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A közlemény a gyorsan változó és bővülő nemzetközi és hazai szakirodalom alapján megkísérli áttekinteni a koronavírus-világjárvány (COVID–19) főbb epidemiológiai adatait. A dolgozat kitér az ún. „hosszú COVID–19” kórképre és a legfrissebb farmakológiai, valamint immunterápiás fejleményekre. A cikk foglalkozik az innovatív vakcinológia jövőjével, a mesterséges intelligenciák és a nanotechnológia segítségével fejlesztett, ún. „pán”-vakcinák lehetőségével is. Orv Hetil. 2022; 163(24): 935–942.

Extracellular vesicles (EVs) are membrane-enclosed subcellular structures released by all cell types. EVs have important roles in both cellular homeostasis and intercellular communication. Recent progress in the field revealed substantial heterogeneity of EVs even within the size-based EV categories. Here we addressed the question whether the exportin-1 (XPO1)-mediated nuclear export of RNAs contributed to the EV heterogeneity. Size-based populations were separated from the conditioned media of three cell lines (U937, THP-1 and 5/4E8) in steady-state condition. The effects of activation and leptomycin B treatment (to inhibit the XPO1-mediated nuclear export of RNAs) were also tested in the case of the two monocytic cell lines. Agilent Pico and Small chips were used to characterize RNAs, fragment analysis was performed, and EV-associated miRNAs were tested by Taqman assays. As expected, we found the highest small RNA/total RNA ratio and the lowest rRNA/total RNA proportion in small EVs (~ 50–150 nm). Profiles of the small RNAs within different size-based EV categories significantly differed based on the activation status of the EV releasing cells. Leptomycin B had a differential inhibition on the tested small RNAs in EVs, even within the same EV size category. A similar heterogeneity of the EV miRNA content was observed upon cellular activation and nuclear export inhibition. Here we complement the already existing knowledge on EV heterogeneity by providing evidence that the RNA cargo varies depending on the EV size-based category, the releasing cell type, the functional status of the releasing cells and the exportin-1-mediated nuclear export of RNAs.

Összefoglaló. Manapság, a COVID–19-járvány közepette, a megfelelő kézmosás segít megelőzni vagy legalábbis lassítani a fertőző betegségek, például a SARS-CoV-2-fertőzés terjedését. A kézmosás rutinjának megfelelő oktatás multilaterális tevékenységet igényel, amely a fiatalok ismeretén, egészségmagatartásán, attitűdjein, tapasztalatain és motivációján alapul. A TANTUdSZ Ifjúsági Egészségnevelési Program kortársoktató pedagógiai és egészségtudományi egyetemi karok hallgatóival, valamint középiskolai kortárssegítőkkel és mintegy 3000, magyarországi óvodás, általános és középiskolás diák bevonásával valósult meg, különböző egészségfejlesztési területeken. A vizsgálatok egyik célja az oktatási program hatékonyságának értékelése érdekében a gyermekek kézhigiénés ismereteinek és készségeinek elemzése és összehasonlítása volt a beavatkozások előtt és után. A jelen közleményben ismertetett longitudinális felmérés alsó tagozatos tanulók (n = 165) kézmosási készségének és attitűdváltozásainak rövid és hosszú távú változását értékeli három időpontban. A mérések önkitöltős, anonim kérdőívvel és kéziszkenner-technológiával (Semmelweis Scanner) készültek, mely utóbbi mérési eszköz a különböző kézterületek tisztaságát kvantitatív és digitális értékelésekkel detektálta. A beavatkozás eredményes volt mind rövid, mind hosszú távon a bemeneti (kezdeti) mérésekhez képest. Az eredmények azonban különbséget mutattak a gyakorlati készségek elsajátításának folyamatában. Jelentős előrelépés történt a kézmosás attitűdjének változásában. Az életkor-specifikus egészségfejlesztési oktatási programokban, különösen a gyermekpopulációban, hangsúlyt kell fektetni az elméleti, a gyakorlati ismeretek, valamint az egészségmagatartás hosszú távú megőrzésére is. Orv Hetil. 2021; 162(46): 1842–1847. Summary. Presently, in the midst of the COVID-19 pandemic, proper hand washing helps prevent or at least slow the spread of infectious diseases such as SARS-CoV-2 infection. Proper education in hand washing routines requires multilateral action based on young people’s knowledge, health behaviors, attitudes, experiences, and motivations. The TANTUdSZ Youth Health Education Program was implemented with students of contemporary teaching faculties of pedagogical and health sciences as well as with secondary school peer helpers and with the involvement of about 3000 pre-school, primary and secondary school students in Hungary in various fields of health development. One of the aims of the studies was to analyze and compare children’s hand hygiene knowledge and skills before and after the pedagogical interventions in order to evaluate the effectiveness of the educational program. The longitudinal survey described in this paper assesses the short- and long-term changes of primary school students’ (from class 1 to 4; n = 165) hand washing skills and the attitudinal changes in their health behaviors at three time points. Measurements were performed using a self-completion, anonymous questionnaire and hand-held scanner technology (Semmelweis Scanner), the latter measuring device detecting the purity of different hand areas with quantitative and digital evaluations. The educational intervention was effective in both short and long term compared to input (initial) measurements. However, the results showed a difference in the process of acquiring practical skills. There has been a significant progress in changing attitudes to hand washing. Age-specific health promotion education programs, especially in the pediatric population, should also focus on the long-term preservation of theoretical, practical knowledge, and health behaviors. Orv Hetil. 2021; 162(46): 1842–1847.

