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The selection pressure imposed by the host immune system impacts on hepatitis B virus (HBV) variability. This study evaluates HBV genetic diversity, nucleos(t)ide analogs resistance and HBsAg escape mutations in HBV patients under distinct selective pressures. One hundred and thirteen individuals in different phases of HBV infection were included: 13 HBeAg-positive chronic infection, 9 HBeAg-positive chronic hepatitis, 47 HBeAg-negative chronic infection (ENI), 29 HBeAg-negative chronic hepatitis (ENH) and 15 acute infected individuals. Samples were PCR amplified, sequenced and genetically analyzed for the overlapping POL/S genes. Most HBV carriers presented genotype A (84/113; 74.3%), subgenotype A1 (67/84; 79.7%), irrespective of group, followed by genotypes D (20/113; 17.7%), F (8/113; 7.1%) and E (1/113; 0.9%). Clinically relevant mutations in polymerase (tL180M/M204V) and in the Major Hydrophilic Region of HBsAg (sY100C, T118A/M, sM133T, sD144A and sG145R) were observed. Our findings, however, indicated that most polymorphic sites were located in the cytosolic loops (CYL1-2) and transmembrane domain 4 (TMD4) of HBsAg. Lower viral loads and higher HBV genetic diversity were observed in ENI and ENH groups (p < 0.001), suggesting that these groups are subjected to a higher selective pressure. Our results provide information on the molecular characteristics of HBV in a diverse clinical setting, and may guide future studies on the balance of HBV quasispecies at different stages of infection.
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Variação Genética , Genótipo , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B , Hepatite B Crônica , Humanos , Vírus da Hepatite B/genética , Hepatite B Crônica/virologia , Hepatite B Crônica/genética , Brasil/epidemiologia , Masculino , Adulto , Feminino , Pessoa de Meia-Idade , Antígenos de Superfície da Hepatite B/genética , Mutação , Farmacorresistência Viral/genética , DNA Viral/genética , Adulto Jovem , Filogenia , Antígenos E da Hepatite B/genéticaRESUMO
INTRODUCTION: Severe acute hepatitis (SAH) is defined by a severe inflammation of hepatocytes in the liver parenchyma which can lead to an acute liver failure, a clinical condition with high mortality rate that can be triggered by several factors but is usually associated to hepatotropic viruses' infection. In 2022, cases of children with severe acute hepatitis of unknown origin hospitalized in Glasgow, Scotland, were reported. Possible causes of this condition include, but are not limited to, undiagnosed viral (and non-viral) infections, autoimmune hepatitis, drug and/or chemical toxicity, mitochondrial chain respiratory and metabolic disorders. AREAS COVERED: Herpesviruses can cause severe acute hepatitis, but little is known about the role and the mechanisms of herpesviruses as a causative agent of this type of hepatitis. We review the role of herpesviruses as causative agent of SAH in children and other possible mechanisms involved in this disease. EXPERT OPINION: Differential diagnosis for herpesvirus in SAH should be implemented in all settings. Alternative fluids, such as saliva and dried blood, could be used in the diagnosis to overwhelm the availability of biological specimens at sufficient volume. In the future, genetic studies could also be added to increase the knowledge about severe acute hepatitis in children.
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Hepatite , Herpesviridae , Viroses , Criança , Humanos , Diagnóstico Diferencial , Doença AgudaRESUMO
Here we describe a new genus and species of cricket belonging to Lernecina from the Brazilian Atlantic Forest. It is presently known only from Ubaíra, State of Bahia, Brazil. The new genus is the only known member of this subtribe having males with a mostly white and hyaline dorsal field of the forewing (an additional genus with that condition is in the process of being described).
