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1.
Commun Biol ; 7(1): 500, 2024 Apr 25.
Article in English | MEDLINE | ID: mdl-38664512

ABSTRACT

Ethnicity has a significant role in shaping the composition of the gut microbiome, which has implications in human physiology. This study intends to investigate the gut microbiome of Bengali people as well as several indigenous ethnicities (Chakma, Marma, Khyang, and Tripura) residing in the Chittagong Hill Tracts areas of Bangladesh. Following fecal sample collection from each population, part of the bacterial 16 s rRNA gene was amplified and sequenced using Illumina NovaSeq platform. Our findings indicated that Bangladeshi gut microbiota have a distinct diversity profile when compared to other countries. We also found out that Bangladeshi indigenous communities had a higher Firmicutes to Bacteroidetes ratio than the Bengali population. The investigation revealed an unclassified bacterium that was differentially abundant in Bengali samples while the genus Alistipes was found to be prevalent in Chakma samples. Further research on these bacteria might help understand diseases associated with these populations. Also, the current small sample-sized pilot study hindered the comprehensive understanding of the gut microbial diversity of the Bangladeshi population and its potential health implications. However, our study will help establish a basic understanding of the gut microbiome of the Bangladeshi population.


Subject(s)
Gastrointestinal Microbiome , South Asian People , Adult , Female , Humans , Male , Bacteria/genetics , Bacteria/classification , Bangladesh , Ethnicity , Feces/microbiology , Gastrointestinal Microbiome/genetics , Indigenous Peoples , RNA, Ribosomal, 16S/genetics
2.
Heliyon ; 9(11): e21466, 2023 Nov.
Article in English | MEDLINE | ID: mdl-38034688

ABSTRACT

Mycoplasma pneumoniae is a significant causative agent of community-acquired pneumonia, causing acute inflammation in the upper and lower respiratory tract as well as extrapulmonary syndromes. In particular, the elderly and infants are at greater risk of developing severe, life-threatening pneumonia caused by M. pneumoniae. Yet, the global increase in antimicrobial resistance against antibiotics for the treatment of M. pneumoniae infection highlights the urgent need to explore novel drug targets. To this end, bioinformatics approaches, such as subtractive genomics, can be employed to identify specific metabolic pathways and essential proteins unique to the pathogen that could be potential targets for new drugs. In this study, we implemented a subtractive genomics approach to identify 61 metabolic pathways and 42 essential proteins that are unique to M. pneumoniae. A subsequent screening in the DrugBank database revealed three druggable proteins with similarity to FDA-approved small-molecule drugs, and finally, the compound CHEBI:97093 was identified as a promising novel putative drug target. These findings can provide crucial insights for the development of highly effective drugs that selectively inhibit the pathogen-specific metabolic pathways, leading to better management and treatment of M. pneumoniae infections.

3.
PLoS One ; 18(6): e0286917, 2023.
Article in English | MEDLINE | ID: mdl-37319252

ABSTRACT

GRIN2A is a gene that encodes NMDA receptors found in the central nervous system and plays a pivotal role in excitatory synaptic transmission, plasticity and excitotoxicity in the mammalian central nervous system. Changes in this gene have been associated with a spectrum of neurodevelopmental disorders such as epilepsy. Previous studies on GRIN2A suggest that non-synonymous single nucleotide polymorphisms (nsSNPs) can alter the protein's structure and function. To gain a better understanding of the impact of potentially deleterious variants of GRIN2A, a range of bioinformatics tools were employed in this study. Out of 1320 nsSNPs retrieved from the NCBI database, initially 16 were predicted as deleterious by 9 tools. Further assessment of their domain association, conservation profile, homology models, interatomic interaction, and Molecular Dynamic Simulation revealed that the variant I463S is likely to be the most deleterious for the structure and function of the protein. Despite the limitations of computational algorithms, our analyses have provided insights that can be a valuable resource for further in vitro and in vivo research on GRIN2A-associated diseases.