Background With the increase of cyberbullying, several intervention programmes have been created that aim at reducing cyber-victimisation and perpetration. Objective Our study presents the effects of the STAnD anti-cyberbullying programme with peer-education both on the short and the long run among lower and upper primary school students, with a focus on the participants’ cyberbullying roles. Method The sample comprised of 536 students who participated in the intervention programme, involving 36% lower and 64% upper primary school students. Participants were measured by a self-reported questionnaire before and right after the programme, then six months later. Results The main effect of the STAnD programme was a positive change in the participants’ willingness to engage in help-seeking and their active-defending reaction, although this effect decreased after six months. The changes were larger among lower primary school students compared to upper primary school participants. Conclusion Our results imply that long-lasting and intensive health promotion programmes are necessary to reach a long-term intervention effect. Anti-cyberbullying programmes should take into consideration participants’ involvement and roles in cyberbullying. As our study was a non-randomised uncontrolled study design, thus interpretation of the effectiveness of the programme is limited.

The article attempts to review the principal epidemiological data of the coronavirus pandemic (COVID-19) based on the rapidly changing and expanding international and domestic literature. The review covers the so-called ,,long COVID-19 as well as the latest pharmacological and immunotherapeutic developments. The manuscript deals with the future of innovative vaccinology, the so-called 'pan-vaccines' developed through artificial intelligences and nano technology.A közlemény a gyorsan változó és bővülő nemzetközi és hazai szakirodalom alapján megkísérli áttekinteni a koronavírus-világjárvány (COVID–19) főbb epidemiológiai adatait. A dolgozat kitér az ún. „hosszú COVID–19” kórképre és a legfrissebb farmakológiai, valamint immunterápiás fejleményekre. A cikk foglalkozik az innovatív vakcinológia jövőjével, a mesterséges intelligenciák és a nanotechnológia segítségével fejlesztett, ún. „pán”-vakcinák lehetőségével is. Orv Hetil. 2022; 163(24): 935–942.

