Prediction of the most deleterious non-synonymous SNPs in the human IL1B gene: evidence from bioinformatics analyses.

BACKGROUND: Polymorphisms in IL1B play a significant role in depression, multiple inflammatory-associated disorders, and susceptibility to infection. Functional non-synonymous SNPs (nsSNPs) result in changes in the encoded amino acids, potentially leading to structural and functional alterations in the mutant proteins. So far, most genetic studies have concentrated on SNPs located in the IL1B promoter region, without addressing nsSNPs and their association with multifactorial diseases. Therefore, this study aimed to explore the impact of deleterious nsSNPs retrieved from the dbSNP database on the structure and functions of the IL1B protein. RESULTS: Six web servers (SIFT, PolyPhen-2, PROVEAN, SNPs&GO, PHD-SNP, PANTHER) were used to analyze the impact of 222 missense SNPs on the function and structure of IL1B protein. Five novel nsSNPs (E100K, T240I, S53Y, D128Y, and F228S) were found to be deleterious and had a mutational impact on the structure and function of the IL1B protein. The I-mutant v2.0 and MUPro servers predicted that these mutations decreased the stability of the IL1B protein. Additionally, these five mutations were found to be conserved, underscoring their significance in protein structure and function. Three of them (T240I, D128Y, and F228S) were predicted to be cancer-causing nsSNPs. To analyze the behavior of the mutant structures under physiological conditions, we conducted a 50 ns molecular dynamics simulation using the WebGro online tool. Our findings indicate that the mutant values differ from those of the IL1B wild type in terms of RMSD, RMSF, Rg, SASA, and the number of hydrogen bonds. CONCLUSIONS: This study provides valuable insights into nsSNPs located in the coding regions of IL1B, which lead to direct deleterious effects on the functional and structural aspects of the IL1B protein. Thus, these nsSNPs could be considered significant candidates in the pathogenesis of disorders caused by IL1B dysfunction, contributing to effective drug discovery and the development of precision medications. Thorough research and wet lab experiments are required to verify our findings. Moreover, bioinformatic tools were found valuable in the prediction of deleterious nsSNPs.

Bacillus thuringiensis pesticidal toxins: A global analysis based on a scientometric study (1980-2021).

Several studies have been conducted on Bacillus thuringiensis (Bt) pesticidal toxins due to their successful environmentally friendly biopesticide activity against various insect pest orders, protozoa, mites, and nematodes. However, no existing study has systematically examined the trends and evolution of research on Bt pesticidal toxins from a scientometric perspective. This study aimed to analyze the trends and hotspots of global research in this field. 5757 publications on Bt pesticidal toxins were extracted from the Web of Science Core Collection (WoS) from 1980 to 2021. Statistical and scientometric analyses were performed using Excel, CiteSpace, and VOSviewer visualization tools to evaluate research evolution, journal contribution and subject categories, contributing countries and institutions, highly influential references, and most used author keywords. The 5757 publications featured in 917 journals spanning 116 subject categories. The top 5 subject categories ranked as Entomology, Biotechnology & Applied Microbiology, Microbiology, Biochemistry & Molecular Biology, and Agriculture. Out of these publications, the USA contributed the most, with 1562 publications, 72,754 citations, and 46.58 average citations per paper (ACPP); however, Belgium had the highest (106.43) ACPP among the top 20 contributing countries. The Chinese Academy of Agricultural Sciences is the leading institution with 298 publications and 21.20 ACPP. The Pasteur Institute is ranked first (90.04) in terms of ACPP. Keywords analyses revealed that recent studies are inclined toward the evolution of insect resistance against Bt toxins. In future, studies related to the development of resistance mechanisms by insects against Bt pesticidal toxins and ways to overcome them will likely receive more attention. This study highlights the past and current situations and prospective directions of Bt pesticidal toxins-related research.

Identification of functional tumor necrosis factor-alpha promoter variants associated with Helicobacter pylori infection in the Sudanese population: Computational approach.