Subject(s)
Epilepsy , Molecular Dynamics Simulation , Humans , Polymorphism, Single Nucleotide , Algorithms , Databases, Factual , Computational Biology
4.
J Biomol Struct Dyn ; 41(24): 15150-15164, 2023.
Article in English | MEDLINE | ID: mdl-36907599

ABSTRACT

Insulin receptor substrate 1(IRS1) is a signaling adapter protein encoded by the IRS1 gene. This protein delivers signals from insulin and insulin-like growth factor-1(IGF-1) receptors to the phosphatidylinositol 3-kinases (P13K)/protein kinase B (Akt) and Extracellular signal-regulated kinases (Erk) - Mitogen-activated protein (MAP) kinase pathways, which regulate particular cellular processes. Mutations in this gene have been linked to type 2 diabetes mellitus, a heightened risk of insulin resistance, and an increased likelihood of developing a number of different malignancies. The structure and function of IRS1 could be severely compromised as a result of single nucleotide polymorphism (SNP) type genetic variants. In this study, we focused on identification of the most harmful non-synonymous SNPs (nsSNPs) of the IRS1 gene as well as prediction of their structural and functional consequences. Six different algorithms made the initial prediction that 59 of the 1142 IRS1 nsSNPs would have a negative impact on the protein structure. In-depth evaluations detected 26 nsSNPs located inside the functional domains of IRS1. Following that, 16 nsSNPs were identified as more harmful based on conservation profile, hydrophobic interaction, surface accessibility, homology modelling, and inter-atomic interactions. Following an in-depth analysis of protein stability, M249T (rs373826433), I223T (rs1939785175) and V204G (rs1574667052) were identified as three most deleterious SNPs and were subjected to molecular dynamics simulation for further insights. These findings will help us understand the implications for disease susceptibility, cancer progression, and the efficacy of therapeutic development against IRS1 gene mutants.Communicated by Ramaswamy H. Sarma.


Subject(s)
Diabetes Mellitus, Type 2 , Humans , Insulin Receptor Substrate Proteins/genetics , Insulin Receptor Substrate Proteins/metabolism , Diabetes Mellitus, Type 2/genetics , Signal Transduction , Extracellular Signal-Regulated MAP Kinases/metabolism , Adaptor Proteins, Signal Transducing/metabolism
5.
J Biomol Struct Dyn ; 41(24): 14730-14743, 2023.
Article in English | MEDLINE | ID: mdl-36927394

ABSTRACT

Vibrio cholerae, the etiological agent of cholera, causes dehydration and severe diarrhea with the production of cholera toxin. Due to the acquired antibiotic resistance, V. cholerae has drawn attention to the establishment of novel medications to counteract the virulence and viability of the pathogen. Centella asiatica is a medicinal herb native to Bangladesh that has a wide range of medicinal and ethnobotanical applications including anti-bacterial properties. In the present investigation, a total of 25 bioactive phytochemicals of C. asiatica have been screened virtually through molecular docking, ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) analyses, and molecular dynamics simulation. Our results revealed four lead compounds as Viridiflorol (-8.7 Kcal/mol), Luteolin (-8.1 Kcal/mol), Quercetin (-8.0 Kcal/mol) and, Geranyl acetate (-7.1 Kcal/mol) against V. cholerae Toxin co-regulated pilus virulence regulatory protein (ToxT). All the lead compounds have been found to possess favorable pharmacokinetic, pharmacodynamics, and molecular dynamics properties. Toxicity analysis revealed satisfactory results with no major side effects. Molecular dynamics simulation was performed for 100 ns that revealed noteworthy conformational stability and structural compactness for all the lead compounds, especially for Quercetin. Target class prediction unveiled enzymes in most of the cases and some experimental and investigational drugs were found as structurally similar analogs of the lead compounds. These findings could aid in the development of novel therapeutics targeting Cholera disease and we strongly recommend in vitro trials of our experimental findings.Communicated by Ramaswamy H. Sarma.


