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1.
Nature ; 586(7831): 741-748, 2020 10.
Artículo en Inglés | MEDLINE | ID: mdl-33116287

RESUMEN

The African continent is regarded as the cradle of modern humans and African genomes contain more genetic variation than those from any other continent, yet only a fraction of the genetic diversity among African individuals has been surveyed1. Here we performed whole-genome sequencing analyses of 426 individuals-comprising 50 ethnolinguistic groups, including previously unsampled populations-to explore the breadth of genomic diversity across Africa. We uncovered more than 3 million previously undescribed variants, most of which were found among individuals from newly sampled ethnolinguistic groups, as well as 62 previously unreported loci that are under strong selection, which were predominantly found in genes that are involved in viral immunity, DNA repair and metabolism. We observed complex patterns of ancestral admixture and putative-damaging and novel variation, both within and between populations, alongside evidence that Zambia was a likely intermediate site along the routes of expansion of Bantu-speaking populations. Pathogenic variants in genes that are currently characterized as medically relevant were uncommon-but in other genes, variants denoted as 'likely pathogenic' in the ClinVar database were commonly observed. Collectively, these findings refine our current understanding of continental migration, identify gene flow and the response to human disease as strong drivers of genome-level population variation, and underscore the scientific imperative for a broader characterization of the genomic diversity of African individuals to understand human ancestry and improve health.


Asunto(s)
Variación Genética , Genoma Humano/genética , Genómica , Salud , Migración Humana , África/etnología , Reparación del ADN/genética , Conjuntos de Datos como Asunto , Femenino , Flujo Génico , Genética Médica , Genética de Población , Salud/historia , Historia Antigua , Migración Humana/historia , Humanos , Inmunidad/genética , Lenguaje , Masculino , Metabolismo/genética , Selección Genética , Secuenciación Completa del Genoma
3.
Genome Res ; 26(2): 271-7, 2016 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-26627985

RESUMEN

The application of genomics technologies to medicine and biomedical research is increasing in popularity, made possible by new high-throughput genotyping and sequencing technologies and improved data analysis capabilities. Some of the greatest genetic diversity among humans, animals, plants, and microbiota occurs in Africa, yet genomic research outputs from the continent are limited. The Human Heredity and Health in Africa (H3Africa) initiative was established to drive the development of genomic research for human health in Africa, and through recognition of the critical role of bioinformatics in this process, spurred the establishment of H3ABioNet, a pan-African bioinformatics network for H3Africa. The limitations in bioinformatics capacity on the continent have been a major contributory factor to the lack of notable outputs in high-throughput biology research. Although pockets of high-quality bioinformatics teams have existed previously, the majority of research institutions lack experienced faculty who can train and supervise bioinformatics students. H3ABioNet aims to address this dire need, specifically in the area of human genetics and genomics, but knock-on effects are ensuring this extends to other areas of bioinformatics. Here, we describe the emergence of genomics research and the development of bioinformatics in Africa through H3ABioNet.


Asunto(s)
Población Negra/genética , Promoción de la Salud , África , Biología Computacional , Sistemas de Computación , Variación Genética , Genética Médica , Genómica , Humanos
4.
Behav Pharmacol ; 29(5): 413-425, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29561292

RESUMEN

Depression is the disease of the modern era. The lack of response to the available antidepressants, which were developed on the basis of the monoaminergic deficit hypothesis of depression, has encouraged scientists to think about new mechanisms explaining the pathogenesis of depression. In this context, the inflammatory theory has emerged to clarify many aspects of depression that the previous theories have failed to explain. Toll-like receptor-4 (TLR-4) has a regulatory role in the brain's immune response to stress, and its activation is suggested to play a pivotal role in the pathophysiology of depression. In this study, we tested eritoran (ERI), a TLR-4 receptor-4 antagonist, as a potential antidepressant. We investigated the effect of long-term administration of ERI in three different doses on behavioral changes, hippocampal and prefrontal cortex (PFC) neurogenesis, and γ-aminobutyric acid (GABA)/glutamate balance in male Wistar rats exposed to chronic restraint stress (CRS). Long-term administration of ERI ameliorated CRS-induced depressive-like symptoms and hypothalamic-pituitary-adrenal axis hyperactivity alongside reducing levels of hippocampal and PFC inflammatory cytokines, restoring GABA and glutamate balance, and enhancing PFC and hippocampal neurogenesis, by increasing BDNF gene and protein expression in a dose-dependent manner. The results demonstrate an antidepressant-like activity of ERI in Wistar rats exposed to CRS, which may be largely mediated by its ability to reduce neuroinflammation, increase BDNF, and restore GABA/glutamate balance in prefrontal cortex and hippocampus. Nonetheless, further studies are needed to characterize the mechanism of the antidepressant effect of ERI.


