Virus-induced host cell metabolic alteration.

Viruses change the host cell metabolism to produce infectious particles and create optimal conditions for replication and reproduction. Numerous host cell pathways have been modified to ensure available biomolecules and sufficient energy. Metabolomics studies conducted over the past decade have revealed that eukaryotic viruses alter the metabolism of their host cells on a large scale. Modifying pathways like glycolysis, fatty acid synthesis and glutaminolysis could provide potential energy for virus multiplication. Thus, almost every virus has a unique metabolic signature and a different relationship between the viral life cycle and the individual metabolic processes. There are enormous research in virus induced metabolic reprogramming of host cells that is being conducted through numerous approaches using different vaccine candidates and antiviral drug substances. This review provides an overview of viral interference to different metabolic pathways and improved monitoring in this area will open up new ways for more effective antiviral therapies and combating virus induced oncogenesis.

Impact of vitamin D binding protein (GC) and vitamin D receptor (VDR) gene polymorphism on the risk of developing preeclampsia.

Objective: Preeclampsia is a multifactorial disease characterized by high blood pressure and protein in the urine. In this study, we investigated the association of vitamin D binding protein (GC) and vitamin D receptor (VDR) gene polymorphism with the risk of developing preeclampsia. Methods: 25-hydroxyvitamin D was measured using High-performance Liquid Chromatography. Vitamin D binding protein and vitamin D receptor gene polymorphisms were determined by polymerase chain reaction-restriction fragment length polymorphism. Results: The control subjects have significant higher level of 25-hydroxyvitamin D (33.5 ± 1.194 ng/mL) relative to patients (23.97 ± 1.604 ng/mL) (p < 0.05). Vitamin D receptor rs1544410 and rs2228570 dominant model (GA + AA; TC + CC) showed significant higher risk of developing Preeclampsia (OR = 4.11, 95% CI = 0.62-27.09, p < 0.01; OR = 3.58, 95%CI = 0.78-16.38, p < 0.001 respectively). Similarly, vitamin D binding protein rs7041 and rs4588, dominant model (TG + GG; CA + AA) showed higher risk of preeclampsia development compared to control people (OR = 1.69, 95%CI = 0.35-8.19, p < 0.05; OR = 1.06, 95%CI = 0.25-4.44, p < 0.05 respectively). AA genotype of rs4588 of GC gene was significantly associated with 25-hydroxyvitamin D level in serum relative to CC and CA (p < 0.05). Conclusion: From our study, we can conclude that a low level of 25-hydroxyvitamin D, GC (rs1544410 and rs2228570), and VDR (rs4588 and rs7041) gene polymorphism is linked with an increased risk of developing preeclampsia.

Cancer stem cells: an insight into the development of metastatic tumors and therapy resistance.

The term "cancer stem cells" (CSCs) refers to cancer cells that exhibit traits parallel to normal stem cells, namely the potential to give rise to every type of cell identified in a tumor microenvironment. It has been found that CSCs usually develops from other neoplastic cells or non-cancerous somatic cells by acquiring stemness and malignant characteristics through particular genetic modifications. A trivial number of CSCs, identified in solid and liquid cancer, can give rise to an entire tumor population with aggressive anticancer drug resistance, metastasis, and invasiveness. Besides, cancer stem cells manipulate their intrinsic and extrinsic features, regulate the metabolic pattern of the cell, adjust efflux-influx efficiency, modulate different signaling pathways, block apoptotic signals, and cause genetic and epigenetic alterations to retain their pluripotency and ability of self-renewal. Notably, to keep the cancer stem cells' ability to become malignant cells, mesenchymal stem cells, tumor-associated fibroblasts, immune cells, etc., interact with one another. Furthermore, CSCs are characterized by the expression of particular molecular markers that carry significant diagnostic and prognostic significance. Because of this, scientific research on CSCs is becoming increasingly imperative, intending to understand the traits and behavior of cancer stem cells and create more potent anticancer therapeutics to fight cancer at the CSC level. In this review, we aimed to elucidate the critical role of CSCs in the onset and spread of cancer and the characteristics of CSCs that promote severe resistance to targeted therapy.

Association of glutathione S-transferase M1 and T1 polymorphisms on the susceptibility of diabetic retinopathy in the Bangladeshi population.