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Críquete , Ortópteros , Masculino , Animais , Brasil , Hialina , Estruturas Animais , Distribuição Animal , Tamanho Corporal , Tamanho do Órgão , FlorestasRESUMO
Hepatitis D virus (HDV) is classified into 8 genotypes (1 to 8) and several subgenotypes. In Brazil, HDV-3 and HDV-1 predominate; however, most of the diagnosis efforts and molecular studies are directed to the area of endemicity of the Amazon Basin. Here, we determined the molecular epidemiological profile of circulating HDV in Brazilian HBsAg-positive patients between 2013 and 2015 in areas of endemicity and non-areas of endemicity. From 38 anti-HDV-positive individuals, 13 (34.2%) had detectable HDV-RNA and 11 (28.9%) were successfully sequenced. Partial HDAg (~320 nt) sequencing followed by phylogenetic analysis with reference sequences resulted in the identification of HDV-3 (9/11; 81.8%), HDV-5 (1/11; 9.1%), and HDV-8 (1/11; 9.1%). Most HDV-3 samples (8/9; 88.9%) were found in the endemic North region, while one was found in Central-West Brazil, a non-area of endemicity. HDV-5 and 8, genotypes native from African countries, were found in São Paulo, a cosmopolitan city from Southeast Brazil with a high circulation of immigrants. Phylogenetic analysis of HDV-8 strains indicated that the sample determined in our study, along with previously reported sequences from Brazil, formed a highly supported monophyletic clade, likely representing a putative novel HDV-8 subgenotype. IMPORTANCE Considered a neglected pathogen until the last 2 decades, an increase in the availability of genetic data of hepatitis D virus (HDV) strains around the world has been noticed recently, resulting in the proposition of different classifications. Our study aimed to determine the molecular epidemiological profile of HDV isolates circulating in areas of endemicity and non-areas of endemicity in Brazil. Based on the analyzed fragment, HDV-8 sequences clustered out of the clades formed by subgenotypes 8a and 8b might suggest the identification of a novel subgenotype, putatively designated subgenotype 8c. Our findings demonstrate the importance of continuous epidemiological surveillance to map HDV spread pathways and the introduction of imported variants. It also reinforces that as the amount of HDV genomes generated and reported increases, we will have changes in viral classification and, consequently, in our understanding of the dynamics of variability of this viral agent.
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Vírus da Hepatite B , Vírus Delta da Hepatite , Humanos , Vírus Delta da Hepatite/genética , Brasil/epidemiologia , Filogenia , Vírus da Hepatite B/genética , Análise de Sequência de DNA , Genótipo , RNA Viral/genéticaRESUMO
OBJECTIVES: the aim of this study was to analyze the prevalence of histopathological diagnoses in oral biopsied tissues obtained from a Brazilian pediatric population. METHODS: an analytical, cross-sectional retrospective study was performed with biopsy files of patients ≤14 years of age from a Brazilian oral pathology laboratory over a 43-year period. Data included sex, age, location, and diagnoses. The prevalence was calculated by means of relative frequency. Associations between sex, age groups and diagnoses were verified with Pearson's chi-square test. RESULTS: from 19,456 oral biopsies, 1480 (7.6%) were obtained from patients aged ≤14 years. Most children were 10-14 years of age (60.1%) and females (55.1%), with an overall M:F of 1:1.2. Children aged 0-9 years and males had a higher frequency of lesions of the oral mucosa, whilst the 10-14 year age group showed a higher frequency of cysts, odontogenic tumors, and salivary gland lesions. The latter was also significantly higher in females. Samples consisted mostly of soft tissue lesions (53%) obtained from the lower lip (30.7%). Intraosseous lesions showed a slight predilection for the mandible (21.2%). Salivary gland lesions (28.8%) was the most common diagnostic category, followed by reactive lesions (18.8%), and cysts (16.1%). Mucocele (33.5%), dentigerous cyst (6.7%), and fibrous hyperplasia (5.9%) were the top three histopathological diagnoses. Malignant lesions affected only 0.9% of this population. CONCLUSION: our results were similar to other retrospective studies. Due to the low frequency of oral biopsies in children, data on the prevalence of oral pathology in this population might aid in the clinical and histopathologic diagnoses.
