RESUMO
Human Papillomavirus (HPV) is the causative agent in the majority of anal, head and neck, oral, oropharyngeal, penile, vaginal, vulvar, and cervical cancers. Cervical cancer is the fourth most common cancer among women worldwide. Of all diagnosed human malignant neoplasms, approximately 4.5% are attributable to HPV, including cervical, anal cancers, vaginal, vulvar, penile, and oropharyngeal cancers. Over 182 HPV types have been identified and sequenced to date however, only certain types of HPV are more frequent in malignant lesions and considered to be a major risk factor in the development of some cancers. Because most HPV infections are transient, and an individual's immunocompetent may clear the infection, HPV infection has received little attention from clinicians, the general public, or policy makers. This lack of attention may underpin a deadly and increasing problem because each newly acquired infection has the potential to persist and become an incurable, lifelong affliction. In addition, no successful treatment of HPV infection currently exists despite the great strides toward understanding the mechanisms underlying HPV pathogenesis. Moreover, ample research has proven that the use of prophylactic vaccines, such as Gardasil and Cervarix, have led to documented progress in decreasing the burden of HPV infection, however not all countries introduced a government-funded National HPV Vaccination Program to protect young men and women. This chapter summarizes the HPV infection, detection and prevention. We also shed light on non-cervical HPV-related cancers, which is rapidly increasing in more developed countries toward cervical cancer.
Assuntos
Alphapapillomavirus , Neoplasias do Ânus , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Feminino , Humanos , Masculino , Papillomaviridae/genética , Infecções por Papillomavirus/epidemiologia , Neoplasias do Colo do Útero/epidemiologiaRESUMO
Neonatal sepsis is a great challenge for clinicians and infection control practitioners, especially in facilities with limited resources. Carbapenem-resistant Klebsiella pneumoniae (CRKP) is rapidly increasing and carriages a major threat to neonates. We aimed to examine phenotypes causing neonatal late onset sepsis (NLOS) in comparison with neonatal early onset sepsis (NEOS) with further investigations of genotypes, and genetic relatedness of CRKP in neonatal late-onset sepsis. Our study included 88 neonates diagnosed with sepsis: 58 with (NLOS) and 30 with (NEOS) from November 2015 to April 2016, at neonatal intensive care unit (NICU) of Cairo University Hospital. K. pneumoniae was the most common encountered pathogen in the NLOS group (37.9%) with a mean sepsis score of 6.39 when compared to the NEOS group (p < 0.05). In Klebsiella group, C-reactive protein and interleukin-6 levels were significantly high (p Ë 0.001) and 56.5% of the isolates were meropenem resistant. The most prevalent carbapenemase gene was OXA-48 which was identified in 14/23 (60.8%) followed by NDM-1 which was identified in 12/23 (52.2%) as detected by multiplex PCR. Coexistence of both carbapenemases was found in 52.2% (12/23). The blaKPC, blaIMP, and blaVIM genes were not harbored in the isolates. By investigating the genetic relatedness of CRKP by pulsed-field gel electrophoresis, 23 isolates of K. pneumoniae revealed various pulsed-field gel electrophoresis (PFGE) patterns, demonstrating that the isolates were non-clonal. Awareness of the existing phenotypes and genotypes is important for proper treatment and infection control practices.
Assuntos
Enterobacteriáceas Resistentes a Carbapenêmicos/genética , Variação Genética , Unidades de Terapia Intensiva Neonatal , Infecções por Klebsiella/epidemiologia , Infecções por Klebsiella/microbiologia , Klebsiella pneumoniae/genética , Sepse Neonatal/epidemiologia , Sepse Neonatal/microbiologia , Antibacterianos/farmacologia , Técnicas de Tipagem Bacteriana , Enterobacteriáceas Resistentes a Carbapenêmicos/classificação , Enterobacteriáceas Resistentes a Carbapenêmicos/efeitos dos fármacos , Estudos Transversais , Egito/epidemiologia , Humanos , Recém-Nascido , Infecções por Klebsiella/tratamento farmacológico , Klebsiella pneumoniae/classificação , Testes de Sensibilidade Microbiana , Sepse Neonatal/tratamento farmacológico , Prognóstico , Vigilância em Saúde Pública , Resultado do TratamentoRESUMO
Background and Objectives. Malaria infection, caused by Plasmodium falciparum, is the most lethal and frequently culminates in severe clinical complications. Interleukin-22 (IL-22) has been implicated in several diseases including malaria. The objective of this study was to investigate the role of IL-22 gene polymorphisms in P. falciparum infection. Material and Methods. Ten single-nucleotide polymorphisms (SNPs), rs976748, rs1179246, rs2046068, rs1182844, rs2227508, rs2227513, rs2227478, rs2227481, rs2227491, and rs2227483, of IL-22 gene were genotyped through PCR-based assays of 250 P. falciparum infection. IL-22 gene promoter activity. RESULTS: We found that the rs2227481 TT genotype (odds ratio 0.254, confidence interval = 0.097-0.663, P. P. falciparum infection. P. P. P. P. CONCLUSION: The study suggests that IL-22 polymorphisms in rs2227481 and rs2227483 could contribute to protection against P. falciparum infection. IL-22 gene promoter activity.