Objectives: This study investigated the role of glutathione-S-transferase gene (GSTM1 and GSTT1) polymorphisms in the predisposition of type 2 diabetes mellitus (T2DM) with or without diabetic retinopathy (DR). Methods: The case-control study included 188 subjects: 50 T2DM with DR, 63 T2DM without DR, and 75 healthy individuals' presenting no clinical signs or evidence of diabetes mellitus. Zinc and magnesium levels were measured using a flame atomic absorption spectrophotometer, and the lipid profile was evaluated using standard methods. The gene polymorphism of GSTs was performed by the multiplex-PCR method. Results: Compared to the control, DR and T2DM had considerably greater total cholesterol, LDL-C, and decreased HDL-C levels. Magnesium levels were significantly lower in DR and T2DM than in control. Total cholesterol, LDL, TG, and magnesium levels didn't differ significantly between DR and T2DM groups. In DR, the GSTT1-null genotype was more prevalent than in T2DM subjects and controls (26.0%, 12.7%, and 10.7%, respectively). GSTT1-null genotype was considerably more common in DR than in controls and associated with 2.94-folds enhancing the chance of developing DR (OR = 2.94; 95% CI = 1.12-7.75; p = 0.02). However, the recurrence of GSTM1-null genotype was not clearly distinguishable among these three populations (28.0%, 38.1% and 29.3%, respectively) and not particularly prone to the risk of DR compared to T2DM subjects and controls (OR = 0.63; 95% CI = 0.28-1.41; p = 0.26; OR = 0.94; 95% CI = 0.42-2.07; p = 0.87, respectively). Conclusions: Taken together, these findings suggest the potential role of GSTT1 deletion mutation as a risk factor for the vulnerability of DR among T2DM patients in the Bangladeshi population.

Association of NAT2, GSTT1, and GSTM1 gene polymorphisms withprostate cancer risk in Bangladeshi population.

One of the leading causes of cancer-related mortality in males is prostate cancer. The latest molecular studies revealed the interconnection of genetic polymorphism of N acetyltransferase (NAT) and Glutathione-S-transferase (GST) gene in the genesis of prostate cancer. The study's aim was to find out the association of NAT2, GSTT1, and GSTM1 gene polymorphisms with the risk of prostate cancer in the Bangladeshi population. This case-control study included 207 histopathologically diagnosed cases of prostate cancer and 200 age-matched healthy controls. After taking informed written consent, 5.0 mL of venous blood was collected to extract genomic DNA for genetic analysis of NAT2, GSTT1& GSTM1 by PCR-RFLP by multiplex PCR methods. In this study, the mean ± SD age of cases and control was 67.3 ± 8.3, and 62.2 ± 6.8 years, respectively. A higher frequency of mutant NAT2*5A, NAT2*6A, and NAT2*7A in prostate cancer cases was observed in this study, in comparison to controls. Prostate cancer risk was found considerably increased in patients with NAT2 slow genotypes, GSTT1 and GSTM1 null genotypes, compared to control. Furthermore, Prostate cancer risk was found very significantly associated with the presence of combined genotypes that included NAT2 (slow), GSTT1 (null), and GSTM1 (null), and the risk rose 9.64-fold when compared to the wild genotype for NAT2, GSTT1, and GSTM1. Again, it was observed that individuals with positive smoking history/family history of cancer along with NAT2 slow genotype had significantly increased risk for prostate cancer. Moreover, the likelihood of developing a moderate to a high-grade tumor (Gleason score 7), as well as locally progressed or metastatic prostate cancer was considerably greater in persons with NAT2 slow genotypes, GSTT1, and GSTM1 null genotypes. This study established the association of genetic polymorphisms of NAT2, GSTT1, and GSTM1 genes with prostate cancer risk in the Bangladeshi population.

Mechanistic insights into the interplays between neutrophils and other immune cells in cancer development and progression.