Subject(s)
Centella , Cholera , Vibrio cholerae , Humans , Cholera/drug therapy , Cholera/microbiology , Molecular Dynamics Simulation , Centella/metabolism , Quercetin/pharmacology , Molecular Docking Simulation , Bacterial Proteins/metabolism , Cholera Toxin/metabolism , Cholera Toxin/pharmacology
6.
Anim Biotechnol ; 34(7): 2007-2016, 2023 Dec.
Article in English | MEDLINE | ID: mdl-35446730

ABSTRACT

CatSper1 and TNP2 genes are known to affect semen quality and fertility parameters, including sperm motility and maturation. However, studies are yet to examine the genes in indigenous and crossbred cattle in Bangladesh. Therefore, this study was conducted to determine the genetic variants of CatSper1 and TNP2 in indigenous and crossbred cattle in Bangladesh. Blood samples were collected from 130 indigenous and 70 crossbred (Holstein Friesian × indigenous) cattle. Nucleotide variation was evaluated by PCR-RFLP and sequencing. The results of the study showed that the indigenous cattle possessed only TT genotype (1.0), whereas the crossbreds possessed both TT (0.91) and CT (0.09) genotypes, which was validated by gene sequencing. Additionally, the CatSper1 was conserved in both the indigenous and crossbred cattle, suggesting good semen quality and fertility. However, the TNP2 was conserved in the indigenous breeds and mostly conserved in the crossbreds. The findings of this study reveal the diversity of CatSper1 and TNP2 genes in indigenous and crossbred cattle.


Subject(s)
Semen Analysis , Sperm Motility , Cattle/genetics , Male , Animals , Sperm Motility/genetics , Bangladesh , Fertility/genetics , Genotype
7.
Sci Rep ; 12(1): 21070, 2022 12 06.
Article in English | MEDLINE | ID: mdl-36473896

ABSTRACT

Developing a common medication strategy for disease control and management could be greatly beneficial. Investigating the differences between diseased and healthy states using differentially expressed genes aids in understanding disease pathophysiology and enables the exploration of protein-drug interactions. This study aimed to find the most common genes in diarrhea-causing bacteria such as Salmonella enterica serovar Typhimurium, Campylobacter jejuni, Escherichia coli, Shigella dysenteriae (CESS) to find new drugs. Thus, differential gene expression datasets of CESS were screened through computational algorithms and programming. Subsequently, hub and common genes were prioritized from the analysis of extensive protein-protein interactions. Binding predictions were performed to identify the common potential therapeutic targets of CESS. We identified a total of 827 dysregulated genes that are highly linked to CESS. Notably, no common gene interaction was found among all CESS bacteria, but we identified 3 common genes in both Salmonella-Escherichia and Escherichia-Campylobacter infections. Later, out of 73 protein complexes, molecular simulations confirmed 5 therapeutic candidates from the CESS. We have developed a new pipeline for identifying therapeutic targets for a common medication strategy against CESS. However, further wet-lab validation is needed to confirm their effectiveness.


Subject(s)
Gene Expression
8.
Mol Biotechnol ; 2022 Nov 10.
Article in English | MEDLINE | ID: mdl-36357534