Asunto(s)
Depresión/tratamiento farmacológico , Disacáridos/farmacología , Fosfatos de Azúcar/farmacología , Animales , Antidepresivos/farmacología , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Depresión/etiología , Trastorno Depresivo/fisiopatología , Disacáridos/metabolismo , Modelos Animales de Enfermedad , Ácido Glutámico/efectos de los fármacos , Hipocampo/efectos de los fármacos , Sistema Hipotálamo-Hipofisario/efectos de los fármacos , Masculino , Neurogénesis/efectos de los fármacos , Sistema Hipófiso-Suprarrenal/efectos de los fármacos , Corteza Prefrontal/efectos de los fármacos , Ratas , Ratas Wistar , Estrés Psicológico/fisiopatología , Fosfatos de Azúcar/metabolismo , Receptor Toll-Like 4/antagonistas & inhibidores , Receptor Toll-Like 4/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Ácido gamma-Aminobutírico/efectos de los fármacos
5.
Tumour Biol ; 39(6): 1010428317698390, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28618938

RESUMEN

Breast cancer is the leading cause of cancer-related mortality. DNA methylations play important roles in cancer development and progression. Formal concept analysis was previously utilized for data mining hypermethylated and hypomethylated genes in breast cancer molecular subtypes in illumina methylation-based microarray database, to laboratory validate their outputs; HS3ST2 (heparan sulfate d-glucosaminyl 3-O-sulfonyl transferase-2) and MUC1 (mucin-1) were retrieved. Both play important roles in progression and invasion of breast cancer. The methylation status of both genes was laboratory validated using methylation-based polymerase chain reaction in breast cancer subtypes luminal A (early stages) and luminal B (late stages) in comparison with benign conditions and normal breast to conclude their roles in tumor invasion and to validate the newly developed algorithm (formal concept analysis). Significant cancer-specific hypermethylation of HS3ST2 was detected in luminal B (chi square = 30.6, p = 0.000), while significant cancer-specific hypomethylation of MUC1 was detected in luminal B (chi square = 30.5, p = 0.001) breast cancer. The median levels of the percentage of methylated allele of both genes were significantly discriminative between luminal A and luminal B subtypes and benign and healthy control groups. Detection of MUC1 and HS3ST2 promoter methylation status appears to be useful molecular markers for assessing the progressive state of the disease and could be helpful in discriminating breast cancer molecular subtypes. These results validate the methylation-based microarray analysis, thus trust their output in the future.


Asunto(s)
Neoplasias de la Mama/genética , Metilación de ADN/genética , Mucina-1/genética , Sulfotransferasas/genética , Neoplasias de la Mama/patología , Islas de CpG , Femenino , Humanos , Estadificación de Neoplasias , Regiones Promotoras Genéticas
7.
Am J Gastroenterol ; 109(2): 199-211, 2014 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-24445571