Assuntos
Interleucinas/genética , Malária/genética , Polimorfismo de Nucleotídeo Único/genética , Intervalos de Confiança , Frequência do Gene/genética , Predisposição Genética para Doença/genética , Genótipo , Haplótipos/genética , Humanos , Razão de Chances , Plasmodium falciparum/patogenicidade , Regiões Promotoras Genéticas/genética , Interleucina 22RESUMO
BACKGROUND/AIMS: The hepatitis B virus X protein (HBx) is a viral trans-activator that plays a crucial role in pathogenesis of hepatocellular carcinoma (HCC) via an unknown mechanism. The role of HBx in modulating cell proliferation and programmed cell death is replete with controversies. Thus, the goal of this study was to elucidate the effect of HBx and its deletion mutants on cell cycle progression in human hepatoma cells. METHODS: Huh7 cells transfected with either full-length or truncated HBx were tested for their mitogenic potential based on their effect on the expression of key cell cycle-related proteins (p27, cyclin D1, p21, and p53) and pro-apoptotic proteins such as cleaved poly (ADP-ribose) polymerase (PARP) and Bax. Western blotting and immunofluorescence techniques were applied to detect changes in the expression levels and intracellular localization, respectively, of the investigated proteins. Also, Quantitative real-time PCR (qRT-PCR) was used to detect changes in RNA levels. RESULTS: An increased anchorage-independent growth of cells transfected with HBx-WT and its deletion mutants was observed. The cell cycle regulatory molecules were differentially modulated by full-length HBx (1-154) and its different N- and C-terminal truncated forms (HBx (31-154), HBx (61-154), HBx (1-94), and HBx (61-124)). An enhanced modulation of p27, p21, and cyclin D1 was associated with HBx (1-154), whereas p53 expression was significantly inhibited by HBx (61-124). Similarly, the expression of cleaved PARP and Bax was efficiently suppressed by HBx (1-94) and HBx (61-154). CONCLUSION: The HBx-WT and its mutants play a critical role in the pathogenesis and progression of HCC by modulating cell cycle regulatory proteins.
Assuntos
Transativadores/metabolismo , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Ciclina D1/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Inibidor de Quinase Dependente de Ciclina p27/metabolismo , Pontos de Checagem da Fase G1 do Ciclo Celular , Vírus da Hepatite B/metabolismo , Humanos , Microscopia de Fluorescência , Mutagênese , Poli(ADP-Ribose) Polimerases/metabolismo , Transativadores/genética , Proteína Supressora de Tumor p53/metabolismo , Proteínas Virais Reguladoras e Acessórias , Proteína X Associada a bcl-2/metabolismoRESUMO
AIM: Vancomycin-resistant enterococci (VRE) are a major cause of nosocomial infections with high mortality and morbidity. There is limited data on the molecular characterization of VRE in Saudi Arabia. This study was carried out to investigate the premise that a shift in VRE epidemiology is occurring in our setting. METHODS: Enterococcus species identification and susceptibility testing plus VRE phenotypic confirmation by vancomycin and teicoplanin E-test were carried out. Vancomycin resistance genes were detected by PCR. Strain typing was conducted using PFGE. RESULTS: Among the strains of Enterococcus spp. investigated in this study, 17 (4.5%) were VRE. With the exception of one isolate from rectal swab, all others were clinical specimens with blood being the commonest source (n = 11; 64.7%), followed by urine (n = 3; 17.6%). The 17 VRE isolates were Enterococcus faecium (n/N = 13/17) and Enterococcus gallinarum (n/N = 4/17). Among E. faecium isolates, vanA(+)/vanB(+) (n/N = 8/13; 62%) exhibiting VanB phenotype were predominant. One of the five vanA(+)E. faecium isolates exhibited a VanB phenotype indicative of vanA genotype-VanB phenotype incongruence. E. gallinarum isolates exhibited a Van C phenotype although two were vanA(+)/vanC1(+). PFGE revealed a polyclonal distribution with eight pulsotypes. CONCLUSION: These findings indicate an evolving VRE epidemiology with vanA(+)/vanB(+) isolates and vanA genotype-VanB phenotype incongruence isolates, which were previously described as colonizers, are now causing clinical infection.