ABSTRACT

Monkeypox Virus (MPXV), the causative agent of Monkeypox (MPX) disease, is an emerging zoonotic pathogen spreading in different endemic and non-endemic nations and creating outbreaks. MPX treatment mainly includes Cidofovir and Tecovirimat but they have several side effects and solely depending on these drugs may promote the emergence of drug-resistant variants. Hence, new drugs are required to control the spread of the disease. In this study, we explored the MPXV proteome to suggest repurposable drugs. DrugBank screening revealed drugs such as Brinzolamide, Dorzolamide, Methazolamide, Zidovudine, Gemcitabine, Hydroxyurea, Fludarabine, and Tecovirimat as controls. Structural analogs of these compounds were extracted from ChEMBL Database. After Molecular docking and Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET)-based screening, we identified Zidovudine (binding affinity-5.9 kcal/mol) and a Harmala alkaloid (2S,4R)-4-(9H-Pyrido[3,4-b]indol-1-yl)-1,2,4-butanetriol (binding affinity - 6.6 kcal/mol) against L2R receptor (Thymidine Kinase). Moreover, Fludarabine (binding affinity - 6.4 kcal/mol) and 5'-Dehydroadenosine (binding affinity - 6.4 kcal/mol) can strongly interact with the I4L receptor (Ribonucleotide reductase large subunit R1). Molecular Dynamics (MD) simulations suggest all of these compounds can change the C-alpha backbone, residue mobility, compactness, and solvent accessible surface area of L2R and I4L. Our results strongly suggest that these drug repurposing small molecules are worth exploring in vivo and in vitro for clinical applications.

9.
Virus Res ; 319: 198859, 2022 Oct 02.
Article in English | MEDLINE | ID: mdl-35809696

ABSTRACT

Hepatitis B virus (HBV) is a major public health concern worldwide. Co-infection of hepatitis B patients with other pathogens intensifies the severity of the disease. We report a novel variant of hepatitis B virus (HBV) in Bangladesh isolated from a patient co-infected with hepatitis C virus (HCV) who exhibited liver cirrhosis. From 150 collected plasma samples, we sequenced HBV complete genome from one HBV-HCV co-infected patient. The complete genome was analysed using bioinformatics tools, NCBI BLAST, Geno2Pheno, and SnapGene software. The strain belongs to genotype A and subgenotype A1. Upon analysing the complete genome of this strain, we found a frameshift deletion of 54 nucleotides at the pre-S2 region, a functional regulator of HBV surface protein. Furthermore, we observed a Y126H mutation in the polymerase protein of this strain. This is the first report with such an unusual pre-S deletion event of the HBV genome in an HCV-co-infected patient associated with liver cirrhosis. These findings may inform scientists about genomic modifications in the HBV genome associated with HCV co-infection.


Subject(s)
Coinfection , Hepatitis B, Chronic , Hepatitis B , Hepatitis C , DNA, Viral/genetics , Genotype , Hepacivirus/genetics , Hepatitis B/complications , Hepatitis B Surface Antigens/genetics , Hepatitis B virus/genetics , Hepatitis C/complications , Humans , Liver Cirrhosis/complications
10.
Biomed Res Int ; 2022: 4558867, 2022.
Article in English | MEDLINE | ID: mdl-35707384

ABSTRACT

HMG-CoA reductase or HMGCR (3-hydroxy-3-methylglutaryl-CoA reductase) is a rate-limiting enzyme involved in cholesterol biosynthesis. HMGCR plays an important role in the possible occurrence of hypercholesterolemia leading to atherosclerosis and coronary heart disease. This enzyme is a major target for cholesterol-lowering drugs such as "statin" which blocks the synthesis of mevalonate, a precursor for cholesterol biosynthesis. This study is aimed at characterizing deleterious mutations and classifying functional single nucleotide polymorphisms (SNPs) of the HMGCR gene through analysis of functional and structural evaluation, domain association, solvent accessibility, and energy minimization studies. The functional and characterization tools such as SIFT, PolyPhen, SNPs and GO, Panther, I-Mutant, and Pfam along with programming were employed to explore all the available SNPs in the HMGCR gene in the database. Among 6815 SNP entries from different databases, approximately 388 SNPs were found to be missense. Analysis showed that seven missense SNPs are more likely to have deleterious effects. A tertiary model of the mutant protein was constructed to determine the functional and structural effects of the HMGCR mutation. In addition, the location of the mutations suggests that they may have deleterious effects because most of the mutations are residing in the functional domain of the protein. The findings from the analysis predicted that rs147043821 and rs193026499 missense SNPs could cause significant structural and functional instability in the mutated proteins of the HMGCR gene. The findings of the current study will likely be useful in future efforts to uncover the mechanism and cause of hypercholesterolemia. In addition, the identified SNPs of HMGCR gene could set up a strong foundation for further therapeutic discovery.