Cancer is considered a major public health concern worldwide and is characterized by an uncontrolled division of abnormal cells. The human immune system recognizes cancerous cells and induces innate immunity to destroy those cells. However, sustained tumors may protect themselves by developing immune escape mechanisms through multiple soluble and cellular mediators. Neutrophils are the most plenteous leukocytes in the human blood and are crucial for immune defense in infection and inflammation. Besides, neutrophils emancipate the antimicrobial contents, secrete different cytokines or chemokines, and interact with other immune cells to combat and successfully kill cancerous cells. Conversely, many clinical and experimental studies signpost that being a polarized and heterogeneous population with plasticity, neutrophils, particularly their subpopulations, act as a modulator of cancer development by promoting tumor metastasis, angiogenesis, and immunosuppression. Studies also suggest that tumor infiltrating macrophages, neutrophils, and other innate immune cells support tumor growth and survival. Additionally, neutrophils promote tumor cell invasion, migration and intravasation, epithelial to mesenchymal transition, survival of cancer cells in the circulation, seeding, and extravasation of tumor cells, and advanced growth and development of cancer cells to form metastases. In this manuscript, we describe and review recent studies on the mechanisms for neutrophil recruitment, activation, and their interplay with different immune cells to promote their pro-tumorigenic functions. Understanding the detailed mechanisms of neutrophil-tumor cell interactions and the concomitant roles of other immune cells will substantially improve the clinical utility of neutrophils in cancer and eventually may aid in the identification of biomarkers for cancer prognosis and the development of novel therapeutic approaches for cancer treatment.

Effect of XPD and TP53 Gene Polymorphisms on the Risk of Platinum-Based Chemotherapy Induced Toxicity in Bangladeshi Lung Cancer Patients.

BACKGROUND: Platinum-based drugs, including cisplatin and carboplatin, are the most active and extensively used agents for treating lung cancer. Genetic polymorphisms of DNA repair gene XPD and tumor suppressor gene TP53 are connected with alterations in enzyme activity. They may help explain interindividual differences in toxicity outcomes after platinum-based chemotherapy for lung cancer. Therefore, this study aimed to investigate XPD Lys751Gln and TP53 Arg72Pro polymorphisms on the risk of platinum-based chemotherapy-induced toxicity in lung cancer patients in the Bangladeshi population. PATIENTS AND METHODS: Study subjects comprised of 180 platinum-based chemotherapy treated histologically confirmed lung cancer patients. Genetic polymorphisms of XPD were ascertained by Polymerase Chain Reaction-based Restriction Fragment Length Polymorphism (PCR-RFLP), while TP53 genotypes were analyzed using the multiplex PCR-based method. Toxicity was assessed based on the Common Terminology Criteria for Adverse Events (CTCAE v5.0). RESULTS: From the results, there was no significant association observed between grade 1-2 or grade 3-4 platinum-based chemotherapy induced toxicities like anemia and XPD codon 751 (Lys/Gln: OR=1.40, 95% CI=0.75-2.64, p>0.05; Gln/Gln: OR=1.07, 95% CI=0.45-2.52, p>0.05 and Lys/Gln+Gln/Gln: OR=1.31, 95% CI=0.73-2.38, p>0.05) or TP53 codon 72 genetic polymorphisms (Arg/Pro: OR=0.64, 95% CI=0.34-1.17, p>0.05; Pro/Pro: OR=0.46, 95% CI=0.15-1.42, p>0.05 and Arg/Pro+Pro/Pro: OR=0.62, 95% CI=0.34-1.15, p>0.05). Similar results were found between neutropenia, leukopenia, thrombocytopenia and gastrointestinal toxicities and XPD Lys751Gln or TP53 Arg72Pro genetic polymorphisms. CONCLUSION: These findings indicated that no significant association was found between either XPD codon 751 or TP53 codon 72 genetic polymorphisms and platinum-based chemotherapy-related toxicities in Bangladeshi lung cancer patients.

Phytochemistry, pharmacological activity, and potential health benefits of Gly cyrrhiza glabra.

Nature has always been an excellent source for many therapeutic compounds providing us with many medicinal plants and microorganisms producing beneficial chemicals. Therefore, the demand for medicinal plants, cosmetics, and health products is always on the rise. One such plant from the Leguminosae family is licorice and the scientific name is Glycyrrhiza glabra Linn. It is an herb-type plant with medicinal value. In the following article, we shall elaborately look at the plants' phytochemical constituents and the pharmacological impact of those substances. Several compounds such as glycyrrhizin, glycyrrhizinic acid, isoliquiritin, and glycyrrhizic acid have been found in this plant, which can provide pharmacological benefit to us with its anti-cancer, anti-atherogenic, anti-diabetic, anti-asthmatic, anti-inflammatory, anti-microbial, and antispasmodic activity. Alongside, these products have a different role in hepatoprotective, immunologic, memory-enhancing activity. They can stimulate hair growth, control obesity, and have anti-depressants, sedatives, and anticoagulant activity. This review examines recent studies on the phytochemical and pharmacological data and describes some side effects and toxicity of licorice and its bioactive components.