Assuntos
Infecções por Bactérias Gram-Positivas/epidemiologia , Enterococos Resistentes à Vancomicina/isolamento & purificação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Arábia , Proteínas de Bactérias/genética , Carbono-Oxigênio Ligases/genética , Criança , Pré-Escolar , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Eletroforese em Gel de Campo Pulsado , Feminino , Genes Bacterianos , Infecções por Bactérias Gram-Positivas/microbiologia , Humanos , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Tipagem Molecular , Reação em Cadeia da Polimerase , Arábia Saudita/epidemiologia , Teicoplanina/farmacologia , Centros de Atenção Terciária , Vancomicina/farmacologia , Enterococos Resistentes à Vancomicina/classificação , Enterococos Resistentes à Vancomicina/genética , Adulto JovemRESUMO
Background. The protein encoded by PARK2 gene is a component of the ubiquitin-proteasome system that mediates targeting of proteins for the degradation pathway. Genetic variations at PARK2 gene were linked to various diseases including leprosy, typhoid and cancer. The present study investigated the association of single nucleotide polymorphisms (SNPs) in the PARK2 gene with the development of hepatitis C virus (HCV) infection and its progression to severe liver diseases. MATERIAL AND METHODS: A total of 800 subjects, including 400 normal healthy subjects and 400 HCV-infected patients, were analyzed in this study. The patients were classified as chronic HCV patients (group I), patients with cirrhosis (group II) and patients with hepatocellular carcinoma (HCC) in the context of cirrhosis (group III). DNA was extracted and was genotyped for the SNPs rs10945859, rs2803085, rs2276201 and rs1931223. RESULTS: Among these SNPs, CT genotype of rs10945859 was found to have a significant association towards the clinical progression of chronic HCV infection to cirrhosis alone (OR = 1.850; 95% C. I. 1.115-3.069; p = 0.016) or cirrhosis and HCC (OR = 1.768; 95% C. I. 1.090-2.867; p value = 0.020). CONCLUSION: SNP rs10945859 in the PARK2 gene could prove useful in predicting the clinical outcome in HCV-infected patients.
Assuntos
Carcinoma Hepatocelular/genética , Hepatite C Crônica/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Polimorfismo de Nucleotídeo Único , Ubiquitina-Proteína Ligases/genética , Adulto , Idoso , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/enzimologia , Carcinoma Hepatocelular/virologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Progressão da Doença , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Haplótipos , Hepatite C Crônica/diagnóstico , Hepatite C Crônica/enzimologia , Hepatite C Crônica/virologia , Humanos , Desequilíbrio de Ligação , Cirrose Hepática/diagnóstico , Cirrose Hepática/enzimologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/enzimologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Razão de Chances , Fenótipo , Fatores de Risco , Adulto JovemRESUMO
Carbapenem-resistant Acinetobacter spp. have been increasingly reported worldwide including Saudi Arabia and Egypt. We examined 64, non-repetitive, Acinetobacter baumannii isolates collected in 2013 and 2014 from four different medical centres (two from Saudi Arabia and two from Egypt). All the isolates were resistant to ceftazidime and ciprofloxacin. The intI1 harbouring blaGES-11 and aac-6'-1b was detected in 19% (n=12) of the isolates. ISAba1 over-expression of blaADC gene was observed in 65% (n=42) of isolates. Of all the isolates 19% (n=12) had ISAba1 upstream of the blaOXA-51-like gene, 69% (n=44) carried the blaOXA-23 gene within the Tn2006 structure, 8% (n=5) had blaOXA-24-like gene and 9% (n=6) harboured either blaVIM-2 or blaNDM-1 gene. Eighty nine percent (n=57) of isolates were resistant to imipenem and had an MIC of ≥8mg/L. Pulsed-field gel electrophoresis (PFGE) typing revealed the presence of 23 different PFGE. Three PFGE types were very widespread, ST236 (CC104) (PFGE type 1, n=15), ST208 (CC92) (PFGE type 2, n=10), ST884 (CC unassigned) (PFGE type 3, n=7) in and across all four medical centres. The blaOXA-23 gene was found to be present on a 60kb transferable plasmid in both PFGE type 1 and 2 but was absent in PFGE type 3. This is the first study to report on the emergence of ST236 in Saudi Arabia and Egypt, and spread of distinct carbapenem resistant A. baumannii clones belonging to ST884, ST945 and ST1096 in Saudi Arabia.
Assuntos
Acinetobacter baumannii/genética , Acinetobacter baumannii/isolamento & purificação , Proteínas de Bactérias/genética , Farmacorresistência Bacteriana Múltipla/genética , Regulação Bacteriana da Expressão Gênica , Genes Bacterianos , Proteínas de Bactérias/metabolismo , Carbapenêmicos/farmacologia , Ceftazidima/farmacologia , Egito , Eletroforese em Gel de Campo Pulsado , Imipenem/farmacologia , Testes de Sensibilidade Microbiana , Dados de Sequência Molecular , Tipagem de Sequências Multilocus , Plasmídeos/genética , Arábia SauditaRESUMO
Torque Teno virus (TTV) has been associated with non A-G hepatitis. The goal of this study was to estimate the infection rates and genotypic characteristics of TTV in the State of Qatar. A total of 644 blood samples representing different nationalities: (i) Qatari (118) and (ii) non-Qatari (526) nationals (mostly from Arab and South Eeast Asia countries) were tested for the presence of TTV DNA by nested PCR. The majority (573) of the blood samples belonged to healthy blood donors, whereas 54 and 53 of the blood samples belonged to patients infected with hepatitis B virus (HBV) and hepatitis C virus (HCV), respectively. The results obtained showed that the TTV infection rates in the healthy blood donors, and those infected with HBV or HCV patients were 81.4, 90.75 and 84.9%, respectively. Significant association between TTV viremia and age, or nationality was observed. Sequence analysis of PCR fragments amplified from the 5'-untranslated region (5'-UTR) of all (531) TTV positive samples showed that 65.5% (348/531) of the PCR fragment sequences were classified into main genogroup 3, followed by main genogroups 5 (24%), 2 (5.8%), and 1 (4.7%). Genogroup 4 was not detected among the our studied subjects. Phylogenetic and pairwise analyses using sequences from TTV viremic samples also showed an overall close similarity to the main genogroup 3. In conclusion, there was no significant difference in the rates of TTV detection among Qataris and non-Qataris and several genotypes, mainly genotype 3, were isolated.