Absztrakt: A COVID–19-járvány mindenkit, szakembert és laikust egyaránt váratlanul érintett, jóllehet egy világméretű pandémia lehetőségét egyrészről az epidemiológusok, infektológusok, másrészről szociológusok, kommunikációs, sőt társadalmi szokásokkal foglalkozó viselkedéstudományi szakemberek elméletben már régóta elképzelhetőnek tartották. Mégis, szembesülve a „real-time” történésekkel, a napi fertőzöttségi és mortalitási statisztikákkal, szinte mindenki tudatlannak, illetve zavaróan tapasztalatlannak érzi magát. A jelen összefoglalás tudományos evidenciákról kíván áttekintést nyújtani. A 2020. március végén összeállított, korántsem teljességre törekedő anyag természetesen nem kevés olyan elemet tartalmaz, amely pár hét múlva meghaladott lesz. A szerzők remélik, hogy egy legközelebbi publikációban mindannyian sokkal jobb és reménytelibb kilátásokról tudósíthatunk. Orv Hetil. 2020; 161(17): 644–651.

In his article “Genetics and ethics: ‘Do not go alone’”! András Falus presents genomics as a network science triggering an entirely new trend in contemporary biology. Based on the advent of molecular biology the complete sequence of human and other genomes has been determined and since all information is available on internet-based databanks, the huge mass of data is being analysed by advanced methods of informatics. The author is focusing on the upcoming ethical aspect of genetics and genomics, then, in the second part of the article he answers the questions of the editor concerning the genetic approach to ethics and ethical approach to genetics.

Based on the findings of common project 29 years ago, the Scandinavian J. of Immunology accepted and published our paper entitled by “FcγR-Dependent Regulation of the Biosynthesis of Complement C3 by Murine Macrophages: the Modulatory Effect of IL-6” (Bajtay et al. in SJI 35:195–201, 1992). In this report we attempt to review the previous results and evaluate them with our current concepts on the interaction between the actors of adaptive and innate immunity. Let us first to summarize the basic results and consequences from the paper from 1992. Abstract from 1991–1992: The effect of murine IgG isotypes (myeloma proteins) on the gene expression and secretion of the third component of complement (C3) has been studied using the in monocytoid cell line P388D1 and oil-elicited mouse peritoneal macrophages. It is demonstrated that the binding of lgG2a and lgG2b but not IgGl and IgG3 isotypes augments the biosynthesis of C3 both in the presence and in the absence of the phorbol myristate acetate in the case of both cell types. The multifunctional cytokine inlerleukin-6 (IL-6) alone reveals no effect on the gene expression of C3, but facilitates the effectiveness of mouse IgG2a and IgG2b. Confirming the role of FcgRll, a strong up-regulation of gene expression and secretion of C3 was found when macrophages were co-cultured with the F(ab')2 fragment of the FcγRII-specific monoclonal antibody 2.4 G2.

Abstract: Basic life support (BLS) teaching by peer-educators to school-age students was studied by evaluating their effectiveness. BLS resuscitation was taught by the internationally accepted four-stage skill teaching approach. The effectiveness of the training was followed by sociological measuring instruments (n = 91). Compared to the students’ previous knowledge and attitudes about resuscitation, an increased willingness to adapt to an unexpected situation can be observed besides acquiring a reproducible method of CPR. The findings did not show significant age differences. Sensitivity and technical training in lay resuscitation is a successful educational process. The applied peer-education model is suitable for transferring resuscitation knowledge and skills. Orv Hetil. 2019; 160(46): 1816–1820.

The COVID-19 epidemic hit everyone, professionals and civilians alike. The possibility of a worldwide pandemic has long been theorized by epidemiologists, infectologists on the one hand, and sociologists and behavioral scientists dealing with communication and social habits on the other. Yet, faced with real-time events, daily infections and mortality statistics, almost everyone feels uninformed or disturbingly inexperienced. This summary aims to provide an overview of the latest scientific evidences. Of course, the incomplete material, compiled in late March 2020, will certainly contain a few elements that likely will be outdated in a few weeks. The authors hope that in the next publication we will all read much better and more hopeful prospects. Orv Hetil. 2020; 161(17): 644–651.A COVID–19-járvány mindenkit, szakembert és laikust egyaránt váratlanul érintett, jóllehet egy világméretű pandémia lehetőségét egyrészről az epidemiológusok, infektológusok, másrészről szociológusok, kommunikációs, sőt társadalmi szokásokkal foglalkozó viselkedéstudományi szakemberek elméletben már régóta elképzelhetőnek tartották. Mégis, szembesülve a „real-time” történésekkel, a napi fertőzöttségi és mortalitási statisztikákkal, szinte mindenki tudatlannak, illetve zavaróan tapasztalatlannak érzi magát. A jelen összefoglalás tudományos evidenciákról kíván áttekintést nyújtani. A 2020. március végén összeállított, korántsem teljességre törekedő anyag természetesen nem kevés olyan elemet tartalmaz, amely pár hét múlva meghaladott lesz. A szerzők remélik, hogy egy legközelebbi publikációban mindannyian sokkal jobb és reménytelibb kilátásokról tudósíthatunk. Orv Hetil. 2020; 161(17): 644–651.