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Neoplasias Bucais , Tumores Odontogênicos , Humanos , Masculino , Feminino , Criança , Adolescente , Estudos Transversais , Estudos Retrospectivos , Brasil/epidemiologia , Tumores Odontogênicos/epidemiologia , Tumores Odontogênicos/patologia , Neoplasias Bucais/epidemiologia , Neoplasias Bucais/patologia , Prevalência , Biópsia , Distribuição por Idade , Neoplasias das Glândulas Salivares/patologia , Cistos/patologiaRESUMO
Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) are more vulnerable to blood-borne viral infections due to frequent invasive procedures. Hepatitis B virus (HBV) infection in this cohort of patients has been a matter of concern worldwide. The objective of this cross-sectional study was to evaluate the frequency of serological markers for hepatitis B, and the occurrence of overt and occult HBV infection (OBI) and its molecular characterization in serum samples from 644 CKD patients in HD units located in Rio de Janeiro, Brazil, from 2013 to 2017. HBV DNA was investigated in HBsAg reactive and "anti-HBc alone" samples to determine infecting genotypes and genetic relatedness between sequences. The prevalence of serological markers HBsAg+, anti-HBc alone, anti-HBc+/anti-HBs+, anti-HBs+, anti-HBc/anti-HBs/HBsAg were 5.9%, 2.8%, 30.7%, 26.6%, 34.0%, respectively. HBV DNA was detected in 39.5% (15/38) of the HBsAg+ and in 5/18 (27.8%) of the "anti-HBc alone" individuals, indicating a high prevalence of OBI within this group. We found a higher prevalence of HBV/A1 (65%), followed by HBV/D3 (20%), and HBV/A2 (15%). Bayesian MCC tree with a highly supported clade, genetic distance comparison, and identical nucleotide sequences suggested a nosocomial spread of HBV in some units. The high prevalence of HBV infection and low number of individuals immune to infection reinforces the need for vaccination in this group. The presence of closely related strains in the same HD unit reinforces the importance of continuous improvement of safety control measures and laboratory surveillance of serological markers to prevent the risk of infection and transmission of HBV.
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Hepatite B , Insuficiência Renal Crônica , Teorema de Bayes , Brasil/epidemiologia , Estudos Transversais , DNA Viral , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Humanos , PrevalênciaRESUMO
This study aims to evaluate the epidemiological and molecular features associated with HAV transmission in adults in Rio de Janeiro during a period of increased registered cases of HAV (2017-2018). Socio-epidemiological data and serum samples from anti-HAV IgM+ individuals were obtained. HAV RNA was RT-PCR amplified and sequenced for further phylogenetic and phylogeographic analyses. From fifty-two HAV IgM+ individuals, most were men (78.85%; p = 0.024), aged 20-30 years old (84.61%; p < 0.001), resided in the Rio de Janeiro north zone (31/52; 59.62%; p = 0.001), and are men who have sex with men (MSM) (57.69%; p = 0.002). Sexual practices were more frequent (96%) than others risk factors (food-borne (44%), water-borne (42.31%), and parenteral (34.62%)). Individuals who traveled to endemic regions had a 7.19-fold (1.93-36.04; p < 0.01) increased risk of HAV. Phylogenetic analysis revealed four distinct clades of subgenotype IA, three of them comprised sequences from European/Asian MSM outbreaks and one from Brazilian endemic strains. Bayesian Inference showed that the imported strains were introduced to Brazil during large mass sportive events. Sexual orientation and sexual practices may play a role in acquiring HAV infection. Public policies targeting key populations must be implemented to prevent further dissemination of HAV and other STIs.
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Vírus da Hepatite A/isolamento & purificação , Hepatite A/epidemiologia , Hepatite A/virologia , Adulto , Anticorpos Antivirais/sangue , Brasil , Estudos Transversais , Genótipo , Hepatite A/sangue , Hepatite A/transmissão , Vírus da Hepatite A/classificação , Vírus da Hepatite A/genética , Vírus da Hepatite A/imunologia , Homossexualidade Masculina/psicologia , Homossexualidade Masculina/estatística & dados numéricos , Humanos , Imunoglobulina M/sangue , Masculino , Filogenia , Filogeografia , Comportamento Sexual , Adulto JovemRESUMO
ABSTRACT Chronic kidney disease (CKD) patients undergoing hemodialysis (HD) are more vulnerable to blood-borne viral infections due to frequent invasive procedures. Hepatitis B virus (HBV) infection in this cohort of patients has been a matter of concern worldwide. The objective of this cross-sectional study was to evaluate the frequency of serological markers for hepatitis B, and the occurrence of overt and occult HBV infection (OBI) and its molecular characterization in serum samples from 644 CKD patients in HD units located in Rio de Janeiro, Brazil, from 2013 to 2017. HBV DNA was investigated in HBsAg reactive and "anti-HBc alone" samples to determine infecting genotypes and genetic relatedness between sequences. The prevalence of serological markers HBsAg+, anti-HBc alone, anti-HBc+/anti-HBs+, anti-HBs+, anti-HBc/anti-HBs/HBsAg were 5.9%, 2.8%, 30.7%, 26.6%, 34.0%, respectively. HBV DNA was detected in 39.5% (15/38) of the HBsAg+ and in 5/18 (27.8%) of the "anti-HBc alone" individuals, indicating a high prevalence of OBI within this group. We found a higher prevalence of HBV/A1 (65%), followed by HBV/D3 (20%), and HBV/A2 (15%). Bayesian MCC tree with a highly supported clade, genetic distance comparison, and identical nucleotide sequences suggested a nosocomial spread of HBV in some units. The high prevalence of HBV infection and low number of individuals immune to infection reinforces the need for vaccination in this group. The presence of closely related strains in the same HD unit reinforces the importance of continuous improvement of safety control measures and laboratory surveillance of serological markers to prevent the risk of infection and transmission of HBV.