Assuntos
Coinfecção , Infecções por Vírus de DNA/epidemiologia , Hepatite B/epidemiologia , Hepatite C/epidemiologia , Torque teno virus/classificação , Torque teno virus/genética , Adolescente , Adulto , Idoso , DNA Viral , Evolução Molecular , Feminino , Genoma Viral , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Filogenia , Vigilância da População , Catar/epidemiologia , Viremia , Adulto JovemRESUMO
BACKGROUND: Hepatitis C virus (HCV) shows a remarkable genetic diversity, contributing to its high persistence and varied susceptibilities to antiviral treatment. Previous studies have reported that the substitution of amino acids in the HCV subgenotype 1b core protein in infected patients is associated with a poor response to pegylated interferon and ribavirin (PEG-IFN/RBV) combined therapy. OBJECTIVES: Because the role of the core protein in HCV genotype 4 infections is unclear, we aimed in this study to compare the full-length core protein sequences of HCV genotype 4 between Saudi patients who responded (SVR) and did not respond (non-SVR) to PEG-IFN/RBV therapy. STUDY DESIGN: Direct sequencing of the full-length core protein and bioinformatics sequence analysis were utilized. RESULTS: Our data revealed that there is a significant association between core protein mutations, particularly at position 70 (Arg70Gln), and treatment outcome in HCV subgenotype 4d patients. However, HCV subgenotype 4a showed no significant association between core protein mutations and treatment outcome. In addition, amino acid residue at position 91 was well-conserved among studied patients where Cys91 is the dominant amino acid residue. CONCLUSIONS: These findings provide a new insight into HCV genotype 4 among affected Saudi population where the knowledge of HCV core gene polymorphisms is inadequate.
Assuntos
Antivirais/uso terapêutico , Variação Genética , Genótipo , Hepacivirus/genética , Antígenos da Hepatite C/genética , Hepatite C/tratamento farmacológico , Interferons/uso terapêutico , Ribavirina/uso terapêutico , Adulto , Antivirais/administração & dosagem , Feminino , Humanos , Interferons/administração & dosagem , Masculino , Pessoa de Meia-Idade , Ribavirina/administração & dosagem , Arábia SauditaRESUMO
BACKGROUND & AIMS: Several genome-wide association studies have shown that genetic variations in the chromosomal region containing interleukin-28B (IL28B) gene are associated with response to treatment in hepatitis C virus (HCV) infection. This study was conducted to examine the role of genetic variations in IL28B on disease progression in Saudi Arabian patients chronically infected with hepatitis B virus (HBV). METHODS: The study included 1128 subjects divided into four categories; 304 clearance subjects, 518 inactive carriers, 212 active carriers and 94 cirrhosis/HCC. RESULTS: Three single nucleotide polymorphisms (SNPs), rs12979860 (OR=1.307; 95% CI 1.046-1.634, χ2=5.57 and P=0.0183), rs12980275 (OR=0.642; CI 0.517-0.798, χ2=16.17 and P=0.0001) and rs8105790 (OR=0.746; CI 0.592-0.941, χ2=6.12 and P=0.0133), were found to be strongly associated with HBV clearance. The frequency of the G allele of rs12980275 and the C allele of rs8105790 were found to be more in clearance group than in patients and could contribute to protection against the disease. On the other hand, only rs12979860 showed significant difference in distribution when inactive group was compared to other groups (OR=1.285; CI 1.030-1.603, χ2=4.95, P=0.0261). No significant association was evident for any of the variants when active carriers were compared to cirrhosis/HCC patients. Haplotype analysis showed that a combination of A-T-T-G of rs12980275, rs8105790, rs8099917, and rs7248668, respectively, was associated with clearance of the virus (frequency=67.5% and P=0.015). CONCLUSION: genetic variations in IL28B gene region may influence the clearance of HBV infection.