Designing potential siRNA molecule for the nucleocapsid(N) gene silencing of different SARS-CoV-2 strains of Bangladesh: Computational approach.

SARS-CoV-2 is a single-stranded RNA (+) virus first identified in China and then became an ongoing global outbreak. In most cases, it is fatal in humans due to respiratory malfunction. Extensive researches are going to find an effective therapeutic technique for the treatment of SARS-CoV-2 infected individuals. In this study, we attempted to design a siRNA molecule to silence the most suitable nucleocapsid(N) gene of SARS-CoV-2, which play a major role during viral pathogenesis, replication, encapsidation and RNA packaging. At first, 270 complete N gene sequences of different strains in Bangladesh of these viruses were retrieved from the NCBI database. Different computational methods were used to design siRNA molecules. A siRNA molecule was built against these strains using the SiDirect 2.0 server. Using Mfold and the OligoCalc server, the siRNA molecule was tested for its secondary structure and GC material. The Clustal Omega tool was employed to evaluate any off-target harmony of the planned siRNA molecule. Herein, we proposed a duplex siRNA molecule that does not fit any off-target sequences for the gene silencing of SARS-CoV-2. To treat SARS-CoV-2 infections, currently, any effective therapy is not available. Our engineered siRNA molecule could give an alternative therapeutic approach against various sequenced SARS-CoV-2 strains in Bangladesh.

Catechol-O-methyltransferase and dopamine receptor D4 gene variants: Possible association with substance abuse in Bangladeshi male.

Genetic risk of substance abuse is encoded mainly by central neurochemical pathways(mostly dopaminergic system) related to reinforcement and reward. In this study a functionalpolymorphism in Catechol-O-methyltransferase (COMT) (Val158Met) and the Dopamine receptor D4 gene (DRD4) (120 bp tandem duplication) has been studied in substance abused subjects. The study was carried out with 183 substance abused subjects and 175 healthy persons with no history of substance abuse. DNA was extracted and polymorphisms were analyzed using allele-specific PCR. The impact of these two polymorphisms was also analyzed on addictive characteristics (age of starting abuse, a pattern of drug habit, and period of addiction). It was found that only the heterozygous variant of COMT polymorphism (Val/Met) (p<0.05, OR = 1.66, 95% CI = 1.044-2.658) and both homozygous (p<0.05, OR = 0.43, 95% CI = 0.193-0.937) and heterozygous (p<0.05, OR = 0.37, 95% CI = 0.172-0.826) derived variants of DRD4 120 bp tandem duplication were significantly associated with risk of substance abuse compared to controls. In case of association of these polymorphisms with an age of onset, no significant difference was found among three different genotypic groups of COMT polymorphism. Whereas, the homozygous derived variant (240 bp/240 bp) of DRD4 gene was found to have a later age of onset (20.5±0.8) for substance abuse compared to heterozygous (120 bp/240 bp) (19.1±0.8) and wild type homozygous variant (120 bp/120 bp) (16.0±0.5), which was statistically significant (p<0.05). Again, in the case of the pattern of drug habit, the frequency of the Val/Val genotype is higher in polysubstance abused (>2 drugs) subjects (p<0.05) compared to the heterozygous Val/Met containing variants. An association of period of addiction was analyzed with an individual type of substance abuse and found that heroin abused subjects have a significantly higher period of addiction (11.6±1.0) compared to other abusers (p<0.01). Further, it was found that Met/Met containing variants of COMT polymorphism has a more extended period of addiction than other genetic variants in heroin abused subjects. These results indicate that genetic variability may influence the susceptibility to the risk of substance abuse and addictive characteristics.

Assessment of angiotensin converting enzyme gene polymorphism in preeclampsia mothers of Bangladesh.