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This contribution describes a new genus and three new species of Agraeciini from the Brazilian Atlantic Forest, Warimiri madiba gen. et sp. nov., Warimiri zumbi gen. et sp. nov., and Warimiri karutasywa gen. et sp. nov.. The new genus resembles the genera Hyperomerus Redtenbacher and Dectinomima Caudell and probably is closely related to them, but the internal and external male genitalia components distinguish the three taxa. We also provide a brief comment about the function of the internal components of the phallic complexes of Warimiri gen. nov. and Hyperomerus.
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Ortópteros , Distribuição Animal , Animais , Brasil , Florestas , MasculinoRESUMO
INTRODUCTION: Hepatitis B virus (HBV) infection is a public health problem; therefore, we aimed to report HBV genotypes in Ceará, Brazil. METHODS: A total of 103 HBsAg-positive samples were subjected to HBV genotyping and subgenotyping. RESULTS: The following genetic compositions of samples were found: F-54% (F2-83.33%), A-40% (A1-65%), D-6%, C2-1%, E-1%, and G-1%. CONCLUSIONS: Some genotypes are only prevalent in certain parts of the world; however, the State of Ceará is a hub for migration and has one of the most important liver transplantation centers in Brazil, which can explain the prevalence of the F genotype.
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Gastroenterologia , Hepatite B , Brasil/epidemiologia , DNA Viral/genética , Genótipo , Hepatite B/epidemiologia , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/genética , Humanos , PrevalênciaRESUMO
Erebonyx catacumbae, new genus and species of a troglobitic phalangopsid cricket are described from Brazil. Few specimens were collected from a limestone cave located in the municipality of Campo Formoso, northern State of Bahia, in a semi-arid zone characterized by the Caatinga vegetation. A brief discussion on troglomorphisms is provided, as well as some ecological remarks and potential threats for this species.
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Gryllidae/classificação , Animais , Brasil , CavernasRESUMO
Abstract INTRODUCTION: Hepatitis B virus (HBV) infection is a public health problem; therefore, we aimed to report HBV genotypes in Ceará, Brazil. METHODS: A total of 103 HBsAg-positive samples were subjected to HBV genotyping and subgenotyping. RESULTS: The following genetic compositions of samples were found: F-54% (F2-83.33%), A-40% (A1-65%), D-6%, C2-1%, E-1%, and G-1%. CONCLUSIONS: Some genotypes are only prevalent in certain parts of the world; however, the State of Ceará is a hub for migration and has one of the most important liver transplantation centers in Brazil, which can explain the prevalence of the F genotype.
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Humanos , Gastroenterologia , Hepatite B/epidemiologia , Brasil/epidemiologia , DNA Viral/genética , Vírus da Hepatite B/genética , Prevalência , Genótipo , Antígenos de Superfície da Hepatite BRESUMO
INTRODUCTION: Brazil's western Amazon basin has the highest prevalence of hepatitis B virus (HBV) infection in the country. Coinfection with hepatitis D virus (HDV) is also endemic. To estimate the prevalence of HBV and HDV markers in a population inhabiting the northwest portion of Mato Grosso state in the western Amazon. METHODS: We performed a cross-sectional study of the seroprevalence of antibodies against HBV core antigen (anti-HBc) in the Três Fronteiras District northwest of Mato Grosso. Anti-HBc-positive subjects were tested for HBV surface antigen (HBsAg). Those positive for this marker were tested for HDV antibodies. Anti-HBc-negative participants were tested for anti-HBsAg. All tests were performed by EIA. RESULTS: A total of 623 individuals in the community were assessed; the majority (67.6%) were male, with a mean age of 30.8 ± 15.4 years. Two hundred and fourteen individuals (34.3%) were anti-HBc-positive, and 47 (7.5%) were HBsAg carriers. Only one individual was anti-HDV-positive. Among the 409 individuals without HBV infection, 18.3% were anti-HBsAg-positive. There was no association between HBV infection and known risk factors. CONCLUSIONS: The study area had intermediate-to-high endemicity for HBV infection, but a low prevalence of HDV. Our serological results suggesting low vaccination-induced protection indicate a need for reinforced immunization programs in the populations of northwest Mato Grosso.