BACKGROUND: Helicobacter pylori (H. pylori) is a ubiquitous bacterium that affects nearly half of the world's population with a high morbidity and mortality rate. Polymorphisms within the tumor necrosis factor-alpha (TNF-A) promoter region are considered a possible genetic basis for this disease. AIM: To functionally characterize the genetic variations in the TNF-A 5'-region (-584 to +107) of Sudanese patients infected with H. pylori using in silico tools. METHODS: An observational study was carried out in major public and private hospitals in Khartoum state. A total of 122 gastric biopsies were taken from patients who had been referred for endoscopy. Genomic DNA was extracted. Genotyping of the TNF-A-1030 polymorphism was performed using PCR with confronting two-pair primer to investigate its association with the susceptibility to H. pylori infection in the Sudanese population. Furthermore, Sanger sequencing was applied to detect single nucleotide polymorphisms in the 5'-region (-584 to +107) of TNF-A in H. pylori-infected patients. Bioinformatics analyses were used to predict whether these mutations would alter transcription factor binding sites or composite regulatory elements in this region. A comparative profiling analysis was conducted in 11 species using the ECR browser and multiple-sequence local alignment and visualization search engine to investigate the possible conservation. Also, a multivariate logistic regression model was constructed to estimate odds ratios and their 95% confidence intervals for the association between TNF-A-1030, sociodemographic characteristics and H. pylori infection. Differences were statistically significant if P < 0.05. Statistical analyses were performed using Stata version 11 software. RESULTS: A total of seven single nucleotide polymorphisms were observed in the TNF-A 5'-region of Sudanese patients infected with H. pylori. Only one of them (T > A, -76) was located at the in silico-predicted promoter region (-146 to +10), and it was predicted to alter transcription factor binding sites and composite regulatory elements. A novel mutation (A > T, +27) was detected in the 5' untranslated region, and it could affect the post-transcriptional regulatory pathways. Genotyping of TNF-A-1030 showed a lack of significant association between -1030T and susceptibility to H. pylori and gastric cancer in the studied population (P = 0.1756) and (P = 0.8116), respectively. However, a significant association was detected between T/C genotype and H. pylori infection (39.34% vs 19.67%, odds ratio = 2.69, 95% confidence interval: 1.17-6.17, P = 0.020). Mammalian conservation was observed for the (-146 to +10) region in chimpanzee (99.4%), rhesus monkey (95.6%), cow (91.8%), domesticated dog (89.3%), mouse (84.3%), rat (82.4%) and opossum (78%). CONCLUSION: Computational analysis was a valuable method for understanding TNF-A gene expression patterns and guiding further in vitro and in vivo experimental validation.

First insights into molecular basis identification of 16 s ribosomal RNA gene of Staphylococcus aureus isolated from Sudan.

OBJECTIVE: In this study, we analyzed the molecular evolution of Staphylococcus aureus isolates using 16S rRNA gene and phylogenetic analysis to detect the prevalence of S. aureus infections in Sudan. RESULTS: Molecular detection of S. aureus has shown that 20 (43.47%) of patients were positive for S. aureus. The phylogenetic tree of 16S rRNA sequences was divided into three lineages of S. aureus isolates detected from wound infections in Sudan. Nucleotides base-pair substitution was appeared at position 249. This mutation do not linked with Macrolides, Lincosamides and Streptogramines b resistant phenotype. Further studies should investigate the effect of that mutation on resistance to other antibiotics.

Epitope-Based Peptide Vaccine Design against Fructose Bisphosphate Aldolase of Candida glabrata: An Immunoinformatics Approach.

BACKGROUND: Candida glabrata is a human opportunistic pathogen that can cause life-threatening systemic infections. Although there are multiple effective vaccines against fungal infections and some of these vaccines are engaged in different stages of clinical trials, none of them have yet been approved by the FDA. AIM: Using immunoinformatics approach to predict the most conserved and immunogenic B- and T-cell epitopes from the fructose bisphosphate aldolase (Fba1) protein of C. glabrata. Material and Method. 13 C. glabrata fructose bisphosphate aldolase protein sequences (361 amino acids) were retrieved from NCBI and presented in several tools on the IEDB server for prediction of the most promising epitopes. Homology modeling and molecular docking were performed. RESULT: The promising B-cell epitopes were AYFKEH, VDKESLYTK, and HVDKESLYTK, while the promising peptides which have high affinity to MHC I binding were AVHEALAPI, KYFKRMAAM, QTSNGGAAY, RMAAMNQWL, and YFKEHGEPL. Two peptides, LFSSHMLDL and YIRSIAPAY, were noted to have the highest affinity to MHC class II that interact with 9 alleles. The molecular docking revealed that the epitopes QTSNGGAAY and LFSSHMLDL have the lowest binding energy to MHC molecules. CONCLUSION: The epitope-based vaccines predicted by using immunoinformatics tools have remarkable advantages over the conventional vaccines in that they are more specific, less time consuming, safe, less allergic, and more antigenic. Further in vivo and in vitro experiments are needed to prove the effectiveness of the best candidate's epitopes (QTSNGGAAY and LFSSHMLDL). To the best of our knowledge, this is the first study that has predicted B- and T-cell epitopes from the Fba1 protein by using in silico tools in order to design an effective epitope-based vaccine against C. glabrata.