RESUMEN

OBJECTIVES: The objective of this study was to characterize the factors that influence the outcome of exposure to hepatitis C virus (HCV) genotype 4 (HCV-G4) and the course of recent infection. METHODS: In this longitudinal study, we prospectively assessed the clinical, genetic, virological, and immunological parameters and retrospectively determined single-nucleotide polymorphisms at interleukin-28B (IL-28B) rs12979860 in a well-characterized large cohort recently exposed to HCV-G4. RESULTS: A total of 136 subjects with acute HCV (new viremia, seroconversion, and HCV-specific T-cell responses) were identified. Forty-eight subjects (35%) had spontaneous viral clearance and 88 subjects developed chronic HCV of which 42 subjects were treated with pegylated interferon monotherapy, with a sustained virologic response (SVR) rate of 88%. Twenty-six subjects developed HCV-specific T-cell immune responses without detectable viremia or seroconversion. IL-28B-CC (odds ratio (OR) 14.22; P<0.0001), multispecific T-cell responses (OR=11.66; P<0.0001), >300 IU/l alanine aminotransferase (ALT) decline within 4 weeks (OR=6.83; P<0.0001), jaundice (OR=3.54; P=0.001), female gender (OR=2.39; P=0.007), and >2.5 log10 HCV-RNA drop within 8 weeks (OR=2.48; P=0.016) were independently associated with spontaneous clearance. ALT normalization and undetectable HCV-RNA predicted SVR. Exposed apparently uninfected participants had a higher frequency of IL-28B-CC than patients with unresolved acute HCV (P<0.001). IL-28B-CC was associated with multispecific T-cell response (r(2)=0.0.835; P<0.001). CONCLUSIONS: IL-28B-CC genotype, multispecific HCV T-cell responses, rapid decline in ALT, and viral load predict spontaneous clearance and response to acute HCV-G 4 therapy. IL-28B-CC genotype correlates with developing early multispecific T-cell responses. These findings have important implications for predicting the outcome of HCV exposure and acute infection and identifying patients likely to benefit from therapy.


Asunto(s)
Antivirales/uso terapéutico , Hepacivirus/genética , Hepatitis C/epidemiología , Hepatitis C/genética , Interleucinas/genética , Viremia/epidemiología , Enfermedad Aguda , Adulto , Distribución por Edad , Estudios de Casos y Controles , Intervalos de Confianza , Progresión de la Enfermedad , Egipto/epidemiología , Femenino , Virus GB-C/genética , Virus GB-C/aislamiento & purificación , Genotipo , Hepacivirus/efectos de los fármacos , Hepatitis C/tratamiento farmacológico , Humanos , Incidencia , Interferones , Estimación de Kaplan-Meier , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Pronóstico , Estudios Prospectivos , ARN Viral/análisis , ARN Viral/genética , Ribavirina/uso terapéutico , Distribución por Sexo , Estadísticas no Paramétricas , Resultado del Tratamiento , Carga Viral/genética , Viremia/genética
8.
Gene ; 813: 146124, 2022 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-34921950

RESUMEN

The knowledge of RNA editing modifications and its subsequent proteomic diversity in is still limited and represents only the tip of the iceberg. Adenosine to inosine (A-to-I) RNA editing is the most prevalent in RNA editome with a rising role for ADARgene family as a major regulator of the dynamic landscape of RNA editing. This study aimed at evaluating the potential chemopreventive effects of the epigenetic regulator "pterostilbene" in diethylnitrosamine (DEN)-exposedrat model. Consequently, the hepatic Adars expression was investigated as a possible mechanism for mediation of the putative pterostilbene-induced chemopreventive effect. The effects of administration of pterostilbene were investigated on the structural changes, immunohistochemical staining, liver function test, serum alpha feto-protein (AFP), IL-6, and hepatic Adar1 and Adar2 relative gene expression at the beginning and at the 6th week of the study. Pterostilbene attenuated DEN-induced liver injury, improves hepatocyte parrafin-1 (Hep Par-1), decreases heat shock protein 70 (HSP70), improved AFP, serum albumin, transaminases, IL-6 with alleviation of disturbed hepatic Adar1 and Adar2 expression. This study spotlights the role of pterostilbene in attenuation of DEN-induced liver injury which could be mediated, at least partially, through the alleviation of the aberrant expression of Adar enzymes. Yet, more in-depth studies are needed to further elucidate the molecular mechanisms underlying the effects of pterostilbene on RNA editing enzymes.