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Hepatite B , Adolescente , Adulto , Brasil/epidemiologia , Estudos Transversais , Hepatite B/epidemiologia , Anticorpos Anti-Hepatite B , Antígenos de Superfície da Hepatite B , Vírus da Hepatite B/imunologia , Hepatite D/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Soroepidemiológicos , Adulto JovemRESUMO
BACKGROUND: Occult hepatitis B virus (HBV) - characterized by the absence of detectable HBsAg in the presence of HBV DNA - represents a potential threat for blood safety. OBJECTIVES: This study was conducted with the aim to investigate the serological and molecular characterization of occult HBV infection (OBI) among blood donors in Mozambique. METHODS: 1,502 blood donors were tested for HBsAg. All HBsAg-negative individuals were tested for HBV DNA. Antibodies against HBV core, surface and HBe antigen (anti-HBc, anti-HBs, HBeAg) were measured in HBV DNA positive individuals. FINDINGS: 1435 serum samples were HBsAg negative and 16 positive for HBV DNA, 14 confirmed to have OBI, corresponding to a frequency of 0.98%. Of the 14 OBI infections identified, 13/14 (92.8%) were positive for anti-HBc, 4/14 (28.5%) for anti-HBs, and no samples were reactive for HBeAg. Of the 14 OBI cases, nine samples (64.2%) were sequenced for the S/P region. Eight samples (88.9%) belonged to genotype A1 and one (11.1%) to genotype E. One escape mutation (T123A) associated with OBI and various amino acid substitutions for genotype A1 and E were observed. MAIN CONCLUSIONS: Our results show the importance of using nucleic acid amplification test to detect occult hepatitis B infection in blood donors in Mozambique.
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Doadores de Sangue , Antígenos de Superfície da Hepatite B/sangue , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B/diagnóstico , Técnicas de Amplificação de Ácido Nucleico/métodos , Adulto , Estudos Transversais , DNA Viral , Feminino , Humanos , Masculino , Moçambique , Filogenia , Reação em Cadeia da PolimeraseRESUMO
Hepatitis B virus (HBV) is an enveloped virus that induces chronic liver disease. HBV has been classified into eight genotypes (A-H) according to its genome sequence by using Sanger sequencing or reverse hybridization. Sanger sequencing is often restricted to analyzing the S gene and is inaccurate for detecting minority genetic variants, whereas reverse hybridization detects only known mutations. Next-generation sequencing (NGS) is a robust tool for clinical virology with different protocols available. The objective of this study was to develop a new method for the study of viral genetic polymorphisms or more accurate genotyping using genome amplification followed by NGS. Plasma obtained from five chronically infected HBV individuals was used for viral DNA isolation. HBV full-genome PCR amplification was the enrichment method for NGS. Primers were used to amplify all HBV genotypes in three overlapping amplicons, following a tagmentation step and Illumina NGS. For phylogenetic analysis, sequences were extracted from the HBVdb database. We were able to amplify a full HBV genome; further, NGS was shown to be a robust method and allowed better genotyping, mainly in patients carrying mixed genotypes, classified according to other techniques. This new method may be significant for whole genome analyses, including other viruses.