Subject(s)
Hydroxymethylglutaryl CoA Reductases , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Hypercholesterolemia , Cholesterol/metabolism , Humans , Hydroxymethylglutaryl CoA Reductases/genetics , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hypercholesterolemia/drug therapy , Hypercholesterolemia/genetics , Mevalonic Acid/metabolism , Polymorphism, Single Nucleotide/genetics
11.
Diabetol Metab Syndr ; 14(1): 18, 2022 Jan 28.
Article in English | MEDLINE | ID: mdl-35090536

ABSTRACT

BACKGROUND: Association of single nucleotide polymorphisms (SNP) rs7756992 A/G and rs7754840 G/C of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1) gene with the susceptibility of gestational diabetes mellitus (GDM) has been studied in a group of Bangladeshi women. METHODS: In this case-control study, 212 GDM patients and 256 control subjects were genotyped for rs7756992 and rs7754840 by PCR-RFLP and TaqMan™ allelic discrimination assay method respectively. Genotyping results were confirmed by DNA sequencing and replicated TaqMan™ assay. The odds ratios and their 95% confidence interval were calculated by logistic regression to determine the associations between genotypes and GDM. RESULTS: The genotype frequencies of rs7756992-AA/AG/GG in the GDM group and the control group were 37%/48%, 53%/45%, 10%/7% and those of rs7754840-CC/CG/GG were 51%/55%, 40.1%/39.8%, 9%/5% respectively. Under dominant and log additive models rs7756992 was revealed significantly associated with GDM after being adjusted for family history of diabetes (FHD) and gravidity. Conversely, rs7754840 was significantly associated (P = 0.047) with GDM only under the recessive model after the same adjustment. The risk allele frequency of both SNPs was higher in the GDM group but significantly (P = 0.029) increased prevalence was observed in the rs7756992 G allele. When positive FHD and risk alleles of these SNPs were synergistically present in any pregnant woman, the chance of developing GDM was augmented by many folds. The codominant model revealed 2.5 and 2.1 folds increase in odds by AG (rs7756992) and GC (rs7754840) genotypes and 3.7 and 4.5 folds by GG (rs7756992) and CC (rs7754840) genotypes respectively. A significant 2.7 folds (P = 0.038) increase in odds of GDM resulted from the interaction of rs7756992 and family history of diabetes under the dominant model. The cumulative effect of multigravidity and risk alleles of these SNPs increased the odds of GDM more than 1.5 folds in different genotypes. CONCLUSION: This study not only revealed a significant association between rs7756992 and rs7754840 with GDM but also provided the possibility as potential markers for foretelling about GDM and type 2 diabetes mellitus in Bangladeshi women.

12.
PLoS One ; 16(9): e0258019, 2021.
Article in English | MEDLINE | ID: mdl-34587212

ABSTRACT

As the COVID-19 pandemic continues to ravage across the globe and take millions of lives and like many parts of the world, the second wave of the pandemic hit Bangladesh, this study aimed at understanding its causative agent, SARS-CoV-2 at the genomic and proteomic level and provide precious insights about the pathogenesis, evolution, strengths and weaknesses of the virus. As of Mid-June 2021, over 1500 SARS-CoV-2 genomesequences have been deposited in the GISAID database from Bangladesh which were extracted and categorized into two waves. By analyzing these genome sequences, it was discovered that the wave-2 samples had a significantly greater average rate of mutation/sample (30.79%) than the wave-1 samples (12.32%). Wave-2 samples also had a higher frequency of deletion, and transversion events. During the first wave, the GR clade was the most predominant but it was replaced by the GH clade in the latter wave. The B.1.1.25 variant showed the highest frequency in wave-1 while in case of wave-2, the B.1.351.3 variant, was the most common one. A notable presence of the delta variant, which is currently at the center of concern, was also observed. Comparison of the Spike protein found in the reference and the 3 most common lineages found in Bangladesh namely, B.1.1.7, B.1.351, B.1.617 in terms of their ability to form stable complexes with ACE2 receptor revealed that B.1.617 had the potential to be more transmissible than others. Importantly, no indigenous variants have been detected so far which implies that the successful prevention of import of foreign variants can diminish the outbreak in the country.