Asunto(s)
Adenosina Desaminasa/biosíntesis , Cirrosis Hepática/tratamiento farmacológico , Estilbenos/farmacología , Adenosina Desaminasa/genética , Inhibidores de la Adenosina Desaminasa/farmacología , Animales , Dietilnitrosamina/administración & dosificación , Expresión Génica , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática/enzimología , Cirrosis Hepática/genética , Cirrosis Hepática/patología , Masculino , Proteómica , Edición de ARN , Proteínas de Unión al ARN/genética , Ratas , Ratas Wistar , Transcriptoma
9.
Front Genet ; 13: 769919, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35571023

RESUMEN

Genomics policy development involves assessing a wide range of issues extending from specimen collection and data sharing to whether and how to utilize advanced technologies in clinical practice and public health initiatives. A survey was conducted among African scientists and stakeholders with an interest in genomic medicine, seeking to evaluate: 1) Their knowledge and understanding of the field. 2) The institutional environment and infrastructure available to them. 3) The state and awareness of the field in their country. 4) Their perception of potential barriers to implementation of precision medicine. We discuss how the information gathered in the survey could instruct the policies of African institutions seeking to implement precision, and more specifically, genomic medicine approaches in their health care systems in the following areas: 1) Prioritization of infrastructures. 2) Need for translational research. 3) Information dissemination to potential users. 4) Training programs for specialized personnel. 5) Engaging political stakeholders and the public. A checklist with key requirements to assess readiness for implementation of genomic medicine programs is provided to guide the process from scientific discovery to clinical application.

10.
J Pers Med ; 12(2)2022 Feb 11.
Artículo en Inglés | MEDLINE | ID: mdl-35207753

RESUMEN

Genomics data are currently being produced at unprecedented rates, resulting in increased knowledge discovery and submission to public data repositories. Despite these advances, genomic information on African-ancestry populations remains significantly low compared with European- and Asian-ancestry populations. This information is typically segmented across several different biomedical data repositories, which often lack sufficient fine-grained structure and annotation to account for the diversity of African populations, leading to many challenges related to the retrieval, representation and findability of such information. To overcome these challenges, we developed the African Genomic Medicine Portal (AGMP), a database that contains metadata on genomic medicine studies conducted on African-ancestry populations. The metadata is curated from two public databases related to genomic medicine, PharmGKB and DisGeNET. The metadata retrieved from these source databases were limited to genomic variants that were associated with disease aetiology or treatment in the context of African-ancestry populations. Over 2000 variants relevant to populations of African ancestry were retrieved. Subsequently, domain experts curated and annotated additional information associated with the studies that reported the variants, including geographical origin, ethnolinguistic group, level of association significance and other relevant study information, such as study design and sample size, where available. The AGMP functions as a dedicated resource through which to access African-specific information on genomics as applied to health research, through querying variants, genes, diseases and drugs. The portal and its corresponding technical documentation, implementation code and content are publicly available.

11.
Database (Oxford) ; 20212021 04 17.
Artículo en Inglés | MEDLINE | ID: mdl-33864455

RESUMEN

African genomic medicine and microbiome datasets are usually not well characterized in terms of their origin, making it difficult to find and extract data for specific African ethnic groups or even countries. The Pan-African H3Africa Bioinformatics Network (H3ABioNet) recognized the need for developing data portals for African genomic medicine and African microbiomes to address this and ran a hackathon to initiate their development. The two portals were designed and significant progress was made in their development during the hackathon. All the participants worked in a very synergistic and collaborative atmosphere in order to achieve the hackathon's goals. The participants were divided into content and technical teams and worked over a period of 6 days. In response to one of the survey questions of what the participants liked the most during the hackathon, 55% of the hackathon participants highlighted the familial and friendly atmosphere, the team work and the diversity of team members and their expertise. This paper describes the preparations for the portals hackathon and the interaction between the participants and reflects upon the lessons learned about its impact on successfully developing the two data portals as well as building scientific expertise of younger African researchers. Database URL: The code for developing the two portals was made publicly available in GitHub repositories: [https://github.com/codemeleon/Database; https://github.com/codemeleon/AfricanMicrobiomePortal].