Assuntos
Variação Genética , Hepatite B Crônica/epidemiologia , Hepatite B Crônica/genética , Interleucinas/genética , Progressão da Doença , Frequência do Gene , Genótipo , Haplótipos/genética , Humanos , Interferons , Razão de Chances , Polimorfismo de Nucleotídeo Único/genética , Arábia Saudita/epidemiologiaRESUMO
OBJECTIVES: Patients with chronic hepatitis B virus (HBV) may exhibit significant liver pathology despite alanine aminotransferase (ALT) and HBV DNA levels below the cutoff values advised by treatment guidelines. We evaluated candidacy for HBV therapy when baseline histopathological changes are taken into consideration. METHODS: Clinical, biochemical, serological, virological, and histopathological (METAVIR score) data of 117 patients with HBeAg-negative chronic HBV genotype D were collected and analyzed. RESULTS: Significant pathology (≥F2 and/or ≥A2) and fibrosis (≥F2 ± ≥A2) were found in 73 (62.4%) and 59 (50.4%) patients, respectively. Based on HBV DNA (>2,000 IU/ml) and ALT levels >2 × 40 U/l (the standard cutoff value), only 31 (26.5%) patients were candidates for therapy. This increased to 58 (49.6%) patients when the new ALT cutoff values (30 U/l for males, and 19 U/l for females) were applied. Relying on either ≥F2 and/or A ≥2 or ≥F2 ± ≥A2 increases the treatment candidacy to 73 (62.4%) and 59 (50.4%) patients, respectively. Also, when compared with standard ALT cutoff values, applying both new ALT cutoff values with either significant pathology or fibrosis increases treatment candidacy to 28 (23.9%) and 42 (35.9%) patients, respectively. CONCLUSION: Liver pathology is more reliable than ALT and HBV DNA in the decision to treat patients with HBeAg-negative chronic HBV genotype D.
Assuntos
Antivirais/uso terapêutico , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/patologia , Fígado/patologia , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Biópsia , Feminino , Genótipo , Antígenos E da Hepatite B/sangue , Vírus da Hepatite B/classificação , Vírus da Hepatite B/genética , Vírus da Hepatite B/isolamento & purificação , Hepatite B Crônica/virologia , Humanos , Fígado/virologia , Masculino , Pessoa de Meia-Idade , Carga Viral , Adulto JovemRESUMO
BACKGROUND: Variations at DEPDC5 gene have been recently reported as genetic markers associated with hepatocellular carcinoma (HCC) progression in chronic HCV-infected patients. This study was conducted to assess the association of DEPDC5 variants with advanced liver cirrhosis and HCC development among chronic HCV-infected patients in Saudi Arabian population. METHODS: Six-hundred and one HCV-infected patients were genotyped for DEPDC5 polymorphisms (rs1012068 and rs5998152), in comparison with 592 non-infected healthy control subjects. The allelic frequency and genotype distribution of both DEPDC5 polymorphisms were determined followed by haplotype frequency estimation and multiple logistic regression analysis. RESULTS: The frequency of the risk alleles of both rs1012068 and rs5998152 was shown to be more in healthy control subjects than in patients (p = 0.0001, OR = 0.704, CI = 0.591-0.839; p = 0.002, OR = 0.761, CI = 0. 0.639-0.907, respectively). Also, our results revealed that GT for SNP rs1012068 (OR =1.715; 95% CI 1.132-2.597; p = 0.0104) and CT for SNP rs5998152 (OR = 1.932; 95% CI 1.276-2.925; p = 0.0017) showed significant association with development of cirrhosis compared with the GG and CC genotypes, respectively. The data also revealed that subjects with the T allele of both SNPs appeared to have a lower susceptibility to HCV-related cirrhosis/HCC than those with the G allele of rs1012068 (p = 0.038, OR = 1.353, 95 % CI 1.017-1.800) and C allele of rs5998152 (p = 0.043, OR = 1.342, 95 % CI 1.010-1.784). Haplotype analysis showed that a combination of T-T alleles of rs1012068 and rs5998152 was significantly associated with liver cirrhosis (frequency = 71.3% and p = 0.027) and with cirrhosis/HCC (frequency = 71.4% and P = 0.045). Also, multiple logistic regression analysis showed that rs5998152 (OR = 2.844, 95% CI 1.333-6.069 and p = 0.007), rs1012068 (OR = 2.793, 95% CI 1.316-5.928 and p = 0.010), age (OR = 1.029, 95% CI 1.001-1.057 and p = 0.041) and HCV genotypes (OR = 0.247, 95% CI 0.097-0.630 and p = 0.003) were independently associated with chronicity of HCV infection. CONCLUSION: Genetic variations in DEPDC5 gene region may influence HCV-associated liver cirrhosis and/or HCC development.
Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença/genética , Hepatite C Crônica/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , Proteínas Repressoras/genética , Adulto , Alelos , Carcinoma Hepatocelular/complicações , Progressão da Doença , Feminino , Proteínas Ativadoras de GTPase , Marcadores Genéticos , Genótipo , Haplótipos , Hepatite C Crônica/complicações , Humanos , Cirrose Hepática/complicações , Neoplasias Hepáticas/complicações , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Arábia SauditaRESUMO
MHC class I polypeptide-related chain A (MICA), mapping to 6p21.33, belongs to the non-classical class I family and its expression is induced by several stress factors including viral infection. A recent genome-wide association study has identified a single nucleotide polymorphism (SNP) of MICA, rs2596542 to be significantly associated with hepatitis C-induced hepatocellular carcinoma (HCC) in a Japanese population. Therefore, this study aims to investigate whether the SNP rs2596542 plays any role in hepatitis B virus (HBV) sero-clearance or in the development of complications associated with chronic HBV such as cirrhosis and/or HCC. TaqMan genotyping assay was used to identify the association of the SNP among 584 normal healthy controls and 777 HBV-infected patients. The patient group was further categorized into inactive carriers (Group I), active carriers (Group II), cirrhosis (Group III) and cirrhosis-HCC (Group IV). Variation at this SNP was found to be significantly more frequent in control subjects than in patients (OR = 0.852; 95% C.I. = 0.730-0.994; p = 0.0415). Also, the SNP was found to have a highly significant association when the inactive carriers were compared to the rest of the patients (OR = 1.308; 95% C.I. = 1.058-1.617; p = 0.0130). The TT genotype was found to occur more frequently among active HBV carriers (groups II, III and IV) when compared to inactive HBV carriers, thus suggesting that the rs2596542-T may be recessively associated with an active HBV infection. However, no significant association was observed in the case of HBV-related cirrhosis or HCC. These findings indicate that the MICA rs2596542 has a significant role in HBV infection.
Assuntos
Carcinoma Hepatocelular/etiologia , Vírus da Hepatite B/genética , Hepatite B Crônica/genética , Antígenos de Histocompatibilidade Classe I/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/etiologia , Polimorfismo de Nucleotídeo Único/genética , Carcinoma Hepatocelular/patologia , Estudos de Casos e Controles , DNA Viral/genética , Hepatite B Crônica/complicações , Hepatite B Crônica/virologia , Humanos , Cirrose Hepática/complicações , Cirrose Hepática/virologia , Neoplasias Hepáticas/patologia , Reação em Cadeia da Polimerase , Prognóstico , Arábia SauditaRESUMO
BACKGROUND/AIM: This study aims to investigate whether the SNPs of CXCR1 gene, could predict the likelihood of viral persistence and/or disease progression. MATERIAL AND METHODS: We investigated the association of two different SNPs (rs2234671, and rs142978743) in 598 normal healthy controls and 662 HBV patients from a Saudi ethnic population. The HBV patients were categorized into inactive carriers (n = 428), active carriers (n = 162), cirrhosis (n = 54) and Cirrhosis-HCC (n = 18) sub-groups. Genetic variants in CXCR1 were determined by polymerase chain reaction (PCR)-based DNA direct sequencing. RESULTS: The frequency of the risk allele 'C' for the SNP, rs2234671 was found to be insignificant when the patient group was compared to the uninfected control group, however, a significant distribution of the allele 'C' of rs2234671 was observed among active HBV carriers + cirrhosis + cirrhosis - HCC vs. inactive HBV carriers with an OR = 1.631 (95% C.I. 1.016-2.616) and p = 0.032. However, no significant association was observed for rs142978743 when the distribution of risk allele was analyzed among the different patient groups (i.e. inactive carriers, active carriers, cirrhosis and HCC). Furthermore, the most common haplotype, Haplo-1 (AG), was found to have an insignificant frequency distribution between HBV cases and controls, while the same haplotype was found to be significantly distributed when active carriers + cirrhosis + cirrhosis - HCC patients were compared to inactive HBV carriers with a frequency of 0.938 and p = 0.0315. Haplo-2 (AC) was also found to be significantly associated with a frequency of 0.058 and p = 0.0163. CONCLUSION: The CXCR1 polymorphism, rs2234671 was found to be associated with chronic HBV infection and may play a role in disease activity.
Assuntos
Hepatite B/genética , Polimorfismo de Nucleotídeo Único , Receptores de Interleucina-8A/genética , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/imunologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Progressão da Doença , Frequência do Gene , Predisposição Genética para Doença , Haplótipos , Hepatite B/epidemiologia , Hepatite B/imunologia , Humanos , Cirrose Hepática/epidemiologia , Cirrose Hepática/genética , Cirrose Hepática/imunologia , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/imunologia , Razão de Chances , Fenótipo , Reação em Cadeia da Polimerase , Prognóstico , Fatores de Risco , Arábia Saudita/epidemiologia , Análise de Sequência de DNARESUMO
Hepatitis B virus (HBV) is the major causative agent of chronic liver complications including cirrhosis and hepatocellular carcinoma (HCC). Individuals infected with HBV show a wide spectrum of disease manifestations ranging from asymptomatic carriers to HCC. TLR3 is part of the innate immune system that recognizes double-stranded RNA (dsRNA) and provides early immune response to exogenous antigens. The genetic polymorphisms such as single nucleotide polymorphisms (SNPs) in the TLR3 could be considered as factors for the susceptibility to viral pathogens including HBV. Due to lack of knowledge on the role of TLR3 polymorphisms in HBV infection, this study investigated the distribution of nine SNPs in the TLR3 gene and its association with Saudi Arabian patients infected with HBV. A total of 707 patients and 600 uninfected controls were examined for different parameters including the nine SNPs (rs5743311, rs5743312, rs1879026, rs5743313, rs5743314, rs5743315, rs111611328, rs78726532 and a newly identified SNP located at position 184322913 of chr4). The association analysis confirmed that only one SNP, rs1879026 (G/T), showed a significant difference (P = 0.0480; OR = 0.809, 95% CI = 0.655-0.999) in the distribution between HBV carriers and uninfected controls. While, the rest of the SNPs showed no significant association with regards to HBV infection or in the progression to cirrhosis of the liver and HCC. Furthermore, haplotype analysis revealed that one haplotype GCGA (rs1879026, rs5743313, rs5743314, and rs5743315, respectively), was associated significantly with HBV infection in this population. These findings indicate that genetic variations in the TLR3 gene could affect the outcome of HBV infection among Saudis.