Subject(s)
COVID-19/epidemiology , Genomics/methods , SARS-CoV-2/genetics , Bangladesh/epidemiology , Disease Outbreaks/prevention & control , Genetic Variation/genetics , Genome, Viral/genetics , Humans , Mutation/genetics , Pandemics , Phylogeny , Proteomics , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/genetics
13.
J Genet Eng Biotechnol ; 19(1): 52, 2021 Apr 02.
Article in English | MEDLINE | ID: mdl-33797663

ABSTRACT

BACKGROUND: Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the etiologic agent of coronavirus disease 2019 (COVID-19), is rapidly acquiring new mutations. Analysis of these mutations is necessary for gaining knowledge regarding different aspects of therapeutic development. Previously, we have reported a Sanger method-based genome sequence of a viral isolate named SARS-CoV-2 NIB-1, circulating in Bangladesh. The genome has four novel non-synonymous mutations in V121D, V843F, A889V, and G1691C positions. RESULTS: Using different computational tools, we have found V121D substitution has the potential to destabilize the non-structural protein-1 (NSP-1). NSP-1 inactivates the type-1 interferon-induced antiviral system. Hence, this mutant could be a basis of attenuated vaccines against SARS-CoV-2. V843F, A889V, and G1691C are all located in nonstructural protein-3 (NSP-3). G1691C can decrease the flexibility of the protein. V843F and A889V might change the binding pattern and efficacy of SARS-CoV-2 papain-like protease (PLPro) inhibitor GRL0617. V843F substitution in PLPro was the most prevalent mutation in the clinical samples. This mutation showed a reduced affinity for interferon-stimulated gene-15 protein (ISG-15) and might have an impact on innate immunity and viral spread. However, V843F+A889V double mutant exhibited the same binding affinity as wild type PLPro. A possible reason behind this phenomenon can be that V843F is a conserved residue of PLPro which damaged the protease structure, but A889V, a less conserved residue, presumably neutralized that damage. CONCLUSIONS: Mutants of NSP-1 could provide attenuated vaccines against coronavirus. Also, these mutations of PLPro might be targeted to develop better anti-SARS therapeutics. We hope our study will help to get better insides during the development of attenuated vaccine and PLPro inhibitors.

14.
Gene ; 771: 145368, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33346100

ABSTRACT

Coronavirus disease-2019 (COVID-19), caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2), has become an immense threat to global public health. In this study, we performed complete genome sequencing of a SARS-CoV-2 isolate. More than 67,000 genome sequences were further inspected from Global Initiative on Sharing All Influenza Data (GISAID). Using several in silico techniques, we proposed prospective therapeutics against this virus. Through meticulous analysis, several conserved and therapeutically suitable regions of SARS-CoV-2 such as RNA-dependent RNA polymerase (RdRp), Spike (S) and Membrane glycoprotein (M) coding genes were selected. Both S and M were chosen for the development of a chimeric vaccine that can generate memory B and T cells. siRNAs were also designed for S and M gene silencing. Moreover, six new drug candidates were suggested that might inhibit the activity of RdRp. Since SARS-CoV-2 and SARS-CoV-1 have 82.30% sequence identity, a Gene Expression Omnibus (GEO) dataset of Severe Acute Respiratory Syndrome (SARS) patients were analyzed. In this analysis, 13 immunoregulatory genes were found that can be used to develop type 1 interferon (IFN) based therapy. The proposed vaccine, siRNAs, drugs and IFN based analysis of this study will accelerate the development of new treatments.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 Drug Treatment , Computational Biology/methods , Gene Expression Profiling/methods , SARS-CoV-2/genetics , Whole Genome Sequencing/methods , Antiviral Agents/therapeutic use , COVID-19/virology , Computer Simulation , Conserved Sequence , Coronavirus M Proteins/genetics , Drug Design , Female , Gene Expression Regulation, Viral/drug effects , Humans , Interferons/pharmacology , Middle Aged , Prospective Studies , RNA-Dependent RNA Polymerase/genetics , SARS-CoV-2/classification , Sequence Analysis, RNA , Spike Glycoprotein, Coronavirus/genetics
15.
Microbiol Resour Announc ; 9(28)2020 Jul 09.
Article in English | MEDLINE | ID: mdl-32646908