Asunto(s)
Biología Computacional , Microbiota , Bases de Datos Factuales , Genoma , Genómica , Humanos , Microbiota/genética
12.
OMICS ; 25(4): 213-233, 2021 04.
Artículo en Inglés | MEDLINE | ID: mdl-33794662

RESUMEN

Following the publication of the first human genome, OMICs research, including genomics, transcriptomics, proteomics, and metagenomics, has been on the rise. OMICs studies revealed the complex genetic diversity among human populations and challenged our understandings of genotype-phenotype correlations. Africa, being the cradle of the first modern humans, is distinguished by a large genetic diversity within its populations and rich ethnolinguistic history. However, the available human OMICs tools and databases are not representative of this diversity, therefore creating significant gaps in biomedical research. African scientists, students, and publics are among the key contributors to OMICs systems science. This expert review examines the pressing issues in human OMICs research, education, and development in Africa, as seen through a lens of computational biology, public health relevant technology innovation, critically-informed science governance, and how best to harness OMICs data to benefit health and societies in Africa and beyond. We underscore the disparities between North and Sub-Saharan Africa at different levels. A harmonized African ethnolinguistic classification would help address annotation challenges associated with population diversity. Finally, building on the existing strategic research initiatives, such as the H3Africa and H3ABioNet Consortia, we highly recommend addressing large-scale multidisciplinary research challenges, strengthening research collaborations and knowledge transfer, and enhancing the ability of African researchers to influence and shape national and international research, policy, and funding agendas. This article and analysis contribute to a deeper understanding of past and current challenges in the African OMICs innovation ecosystem, while also offering foresight on future innovation trajectories.


Asunto(s)
Investigación Biomédica , Biología Computacional , África , Ecosistema , Genómica , Humanos
13.
Per Med ; 17(2): 155-170, 2020 03.
Artículo en Inglés | MEDLINE | ID: mdl-32125935

RESUMEN

Effective interventions and treatments for complex diseases have been implemented globally, however, coverage in Africa has been comparatively lower due to lack of capacity, clinical applicability and knowledge on the genetic contribution to disease and treatment. Currently, there is a scarcity of genetic data on African populations, which have enormous genetic diversity. Pharmacogenomics studies have the potential to revolutionise treatment of diseases, therefore, African populations are likely to benefit from these approaches to identify likely responders, reduce adverse side effects and optimise drug dosing. This review discusses clinical pharmacogenetics studies conducted in African populations, focusing on studies that examined drug response in complex diseases relevant to healthcare. Several pharmacogenetics associations have emerged from African studies, as have gaps in knowledge.


Asunto(s)
Población Negra/genética , Variantes Farmacogenómicas , Ensayos Clínicos como Asunto , Estudios de Asociación Genética , Humanos
14.
Gene ; 706: 97-105, 2019 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-31034943

RESUMEN

Micro RNA-34a-5p (miR-34a-5p) is an important molecule that can act as a modulator of tumor growth. It controls expression of a plenty of proteins controlling cell cycle, differentiation and apoptosis and opposing processes that favor viability of cancer cells, their metastasis and resistance to chemotherapy. Bioinformatics analysis indicated that minichromosome maintenance protein 2 (MCM2) is a target gene of miR-34a-p. In this study, RT-qPCR was employed to detect the expression of miR-34a-5p and MCM2 in 10 hepatocellular carcinoma (HCC) tissues. The functional role of miR-34a-5p in HCC was investigated and the interaction between miR-34a-5p and MCM2 was explored. Results showed miR-34a-5p expression in HCC tissues was significantly lower than in non HCC liver tissues (P < 0.05), but MCM2 expression in HCC tissues was markedly higher than in non HCC liver tissues (P < 0.05). In addition, miR-34a-5p expression was negatively related to MCM2 expression. To confirm effect of miR-34a-5p on tumor growth and its possible effect on MCM2, miR-34a-5p mimic and inhibitor was transfected into HCC cell lines (HepG2). MTS assay, showed miR-34a-5p over-expression could inhibit the proliferation of HCC cells. RT-qPCR was done to detect the expression of miR-34a-5p and MCM2 in HepG2 cells before and after transfection. Results showed that MCM2 expression in HCC tissues was markedly lower in mimic transfected group than in inhibitor transfected group and control group (P < 0.05) while miR-34a-5p expression in HepG2 cells was significantly higher in mimic transfected group than in inhibitor transfected group and control group (P < 0.05). Thus, miR-34a-5p may inhibit the proliferation of HCC cells via regulating MCM2 expression. These findings provide an evidence for the emerging role of microRNAs as diagnostic markers and therapeutic targets in HCC.