Introduction Marked gender differences have been identified in cyberbullying perpetration and victimization in adolescence. Age and phenotypic traits, including impulsivity and problematic internet use may mediate the association between gender and cyberbullying intervention outcomes. This study thus aimed to explore gender differences and the potential mediating role of age, impulsivity and problematic internet use regarding the outcomes of an elementary school cyberbullying program. Methods The peer-led STAnD project shapes students' attitudes towards cyberbullying, and promotes help-seeking behaviors. Baseline sample consisted of 933 respondents (51.3% females, mean age = 11.25, sd = 1.64), and after a 42.55% drop-out, 536 remained in the sample for 6-month follow-up. Four primary outcome measures represented protective factors against cyberbullying. Results Three of the intervention outcomes – change in 1) helpline knowledge, 2) empathy towards the victims of cyberbullying, and 3) risk perception regarding online hazards - were best predicted by gender. A gender-specific path analysis model indicated that higher amount of time spent online might put a barrier to changes in risk awareness among females and in help-seeking willingness among males. Conclusions Future cyberbullying programs may design separate interventions for adolescent boys and girls with different emphasis placed on empathy training, or the barriers to help-seeking.

Health-related attitudes can be modified and supported most effectively at young ages. Young generations require more interpersonal and interactive pedagogical methods in programs engaged in health promotion, as well. The aim of the authors was to get an insight into a relatively novel pedagogical method, called peer education. This multilateral activity is focusing the procedure on attitudes, experience, and motivation of youngsters in connection with health promotion programs and community service work. In this article, the authors describe 1) the theory, origin, and principal influences of peer education compared to traditional teaching methods and 2) the new, efficiency-oriented and science-based methodology of health education program.

Purpose The authors intended to develop a novel procedure and research method that follows the effectiveness of the peer-educational approach in handwashing among school children. Materials and methods To ask the children about their sociodemographic background, health behaviour, hand hygiene knowledge, and health attitudes, and questionnaires were applied. The education on proper handwashing procedures was followed by a test with a mobile UV-light detection system (Semmelweis Scanner, http://www.handinscan.com/), and the scans were evaluated through an intrinsic computer software. Results Our newly developed questionnaire-based research method and the hand-rubbing technique followed by a test with a mobile UV-light detection system may become a reliable and valid scientific measurement of the effectiveness of hand hygiene training programmes. Conclusions The Hand-in-Scan technology and questionnaire-based research method provide proper tools for evaluating the successful peer education method. It can significantly elevate the level of children’s compliance, which leads to a better hygienic consciousness.

Abstract: Introduction and aim: In the case of primary school children in Budapest (n = 165), data on their social status and their previous knowledge on hand hygiene were elicited with the help of pre-knowledge questionnaires issued by students of higher education. The aim of the research was introducing a novel pedagogical procedure – application and optimization of peer education in the development of proper hand hygiene among primary school students. Method: The knowledge-based survey was conducted after four (n = 85) and eight hours of teaching (n = 36). In addition, the effectiveness of hand washing was tested immediately before (n = 166) and after the four (n = 74) and eight hours of teaching (n = 35) with Semmelweis Scanner after rubbing the hand with fluorescent cream. Results: Prior knowledge of hand hygiene significantly increased after the four-hour and eight-hour trainings. In the case of smaller children, the effect of the eight-hour training was more pronounced. Similar results were obtained with regards to the changes in the number of areas missed while rubbing the surface of the hand as a result of the teaching. Conclusion: Sociological surveys on hand hygiene knowledge and direct physical measurements indicate that training with appropriate pedagogical procedures is effective and contributes to the environmentally conscious hygiene culture of children aged 6 to 10. Orv Hetil. 2018; 159(12): 485–490.