ABSTRACT

A coding-complete genome sequence of a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) isolate was revealed. The sample for the virus was isolated from a female patient from Dhaka, Bangladesh, suffering from coronavirus disease-2019 (COVID-19).

16.
Mol Genet Genomic Med ; 8(2): e1073, 2020 02.
Article in English | MEDLINE | ID: mdl-31816668

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a chronic disorder of which stress is a major contributor. Under stressful condition, body synthesizes a family of molecular chaperone called Heat-shock proteins (HSPs). Current study assessed the frequency and association of HSP70-hom + 2,437 T/C polymorphism with T2DM risk among Bangladeshis. METHODS: This polymorphism was selected through bioinformatics analyses and identified by PCR-RFLP method. RESULTS: Bioinformatics analysis identified this SNP as missense mutation which could destabilize the final HSP product. Heterozygous mutant (CT) genotype was significantly associated with T2DM incidence among the studied populations (p = .015). Further analysis revealed a strong association with female patients (p = .002), while the male group showed no association (p = .958). Moreover, the C allele was significantly associated among all diabetic patients (p = .016) and particularly in the female patient group (p = .001). However, under stressful condition, males with CT genotype were at high risk for T2DM incidence whereas, females with CT genotype showed no significant association. CONCLUSIONS: HSP70-hom + 2,437 T/C polymorphism was found to be significantly associated with T2DM incidence in the Bangladeshi population in both stress-dependent and independent manners.


Subject(s)
Diabetes Mellitus, Type 2/genetics , HSP70 Heat-Shock Proteins/genetics , Polymorphism, Single Nucleotide , Adult , Bangladesh , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/psychology , Heterozygote , Humans , Middle Aged , Sex Factors , Stress, Psychological/epidemiology
17.
F1000Res ; 7: 1023, 2018.
Article in English | MEDLINE | ID: mdl-30228877

ABSTRACT

The burden of chronic hepatitis B virus (HBV) infections is increasingly detected nowadays. Herein, we report a complete genome of HBV subgenotype C2 (HBV/C2) from a HBV infected patient. Complete genome analysis revealed that the isolated strain was a non-recombinant wild type and had several regular substitutions in the reverse transcriptase domain and small surface proteins of HBV. This study may help clinicians and scientists gain in-depth knowledge on the current substitutions of HBV/C2 genome and to identify potential therapies against HBV infections.


Subject(s)
DNA, Viral , Genome, Viral , Hepatitis B virus/genetics , Hepatitis B, Chronic/genetics , Humans , Male , Middle Aged
18.
Virus Res ; 255: 154-156, 2018 08 15.
Article in English | MEDLINE | ID: mdl-30040979

ABSTRACT

We report a novel tri-genotypic recombinant Hepatitis B virus (HBV) strain circulating in Bangladesh. The strain is recombinant with the genotypes D, C and E, of which, genotype E was not reported before in Bangladesh. Additionally, the complete genome has a frameshift deletion of nine nucleotides from overlapping Surface and Polymerase genes, and a vaccine escape mutation, A128 V, in the surface protein. This is the first report with such unusual recombination event responsible for rapid liver cirrhosis in a 13 year old patient in Bangladesh. This report may alert the clinicians to take the measure to prevent an upcoming outbreak of recombinant HBV.


