Background: Tuberculosis (TB) is a bacterial disease considered as a global public health emergency by the World Health Organization (WHO) since 1993. In Sudan, MDR-TB represents a growing threat and one of the most important challenges that faced national tuberculosis program to establish a comprehensive multidrug-resistant tuberculosis management system.Objective: To characterize the diversity and frequency of mutations in Sudanese MDR-TB strains isolated from Wad Madani, Al-Gadarif and Khartoum using 16S rRNA and phylogeny approach.Material and Methods: A total of 60 MDR-TB isolates from Wad-Madani, Al-Gadarif and Khartoum were tested with molecular LPA (Genotype MTBDR plus) and GeneXpert MTB/RIF assay and Spoligotyping to confirm their resistance to RIF and INH. Sequencing and phylogenetic analysis was carried out using in silico tools.Result: This study revealed the circulation of different Sudanese MDR-TB strains isolated from Wad Madani and Al-Gadarif belonging to two distinct common ancestors. Two isolates from Wad Madani (isolate3 and isolate11) found in one main group which characterized by a novel mutation G511T in the 530 loop.Conclusion: The recurrence of C217A mutation in Wad Madani (isolate11) indicates the spread of this mutation in Sudanese MDR-TB strains and the diversity of this inheritance leading to generate new G511T novel mutation. So, understanding the molecular characterization of resistance mechanisms in MD-TB can facilitate the early detection of resistance, the choice of appropriate treatment and ultimately the management of MD-TB transmission. Bioinformatics approaches provide helpful tools for analyzing molecular mechanisms of resistance in pathogens.
Background: Esophageal carcinoma (EC) represents the 1 st rank among all gastrointestinal cancers in Sudan. Despite little publications, there is a deep absence of literature about the molecular pathogenesis of EC considering TP53 gene from Sudanese population. Aims:In this study, we performed the expression analysis on p53 protein level by immunohistochemical staining and examined its overexpression with p53 mutations in exons 4 and 8 among esophageal cancer patients in Sudan. Material and Methods:Fixed tissue with 10% buffered formalin was stained by Hematoxlin and Eosin (H&E), Alcian blue-Periodic Acid Schiff (PAS) and Immunohistochemistry stain. PCR-RFLP was used to study the frequencies of p53 codon 72 R/P polymorphism. Conventional PCR and sanger sequencing were applied for exon 4 and exon 8. Then detection and functional analysis of SNPs and mutations were performed using various in bioinformatics tools. Result:Nuclear accumulations for p53 protein was detected in all of the esophageal carcinomas examined while no accumulations were observed in normal control sections. Four patients with immune-positive for p53 showed no mutations in p53 gene (exon4 and exon8). The incidence of the homozygous mutant variant Pro/Pro was higher in esophageal cancerous patients comparing to healthy control subject 20(71. 4%) vs. 1(10%), respectively (p=0.0026). In exon 4, no mutation was detected other than NG_017013.2:g. Conclusion:we found a significant association between the overexpression of TP53 protein and mutation in exon 4 and 8. A silent mutation P301P was detected in all of examined cases. Two patients who diagnosed with small cell sarcoma have shared the same mutations in exon8. Further studies with large sample size are required to demonstrate the usefulness of these mutations in the screening of EC especially SCCE.
Sin Nombre virus is a category A pathogen with a reported mortality rate ranging from 30% to 50%. It was responsible for the 2012 Yosemite National Park outbreak. Until now, Specific therapy is not available for the treatment of HCPS caused by SNV. Despite many efforts to develop safe and effective vaccines against SNV, included conventional approaches as well as molecular vaccine approaches, to date there are no vaccines proven to be highly efficacious against SNV. In our study, we analyzed envelope glycoprotein and nucleocapsid of SNV by using immunoinformatics tools housed in IEDB resources; in order to determine the most conserved and immunogenic epitopes for B-and T-cells. Then the predicted epitopes were assessed for the population coverage against the whole world population with the MHC-I and MHC-II restricted alleles. Among predicted epitopes for B-cell, the best candidates for glycoprotein and nucleocapsid were the epitope 743CKKYAYPWQT752 and the epitope 271QVDESKVS278, respectively. For glycoprotein CD8 + T cell predicted epitopes, the epitopes 208MTLPVTCFL216 and 458YTFTSLFSL466 were selected. Interestingly, the best candidates epitopes for nucleocapsid were the epitopes 25YILSFALPI133 and 239FLAARCPFL247 which had high affinity to interact with both MHC classes, I and II, and they had an excellent population coverage for Class I and II alleles throughout the world. To the best of our knowledge, our study for the first time has predicted a cocktail of B-and T-cell epitopes for designing an effective vaccine against HCPS caused by SNV
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