First insights into the molecular basis association between promoter polymorphisms of the IL1B gene and Helicobacter pylori infection in the Sudanese population: computational approach.

BACKGROUND: Helicobacter pylori (H. pylori) infects nearly half of the world's population with a variation in incidence among different geographic regions. Genetic variants in the promoter regions of the IL1B gene can affect cytokine expression and creates a condition of hypoacidity which favors the survival and colonization of H. pylori. Therefore, the aim of this study was to characterize the polymorphic sites in the 5'- region [-687_ + 297] of IL1B in H. pylori infection using in silico tools. RESULTS: A total of five nucleotide variations were detected in the 5'-regulatory region [-687_ + 297] of IL1B which led to the addition or alteration of transcription factor binding sites (TFBSs) or composite regulatory elements (CEs). Genotyping of IL1B - 31 C > T revealed a significant association between -31 T and susceptibility to H. pylori infection in the studied population (P = 0.0363). Comparative analysis showed conservation rates of IL1B upstream [-368_ + 10] region above 70% in chimpanzee, rhesus monkey, a domesticated dog, cow and rat. CONCLUSIONS: In H. pylori-infected patients, three detected SNPs (- 338, - 155 and - 31) located in the IL1B promoter were predicted to alter TFBSs and CE, which might affect the gene expression. These in silico predictions provide insight for further experimental in vitro and in vivo studies of the regulation of IL1B expression and its relationship to H. pylori infection. However, the recognition of regulatory motifs by computer algorithms is fundamental for understanding gene expression patterns.

Molecular Phylogenetic Analysis of 16S rRNA Sequences Identified Two Lineages of Helicobacter pylori Strains Detected from Different Regions in Sudan Suggestive of Differential Evolution.

BACKGROUND: Helicobacter pylori (H. pylori) is ubiquitous among humans and one of the best-studied examples of an intimate association between bacteria and humans. Phylogeny and Phylogeography of H. pylori strains are known to mirror human migration patterns and reflect significant demographic events in human prehistory. In this study, we analyzed the molecular evolution of H. pylori strains detected from different tribes and regions of Sudan using 16S rRNA gene and the phylogenetic approach. Materials and methods. A total of 75 gastric biopsies were taken from patients who had been referred for endoscopy from different regions of Sudan. The DNA extraction was performed by using the guanidine chloride method. Two sets of primers (universal and specific for H. pylori) were used to amplify the 16S ribosomal gene. Sanger sequencing was applied, and the resulted sequences were matched with the sequences of the National Center for Biotechnology Information (NCBI) nucleotide database. The evolutionary aspects were analyzed using MEGA7 software. RESULTS: Molecular detection of H. pylori has shown that 28 (37.33%) of the patients were positive for H. pylori and no significant differences were found in sociodemographic characteristics, endoscopy series, and H. pylori infection. Nucleotide variations were observed at five nucleotide positions (positions 219, 305, 578, 741, and 763-764), and one insertion mutation (750_InsC_751) was present in sixty-seven percent (7/12) of our strains. These six mutations were detected in regions of the 16S rRNA not closely associated with either tetracycline or tRNA binding sites; 66.67% of them were located in the central domain of 16S rRNA. The phylogenetic analysis of 16S rRNA sequences identified two lineages of H. pylori strains detected from different regions in Sudan. The presence of Sudanese H. pylori strains resembling Hungarian H. pylori strains could reflect the migration of Hungarian people to Sudan or vice versa. CONCLUSION: This finding emphasizes the significance of studying the phylogeny of H. pylori strains as a discriminatory tool to mirror human migration patterns. In addition, the 16S rRNA gene amplification method was found useful for bacterial identification and phylogeny.