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| 1 | Characterization of hepatitis B virus X gene quasispecies complexity in mono-infection and hepatitis delta virus superinfection显示文摘Hepatitis delta virus(HDV) seems to strongly suppress hepatitis B virus(HBV)replication, although little is known about the mechanism of this interaction. Both these viruses show a dynamic distribution of mutants, resulting in viral quasispecies. Next-generation sequencing is a viable approach for analyzing the composition of these mutant spectra. As the regulatory hepatitis B X protein(HBx) is essential for HBV replication, determination of HBV X gene(HBX)quasispecies complexity in HBV/HDV infection compared to HBV monoinfection may provide information on the interactions between these two viruses.AIM To compare HBV quasispecies complexity in the HBX 5' region between chronic hepatitis delta(CHD) and chronic HBV mono-infected patients.METHODS Twenty-four untreated patients were included: 7/24(29.2%) with HBeAgnegative chronic HBV infection(CI, previously termed inactive carriers), 8/24(33.3%) with HBeAg-negative chronic hepatitis B(CHB) and 9/24(37.5%) with CHD. A serum sample from each patient was first tested for HBV DNA levels.The HBX 5' region [nucleotides(nt) 1255-1611] was then PCR-amplified for subsequent next-generation sequencing(MiSeq, Illumina, United States). HBV quasispecies complexity in the region analyzed was evaluated using incidencebased indices(number of haplotypes and number of mutations), abundancebased indices(Hill numbers of order 1 and 2), and functional indices(mutation frequency and nucleotide diversity). We also evaluated the pattern of nucleotide changes to investigate which of them could be the cause of the quasispecies complexity.RESULTS CHB patients showed higher median HBV-DNA levels [5.4 logIU/mL,interquartile range(IQR) 3.5-7.9] than CHD(3.4 logIU/mL, IQR 3-7.6)(P = n.s.)or CI(3.2 logIU/mL, IQR 2.3-3.5)(P < 0.01) patients. The incidence and abundance indices indicated that HBV quasispecies complexity was significantly greater in CI than CHB. A similar trend was observed in CHD patients, although only Hill numbers of order 2 showed statistically significant differences(CHB2.81, IQR 1.11-4.57 vs CHD 8.87, 6.56-11.18, P = 0.038). There were no significant differences in the functional indices, but CI and CHD patients also showed a trend towards greater complexity than CHB. No differences were found for any HBV quasispecies complexity indices between CHD and CI patients. G-to-A and C-to-T nucleotide changes, characteristic of APOBEC3 G, were higher in CHD and CI than in CHB in genotype A haplotypes, but not in genotype D. The proportion of nt G-to-A vs A-to-G changes and C-to-T vs T-to-C changes in genotype A and D haplotypes in CHD patients showed no significant differences. In CHB and CI the results of these comparisons were dependent on HBV genotype.CONCLUSION The lower-replication CHD and CI groups show a trend to higher quasispecies complexity than the higher-replication CHB group. The mechanisms associated with this greater complexity require elucidation. | Cristina Godoy David Tabernero Sara Sopena Josep Gregori Maria Francesca Cortese Carolina González Rosario Casillas Mar?al Yll Ariadna Rando Rosa López-Martínez Josep Quer Gloria González-Aseguinolaza Rafael Esteban Mar Riveiro-Barciela Maria Buti Francisco Rodríguez-Frías | 2019 | World Journal of Gastroenterology2019，25，13： | 6 |