Asunto(s)
Carcinoma Hepatocelular/genética , MicroARNs/genética , ARN Largo no Codificante/genética , Apoptosis/genética , Carcinoma Hepatocelular/fisiopatología , Ciclo Celular/genética , Línea Celular Tumoral , Proliferación Celular/genética , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/fisiopatología , Masculino , MicroARNs/fisiología , Persona de Mediana Edad , Componente 2 del Complejo de Mantenimiento de Minicromosoma/genética , Componente 2 del Complejo de Mantenimiento de Minicromosoma/fisiología , ARN Largo no Codificante/metabolismo , Transducción de Señal
15.
Gene ; 649: 74-79, 2018 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-29374597

RESUMEN

Ghrelin (GHRL) has important implications for liver disease. It has anti-inflammatory effects, regulates cell proliferation, modulates the fibrogenic response and protects liver tissue. Genetic variations in the GHRL gene may play a crucial role in the development of chronic hepatitis (CH), liver cirrhosis (LC) and hepatocellular carcinoma (HCC). Therefore, we examined the association of GHRL gene polymorphisms (rs26312 and rs27647), and its serum level to virologic responses to combined sofosbuvir and Simeprevir therapy for a course of 12 successive weeks in Egyptian chronic hepatitis C (CHC) patients. METHODS: Human genomic and clinical data were collected from 100 Egyptian participants in this study, 90 HCV patients who received sofosbuvir and Simeprevir and 10 non-HCV healthy subjects. Genotyping of GHRL rs26312 and rs27647, were determined with the TaqMan qRT-PCR allele detection assay. The serum GHRL concentrations were determined using enzyme-linked immunosorbent assay (ELISA). RESULTS: GHRL polymorphisms (rs26312 and rs27647) genotype distributions and allele frequencies did not differ between HCV patients and normal healthy subjects or between patient groups when compared according to the therapeutic response. In addition, we found significant lower serum GHRL levels in CHC patients compared with the healthy controls. However, there was no significant association of the GHRL rs26312 and rs27647 polymorphisms with GHRL levels in CHC patients. We conclude that GHRL SNPs (rs26312 and rs27647) do not affect response to combined sofosbuvir and Simeprevir treatment in chronic Egyptian HCV patients.


Asunto(s)
Ghrelina/genética , Hepatitis C Crónica/genética , Adulto , Alelos , Antivirales/uso terapéutico , Biomarcadores/sangre , Carcinoma Hepatocelular/genética , Egipto , Femenino , Frecuencia de los Genes , Marcadores Genéticos , Pruebas Genéticas/métodos , Genotipo , Ghrelina/sangre , Ghrelina/metabolismo , Hepacivirus/genética , Hepacivirus/patogenicidad , Hepatitis C Crónica/terapia , Humanos , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple/genética , Simeprevir , Resultado del Tratamiento
16.
Clin Biochem ; 40(16-17): 1173-9, 2007 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-17888896

