The evaluation of biocompatibility of soluble polymers and assessment of their potential as specific drug delivery systems

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Impact of helicobacter pylori infection and its major virulence factor caga on dna damage repair

Helicobacter pylori infection induces a plethora of DNA damages. Gastric epithelial cells, in order to maintain genomic integrity, require an integrous DNA damage repair (DDR) machinery, which, however, is reported to be modulated by the infection. CagA is a major H. pylori virulence factor, associated with increased risk for gastric carcinogenesis. Its pathogenic activity is partly regulated by phosphorylation on EPIYA motifs. Our aim was to identify effects of H. pylori infection and CagA on DDR, investigating the transcriptome of AGS cells, infected with wild-type, ∆CagA and EPIYA-phosphorylation-defective strains. Upon RNA-Seq-based transcriptomic analysis, we observed that a notable number of DDR genes were found deregulated during the infection, potentially resulting to base excision repair and mismatch repair compromise and an intricate deregulation of nucleotide excision repair, homologous recombination and non-homologous end-joining. Transcriptome observations were further investigated on the protein expression level, utilizing infections of AGS and GES-1 cells. We observed that CagA contributed to the downregulation of Nth Like DNA Glycosylase 1 (NTHL1), MutY DNA Glycosylase (MUTYH), Flap Structure-Specific Endonuclease 1 (FEN1), RAD51 Recombinase, DNA Polymerase Delta Catalytic Subunit (POLD1), and DNA Ligase 1 (LIG1) and, contrary to transcriptome results, Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APE1) upregulation. Our study accentuates the role of CagA as a significant contributor of H. pylori infection-mediated DDR modulation, potentially disrupting the balance between DNA damage and repair, thus favoring genomic instability and carcinogenesis. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Impact of helicobacter pylori infection and its major virulence factor caga on dna damage repair

Helicobacter pylori infection induces a plethora of DNA damages. Gastric epithelial cells, in order to maintain genomic integrity, require an integrous DNA damage repair (DDR) machinery, which, however, is reported to be modulated by the infection. CagA is a major H. pylori virulence factor, associated with increased risk for gastric carcinogenesis. Its pathogenic activity is partly regulated by phosphorylation on EPIYA motifs. Our aim was to identify effects of H. pylori infection and CagA on DDR, investigating the transcriptome of AGS cells, infected with wild-type, ∆CagA and EPIYA-phosphorylation-defective strains. Upon RNA-Seq-based transcriptomic analysis, we observed that a notable number of DDR genes were found deregulated during the infection, potentially resulting to base excision repair and mismatch repair compromise and an intricate deregulation of nucleotide excision repair, homologous recombination and non-homologous end-joining. Transcriptome observations were further investigated on the protein expression level, utilizing infections of AGS and GES-1 cells. We observed that CagA contributed to the downregulation of Nth Like DNA Glycosylase 1 (NTHL1), MutY DNA Glycosylase (MUTYH), Flap Structure-Specific Endonuclease 1 (FEN1), RAD51 Recombinase, DNA Polymerase Delta Catalytic Subunit (POLD1), and DNA Ligase 1 (LIG1) and, contrary to transcriptome results, Apurinic/Apyrimidinic Endodeoxyribonuclease 1 (APE1) upregulation. Our study accentuates the role of CagA as a significant contributor of H. pylori infection-mediated DDR modulation, potentially disrupting the balance between DNA damage and repair, thus favoring genomic instability and carcinogenesis. © 2020 by the authors. Licensee MDPI, Basel, Switzerland

Helicobacter pylori isolates from Greek children express type 2 and type 1 Lewis and \u3b11, 6-glucan antigens in conjunction with a functional type IV secretion system