The study aimed to assess the association of ACE insertion/deletion (I/D) polymorphisms with the susceptibility for preeclampsia in Bangladesh. It was a case-control study involving 220 subjects (100 preeclamptic and 120 normal pregnant women). The ACE (I/D) genotyping was done using the conventional PCR method. Overall, the frequency of ACE II genotypes was significantly (p<.05) higher in normal pregnant women than the preeclamptic women. The pregnant mother with DD genotype was at 3.43-fold higher risk (OR = 3.43; p<.01) of developing preeclampsia while pregnant mother with ID genotype was at lower risk (OR = 1.32; p>.05). On the other hand, patients having either DD or ID genotypes showed 1.9 fold (OR = 1.90; p>.05) increased risk of developing preeclampsia compared to the control group but not statistically significant. This study suggested that ACE (DD) genotypes may have strong associations with the occurrence of preeclampsia.Impact StatementWhat is already known on this subject? The study was conducted among 100 preeclamptic and 120 normal pregnant women. The preeclamptic patients were diagnosed by protein in urine and high blood pressure. The normal pregnant women were selected with no known complications.What the results of this study add? Overall, the pregnant mothers with DD genotype were at 3.43-fold higher risk of developing preeclampsia while pregnant mothers with ID or II genotypes were at a lower risk.What the implications are of these findings for clinical practice and/or further research? ACE (I/D) gene would be a biomarker of early diagnosis of preeclampsia and also be helpful to intervene in personalised medicine and gene therapy as a novel treatment of preeclampsia.

Volatile compounds of black cumin (Nigella sativa L.) seeds cultivated in Bangladesh and India.

The compositional analysis of volatile compounds of Nigella sativa L. seeds obtained from India and Bangladesh was carried out in this study. Apart from the proportion of volatile compounds, the chemical composition of seeds from both sources were similar. The major volatile compounds in Bangladesh seeds were p-cymene (36.35%), thymoquinone (29.77%), α-thujene (12.40%), carvacrol (2.85%), ß-pinene (2.41%), limonene (1.64%), methyl linoleate (1.33%) and sabinene (1.18%), contribution of these is 87.93% of the total volatile oil. On the other hand, the major volatile compounds in Indian seeds were p-cymene (41.80%), α-thujene (13.93%), thymoquinone (10.27%), methyl linoleate (4.02%), carvacrol (3.65%), ß-pinene (2.96%), d-limonene (2.11%), 4,5-epoxy-1-isopropyl-4- methyl-1-cyclohexene (1.80%), sabinene (1.50%) and 4-terpineol (1.22%); contribution of these were 83.24% of the total volatile oil. In both seeds, p-cymene, thymoquinone, and α-thujene were the major components. Importantly, N. sativa seeds of Bangladesh contained almost 3-fold thymoquinone compared to Indian seeds. In conclusion, the seeds from Bangladesh contain a higher amount of terpene ketones (29.86%) represented by thymoquinone in comparison to Indian seeds (10.61%); on the other hand, Indian seeds contained a higher amount of terpene hydrocarbons (63.18%) mainly p-cymene, compared to Bangladesh seeds (54.53%). This is the first study to report detailed compositional analysis and comparison of Nigella sativa L. seeds from Bangladesh and India.

Plant-Produced Monoclonal Antibody as Immunotherapy for Cancer.

Plant-based products have expanded to include cancer immunotherapy, which has made great strides over recent years. Plants are considered inexpensive and facile production platforms for recombinant monoclonal antibody (mAb) due to the latest advancements and diversification of transgenic techniques. Current human biologics, including those based on mAbs produced by fermentation technologies using primarily mammalian cell cultures, have been replaced by plant-produced mAbs, which are cost effective, more scalable, speedy, versatile, and safer. Moreover, the use of animals for antibody production is always a question of ethical unambiguity, and the suitability of animal models for predicting the immunogenicity of therapeutic mAbs in humans and transposition of the immunogenic potential of therapeutic antibodies in animals to the human situation has no scientific rationale. Quite a few plant-based mAbs are approved for the treatment of cancer, ranging from tumors to hematological malignancies. This review focuses on the cutting-edge approaches for using plant-derived mAbs to suppress or prevent cancers. It also discusses the avenues taken to prevent infection by oncogenic viruses, solid tumors, lymphomas, and other cancerous conditions using mAbs. The review emphasizes the use of a plant-derived monoclonal antibody as a premier platform to combat cancer.

TP53 Arg72Pro and XPD Lys751Gln Gene Polymorphisms and Risk of Lung Cancer in Bangladeshi Patients.