Assuntos
Vírus da Hepatite B , Hepatite B Crônica/genética , Polimorfismo de Nucleotídeo Único , Receptor 3 Toll-Like/genética , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Estudos de Associação Genética , Haplótipos , Hepatite B Crônica/sangue , Hepatite B Crônica/virologia , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Arábia Saudita , Análise de Sequência de DNA , Carga ViralRESUMO
BACKGROUND: Infection due to community-acquired strains of methicillin-resistant Staphylococcus aureus (CA-MRSA) has been reported with increasing frequency. Herein is described the nosocomial transmission of CA-MRSA involving 13 neonates and two mothers in a well-infant nursery in a teaching hospital in Saudi Arabia. METHODS: From October to November 2009, temporally related cases of CA-MRSA skin and soft-tissue infection occurred in newborns shortly after discharge from a well-infant nursery. An outbreak investigation including case identification, review of medical records, staff screening, environmental cultures, pulsed-field gel electrophoresis, and a case-control study were conducted. Controls were selected from among asymptomatic neonates admitted to the same nursery and matched for the day of admission. RESULTS: Fifteen subjects were found to be CA-MRSA positive: 13 neonates and two mothers. The crude attack rate among neonates was 5.5% during the outbreak period. All 13 neonates presented with skin and soft-tissue infection; one of the mothers had mastitis and a breast abscess. The source of the outbreak was not evident. Pulsed-field gel electrophoresis showed that all of the tested isolates from one strain except one, all contained the staphylococcal cassette chromosome mec (SCCmec) type IV. CONCLUSION: MRSA strains that initially emerged in the community are now causing disease in health-care settings. Adherence to standard infection control practices, including consistent hand hygiene, in newborn nurseries is important to prevent transmission in such settings.
Assuntos
Infecção Hospitalar/transmissão , Surtos de Doenças/estatística & dados numéricos , Hospitais de Ensino/estatística & dados numéricos , Resistência a Meticilina , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/transmissão , Estudos de Casos e Controles , Infecção Hospitalar/epidemiologia , Infecção Hospitalar/microbiologia , Feminino , Humanos , Incidência , Recém-Nascido , Masculino , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Infecções Estafilocócicas/epidemiologia , Infecções Estafilocócicas/microbiologiaRESUMO
The emergence of chloroquine resistance in Plasmodium falciparum is a significant public health problem where malaria is endemic. We aimed to evaluate the efficacy of pyrosequencing to assess chloroquine resistance among P. falciparum isolates from the southwestern region of Saudi Arabia by analyzing the K76T and N86Y mutations in the P. falciparum chloroquine resistance transporter (PfCRT) and P. falciparum multidrug resistance 1 (PfMDR1) genes, respectively. Blood samples (n = 121) from microscopically positive P. falciparum cases were collected. DNA was extracted, and fragments from each of the genes were amplified by PCR using new sets of primers. The amplicons were sequenced using a pyrosequencer. All of the 121 samples were amplified for assessment of the PfCRT K76T and PfMDR1 N86Y mutations. All of the samples amplified for the PfCRT 76T mutation harbored the ACA codon (121/121; 100%), indicating the presence of the 76T mutation. For the PfMDR1 N86Y mutation, 72/121 samples (59.5%) had the sequence AAT at that position, indicating the presence of the wild-type allele (86N). However, 49/121 samples (40.5%) had a TAT codon, indicating the mutant allele (Y) at position 86. This study shows that pyrosequencing could be useful as a high throughput, rapid, and sensitive assay for the detection of specific single nucleotide polymorphisms in drug-resistant P. falciparum strains. This will help health authorities in malaria-endemic regions to adopt new malaria control strategies that will be applicable for diagnostic and drug resistance assays for malaria and other life-threatening pathogens that are endemic in their respective countries.