Our study analyzed lymphocyte subpopulations of 32 monozygotic twins and compared the level of the catalytic reverse transcriptase protein subunit (hTERT) in T lymphocytes (Tly), helper- (Th), cytotoxic- (Tc) and regulatory T cell (Treg) subgroups. Four variables related to telomere and mitochondrial biology were simultaneously assessed, applying multi-parametric flow cytometry, TRAP-ELISA assay and qPCR standard curve method on peripheral blood mononuclear cell (PBMC) samples of genetically matched individuals. Twin data of telomerase activity (TA), hTERT protein level, telomere length (TL) and mitochondrial DNA copy number (mtDNAcn) were analyzed for co-twin similarity. The present study has provided novel information by demonstrating very high intraclass correlation (ICC) of hTERT protein level in T lymphocytes (0.891) and in both Th (0.896), Treg (0.885) and Tc (0.798) cell subgroups. When comparing results measured from PBMCs, intraclass correlation was also high for telomere length (0.815) and considerable for mtDNA copy number (0.524), and again exceptionally high for the rate-limiting telomerase subunit, hTERT protein level (0.946). In contrast, telomerase activity showed no co-twin similarity (ICC 0). By comparing relative amounts of hTERT protein levels in different lymphocyte subgroups of twin subjects, in Treg cells significantly higher level could be detected compared to Tly, Th or Tc cell subgroups. This is the first study that simultaneously analyzed co-twin similarity in MZ twins for the above four variables and alongside assessed their relationship, whereby positive association was found between TL and mtDNAcn.

Basic life support (BLS) teaching by peer-educators to school-age students was studied by evaluating their effectiveness. BLS resuscitation was taught by the internationally accepted four-stage skill teaching approach. The effectiveness of the training was followed by sociological measuring instruments (n = 91). Compared to the students' previous knowledge and attitudes about resuscitation, an increased willingness to adapt to an unexpected situation can be observed besides acquiring a reproducible method of CPR. The findings did not show significant age differences. Sensitivity and technical training in lay resuscitation is a successful educational process. The applied peer-education model is suitable for transferring resuscitation knowledge and skills. Orv Hetil. 2019; 160(46): 1816-1820.Absztrakt: A kutatási cél az alapszintű újraélesztés (laikus újraélesztés – basic life support, BLS) kortársoktatók által iskoláskorú diákok számára történő készségszintű megtanítása és annak tudományos mérőeszközzel történő hatékonyságvizsgálata. Az újraélesztést a nemzetközileg elterjedt négylépcsős készségátadási módszerrel oktattuk. A betanítás eredményességét kérdőíves módszerrel, szociológiai szempontok bevonásával is követtük (n = 91). Az újraélesztésre vonatkozó korábbi tudás és attitűd felmérése után, az általunk alkalmazott eljárás reprodukálható elsajátítása mellett kiemelhető egy váratlan szituációhoz való alkalmazkodásra történő hajlandóság fokozása is. Mindez jelentős életkori eltéréseket nem mutatott. A laikus újraélesztés vállalására irányuló érzékenyítő és technikai tréning eredményes nevelési eljárást igazol. Az alkalmazott kortársoktatási modell alkalmasnak mutatkozik az újraélesztési ismeretek átadására. Orv Hetil. 2019; 160(46): 1816–1820.

