Miscellanea. Beszámoló. Könyvismertetés

Beszámoló. Az oxidatív stressz és a betegségek Országos konferencia Budapest, 2014. november 6–7. | Könyvismertetés. Michael Schönberger Glossar der Handchirurgie © Michaela Schnur Verlag, Drezda, 2007 ISBN-10: 3-937890-04-1 ISBN-13: 978-3-937890-04-3 | Dr. Ralovich Béla Adatok a mikrobiológiával kapcsolatos ismeretek oktatás- és kutatástörténetéhez – II. Magánkiadás, Balatonberény, 2014 ISBN: 978-963-08-9753-2 Ára: 49,95 € (~18 700 HUF

Prevalence of resistance mutations associated with integrase inhibitors in therapy-naive HIV-positive patients in Hungary

Widespread introduction of HIV integrase inhibitors into clinical care may result in appearance of drug resistance mutations affecting treatment outcome. The aim of our study was to monitor the resistance patterns of integrase inhibitors beside protease and reverse transcriptase inhibitors in newly diagnosed therapy-naive HIV-positive patients in Hungary between 2017 and 2019.Genotype-based resistance testing of HIV integrase, protease and reverse transcriptase was performed by amplification and Sanger population sequencing from plasma samples. Drug resistance mutations were identified by the algorithm of Stanford HIV Drug Resistance Database.Potentially transmitted, non-polymorphic integrase major mutation was detected in 1 out of 249 samples, while accessory mutations were observed in further 31 patients (12.4%). The overall prevalence of transmitted drug resistance (TDR) mutations related to protease and reverse transcriptase inhibitors was 5.8% (10/173) between the end of 2017 and 2019. Nucleoside reverse transcriptase inhibitor associated resistance mutations were the most frequent indicators of TDR (6/173; 3.5%), followed by resistance mutations associated with protease (3/173; 1.7%) and non-nucleoside reverse transcriptase inhibitors (2/173, 1.2%).The first detection of integrase major mutation and the changing patterns of other resistance mutations in Hungarian untreated HIV-positive population indicate the necessity of continuous molecular surveillance of Hungarian HIV epidemic

Bioaugmentation of biogas production by a hydrogen-producing bacterium

The rate-limiting nature of the hydrogen concentration prevailing in the anaerobic digester has been recognized, but the associated alterations in the microbial community are unknown. In response to the addition of Enterobacter cloacae cells in laboratory anaerobic digesters, the level of biogas production was augmented. Terminal restriction fragment length polymorphism (T-RFLP) and real-time polymerase chain reaction (Real-Time PCR) were used to study the survival of mesophilic hydrogen-producing bacteria and the effects of their presence on the composition of the other members of the bacterial community. E. cloacae proved to maintain a stable cell number and to influence the microbial composition of the system. Bioaugmentation by a single strain added to the natural biogas-producing microbial community was demonstrated. The community underwent pronounced changes as a result of the relatively slight initial shift in the microbiological system, responding sensitively to the alterations in local hydrogen concentration. © 2015 The Authors

Fehérje-DNS kölcsönhatások és metilációs mintázat analízise Epstein-Barr vírus onkogénjeinek regulátor régióiban nazofaringeális karcinóma sejtekben = Analysis of protein-DNA interactions and methylation patterns in regulatory regions of oncogenes of Epstein-Barr virus in nasopharygeal carcinoma cells

Az Epstein-Barr vírus (EBV; egy humán herpeszvírus) számos rosszindulatú daganattal kapcsolatban áll. A virális onkogének promótereinek aktivitása sejttípus specifikus. Ennek alapján a látens EBV genomok három fő látencia típusa különíthető el. Az I és III típus limfoid sejtekre jellemző, a II típus képviselője a nazofaringeális carcinóma (NPC). Limfoid sejtekben a fő látens EBV promóterek aktivitását DNS metiláció és protein-DNS kölcsönhatások regulálják. Utóbbiak szerepe a II látencia típus (NPC) esetében korábban nem volt vizsgálható. A C666-1 NPC sejtvonal megalapítása lehetővé tette a protein-DNS kölcsönhatások vizsgálatát epitheliális eredetű sejtekben is. Ellvégeztük a C666-1 sejtek által hordozott EBV genomok látens promótereinek metilációs analízisét. Megállapítottuk, hogy az inaktív Cp és LMP1 és LMP2A promóterek erősen metiláltak, míg az aktív Qp, EBER 1 és EBER 2 promóterek metilálatlanok. Nem találtunk metilált CpG dinukleotidokat a látens replikációs origó (oriP) területén sem, mely enhancer-ként is működik. Két nude egérben passzált NPC sejtvonal metilációs analízise hasonló eredményt adott. A C666-1 sejtek látens promótereinek fehérje-DNS kölcsönhatásait az in vivo footprinting módszerével analizáltuk. Megállapítottuk, hogy a Cp és Qp és EBER1p valamint oriP hasonló fehérjéket köt, mint az I. típusú Burkitt limfóma sejtekben. Megállapítottuk, hogy az aktív Qp egy módosított hisztonnal (H3MK4) asszociált. | Epstein-Barr virus (EBV; a human herpesvirus) is associated with a series of malignant neoplasms. The activity of the promoters of viral oncogenes is cell type specific. Accordingly, there are three main latency types of EBV: type I and III is characteristic for lymphoid cells whereas type II is exemplified by nasopharyngeal carcinoma (NPC). In lymphoid cells the activity of tha major latent EBV promoters is regulated by DNA methylation and protein-DNA interactions. In NPC the role of protein-DNA interactions could not be studied erlier due to the lack of an in vitro model. Establishment of the cell line C666-1 permitted, however, the analysis of protein-DNA interactions in an epithelial cell type. We made a detailed methylation map of latent promoters in EBV genomes carried by C666-1 cells. We found that the silent Cp, LMP1p and LMP2Ap promoters are heavily methylated. In contrast, the active Qp, EBER1p, and EBER2p were found to be unmethylated. Methylation analysis of two nude mouse-passaged NPC lines gave similar results. In vivo footprinting of latent EBV promoters showed that similar proteins bind to Cp, Qp, EBER1p and oriP in C666-1 cells and type I Burkitt's lymphoma cells. We found that active Qp is marked with a modified histone (H3MK4)