| 2 | Detection of hyper-conserved regions in hepatitis B virus X gene potentially useful for gene therapy显示文摘AIM To detect hyper-conserved regions in the hepatitis B virus(HBV) X gene(HBX) 5' region that could be candidates for gene therapy.METHODS The study included 27 chronic hepatitis B treatmentnaive patients in various clinical stages(from chronic infection to cirrhosis and hepatocellular carcinoma, both HBeA g-negative and HBeA g-positive), and infected with HBV genotypes A-F and H. In a serum sample from each patient with viremia > 3.5 log IU/m L, the HBX 5' end region [nucleotide(nt) 1255-1611] was PCRamplified and submitted to next-generation sequencing(NGS). We assessed genotype variants by phylogenetic analysis, and evaluated conservation of this region by calculating the information content of each nucleotide position in a multiple alignment of all unique sequences(haplotypes) obtained by NGS. Conservation at the HBx protein amino acid(aa) level was also analyzed.RESULTS NGS yielded 1333069 sequences from the 27 samples, with a median of 4578 sequences/sample(2487-9279, IQR 2817). In 14/27 patients(51.8%), phylogenetic analysis of viral nucleotide haplotypes showed a complex mixture of genotypic variants. Analysis of the information content in the haplotype multiple alignments detected 2 hyper-conserved nucleotide regions, one in the HBX upstream non-coding region(nt 1255-1286) and the other in the 5' end coding region(nt 1519-1603). This last region coded for a conserved amino acid region(aa 63-76) that partially overlaps a Kunitz-like domain.CONCLUSION Two hyper-conserved regions detected in the HBX 5' end may be of value for targeted gene therapy, regardless of the patients' clinical stage or HBV genotype. | Carolina González David Tabernero Maria Francesca Cortese Josep Gregori Rosario Casillas Mar Riveiro-Barciela Cristina Godoy Sara Sopena Ariadna Rando Marcal Yll Rosa Lopez-Martinez Josep Quer Rafael Esteban Maria Buti Francisco Rodríguez-Frías | 2018 | World Journal of Gastroenterology2018，24，19： | 6 |
| 3 | Analysis of hepatitis B virus preS1 variability and prevalence of the rs2296651 polymorphism in a Spanish population显示文摘AIM To determine the variability/conservation of the domain of hepatitis B virus(HBV) pre S1 region that interacts with sodium-taurocholate cotransporting polypeptide(hereafter, NTCP-interacting domain) and the prevalence of the rs2296651 polymorphism(S267 F, NTCP variant) in a Spanish population. METHODS Serum samples from 246 individuals were included and divided into 3 groups: patients with chronic HBV infection(CHB)(n = 41, 73% Caucasians), patients with resolved HBV infection(n = 100, 100% Caucasians) and an HBV-uninfected control group(n = 105, 100% Caucasians). Variability/conservation of the amino acid(aa) sequences of the NTCPinteracting domain,(aa 2-48 in viral genotype D) and a highly conserved pre S1 domain associated with virion morphogenesis(aa 92-103 in viral genotype D) were analyzed by next-generation sequencing and compared in 18 CHB patients with viremia > 4 log IU/mL. The rs2296651 polymorphism was determined in all individuals in all 3 groups using an in-house real-time PCR melting curve analysis.RESULTS The HBV pre S1 NTCP-interacting domain showed a high degree of conservation among the examined viral genomes especially between aa 9 and 21(in the genotype D consensus sequence). As compared with the virion morphogenesis domain, the NTCPinteracting domain had a smaller proportion of HBV genotype-unrelated changes comprising > 1% of the quasispecies(25.5% vs 31.8%), but a larger proportion of genotype-associated viral polymorphisms(34% vs 27.3%), according to consensus sequences from Gen Bank patterns of HBV genotypes A to H. Variation/conservation in both domains depended on viral genotype, with genotype C being the most highly conserved and genotype E the most variable(limited finding, only 2 genotype E included). Of note, proline residues were highly conserved in both domains, and serine residues showed changes only to threonine or tyrosine in the virion morphogenesis domain. The rs2296651 polymorphism was not detected in any participant.CONCLUSION In our CHB population, the NTCP-interacting domain was highly conserved, particularly the proline residues and essential amino acids related with the NTCP interaction, and the prevalence of rs2296651 was low/null. | Rosario Casillas David Tabernero Josep Gregori Irene Belmonte Maria Francesca Cortese Carolina González Mar Riveiro-Barciela Rosa Maria López Josep Quer Rafael Esteban Maria Buti Francisco Rodríguez-Frías | 2018 | World Journal of Gastroenterology2018，24，6： | 5 |
