regions. Currently, the role of this bacterium in the pathogenesis of the most common inflammatory skin disease acne vulgaris is a topic of intense scientific debate. Recent results suggest that Westernization strongly increases the dominance of the Propionibacterium genus in human skin compared to natural populations living more traditional lifestyles. According to the disappearing microbiota hypothesis proposed by Martin Blaser a few years ago, such alterations in the composition of our microbiota are the possible consequences of socioeconomic and lifestyle changes occurring after the industrial revolution. Evanescence of species that were important elements of the human ecosystem might lead to the overgrowth and subsequent dominance of others because of the lack of ecological competition. Such changes can disturb the fine-tuned balance of the human body and, accordingly, our microbes developed through a long co-evolutionary process. These processes might lead to the transformation of a seemingly harmless species into an opportunistic pathogen through bacterial dysbiosis. This might have happen in the case of P. acnes in acne pathogenesis. This article is protected by copyright. All rights reserved.


Csoma Z.R.,University of Szeged | Meszes A.,University of Szeged | Abraham R.,University of Szeged | Kemeny L.,University of Szeged | And 3 more authors.
Pediatric Dermatology | Year: 2016

Background/Objectives: Recent technological advances and diagnostic and therapeutic innovations have resulted in an impressive improvement in the survival of newborn infants requiring intensive care. Consequently, with the use of modern invasive diagnostic and therapeutic procedures, the incidence of iatrogenic events has also increased. The aim of this study was to assess various iatrogenic complications in neonates requiring intensive care and determine possible contributing factors to the injuries. Methods: Our prospective cross-sectional cohort survey was conducted in a central regional level III neonatal intensive care unit (NICU). Correlations between intensive therapeutic interventions, complications, factors influencing attendance and prognosis, and the prevalence of iatrogenic skin injuries (ISIs) were investigated over a 2-year study period. Results: Between January 31, 2012, and January 31, 2014, 460 neonates were admitted to the NICU, 83 of whom exhibited some kind of ISI. The major risk factors for ISIs were low birthweight, young gestational age, long NICU stay, use of the intubation–surfactant–extubation (INSURE) technique, surfactant use, mechanical ventilation, insertion of an umbilical arterial catheter, circulatory and cardiac support with dopamine or dobutamine, pulmonary hemorrhage, intracranial hemorrhage, patent ductus arteriosus, bronchopulmonary dysplasia, and positive microbiology culture results. Conclusion: To prevent ISIs, careful consideration of risk factors and the creation of protocols ensuring efficient treatment of injuries are needed. © 2016 Wiley Periodicals, Inc.


Szell M.,University of Szeged | Szell M.,MTA SZTE Dermatological Research Group | Danis J.,University of Szeged | Bata-Csorgo Z.,MTA SZTE Dermatological Research Group | And 3 more authors.
Pflugers Archiv European Journal of Physiology | Year: 2016

In the last few years with the recent emergence of high-throughput technologies, thousands of long non-coding RNAs (lncRNAs) have been identified in the human genome. However, assigning functional annotation and determining cellular contexts for these RNAs are still in its infancy. As information gained about lncRNA structure, interacting partners, and roles in human diseases may be helpful in the characterization of novel lncRNAs, we review our knowledge on a selected group of lncRNAs that were identified serendipitously years ago by large-scale gene expression methods used to study human diseases. In particular, we focus on the Psoriasis-susceptibility-Related RNA Gene Induced by Stress (PRINS) lncRNA, first identified by our research group as a transcript highest expressed in psoriatic non-lesional epidermis. Results gathered for PRINS in the last 10 years indicate that it is conserved in primates and plays a role in keratinocyte stress response. Elevated levels of PRINS expression in psoriatic non-lesional keratinocytes alter the stress response of non-lesional epidermis and contribute to disease pathogenesis. Finally, we propose a categorization for the PRINS lncRNA based on a recently elaborated system for lncRNA classification. © 2016 The Author(s)


Fernandez-Calvino L.,CSIC - Biological Research Center | Martinez-Priego L.,CSIC - Biological Research Center | Szabo E.Z.,University of Szeged | Guzman-Benito I.,CSIC - Biological Research Center | And 5 more authors.
Journal of General Virology | Year: 2016

The cysteine-rich 16K protein of tobacco rattle virus (TRV), the type member of the genus Tobravirus, is known to suppress RNA silencing. However, the mechanism of action of the 16K suppressor is not well understood. In this study, we used a GFP-based sensor strategy and an Agrobacterium-mediated transient assay in Nicotiana benthamiana to show that 16K was unable to inhibit the activity of existing small interfering RNA (siRNA)- and microRNA (miRNA)- programmed RNA-induced silencing effector complexes (RISCs). In contrast, 16K efficiently interfered with de novo formation of miRNA- and siRNA-guided RISCs, thus preventing cleavage of target RNA. Interestingly, we found that transiently expressed endogenous miR399 and miR172 directed sequence-specific silencing of complementary sequences of viral origin. 16K failed to bind small RNAs, although it interacted with ARGONAUTE 4, as revealed by bimolecular fluorescence complementation and immunoprecipitation assays. Site-directed mutagenesis demonstrated that highly conserved cysteine residues within the N-terminal and central regions of the 16K protein are required for protein stability and/or RNA silencing suppression. © 2015 The Authors.


Szabo E.Z.,University of Szeged | Kemeny L.,University of Szeged | Kemeny L.,MTA SZTE Dermatological Research Group | Lakatos L.,University of Szeged | Lakatos L.,MTA SZTE Dermatological Research Group
Acta Biologica Szegediensis | Year: 2014

RNA silencing is a part of the plant innate immune system that could effectively cope with intruders, like viruses. However, viruses evolved proteins that can suppress RNA silencing thus supporting virus spreading in the host. To counteract RNA silencing, suppressor proteins attack different players of RNA silencing pathway. The P1 protein of the Sweet potato mild mottle virus binds and inactivates small RNA loaded RISC complexes. Using a deletion series in the P1 protein we aimed to identify the possible smallest working version of P1. Our results revealed that the minimal RNA silencing suppressor domain of P1 is as small as 210 amino acids in size.

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