BACKGROUND: Tumor suppressor gene (TP53) is considered as the most frequently mutated gene in almost all forms of human cancer. Moreover, genetic variations in the XPD gene affect the DNA repair capacity increasing cancer susceptibility. Polymorphisms within these genes can play a major role in determining individual lung cancer susceptibility. However, several studies have investigated this possibility; but reported conflicting results. Therefore, the objective of this study was to investigate the role of TP53 Arg72Pro and XPD Lys751Gln gene polymorphisms on lung cancer susceptibility in the Bangladeshi population. MATERIALS AND METHODS: Study subjects comprised of 180 lung cancer patients and 200 healthy volunteers. Genetic polymorphism of TP53 was determined by multiplex PCR-based method, while XPD genotypes were analyzed using Polymerase Chain Reaction-based Restriction Fragment Length Polymorphism (PCR-RFLP) method. Lung cancer risk was estimated as odds ratio (OR) and 95% confidence interval (CI). RESULTS: From the results, no significant association between TP53 Arg72Pro polymorphism and lung cancer risk was observed. Whereas, patients with homozygous mutant variants (Gln/Gln) of XPD at codon 751 were found significantly associated with lung cancer risk when compared to the control (OR=3.58; 95% CI=1.58-8.09; p=0.002). Lung cancer risk was found significantly higher with Gln/Gln variants of XPD among smokers (OR=4.03; 95% CI=1.11-14.63; p=0.026). Significant increased risk of lung cancer was found with Arg/Pro genotypes of TP53, Lys/Gln and Gln/Gln variants of XPD in individuals with family history of cancer (OR=3.44; 95% CI=1.36-8.72; p=0.011; OR=3.17; 95% CI=1.20-8.39; p=0.024; OR=16.35; 95% CI=0.92-289.5; p=0.007, respectively). CONCLUSION: The findings indicated that homozygous mutant variants (Gln/Gln) of XPD were associated with increased lung cancer risk, whereas TP53 Arg72Pro polymorphism was not associated with risk of lung cancer among Bangladeshi patients.
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A Dynamic Mathematical Modeling Revelation about the Impact of Vaccination on Hepatitis B Virus-induced Infection and Death Rate in Bangladesh.

AIM: Attainment of sustainable development goal (SDG) targets requires reducing the rate of new hepatitis B virus (HBV)-induced infection and mortality rate to 90% and 65%, respectively, by 2030. Therefore, it is important to investigate the feasibility of reducing the required rates of HBV-induced infection and death incidents at the current rate of vaccination coverage in Bangladesh. Moreover, factors influencing vaccination coverage like negative bias toward girls during immunization can affect the current vaccination program and ultimately hinder the efforts to reduce HBV-induced infection and death rates. To investigate the possibility of reducing HBV-induced infection and death rates with current vaccination coverage, we adopted mathematical molding-based approach. MATERIALS AND METHODS: We developed a mathematical model based on the susceptible-infectious-recovered model to simulate the HBV-induced infection in children under the age of five at three different vaccination rates: 80, 90, and 95%. Additionally the impact of current vaccination coverage was assessed on HBV-induced death rates in the future. Moreover, we took advantage of the mathematical model to investigate the impact of negative bias toward girls in vaccination program on HBV-induced infection and death rates. RESULTS: The model simulations revealed that 10% increase in the vaccination rate from 80 to 90% can potentially contribute to the significant lowering (around 40%) of HBV-induced infection rate among children. When increased by 5% of vaccination rate from 90 to 95%, the HBV-infection rate is likely to be decreased by another 22%. Likewise, 44% reduction in HBV-induced death rate in the future (2050 onward) can potentially be achieved by 10% increase in the current vaccination rate from 80 to 90%, whereas 5% increase in the current vaccination rate (90-95%) may lead to 24% further reduction of death rate. These results underscored the significant impact of vaccination in reducing HBV-induced infection among children and future death rates in adults. Moreover, at 90% vaccination coverage, the negative bias of vaccination toward girls contributes to an increase of 15 and 12% of HBV-induced infection and death rates, respectively, in female subjects compared to their male counterparts. CONCLUSION: The current vaccination coverage (80-90%) is further aggravated by untimely vaccination, dropouts from vaccination program, and negative bias toward girls in vaccination program. Therefore, if the current situation persists, it will not be possible to accomplish the required reduction in HBV-induced infection and death rates by 2030, according to the SDG guidelines. Moreover negative bias in the vaccination program may intensify the HBV-induced infection and death rates in the future. CLINICAL SIGNIFICANCE: In light of the mathematical model, we suggest that the vaccination coverage should be increased to 95% without any negative bias toward girls. To accomplish this, the concerning authorities must ensure timely and full completion of the HBV vaccine schedules, reducing dropouts from vaccination program, and lastly preventing negative bias toward girls to uplift vaccination coverage to more than 95% with gender equality. Without these strategies, the necessary reduction in the HBV-induced infection and death rates in Bangladesh may not be attained per SDG directives. HOW TO CITE THIS ARTICLE: Chakraborty S, Chakravorty R, Alam S, et al. A Dynamic Mathematical Modeling Revelation about the Impact of Vaccination on Hepatitis B Virus-induced Infection and Death Rate in Bangladesh. Euroasian J Hepato-Gastroenterol 2019;9(2):84-90.