Subject(s)
Hepatitis B virus/classification , Hepatitis B virus/genetics , Hepatitis B/virology , Liver Cirrhosis/virology , Phylogeny , Recombination, Genetic/genetics , Adolescent , Bangladesh , Base Composition , DNA, Viral , Genome Size , Genome, Viral/genetics , Genotype , Humans , Polymorphism, Genetic , Sequence Analysis, DNA , Sequence Deletion
19.
Front Chem ; 6: 246, 2018.
Article in English | MEDLINE | ID: mdl-30035107

ABSTRACT

An outbreak of West Nile Virus (WNV) like the recent Ebola can be more epidemic and fatal to public health throughout the world. WNV possesses utmost threat as no vaccine or drug is currently available for its treatment except mosquito control. The current study applied the combined approach of immunoinformatics and pharmacoinformatics to design potential epitope-based vaccines and drug candidates against WNV. By analyzing the whole proteome of 2994 proteins, the WNV envelope glycoprotein was selected as a therapeutic target based on its highest antigenicity. After proper assessment "KSFLVHREW" and "ITPSAPSYT" were found to be the most potential T and B-cell epitopes, respectively. Besides, we have designed and validated four novel drugs from a known WNV inhibitor, AP30451 by adopting computational approaches. Toxicity assessment and drug score confirmed the effectiveness of these drug candidates. This in silico research might greatly facilitate the wet lab experiments to develop vaccine and drug against WNV.

20.
PLoS One ; 13(6): e0198170, 2018.
Article in English | MEDLINE | ID: mdl-29883471

ABSTRACT

The bacterial species Campylobacter jejuni RM1221 (CjR) is the primary cause of campylobacteriosis which poses a global threat for human health. Over the years the efficacy of antibiotic treatment is becoming more fruitless due to the development of multiple drug resistant strains. Therefore, identification of new drug targets is a valuable tool for the development of new treatments for affected patients and can be obtained by targeting essential protein(s) of CjR. We conducted this in silico study in order to identify therapeutic targets by subtractive CjR proteome analysis. The most important proteins of the CjR proteome, which includes chokepoint enzymes, plasmid, virulence and antibiotic resistant proteins were annotated and subjected to subtractive analyses to filter out the CjR essential proteins from duplicate or human homologous proteins. Through the subtractive and characterization analysis we have identified 38 eligible therapeutic targets including 1 potential vaccine target. Also, 12 potential targets were found in interactive network, 5 targets to be dealt with FDA approved drugs and one pathway as potential pathway based drug target. In addition, a comprehensive database 'CampyNIBase' has also been developed. Besides the results of this study, the database is enriched with other information such as 3D models of the identified targets, experimental structures and Expressed Sequence Tag (EST) sequences. This study, including the database might be exploited for future research and the identification of effective therapeutics against campylobacteriosis. URL: (http://nib.portal.gov.bd/site/page/4516e965-8935-4129-8c3f-df95e754c562#Banner).


Subject(s)
Campylobacter Infections , Campylobacter jejuni , Databases, Protein , Drug Discovery/methods , Molecular Targeted Therapy/methods , Signal Transduction/genetics , Anti-Bacterial Agents/isolation & purification , Anti-Bacterial Agents/therapeutic use , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Bacterial Vaccines/isolation & purification , Bacterial Vaccines/therapeutic use , Campylobacter Infections/genetics , Campylobacter Infections/metabolism , Campylobacter Infections/therapy , Campylobacter jejuni/genetics , Campylobacter jejuni/growth & development , Campylobacter jejuni/pathogenicity , Datasets as Topic , Genome, Bacterial , Host-Pathogen Interactions/genetics , Humans , Virulence/genetics
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