Sequence analysis of the Epstein-Barr virus (EBV) BRLF1 gene in nasopharyngeal and gastric carcinomas

<p>Abstract</p> <p>Background</p> <p>Epstein-Barr virus (EBV) has a biphasic infection cycle consisting of a latent and a lytic replicative phase. The product of immediate-early gene BRLF1, Rta, is able to disrupt the latency phase in epithelial cells and certain B-cell lines. The protein Rta is a frequent target of the EBV-induced cytotoxic T cell response. In spite of our good understanding of this protein, little is known for the gene polymorphism of BRLF1.</p> <p>Results</p> <p>BRLF1 gene was successfully amplified in 34 EBV-associated gastric carcinomas (EBVaGCs), 57 nasopharyngeal carcinomas (NPCs) and 28 throat washings (TWs) samples from healthy donors followed by PCR-direct sequencing. Fourteen loci were found to be affected by amino acid changes, 17 loci by silent nucleotide changes. According to the phylogenetic tree, 5 distinct subtypes of BRLF1 were identified, and 2 subtypes BR1-A and BR1-C were detected in 42.9% (51/119), 42.0% (50/119) of samples, respectively. The distribution of these 2 subtypes among 3 types of specimens was significantly different. The subtype BR1-A preferentially existed in healthy donors, while BR1-C was seen more in biopsies of NPC. A silent mutation A/G was detected in all the isolates. Among 3 functional domains, the dimerization domain of Rta showed a stably conserved sequence, while DNA binding and transactivation domains were detected to have multiple mutations. Three of 16 CTL epitopes, NAA, QKE and ERP, were affected by amino acid changes. Epitope ERP was relatively conserved; epitopes NAA and QKE harbored more mutations.</p> <p>Conclusions</p> <p>This first detailed investigation of sequence variations in BRLF1 gene has identified 5 distinct subtypes. Two subtypes BR1-A and BR1-C are the dominant genotypes of BRLF1. The subtype BR1-C is more frequent in NPCs, while BR1-A preferentially presents in healthy donors. BR1-C may be associated with the tumorigenesis of NPC.</p

Inhibition of Intestinal Adenoma Formation in APCMin/+ Mice by Riccardin D, a Natural Product Derived from Liverwort Plant Dumortiera hirsuta

BACKGROUND: Mutation of tumor suppressor gene, adenomatous polyposis coli (APC), is the primary molecular event in the development of most intestinal carcinomas. Animal model with APC gene mutation is an effective tool for study of preventive approaches against intestinal carcinomas. We aimed to evaluate the effect of Riccardin D, a macrocyclic bisbibenzyl compound, as a chemopreventive agent against intestinal adenoma formation in APC(Min/+) mice. METHODS: APC(Min/+) mice were given Riccardin D by p.o. gavage for 7 weeks. Mice were sacrificed, and the number, size and histopathology of intestinal polyps were examined under a microscope. We performed immunohistochemical staining, western blotting, reverse transcriptase-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) in intestinal polyps to investigate the mechanism of chemopreventive effect of Riccardin D. RESULTS: Riccardin D treatment resulted in a significant inhibition of intestinal adenoma formation, showing a reduction of polyp number by 41.7%, 31.1% and 44.4%, respectively, in proximal, middle and distal portions of small intestine. The activity of Riccardin D against polyp formation was more profound in colon, wherein Riccardin D decreased polyp number by 79.3%. Size distribution analysis revealed a significant reduction in large-size polyps (2-3 mm) by 40.0%, 42.5% and 33.3%, respectively, in proximal, middle and distal portions of small intestine, and 77.8% in colon. Histopathological analysis of the intestinal polyps revealed mostly hyperplastic morphology without obvious dysplasia in Riccardin D-treated mice. Molecular analyses of the polyps suggested that the inhibitory effect of Riccardin D on intestinal adenoma formation was associated with its abilities of reduction in cell proliferation, induction of apoptosis, antiangiogenesis, inhibition of the Wnt signaling pathway and suppression of inflammatory mediators in polyps. CONCLUSIONS: Our results suggested that Riccardin D exerts its chemopreventive effect against intestinal adenoma formation through multiple mechanisms including anti-proliferative, apoptotic, anti-angiogenic and anti-inflammatory activity

Wpływ ekstremalnych warunków klimatycznych na względną zależność "plon - ewapotranspiracja"

The relative relationships "yield - evapotranspiration" were used long time ago. The well known linear relationship yi = 1 - ky (1 - ei), where yi is relative yield, ky - yield response factor and ei - relative evapotranspiration was proposed. It's usually assumed that ky is constant for a given crop and climatic conditions. It was found, however, that ky for late variety of maize H 708 varied through the study years (1984-1990) in the Plovdiv region ( South Bulgaria , altitude 150 m). During the dry years it was significantly higher than in the medium and humid years. The range of ky for maize in this location was 1.12-1.90, the average value being 1.50. The climate in the Sofia region (the experimental field of Chelopechene, altitude 550 m) is comparatively more humid. The two regions approximately outlined the boundaries of the appropriate economical conditions for grain maize production. The experiments in the Sofia region were carried out in the years 1994-2000. The seven years results for mean variety maize showed that the relationships "yield - evapotranspiration" and, respectively, ky varied at these climatic conditions too. The highest ky value was 1.41 for the driest year (2000) and the lowest value - 1.05 for the most wet years (1995, 1999). The value of ky for average years was 1.21. The yield response factor ky is of more significance when the relative evapotranspiration is less than 0.7-0.8. Thus, the extreme or the average values of ky could be used for the corresponding climatic regions. The relationships between ky and relative yield were established without considering irrigation.W pracy przedstawiono wyniki badań nad plonami i ewapotranspiracją dwóch mieszańców kukurydzy. Badania te prowadzono w różnych okresach siedmioletnich w dwóch odmiennych klimatycznie regionach Bułgarii. Analizowane regiony wyznaczają granice obszarów opłacalnej uprawy kukurydzy na ziarno w tych warunkach klimatycznych. Przedstawiono analizę wartości wskaźnika ky w latach suchych, średnich i mokrych. Wykazano wyraźne zależności korelacyjne między plonami a ewapotranspiracją, potwierdzone bardzo wysokimi wartościami współczynników determinacji R2. Wartości ewapotranspiracji aktualnej ETa i potencjalnej ETm wyznaczono na podstawie zaleceń FAO. Badania udowodniły, że wartość ewapotranspiracji może ulec istotnej zmianie w wyniku ewentualnej zmiany klimatu. Już obecnie obserwuje się w Bułgarii wzrost temperatury i zmniejszenie opadów atmosferycznych, co może mieć duży wpływ na plonowanie roślin uprawnych

Analysis of Registered Cases of Acute Flaccid Paralysis in Stara Zagora District as a Part of Polio Eradication Strategy

Poliomyelitis is the infection that, after smallpox, is a “serious candidate” for eradication worldwide. In accordance with the WHO strategy for 2022-2026, epidemiological surveillance of acute flaccid paralysis (AFP) is carried out with the aim of poliomyelitis eradication

A study of the effectiveness of the administrative anti-smoking measures in work and public places in the town of Haskovo

Scripta Scientifica Medica 2007; 39(2):115-11