Association of glutathione S-transferase theta 1 and glutathione S-transferase mu 1 gene polymorphism with the risk of pre-eclampsia during pregnancy in Bangladesh.

AIM: In this study, we analyzed the risk of developing pre-eclampsia with respect to glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase mu 1 (GSTM1) genotypes. We also tried to find relationship between genotypes and biochemical parameter change in pre-eclampsia patients. METHODS: In total, 104 pre-eclampsia patients and 200 healthy controls were recruited for the study. Peripheral venous blood was drawn from study subjects and DNA was extracted from whole blood and multiplex polymerase chain reaction method was used to identify genotypes of GSTT1 and GSTM1 gene. All biochemical parameters were measured using colorimetric method. RESULTS: Serum glutamic pyruvic transaminase level was significantly higher (P < 0.01) and hemoglobin level was significantly lower (P < 0.001) in pre-eclampsia patients compared to control subjects. Significant association was found in GSTM1 null genotype with pre-eclampsia (P < 0.001) with an odds ratio (OR) analysis showing more than four-fold increased risk (OR = 4.75; 95% CI = 2.17-10.39; P <0.001). But for GSTT1 gene, null genotype was not associated with increased risk of developing pre-eclampsia (P > 0.05). In case of GSTT1 and GSTM1, the patients having both null genotypes for GSTT1 and GSTM1 showed significant (P < 0.001) higher risk of developing pre-eclampsia (OR = 7.64; 95% CI = 2.38-24.60; P < 0.001). CONCLUSION: GSTM1 null genotype increases the risk of pre-eclampsia. Combined GSTT1 and GSTM1 null genotype, the risk was even higher.

Lead Molecule Prediction and Characterization for Designing MERS-CoV 3C-like Protease Inhibitors: An In silico Approach.

BACKGROUND: 3C-like protease also called the main protease is an essential enzyme for the completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of Middle East Respiratory Syndrome Coronavirus using in silico methods. METHODS: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease was identified by structure-based virtual screening and ligand-based virtual screening method. Further, the compounds were validated through absorption, distribution, metabolism and excretion filtering. RESULTS: Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3 compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079) having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining 7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a substrate of P-glycoprotein. CONCLUSION: Our predicted compounds may be capable of inhibiting 3C-like protease but need some further validation in wet lab.

Association of ATP binding cassette transporter 1 (ABCA 1) gene polymorphism with type 2 diabetes mellitus (T2DM) in Bangladeshi population.

AIMS: ATP-binding cassette transporter 1 (ABCA1) gene polymorphism has been reported as one of the genetic risk factors for T2DM in various populations with conflicting results. The aim of this study is to investigate the association of ABCA1 C69T polymorphism and lipid profile with T2DM in Bangladeshi population. MATERIALS AND METHODS: A total of 102 T2DM subjects and 98 healthy controls were recruited and their genotypes for ABCA1 gene polymorphisms were determined based on the PCR-RFLP technique. Serum lipid profiles (total cholesterol, HDL-C, LDL-C and TG) were also estimated by using standard methods. RESULTS: ABCA 1 (C69T) genotypes frequencies were estimated. The percentages of CC, CT and TT genotypes at 69 position of ABCA1 gene were 31.63%, 58.16% and 10.21% in control as well as 22.54%, 69.60% and 7.86% in diabetes group respectively. Significant association was not found between ABCA1 (C69T) genotypes and T2DM in Bangladeshi population (Odd Ratio: 1.67; 95% Confidence Interval: 0.88 to 3.19 for CT genotype and Odd Ratio: 1.07; Confidence Interval: 0.36 to 3.16 for TT genotype; p > 0.05). Serum lipid profiles were not associated with T2DM. CONCLUSION: ABCA1 gene polymorphism might not be a genetic risk factor for T2DM subjects among Bangladeshis. We did not find a relationship between genotypes and lipid concentrations in our two groups. Study with a larger sample size will help us to understand the relationship of ABCA1 C69T genotype and lipid profile with T2DM.