Introduction: Health-related attitudes can be encouraged most effectively at young ages. Young generations would require more interactive methods in programs engaged in health promotion. Aim: The aim of the authors was to get an insight into the attitudes, experience and motivation of youngsters in connection with health promotion programs and the community service work. Method: The questionnaires were filled in by high school students studying in Budapest and in the countryside (N = 898). Results: 44.4% of the students did not have lessons or extracurricular activities dealing with health promotion. Concerning health promotion programs, youngsters in Budapest had more positive experience, while female students showed a more adoptive attitude. Conclusions: It was concluded that in one of the most susceptible life stages, many youngsters either do not participate in programs dealing with health promotion, or participate in programs that are within the framework of school subjects or extracurricular activities building on traditional teaching methods. Orv. Hetil., 2016, 157(2), 65–69.

Introduction Recent experimental and population studies have highlighted the existence of telomere-mitochondria interplay. Besides studies revealing the molecular mechanisms underlying the associations of telomere defects and mitochondrial functions, investigations of mitochondrial DNA copy number (mtDNAcn) and telomere length (TL) in healthy and disease phenotypes have likewise begun, with the aim of gaining more insights about their relationship in humans. Material and methods A total of 142 asymptomatic adult twins, comprising 96 monozygotic (MZ) and 46 dizygotic (DZ) twins (mean age: 50.54 ±15.43 years), members of the Hungarian Twin Registry, were included in the analysis. Applying the qPCR standard curve method, we investigated the relationship of mtDNA copy number, telomere length and clinical data, besides assessing co-twin similarities of MZ and DZ twins for their mtDNAcn and TL measures. Results We found that twins were similar in their intraclass correlation coefficients irrespective of zygosity, suggesting a possibly more important role of common (shared) environmental factors compared to non-shared (unique) environmental and to a smaller degree also individual genetic influences. We confirmed a significant positive association between mtDNAcn and TL (r = 0.28, p < 0.01) in age- and sex-corrected analysis. Following bivariate estimates and correction with significant predictors, the independent positive associations were further verified. Conclusions Our results extend the until now modest number of studies investigating mtDNAcn and TL simultaneously in humans. In addition, we are the first to examine the relationship between mtDNAcn and telomere length in MZ and DZ twin subjects.

In the case of primary school children in Budapest (n = 165), data on their social status and their previous knowledge on hand hygiene were elicited with the help of pre-knowledge questionnaires issued by students of higher education. The aim of the research was introducing a novel pedagogical procedure - application and optimization of peer education in the development of proper hand hygiene among primary school students.The knowledge-based survey was conducted after four (n = 85) and eight hours of teaching (n = 36). In addition, the effectiveness of hand washing was tested immediately before (n = 166) and after the four (n = 74) and eight hours of teaching (n = 35) with Semmelweis Scanner after rubbing the hand with fluorescent cream.Prior knowledge of hand hygiene significantly increased after the four-hour and eight-hour trainings. In the case of smaller children, the effect of the eight-hour training was more pronounced. Similar results were obtained with regards to the changes in the number of areas missed while rubbing the surface of the hand as a result of the teaching.Sociological surveys on hand hygiene knowledge and direct physical measurements indicate that training with appropriate pedagogical procedures is effective and contributes to the environmentally conscious hygiene culture of children aged 6 to 10. Orv Hetil. 2018; 159(12): 485-490.

Under physiological and pathological conditions, extracellular vesicles (EVs) are present in the extracellular compartment simultaneously with soluble mediators. We hypothesized that cytokine effects may be modulated by EVs, the recently recognized conveyors of intercellular messages. In order to test this hypothesis, human monocyte cells were incubated with CCRF acute lymphoblastic leukemia cell line-derived EVs with or without the addition of recombinant human TNF, and global gene expression changes were analyzed. EVs alone regulated the expression of numerous genes related to inflammation and signaling. In combination, the effects of EVs and TNF were additive, antagonistic, or independent. The differential effects of EVs and TNF or their simultaneous presence were also validated by Taqman assays and ELISA, and by testing different populations of purified EVs. In the case of the paramount chemokine IL-8, we were able to demonstrate a synergistic upregulation by purified EVs and TNF. Our data suggest that neglecting the modulating role of EVs on the effects of soluble mediators may skew experimental results. On the other hand, considering the combined effects of cytokines and EVs may prove therapeutically useful by targeting both compartments at the same time.