Assuntos
Antimaláricos/farmacologia , Resistência a Medicamentos , Malária Falciparum/parasitologia , Proteínas de Membrana Transportadoras/genética , Proteínas Associadas à Resistência a Múltiplos Medicamentos/genética , Mutação de Sentido Incorreto , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Substituição de Aminoácidos/genética , Cloroquina/farmacologia , Primers do DNA/genética , DNA de Protozoário/química , DNA de Protozoário/genética , Humanos , Testes de Sensibilidade Parasitária/métodos , Parasitologia/métodos , Plasmodium falciparum/isolamento & purificação , Reação em Cadeia da Polimerase , Arábia Saudita , Análise de Sequência de DNA/métodosRESUMO
An innate immune response is essential to mobilize protective immunity upon the infection of respiratory epithelial cells with influenza A virus (IAV). The response is classified as early (nonspecific effectors), local systematic (effector cells recruitment) and late (antigen to lymphoid organ transport, naive B and T cells recognition, effector cells clonal expansion and differentiation). Virus particles are detected by the host cells as non-self by various sensors that are present on the cell surface, endosomes and cytosol. These sensors are collectively termed as pattern recognition receptors (PRRs). The PRRs distinguish unique molecular signatures known as pathogen-associated molecular pattern, which are present either on the cell surface or within intracellular compartments. PRRs have been classified into five major groups: C-Type Lectin Receptor (CLR), Toll-like receptor (TLR), Nod-like receptor (NLR), Retinoic acid-inducible gene-I-like receptor (RLR), which play a role in innate immunity to IAV infection, and the pyrin and hematopoietic interferon-inducible nuclear (PYHIN) domain protein. Here, we discuss the role of PRRs in cellular infectivity of IAV and highlight the recent progress.
Assuntos
Vírus da Influenza A/fisiologia , Vírus da Influenza A/patogenicidade , Influenza Humana/imunologia , Influenza Humana/virologia , Receptores de Reconhecimento de Padrão/fisiologia , Transdução de Sinais , Animais , Proteína DEAD-box 58/fisiologia , Interações entre Hospedeiro e Microrganismos , Humanos , Imunidade Inata , Lectinas Tipo C/fisiologia , Proteína Adaptadora de Sinalização NOD1/fisiologia , Proteínas Nucleares/fisiologia , Receptores Imunológicos/fisiologia , Receptores Virais/fisiologia , Receptores Toll-Like/fisiologiaRESUMO
BACKGROUND: Data on human papillomavirus (HPV) prevalence and survival rates among HPV-infected women are scarce in Saudi Arabia. OBJECTIVE: Assess the prevalence of HPV genotypes in cervical biopsy specimens and its effect on survival over a 10-year timeframe. DESIGN: Retrospective, cross-sectional. SETTINGS: Saudi referral hospital. PATIENTS AND METHODS: Cervical biopsy specimens were collected from women aged 23-95 years old who underwent HPV detection, HPV genotyping, p16INK4a expression measurement using immunohistochemistry. Kaplan-Meier plots were constructed to analyze overall survival rates. MAIN OUTCOME MEASURES: Survival rate of HPV-positive cervical cancer patients. SAMPLE SIZE: 315 cervical biopsy specimens. RESULTS: HPV was detected in 96 patients (30.4%): 37.3% had cervical cancer; 14.2% cervical intraepithelial neoplasia (CIN) III, 4.1% CIN II, and 17.0% CIN I. A significant association was found between HPV presence and cervical cancer (χ2=56.78; P<.001). The expression of p16INK4a was a significant predictor of survival: women who had p16INK4a overexpression had poorer survival rates (multivariate Cox regression, hazard ratio, 3.2; 95% CI, 1.1-8.8). In addition, multivariate models with HPV status and cervical cancer diagnosis showed that HPV status was a significant predictor of survival: HPV-positive women had better survival rates than HPV-negative women. CONCLUSION: These findings suggest that implementing cervical and HPV screening programs may decrease cervical cancer rates and improve survival rates of women in Saudi Arabia. LIMITATION: Single center and small sample size. CONFLICT OF INTEREST: None.
Assuntos
Infecções por Papillomavirus , Displasia do Colo do Útero , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/epidemiologia , Prognóstico , Estudos Retrospectivos , Arábia Saudita/epidemiologia , Adulto JovemRESUMO
Cadmium telluride quantum dots (CdTe-QDs) are acquiring great interest in terms of their applications in biomedical sciences. Despite earlier sporadic studies on possible oncogenic roles and anticancer properties of CdTe-QDs, there is limited information regarding the oncogenic potential of CdTe-QDs in cancer progression. Here, we investigated the oncogenic effects of CdTe-QDs on the gene expression profiles of Chang cancer cells. Chang cancer cells were treated with 2 different doses of CdTe-QDs (10 and 25 µg/ml) at different time intervals (6, 12, and 24 h). Functional annotations helped identify the gene expression profile in terms of its biological process, canonical pathways, and gene interaction networks activated. It was found that the gene expression profiles varied in a time and dose-dependent manner. Validation of transcriptional changes of several genes through quantitative PCR showed that several genes upregulated by CdTe-QD exposure were somewhat linked with oncogenesis. CdTe-QD-triggered functional pathways that appear to associate with gene expression, cell proliferation, migration, adhesion, cell-cycle progression, signal transduction, and metabolism. Overall, CdTe-QD exposure led to changes in the gene expression profiles of the Chang cancer cells, highlighting that this nanoparticle can further drive oncogenesis and cancer progression, a finding that indicates the merit of immediate in vivo investigation.