Vitamin A Supplementation during Pregnancy Enhances Pandemic H1N1 Vaccine Response in Mothers, but Enhancement of Transplacental Antibody Transfer May Depend on When Mothers Are Vaccinated during Pregnancy.

Background: In the growing embryo, the vitamin A requirement is tightly regulated. Maternal vitamin A deficiency during pregnancy may alter maternal immune function to accommodate the fetus. Objective: Our primary objective was to determine the effect of oral vitamin A supplementation (VAS) during pregnancy and until 6 mo postpartum on pandemic H1N1-vaccine responses in mothers and their infants at 6 mo of age. Methods: In this randomized controlled clinical trial, pregnant women (n = 112) during the second trimester (mean ± SD: 14 ± 1 wk) were assigned to receive either an oral dose of 10,000 IU vitamin A or placebo weekly until 6 mo postpartum. During the third trimester, mothers received a single dose of inactivated pandemic H1N1-influenza vaccine. Hemagglutination-inhibition (HAI) titer was measured in cord, infant, and maternal blood samples. Multivariate regressions with adjustments were used for data analysis. Results: Seventy-six percent of women had low plasma retinol concentrations (<1.05 µmol/L) in their second trimester. VAS of mothers increased vitamin A concentrations in cord blood by 21.4% and in colostrum by 40.7%. At 6 mo postpartum, women in the vitamin A group had 38.7% higher HAI titers and a higher proportion of HAI titer of ≥1:40 of the cutoff compared with the placebo group. A total of 54.5% of infants had an HAI titer ≥1:40 at 6 mo of age, but there was no difference in HAI titer in infants between groups. Overall, HAI in cord blood did not differ between groups, but in the placebo group, cord blood HAI was negatively associated with maternal "vaccination-to-delivery intervals" (rs = -0.401; P = 0.5), and maternal VAS increased cord blood HAI 6-fold if antenatal immunization was administered ≥10 wk before delivery. Conclusions: In a community with low vitamin A status, weekly maternal VAS during pregnancy and postpartum increases the breast-milk vitamin A concentration and enhances prenatal H1N1-vaccine responses in mothers, but the benefits of maternal VAS in transplacental antibody transfer may depend on the time of gestation when mothers were vaccinated. This trial was registered at clinicaltrials.gov as NCT00817661.

Association of vitamin D and vitamin D binding protein (DBP) gene polymorphism with susceptibility of type 2 diabetes mellitus in Bangladesh.

AIMS: Polymorphism in vitamin D binding protein gene may have an impact on serum vitamin D transport and thus may have relation with type 2 diabetes mellitus. In our study, we investigated the association of serum vitamin D level and vitamin D-binding protein gene polymorphism with the onset of type 2 diabetes mellitus. MATERIALS AND METHODS: Blood samples were collected from 104 type 2 diabetic patients and 107 healthy volunteers. Serum vitamin D was measured by high-performance liquid chromatography. Genetic analysis of vitamin D-binging protein gene was carried out by polymerase chain reaction - restriction fragment length polymorphism method. RESULTS: We found significantly (p<0.001) lower level of vitamin D in type 2 diabetic patients compared to control subjects. A significantly negative correlation (r=-0.25, p<0.05) between vitamin D level and fasting blood glucose level was found among type 2 diabetic subjects. The Glu/Glu at codon 416 (rs7041) (p<0.05) and Lys/Lys at codon 420 (rs4588) (p<0.01) variants of vitamin D binding protein gene was significantly higher in type 2 diabetic subjects than controls. The patients with Glu/Glu and Lys/Lys genotypes respectively at codon 416 (odds ratio=2.87; 95% confidence interval=1.19 to 6.95) and 420 (odds ratio=8.9; 95% confidence interval=1.89 to 41.99) were at high risk of developing type 2 diabetes. CONCLUSIONS: Our present study strongly suggests that there might have an association of vitamin D, and vitamin D-binding protein gene (codon 416 & 420) polymorphisms with the occurrence of type 2 diabetes mellitus.