Hemophagocytic lymphohistiocytosis is a multisystem inflammation, generated by the uncontrolled and excessive activation of cytotoxic T lymphocytes and natural killer cells. Severe immunodeficiency and generalized macrophage activation can often be detected in the background of this life threatening disorder. It is classified as a primary immunodeficiency. Functional abnormalities of the perforin protein or defects in granule secretory mechanisms are caused by gene mutations in most cases. Diagnostic criteria of hemophagocytic lymphohistiocytosis are the following: fever, splenomegaly, cytopenias affecting at least two of the 3 lineages in peripheral blood, hypertriglyceridemia and hyperferritinemia, elevated serum level of soluble interleukin-2 receptor (sCD25), hypofibrinogenemia, hemophagocytosis in bone marrow and decreased cytotoxic T cell and natural killer cell activity. In this case report the authors summarize the utility of functional flow cytometry in the diagnosis of hemophagocytic lymphohistiocytosis. Using flow cytometry, elevated intracellular perforin content, decreased killing activity of cytotoxic T cells and natural killer cells, and impaired cell surface expression of CD107a (LAMP1 protein) from in vitro stimulated blood lymphocytes were detected. Abnormal secretion of perforin was also demonstrated. Genetic testing revealed mutation of the MUNC 13-4 gene, which confirmed the base of the abnormal flow cytometric findings. This case report demonstrates the value of functional flow cytometry in the rapid diagnosis of genetically determined hemophagocytic lymphohistiocytosis, a condition in which early diagnosis is critical for optimal management. The authors emphasize the significance of functional flow cytometry in the differential diagnosis of immunodeficiencies. Orv. Hetil., 2014, 155(10), 389–395.

The discovery that submicron-sized extracellular vesicles (EVs) are generated by both prokaryotic and eukaryotic cells might have a profound effect on experimental and clinical sciences, and could pave the way for new strategies to combat various diseases. EVs are carriers of pathogen-associated and damage-associated molecular patterns, cytokines, autoantigens and tissue-degrading enzymes. In addition to a possible role in the pathogenesis of a number of inflammatory conditions, such as infections and autoimmune diseases, EVs, including microvesicles (also known as microparticles), exosomes and apoptotic vesicles, have therapeutic potential and might be used as biomarkers for inflammatory diseases. Therefore, molecular diagnostics and targeted therapy could benefit from expanding knowledge in the field. In this Review, we summarize important developments and propose that extracellular vesicles could be used as therapeutic vehicles and as targets for the treatment and prevention of inflammatory diseases.

The currently available medical treatment options of adrenocortical cancer (ACC) are limited. In our previous meta-analysis of adrenocortical tumor genomics data, ACC was associated with reduced retinoic acid production and retinoid X receptor-mediated signaling. Our objective has been to study the potential antitumoral effects of 9-cis retinoic acid (9-cisRA) on the ACC cell line NCI-H295R and in a xenograft model. Cell proliferation, hormone secretion, and gene expression have been studied in the NCI-H295R cell line. A complex bioinformatics approach involving pathway and network analysis has been performed. Selected genes have been validated by real-time qRT-PCR. Athymic nude mice xenografted with NCI-H295R have been used in a pilot in vivo xenograft model. 9-cisRA significantly decreased cell viability and steroid hormone secretion in a concentration- and time-dependent manner in the NCI-H295R cell line. Four major molecular pathways have been identified by the analysis of gene expression data. Ten genes have been successfully validated involved in: (1) steroid hormone secretion (HSD3B1, HSD3B2), (2) retinoic acid signaling (ABCA1, ABCG1, HMGCR), (3) cell-cycle damage (GADD45A, CCNE2, UHRF1), and the (4) immune response (MAP2K6, IL1R2). 9-cisRA appears to directly regulate the cell cycle by network analysis. 9-cisRA also reduced tumor growth in the in vivo xenograft model. In conclusion, 9-cisRA might represent a promising new candidate in the treatment of hormone-secreting adrenal tumors and adrenocortical cancer.