| 4 | Multi-element determination of Cu, Fe, Ni and Zn content in vegetable oils samples by high-resolution continuum source atomic absorption spectrometry and microemulsion sample preparation显示文摘 | Luana S. Nunes José T.P. Barbosa Andréa P. Fernandes Valfredo A. Lemos Walter N.L. dos Santos Maria Gra?as A. Korn Leonardo S.G. Teixeira | 2011 | Food Chemistry2011，，2： | 4 |
| 5 | High prevalence of vitamin A deficiency in Crohn's disease patients according to serum retinol levels and the relative dose-response test显示文摘AIM:To assess the vitamin A status of patients with Crohn's disease(CD) by evaluating serum retinol levels and the relative dose response(RDR) test(liver retinol stores).METHODS:Vitamin A nutritional status was measured by serum retinol obtained by high performance liquid chromatography and the RDR test for evaluation of the hepatic stores.Body composition was performed by densitometry by dual-energy X-ray absorptiometry.Vitamin A dietary intake was assessed from a semiquantitative food frequency questionnaire.RESULTS:This study included 38 CD patients and 33 controls.Low serum retinol concentrations were detected in 29% of CD patients vs 15% in controls(P < 0.005).The RDR test was positive in 37% of CD patients vs 12% in controls,which indicated inadequate hepatic vitamin A stores(P < 0.005).Individuals with hypovitaminosis A had lower BMI and body fat compared with those without this deficiency.There was no association between vitamin A deficiency and its dietary intake,ileal location,presence of disease activity and prior bowel resections.CONCLUSION:Patients with CD have higher prevalence of vitamin A deficiency,as assessed by two independent methods. | Márcia Soares-Mota Tianny A Silva Luanda M Gomes Marco AS Pinto Laura MC Mendon?a Maria Lúcia F Farias Tiago Nunes Andrea Ramalho Cyrla Zaltman | 2015 | World Journal of Gastroenterology2015，21，5： | 4 |
| 6 | Porcine circovirus type 2 (PCV2) Cap and Rep proteins are involved in the development of cell-mediated immunity upon PCV2 infection显示文摘 | Maria Fort Marina Sibila Miquel Nofrarías Eva Pérez-Martín Alex Olvera Enric Mateu Joaquim Segalés | 2010 | Veterinary Immunology and Immunopathology2010，，3： | 2 |
| 7 | Aspergil us endocarditis presenting as femoral artery embolism显示文摘 | Verghese S Maria CF Mul aseri AS | | 0，，5： | 1 |
| 8 | Affinity purification of copper chelating peptides from chickpea protein hydrolysates显示文摘 | Cristina Megías Justo Pedroche Maria M Yust | 2007 | Journal of Agricultural and Food Chemistry2007，50，10： | 1 |
| 9 | Risk factors for congenital hypothytoidism: results of a population case conr tol study(1997-2003) 显示文摘 | Emanuela M Olivieri A Maria AS | 2005 | Eur J Endocrinology2005，153，7： | 1 |
| 10 | High Zn and Cd accumulation in the oyster Crassostrea rhizophorae , and its relevance as a sentinel species显示文摘 | Mauro de Freitas Rebelo Maria Clara Rebou?as do Amaral Wolfgang Chritstian Pfeiffer | 2003 | Marine Pollution Bulletin2003，，10： | 1 |
| 11 | Lipoxygenase inhibition by flavonoids: semiempirical study of the structure–activity relation显示文摘 | Modesto Redrejo-Rodriguez Adrian Tejeda-Cano Maria del Carmen Pinto Pedro Mac??as | 2003 | Journal of Molecular Structure: THEOCHEM2003，，1： | 1 |
| 12 | Immune Reconstitution Inflammatory Syndrome Emergence of a Unique Syndrome During Highly Active Antiretroviral Therapy显示文摘 | Samuel AS Richard J H Maria CRB | 2002 | Medicine2002，81，3： | 1 |
| 13 | The role of l -arginine-nitric oxide pathway in bacterial translocation显示文摘 | Mirelle Lomar Viana Rosana das Gra?as Carvalho Santos Simone de Vasconcelos Generoso Jacques Robert Nicoli Flaviano dos Santos Martins José Augusto Nogueira-Machado Rosa Maria Esteves Arantes Maria Isabel Toulson Davisson Correia Valbert Nascimento Cardos | 2013 | Amino Acids2013，，： | 1 |