RESUMEN

OBJECTIVES: We aimed to study the effect of hepatitis C virus (HCV) and sera of chronic HCV patients on phytohemagglutinin (PHA)-stimulated normal donor PBMCs and to study the effect of chronic HCV infection on some cytokine profile. SUBJECTS AND METHODS: (3)H-Thymidine uptake was utilized to study effect of pelleted virus and patients sera on PBMCs proliferation in vitro. The study included 337 Egyptian chronic liver patients from Ain Shams University Hospitals and 90 healthy control subjects. The patients' group included chronic hepatitis C (250 subjects), and other chronic liver diseases (87 subjects). All subjects' sera were subjected to RT-PCR for HCV RNA detection, IL-4, IL-1beta, and TNF-alpha measurement by EIA, and biochemical measurement of ALT and albumin. RESULTS: Treatment of PHA-stimulated normal donor PBMCs with pelleted virus led to decrease (dose response) in their rate of proliferation. This was partially reversed after addition of HCV RNA positive patients' sera. HCV RNA positive patients were significantly higher in IL-4 and ALT, and lower in IL-1beta and albumin than HCV RNA negative patients. CONCLUSION: HCV infection suppresses early immune response. This leads to increased IL-4 Th2 cytokine.


Asunto(s)
Proliferación Celular/efectos de los fármacos , Hepacivirus/efectos de los fármacos , Leucocitos Mononucleares/efectos de los fármacos , Mitógenos/farmacología , Animales , Egipto , Hepacivirus/genética , Hepacivirus/crecimiento & desarrollo , Hepatitis C Crónica/sangre , Interleucina-1beta/sangre , Interleucina-1beta/metabolismo , Interleucina-4/sangre , Interleucina-4/metabolismo , Leucocitos Mononucleares/citología , Leucocitos Mononucleares/virología , Pruebas de Función Hepática , ARN Viral/genética , ARN Viral/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/metabolismo
18.
Glob Heart ; 12(2): 91-98, 2017 06.
Artículo en Inglés | MEDLINE | ID: mdl-28302555

RESUMEN

BACKGROUND: Although pockets of bioinformatics excellence have developed in Africa, generally, large-scale genomic data analysis has been limited by the availability of expertise and infrastructure. H3ABioNet, a pan-African bioinformatics network, was established to build capacity specifically to enable H3Africa (Human Heredity and Health in Africa) researchers to analyze their data in Africa. Since the inception of the H3Africa initiative, H3ABioNet's role has evolved in response to changing needs from the consortium and the African bioinformatics community. OBJECTIVES: H3ABioNet set out to develop core bioinformatics infrastructure and capacity for genomics research in various aspects of data collection, transfer, storage, and analysis. METHODS AND RESULTS: Various resources have been developed to address genomic data management and analysis needs of H3Africa researchers and other scientific communities on the continent. NetMap was developed and used to build an accurate picture of network performance within Africa and between Africa and the rest of the world, and Globus Online has been rolled out to facilitate data transfer. A participant recruitment database was developed to monitor participant enrollment, and data is being harmonized through the use of ontologies and controlled vocabularies. The standardized metadata will be integrated to provide a search facility for H3Africa data and biospecimens. Because H3Africa projects are generating large-scale genomic data, facilities for analysis and interpretation are critical. H3ABioNet is implementing several data analysis platforms that provide a large range of bioinformatics tools or workflows, such as Galaxy, the Job Management System, and eBiokits. A set of reproducible, portable, and cloud-scalable pipelines to support the multiple H3Africa data types are also being developed and dockerized to enable execution on multiple computing infrastructures. In addition, new tools have been developed for analysis of the uniquely divergent African data and for downstream interpretation of prioritized variants. To provide support for these and other bioinformatics queries, an online bioinformatics helpdesk backed by broad consortium expertise has been established. Further support is provided by means of various modes of bioinformatics training. CONCLUSIONS: For the past 4 years, the development of infrastructure support and human capacity through H3ABioNet, have significantly contributed to the establishment of African scientific networks, data analysis facilities, and training programs. Here, we describe the infrastructure and how it has affected genomics and bioinformatics research in Africa.