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The cancer multidrug resistance is involved in the failure of several treatments during cancer treatment. It is a phenomenon that has been receiving great attention in the last years due to the sheer amount of mechanisms discovered and involved in the process of resistance which hinders the effectiveness of many anti-cancer drugs. Among the mechanisms involved in the multidrug resistance, the participation of ATP-binding cassette (ABC) transporters is the main one. The ABC transporters are a group of plasma membrane and intracellular organelle proteins involved in the process of externalization of substrates from cells, which are expressed in cancer. They are involved in the clearance of intracellular metabolites as ions, hormones, lipids and other small molecules from the cell, affecting directly and indirectly drug absorption, distribution, metabolism and excretion. Other mechanisms responsible for resistance are the signaling pathways and the anti- and pro-apoptotic proteins involved in cell death by apoptosis. In this study we evaluated the influence of three nanosystem (Graphene Quantum Dots (GQDs), mesoporous silica (MSN) and poly-lactic nanoparticles (PLA)) in the main mechanism related to the cancer multidrug resistance such as the Multidrug Resistance Protein-1 and P-glycoprotein. We also evaluated this influence in a group of proteins involved in the apoptosis-related resistance including cIAP-1, XIAP, Bcl-2, BAK and Survivin proteins. Last, colonogenic and MTT (3-(4,5-dimethylthiazol-2-yl)- 2,5-diphenyltetrazolium bromide) assays have also been performed. The results showed, regardless of the concentration used, GQDs, MSN and PLA were not cytotoxic to MDA-MB-231 cells and showed no impairment in the colony formation capacity. In addition, it has been observed that P-gp membrane expression was not significantly altered by any of the three nanomaterials. The results suggest that GQDs nanoparticles would be suitable for the delivery of other multidrug resistance protein 1 (MRP1) substrate drugs that bind to the transporter at the same binding pocket, while MSN can strongly inhibit doxorubicin efflux by MRP1. On the other hand, PLA showed moderate inhibition of doxorubicin efflux by MRP1 suggesting that this nanomaterial can also be useful to treat MDR (Multidrug resistance) due to MRP1 overexpression.
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Transportadores de Cassetes de Ligação de ATP/genética , Transportadores de Cassetes de Ligação de ATP/metabolismo , Resistência a Múltiplos Medicamentos , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Membro 1 da Subfamília B de Cassetes de Ligação de ATP/metabolismo , Antineoplásicos/administração & dosagem , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Imunofluorescência , Expressão Gênica , Grafite/química , Humanos , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Nanopartículas/química , Nanoestruturas/química , Nanomedicina TeranósticaRESUMO
Recent studies have investigated whether the human histo-blood group antigen (HBGAs) could affect the effectiveness of the oral rotavirus vaccines, suggesting secretor positive individuals develop a more robust response. We investigated the Rotavirus A (RVA) shedding in association with the host susceptibility profile in children from a birth community-cohort in Rio de Janeiro, Brazil, from 2014 to 2018. A total of 132 children were followed-up between 0 to 11-month-old, stool samples were collected before/after the 1st/2nd RV1 vaccination doses and saliva samples were collected during the study. RVA shedding was screened by RT-qPCR and G/P genotypes determined by multiplex RT-PCR and/or Sanger nucleotide sequencing. The sequencing indicated an F167L amino acid change in the RV1 VP8* P[8] in 20.5% of shedding follow-ups and these mutant subpopulations were quantified by pyrosequencing. The HBGA/secretor status was determined and 80.3% of the children were secretors. Twenty-one FUT2 gene SNPs were identified and two new mutations were observed. The mutant F167L RV1 VP8* P[8] was detected significantly more in Le (a+b+) secretors (90.5%) compared to non-secretors and even to secretors Le (a-b+) (9.5%). The study highlights the probable association between RV1 shedding and HBGAs as a marker for evaluating vaccine strain host susceptibility.
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Gastroenteropatias/prevenção & controle , Gastroenteropatias/virologia , Brasil , Feminino , Gastroenteropatias/imunologia , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Rotavirus/imunologia , Rotavirus/patogenicidade , Infecções por Rotavirus/imunologia , Infecções por Rotavirus/prevenção & controle , Infecções por Rotavirus/virologia , Vacinas contra Rotavirus/imunologia , Vacinas contra Rotavirus/uso terapêutico , Vacinas Atenuadas/imunologia , Vacinas Atenuadas/uso terapêuticoRESUMO
Kidney transplantation is the treatment of choice for patients with end-stage renal disease. In the posttransplant period, the induced immunosuppression leads to an increased risk of developing infectious diseases, a leading cause of death after kidney transplantation. Human pegivirus-1 (HPgV-1) is considered a nonpathogenic human virus and is highly frequent in individuals parenterally exposed, however, its impact on kidney transplantation outcome is poorly understood. Given the scarcity of epidemiological data for this infection on organ recipients in Brazil, we conducted a study in a single center for kidney transplantation in Rio de Janeiro, aiming to determine HPgV-1 prevalence and genotypic distribution. Serum samples from 61 renal recipients, followed up for the first year after transplantation, were evaluated for viral RNA and genotypes were determined by sequencing of the 5'-untranslated region. HPgV-1 RNA was detected in 36.1% (22/61) of patients. Genotype 2 was the most commonly found (80.9%), followed by genotypes 3 (9.5%), 1, and 5, in 4.8% each. Statistical comparisons did not reveal any significant impact of HPgV-1 in patient outcome. Further epidemiologic studies are needed to understand if immunosuppression may interfere in HPgV-1 persistence rates and if viremia might impact graft dysfunction rates in kidney recipients.