| 14 | Divergent outcomesof intrachromosomal recombination on the human Y chromosome: male infertility and recurrent polymorphism 显示文摘 | Patricia B Maria S Carole AS | 2000 | Med Genet2000，37，： | 1 |
| 15 | A comparative study of ultra-deep pyrosequencing and cloning to quantitatively analyze the viral quasispecies using hepatitis B virus infection as a model显示文摘 | Clara Ramírez Josep Gregori Maria Buti David Tabernero Sílvia Camós Rosario Casillas Josep Quer Rafael Esteban Maria Homs Francisco Rodriguez-Frías | 2013 | Antiviral Research2013，，2： | 1 |
| 16 | Divergent out comes of intrachromosomal recombination on the human Y chromosome:male infertility and recurrent polymorphism显示文摘 | Patricia B Maria S Carole AS | 2000 | J Med Genet2000，37，： | 1 |
| 17 | ANALYSIS OF MATHEMATICAL MODELS TO DESCRIBE THE MIGRATION OF ADDITIVES FROM PACKAGING PLASTICS TO FOODS显示文摘 | MARIA F. PO?AS JORGE C. OLIVEIRA RAINER BRANDSCH TIMOTHY HOGG | 2011 | Journal of Food Process Engineering2011，，4： | 1 |
| 18 | Evaluation of food additives and low‐toxicity compounds as alternative chemicals for the control of Penicillium digitatum and Penicillium italicum on citrus fruit显示文摘 | LluísPalou JosepUsall Joseph LSmilanick Maria‐JoséAguilar InmaculadaVi?as | 2002 | Pest Manag Sci2002，，5： | 1 |
| 19 | Bioactive extracts of red seaweeds Pterocladiella capillacea and Osmundaria obtusiloba(Floridophyceae:Rhodophyta) with antioxidant and bacterial agglutination potential显示文摘Objective:To evaluate the antioxidant,antibacterial and bacterial cell agglutination activities of the hexane(Hex) and 70%ethanol(70%EtOH) extracts of two species of red seaweeds Pterocladiella capillacea(P.capillacea) and Osmundaria obtusiloba.Methods:In vitro antioxidant activity was determined by DPPH radical scavenging assay,ferric-reducing antioxidant power assay,ferrous ion chelating assay,β-carotene bleaching assay and total phenolic content quantification.Antimicrobial activity was tested using the method of disc diffusion on Mueller-Hinton medium.The ability of algal extracts to agglutinate bacterial cells was also tested.Results:The 70%EtOH extract of the two algae showed the highest values of total phenolic content compared to the Hex extract.The results of DPPH for both extracts(Hex,70%EtOH) of Osmundaria obtusiloba(43.46%and 99.47%) were higher than those of P.capillacea(33.04%and 40.81%) at a concentration of 1 000 μg/mL.As for the ferrous ion chelating,there was an opposite behavior,extracts of P.capillacea had a higher activity.The extracts showed a low ferric-reducing antioxidant power,with optical density ranging from0.054 to 0.180.Antioxidant activities of all extracts evaluated for β-carotene bleaching were above 40%.There was no antibacterial activity against bacterial strains tested.However,the extracts of both species were able to agglutinate bacterial Gram positive cells of Staphylococcus aureus and Gram negative cells of Escherichia coli,multidrug-resistant Salmonella and Vibrio harveyi.Conclusions This is the first report of the interaction between these algal extracts,rich in natural compounds with antioxidant potential,and Gram positive and Gram negative bacterial cells. | Daniel Barroso de Alencar Fátima Cristiane Teles de Carvalho Rosa Helena Rebouas Daniel Rodrigues dos Santos Kelma Maria dos Santos Pires-Cavalcante Rebeca Larangeira de Lima Bárbara Mendes Baracho Rayssa Mendes Bezerra Francisco Arnaldo Viana Regine Helena Silva dos Fernandes Vieira Alexandre Holanda Sampaio Oscarina Viana de Sousa Silvana Saker-Sampaio | 2016 | Asian Pacific Journal of Tropical Medicine2016，9，4： | 1 |
| 20 | Inheritance of foliar zingiberene contents and their relationship to trichome densities and whitefly resistance in tomatoes 显示文摘 | Freitas J A Maluf W R Maria das Gra as Cardoso3 Luiz A A Gomes5 Eduardo Bearzotti | 2002 | Euphytica2002，127，： | 1 |
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