Asunto(s)
Investigación Biomédica/métodos , Biología Computacional/tendencias , Genómica/métodos , África , Humanos
19.
Dis Markers ; 18(3): 137-42, 2002.
Artículo en Inglés | MEDLINE | ID: mdl-12515909

RESUMEN

Nitric oxide (NO), a recently discovered free radical, is overproduced in liver cirrhosis. Hepatitis C virus (HCV) might increase NO levels via increased inducible NO synthase (iNOS). This work was carried out to study the effect of HCV-induced liver cirrhosis on NO levels among Egyptian patients. The study included 46 patients with liver cirrhosis, and 30 healthy individuals of matched age and sex. NO levels determined as the stable endproduct nitrate, showed a statistically significant increase among patients compared to the control group (P < 0.001). Furthermore, NO levels increased proportionally with the severity of liver cirrhosis as assessed by Child's classification (P < 0.05). Moreover, schistosomial infection enhanced NO levels in cirrhotic patients with HCV infection compared to non-bilharzial patients (P < 0.001). Polymerase chain reaction (PCR) and branched DNA assays were used for detection of HCV RNA positivity, and measurement of the virus load, respectively. Both showed a positive correlation with the NO levels (P < 0.001). At a nitrate cutoff value of 70 micromol/L, the sensitivity and specificity were 83.0% and 73.0%, respectively. Chi square analysis showed a significant correlation between ALT levels and both HCV RNA positivity by polymerase chain reaction (PCR) (P < 0.02), and virus load (P<0.05). Interestingly enough, there was a significant positive correlation between HCV RNA and schistosomal antibody titer as measured by hemaglutination inhibition assay (HAI) (P < 0.05). The data presented in this report indicated an association between NO levels and the development and progression of liver cirrhosis. Furthermore, the findings obtained from this study demonstrated that schistomiasis is an important risk factor involved in enhancement of NO levels and virus replication. The latter may aggravate liver cell injury and hence the development of cirrhosis.


Asunto(s)
Hepatitis C/sangre , Cirrosis Hepática/complicaciones , Óxido Nítrico/sangre , Esquistosomiasis/complicaciones , Egipto , Hepacivirus/genética , Hepatitis C/complicaciones , Hepatitis C/enzimología , Humanos , Cirrosis Hepática/enzimología , Óxido Nítrico Sintasa/metabolismo , Óxido Nítrico Sintasa de Tipo II , Reacción en Cadena de la Polimerasa , ARN Viral/sangre , Esquistosomiasis/enzimología
20.
Clin Biochem ; 35(5): 369-75, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12270766

RESUMEN

BACKGROUND: The role of cytokines and reactive oxygen species formation in the pathogenesis of chronic sinusitis is still not fully understood. This work was designed to determine if patients with chronic sinusitis demonstrate altered levels of serum IL-12 and/or tissue antioxidants. SUBJECTS AND METHODS: Mucosal biopsy specimens from the uncinate process of patients with chronic sinusitis were obtained from 52 patients using functional endoscopic sinus surgery. Normal mucosa samples were collected from 20 healthy controls. Patients' group was further classified according to computerized tomography findings into mild and severe subgroups. Serum IL-12 was estimated using enzyme immunoassay (EIA). The levels of tissue uric acid, and reduced glutathione were determined biochemically, alpha-tocopherol was measured by HPLC. Superoxide dismutase (SOD) activity was determined by spectrophotometry. RESULTS: A significant decrease in serum IL-12, tissue alpha-tocopherol and SOD in patient group was demonstrated (p < 0.05). Tissue uric acid and reduced glutathione showed primary increase in mild subgroup followed by significant drop in severe subgroup (p < 0.05). Negative significant correlation was observed between glutathione, uric acid, and SOD, and the severity of the disease (p < 0.05) independent of the cellularity of the biopsy. CONCLUSION: The presented data suggests a possible role of IL-12, and tissue antioxidants in development and progression of chronic sinusitis. Adjuvant antioxidant treatment may have role in achieving better prognosis of the disease.


Asunto(s)
Antioxidantes/análisis , Interleucina-12/sangre , Sinusitis/sangre , Sinusitis/metabolismo , Cromatografía Líquida de Alta Presión , Enfermedad Crónica , Femenino , Glutatión/análisis , Humanos , Masculino , Senos Paranasales/química , Senos Paranasales/enzimología , Senos Paranasales/metabolismo , Especies Reactivas de Oxígeno/análisis , Superóxido Dismutasa/metabolismo , Ácido Úrico/análisis , alfa-Tocoferol/análisis
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