Helicobacter pylori infection is often acquired in childhood and can persist for life. Previous studies in adult patients have shown that H. pylori isolates from North American and European hosts express predominantly type 2 Lewis x (Le x) and Le y epitopes, while Asian strains have the capacity to express type 1 Le a and Le b structures. In order to understand the influence of environmental and host factors on the expression of Le antigens, we analysed 50 Greek H. pylori isolates from symptomatic children. Both CagA-positive and-negative strains were evaluated. The expression of Le antigens was determined by whole-cell indirect ELISA (WCE), and LPS profiles were assessed by gel electrophoresis and immunoblotting. Occurrence of Le x and/or Ley antigens was confirmed in 35 of the isolates (70 %) while 15 of the isolates were non-typable. It was found that 11 of the paediatric isolates had the propensity to express type 1 Le b blood-group antigen (22 %), a feature relatively uncommon in H. pylori isolates from adults. One strain expressed both Le b and Le a antigens. The majority of the isolates (49/50, 98 %) expressed \u3b11,6-glucan, an antigenic non-Le determinant present in the outer core region of H. pylori LPS. All Le x-and Leyexpressing strains also carried a functional cag pathogenicity island-encoding a type IV secretion system, capable of translocating CagA protein, as well as the vacAs1 allele, suggesting that Le x and Ley epitopes may aid the persistence of more aggressive strains. No association between bacterial virulence characteristics and the histopathological observations was evident. \ua9 2012 National Research Council of Canada.Peer reviewed: YesNRC publication: Ye

Endoscopic tests for the diagnosis of helicobacter pylori infection in children: Validation of rapid urease test

Background: Rapid urease test (CLO-test) is an inexpensive and quick method for diagnosis of Helicobacter pylori infection with controversial results in children. We evaluated the performance of CLO-test in relation to endoscopic and histological findings in children with H. pylori infection. Materials and methods: We studied the medical records of children with H. pylori infection who were diagnosed between 1989 and 2009. Noninfected children were used as controls. H. pylori infection was defined by positive culture or by two other positive tests (histology and CLO-test, or urea breath test when a single test was positive). All children had histology together with CLO-test. Tissue culture was performed whenever possible. Results: Five hundred thirty infected children (10.4 ± 3.0 years) and 1060 controls (7.3 ± 4.4 years) were studied. Sensitivity of CLO-test was 83.4% (95% CI, 79.9-86.3%), of culture 84.6% (95% CI, 78.7-89.1%), of histology 93.2% (95% CI, 90.7-95.1%), and specificity 99% (95% CI, 98.2-99.4%), 100%, and 100% respectively. CLO-test positivity was correlated with higher bacterial density (p <.001), activity (p <.001) and severity of gastritis (p <.01), older age (p <.01), and the presence of antral nodularity (p <.001). When CLO-test was positive, the concordance with histology and culture was high (95.5 and 89.2% respectively), whereas low concordance was observed when CLO-test was negative (17.05 and 45.83% respectively). Conclusions: CLO-test had lower sensitivity and comparable specificity with histology. Both tests should be performed concurrently to accurately diagnose H. pylori infection in children. © 2010 Blackwell Publishing Ltd

CagA and VacA polymorphisms are associated with distinct pathological features in Helicobacter pylori-infected adults with peptic ulcer and non-peptic ulcer disease

Polymorphic variability in Helicobacter pylori factors CagA and VacA contributes to bacterial virulence. The presence of one CagA EPIYA-C site is an independent risk factor for gastroduodenal ulceration (odds ratio [OR], 4.647; 95% confidence interval [CI], 2.037 to 10.602), while the presence of the vacA i1 allele is a risk factor for increased activity (OR, 5.310; 95% CI, 2.295 to 12.287) and severity of gastritis (OR, 3.862; 95% CI, 1.728 to 8.632). Copyright © 2010, American Society for Microbiology. All Rights Reserved

Sars‐cov‐2 molecular transmission clusters and containment measures in ten european regions during the first pandemic wave

Background: The spatiotemporal profiling of molecular transmission clusters (MTCs) using viral genomic data can effectively identify transmission networks in order to inform public health actions targeting SARS‐CoV‐2 spread. Methods: We used whole genome SARS‐CoV‐2 sequences derived from ten European regions belonging to eight countries to perform phylogenetic and phylodynamic analysis. We developed dedicated bioinformatics pipelines to identify regional MTCs and to assess demographic factors potentially associated with their formation. Results: The total number and the scale of MTCs varied from small household clusters identified in all regions, to a super‐spreading event found in Uusimaa‐FI. Specific age groups were more likely to belong to MTCs in different regions. The clustered sequences referring to the age groups 50–100 years old (y.o.) were increased in all regions two weeks after the establishment of the lockdown, while those referring to the age group 0–19 y.o. decreased only in those regions where schools’ closure was combined with a lockdown. Conclusions: The spatiotemporal profiling of the SARS‐CoV‐2 MTCs can be a useful tool to monitor the effectiveness of the interventions and to reveal cryptic transmissions that have not been identified through contact tracing. © 2021 by the authors. Licensee MDPI, Basel, Switzerland