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The current treatment of Chagas disease is based on the use of two drugs, nifurtimox (Nfx) and benznidazole (Bnz), both of which present limited efficacy in the chronic stage of the disease and toxic side effects. Thus, the discovery of novel compounds is urgently required. Herein, we report the successful synthesis of 4-nitroimidazole analogs of Bnz via nucleophilic aromatic substitution or cycloaddition reactions. The analogs were biologically evaluated, and compound 4 (4-cyclopropyl-1-(1-methyl-4-nitro-1H-imidazole-5-yl)-1H-1,2,3-triazole) was identified as the most potent against both the trypomastigote (IC50 = 5.4 µM) and amastigote (IC50 = 12.0 µM) forms of T. cruzi, showing activity in the same range as Bnz (IC50 = 8.8 and 8.7 µM, respectively). The cytotoxic and genotoxic activities of compounds 5, 4 and 11 were assessed. These three compounds were cytotoxic and genotoxic to RAW and HepG2 cells and mutagenic to Salmonella enterica strains. However, 4 exhibited toxic effects only at concentrations higher than those needed for trypanocidal activity. Molecular docking of 4 showed the importance of the size and π-π interactions between the nitroimidazole and the cofactor (flavin mononucleotide) of T.cruzi-nitroreductase (TcNTR). Moreover, the residues His503 and Tyr545 are relevant for binding to TcNTR. Our design strategy was capable of generating novel and active Bnz analogs.
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Antiprotozoários/farmacologia , Nitroimidazóis/farmacologia , Salmonella enterica/efeitos dos fármacos , Tripanossomicidas/farmacologia , Trypanosoma cruzi/efeitos dos fármacos , Animais , Antiprotozoários/síntese química , Antiprotozoários/química , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Chlorocebus aethiops , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Células Hep G2 , Humanos , Camundongos , Testes de Sensibilidade Microbiana , Modelos Moleculares , Estrutura Molecular , Nitroimidazóis/síntese química , Nitroimidazóis/química , Nitrorredutases/antagonistas & inibidores , Nitrorredutases/metabolismo , Células RAW 264.7 , Relação Estrutura-Atividade , Tripanossomicidas/síntese química , Tripanossomicidas/química , Trypanosoma cruzi/enzimologiaRESUMO
Abstract INTRODUCTION: Brazil's western Amazon basin has the highest prevalence of hepatitis B virus (HBV) infection in the country. Coinfection with hepatitis D virus (HDV) is also endemic. To estimate the prevalence of HBV and HDV markers in a population inhabiting the northwest portion of Mato Grosso state in the western Amazon. METHODS: We performed a cross-sectional study of the seroprevalence of antibodies against HBV core antigen (anti-HBc) in the Três Fronteiras District northwest of Mato Grosso. Anti-HBc-positive subjects were tested for HBV surface antigen (HBsAg). Those positive for this marker were tested for HDV antibodies. Anti-HBc-negative participants were tested for anti-HBsAg. All tests were performed by EIA. RESULTS: A total of 623 individuals in the community were assessed; the majority (67.6%) were male, with a mean age of 30.8 ± 15.4 years. Two hundred and fourteen individuals (34.3%) were anti-HBc-positive, and 47 (7.5%) were HBsAg carriers. Only one individual was anti-HDV-positive. Among the 409 individuals without HBV infection, 18.3% were anti-HBsAg-positive. There was no association between HBV infection and known risk factors. CONCLUSIONS: The study area had intermediate-to-high endemicity for HBV infection, but a low prevalence of HDV. Our serological results suggesting low vaccination-induced protection indicate a need for reinforced immunization programs in the populations of northwest Mato Grosso.