The P70-84 peptide (also called 5/4E8 epitope) of the human cartilage proteoglycan (PG) aggrecan is the dominant/arthritogenic epitope in both humans and arthritis-prone BALB/c mice (PG-induced arthritis, PGIA). An elevated T cell reactivity was demonstrated to a citrullinated version of the P70-84 epitope in most of the patients with rheumatoid arthritis (RA). The goal of this study was to understand better how a T cell epitope, if citrullinated, may affect antigenicity/arthritogenicity in PGIA, a murine model of RA. T cell reactivity to differentially citrullinated versions of either the human PG aggrecan P70-84 peptide or the corresponding mouse sequence was assessed in peptide or aggrecan-immunized and arthritic BALB/c mice as well as in T cell receptor transgenic mice specific for peptide P70-84 sequence. Peripheral T cell responses were induced by priming BALB/c mice with either the human wild-type or its citrullinated versions. Unexpectedly, priming with the citrullinated self-peptide induced a higher T cell response compared to the wild-type sequence (p

Resume La citrullination, modification enzymatique post-traductionnelle, est un sujet d’actualite tres developpe recemment en raison de son implication dans divers processus physiologiques et pathologiques. Les anticorps antiproteines citrullinees constituent des facteurs diagnostiques et pronostiques de la polyarthrite rhumatoide, et sont specifiques de cette maladie. La citrullination a un role important dans le fonctionnement normal du systeme immunitaire, la keratinisation de la peau, la protection des neurones et la plasticite du systeme nerveux central, et joue un role essentiel dans la regulation des genes. Des anomalies de citrullination jouent sans doute un role dans la sclerose en plaques et la maladie d’Alzheimer. De plus, des recherches recentes ont permis de montrer son implication dans la tumorigenese. Il est cependant difficile de savoir si la citrullination est la cause ou la consequence de ces pathologies. Dans cette revue, nous aborderons les aspects cruciaux de la citrullination en situations physiologique et pathologique.

BACKGROUND Human fetuin A (AHSG) has been associated with the development of obesity, insulin resistance, type 2 diabetes mellitus, and atherosclerosis. Observations on the role of AHSG rs4918 single-nucleotide polymorphism are contradictory. We investigated the association between variants of rs4918 and parameters of obesity, lipid status, tumor necrosis factor-α (TNFα), adipokines (adiponectin, resistin, leptin), and insulin resistance in healthy persons and in patients with previous myocardial infarction. MATERIAL AND METHODS This was a cross-sectional study comprising cohort 1 (81 healthy individuals) and cohort 2 (157 patients with previous myocardial infarction). We used the allele-specific KASP genotyping assay to detect rs4918 polymorphism. RESULTS In cohort 1, G-nucleotide carriers had significantly lower serum TNFα, adiponectin, and higher leptin concentrations than in non-G carriers. These differences, however, were not observed in cohort 2. In cohort 2, G-carriers had lower BMI and waist circumferences than in non-G carriers. The G allele was more frequent among lean than obese patients (RR=1.067, 95%CI=1.053-2.651, p=0.015). An association between BMI and rs4918 polymorphism was observed among patients without diabetes (CC/CG/GG genotypes: p=0.003, G vs. non-G allele: p=0.008) but not in diabetics. In addition, a strong linearity between BMI and the CC/CG/GG genotypes (association value: 4.416, p=0.036) and the frequency of the G allele (7.420, p=0.006) could be identified. In cohort 2, non-obese, non-diabetic G-carriers still had lower BMI and waist circumferences than in non-G carriers. CONCLUSIONS The rs4918 minor variant is associated with lower TNFα and adiponectin, higher leptin levels in healthy persons, and more favorable anthropomorphic parameters of obesity in cohort 2.