Flavonol 7-O-Glucoside Herbacitrin Inhibits HIV-1 Replication through Simultaneous Integrase and Reverse Transcriptase Inhibition

Here we report the evaluation of the antiretroviral effect of two flavonoid 7-O-glucosides, herbacitrin (1) and gossypitrin (2), together with quercetin (3), a well-studied flavonol. Antiviral activity of the flavonoids was assessed by analyzing HIV-1 p24 core protein levels in the supernatants of HIV-1 infected MT-4 and MT-2 cell cultures. The compounds showed mild to weak cytotoxic activities on the host cells; herbacitrin was the strongest in this regard (CC50=27.8 and 63.64 μM on MT-4 and MT-2 cells, respectively). In nontoxic concentrations, herbacitrin and quercetin reduced HIV-1 replication, whereas gossypitrin was ineffective. Herbacitrin was found to inhibit reverse transcriptase at 21.5 μM, while it was a more potent integrase inhibitor already active at 2.15 μM. Therefore, our observations suggest that herbacitrin exerts antiretroviral activity through simultaneously acting on these two targets of HIV-1 and that integrase inhibition might play a major role in this activity

Toward Personalized Oral Diagnosis: Distinct Microbiome Clusters in Periodontitis Biofilms

Periodontitis is caused by pathogenic subgingival microbial biofilm development and dysbiotic interactions between host and hosted microbes. A thorough characterization of the subgingival biofilms by deep amplicon sequencing of 121 individual periodontitis pockets of nine patients and whole metagenomic analysis of the saliva microbial community of the same subjects were carried out. Two biofilm sampling methods yielded similar microbial compositions. Taxonomic mapping of all biofilms revealed three distinct microbial clusters. Two clinical diagnostic parameters, probing pocket depth (PPD) and clinical attachment level (CAL), correlated with the cluster mapping. The dysbiotic microbiomes were less diverse than the apparently healthy ones of the same subjects. The most abundant periodontal pathogens were also present in the saliva, although in different representations. The single abundant species Tannerella forsythia was found in the diseased pockets in about 16–17-fold in excess relative to the clinically healthy sulcus, making it suitable as an indicator of periodontitis biofilms. The discrete microbial communities indicate strong selection by the host immune system and allow the design of targeted antibiotic treatment selective against the main periodontal pathogen(s) in the individual patients

Anaerobic bacterial communities associated with oral carcinoma: Intratumoral, surface-biofilm and salivary microbiota

It was estimated that more than 700 bacterial species inhabit the oral cavity of healthy humans. Anaerobes comprise a significant fraction of the oral bacteriome and play an important role in the formation of multi-species biofilms attached to various anatomical sites. Bacterial biofilms are also associated with pathologic laesions of the oral cavity, including oral squamous cell carcinoma (OSCC), and distinct oral taxa could also be detected within the tumors, i.e. in deep biopsy samples. These observations suggested that certain oral bacteria or oral bacterial communities may play a causative role in oral carcinogenesis, in addition to the well characterized risk factors of oral cancer. Alternatively, it was also proposed that a subset of oral bacteria may have a growth advantage in the unique microenvironment of OSCC. Recently, a series of studies analysed the OSCC-associated bacterial communities using metataxonomic, metagenomic and metatranscriptomic approaches. This review outlines the major differences between the community structure of microbiota in tumor biopsy, surface-biofilm and salivary or oral wash samples collected from OSCC patients, compared to corresponding samples from control persons. A special emphasis is given to the anaerobic bacteria Fusobacterium nucleatum and Fusobacterium periodonticum that were characterised repeatedly as „OSCC-associated” in independent studies. Predicted microbial functions and relevant in vivo experimental models of oral carcinogenesis will also be summarized. © 2020 Elsevier Lt