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.

XRCC1 and XPD polymorphisms: clinical outcomes and risk of prostate cancer in Bangladeshi population.

BACKGROUND: In Bangladesh, only a fraction of prostate cancer patients are diagnosed annually due to lack of symptom awareness and screening challenges, resulting in high mortality. Aiming to improve screening methods, we evaluated X-ray cross-complementing gene 1 (XRCC1) Arg194Gln and Xeroderma pigmentosum group D (XPD) Lys751Gln polymorphisms to determine their relevance as potential markers for predicting prostate cancer risk, severity and clinical parameters in Bangladeshi population. METHODS AND RESULTS: This study included 132 prostate cancer patients and 135 healthy controls. Genotype analysis was done from blood samples by the PCR-RFLP method. The XRCC1 Trp/Trp genotype was associated with prostate cancer (ORadj = 5.51; 95% CI = 1.13-26.78; p-value = 0.03) compared to Arg/Arg genotype. No significant association was found between the XPD variants and prostate cancer risk. The XRCC1 Trp/Trp genotype increased prostate cancer risk in smokers and non-smokers but was statistically non-significant. In individuals without a family history of cancer, the XRCC1 Trp/Trp genotype had a non-significant 4.64-fold higher risk (ORadj=4.64; 95% CI = 0.88-24.36; p-value = 0.07), while the XPD Gln/Gln had a 2.66-fold non-significant higher risk (ORadj=2.66; 95% CI = 0.88-8.10; p-value = 0.09). The XRCC1 Trp/Trp variant was associated with hematuria risk, higher mean serum creatinine, and mean prostate-specific antigen (PSA) levels in prostate cancer patients. The XPD Gln/Gln variant was only associated with higher mean serum creatinine levels. CONCLUSION: Our findings suggest that XRCC1 screening may be used as a biomarker for prostate cancer to improve early diagnosis in Bangladesh.

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.

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.

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.

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.

Chickpeas suppress postprandial blood glucose concentration, and appetite and reduce energy intake at the next meal.

The current study was designed to explore the beneficial properties of chickpeas consumption on suppressing appetite, excessive blood glucose excursions, and energy intake (EI) from a subsequent meal. Two caloric preloaded foods, chickpeas, and white bread were compared to water control, fed to healthy female subjects at equal energy density, volume, and available carbohydrate content in two experiments spanning over 60 and 120 min. Blood glucose was measured by a portable glucometer and satiety by using a visual analogue scale questionnaire at baseline and every 15 up to 60 min in both experiments and then every 30 until 120 min in Experiment 2 after the preloads ingestion. A test meal was served at the end of both experiments to calculate EI and percent energy compensation (%EC). The results suggest a reduction of 29-36% in blood glucose concentration, and 83-98% EC after the chickpeas in Experiments 1 and 2 respectively compared to white bread. The average appetite showed a positive association with EI. We conclude that the consumption of chickpeas is beneficial on glycemic control and may help in body weight management through suppressing appetite and energy intake.

Maternal zinc supplementation improves hepatitis B antibody responses in infants but decreases plasma zinc level.

PURPOSE: The World Health Report identifies zinc deficiency as one of the major causes of disease in developing countries, and infants are at particular risk. We aimed to investigate the effect of maternal zinc supplementation on the infant's immune function in a population at risk of deficiency. METHODS: In a randomized, double-blind placebo-controlled trial, mothers were supplemented either with 20 mg/day of elemental zinc (n = 20) or placebo (n = 19) at the beginning of second trimester, which continued until 6 months postpartum. Indicators of the infants' immune function measured included interleukin (IL)-7, thymic size and response to hepatitis B vaccination. RESULTS: Infants born from mothers receiving zinc supplements during pregnancy and postpartum had significantly lower plasma zinc (p < 0.05) but marginally higher IL-7 and antibody responses to hepatitis B vaccination (p < 0.10) than infants born from mothers not receiving zinc. Maternal zinc supplementation showed no negative impact on copper status of mothers or their infants. Maternal zinc supplementation did not influence infant thymic size, but cord blood IL-7 was found positively associated with thymus size at 1 month of age (r = 0.392) and with hepatitis B vaccine response at 6 months of age (r = 0.386). CONCLUSION: Prenatal and postnatal zinc supplementation marginally improved T cell-dependent antibody responses in infants along with IL-7, a cytokine involved in human T cell development and maintaining homeostasis.

Association of TP53 gene polymorphisms with susceptibility of bladder cancer in Bangladeshi population.

TP53 is considered to be the most frequently mutated gene in every forms of human cancer. The objective of this study was to evaluate the association of TP53 codon 72 and 248 polymorphisms with the susceptibility and severity of bladder cancer in Bangladeshi population. A case-control study on 102 bladder cancer patients and 140 control subjects was conducted. The genotype analysis was done by polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) method. The patients with Pro/Pro genotypes at 72 position were at high risk (odds ratio (OR) = 3.02; 95 % confidence interval (95 % CI) = 1.42 to 6.40) of developing bladder cancer. The cigarette smokers with Pro/Pro genotypes at 72 position were found to have a 3.91-fold increased risk to develop bladder cancer (OR = 3.91; 95 % CI = 1.33 to 11.5). There was no significant association of codon 248 polymorphisms with bladder cancer in the study population. Taken together, these findings indicate an association between p53 codon72 polymorphism and bladder cancer risk in Bangladeshi population.

Dissecting the multifaceted roles of autophagy in cancer initiation, growth, and metastasis: from molecular mechanisms to therapeutic applications.

Autophagy is a cytoplasmic defense mechanism that cells use to break and reprocess their intracellular components. This utilization of autophagy is regarded as a savior in nutrient-deficient and other stressful conditions. Hence, autophagy keeps contact with and responds to miscellaneous cellular tensions and diverse pathways of signal transductions, such as growth signaling and cellular death. Importantly, autophagy is regarded as an effective tumor suppressor because regular autophagic breakdown is essential for cellular maintenance and minimizing cellular damage. However, paradoxically, autophagy has also been observed to promote the events of malignancies. This review discussed the dual role of autophagy in cancer, emphasizing its influence on tumor survival and progression. Possessing such a dual contribution to the malignant establishment, the prevention of autophagy can potentially advocate for the advancement of malignant transformation. In contrast, for the context of the instituted tumor, the agents of preventing autophagy potently inhibit the advancement of the tumor. Key regulators, including calpain 1, mTORC1, and AMPK, modulate autophagy in response to nutritional conditions and stress. Oncogenic mutations like RAS and B-RAF underscore autophagy's pivotal role in cancer development. The review also delves into autophagy's context-dependent roles in tumorigenesis, metastasis, and the tumor microenvironment (TME). It also discusses the therapeutic effectiveness of autophagy for several cancers. The recent implication of autophagy in the control of both innate and antibody-mediated immune systems made it a center of attention to evaluating its role concerning tumor antigens and treatments of cancer.

Relationship between perceived body image and recorded body mass index among Kuwaiti female university students.

The associations between body image and attitudes toward obesity and thinness and their associations with measured body mass index (BMI) among female students of Kuwait University (n = 137) was examined in 2008. The body image perceptions were assessed using nine female silhouettes figures. The difference between current perceived body image (PBI) and ideal body image (IBI) was used as a measure of body image dissatisfaction (BID). Students tended to have a bigger PBI and smaller IBI than would be expected from their BMI category, leading to high levels of BID in each BMI category. PBI, IBI, BID, RBI were highly correlated with each other, and BMI was significantly correlated with each of them. The coefficients of these associations were not significantly altered in multiple regression analysis by the addition of potential confounding variables, such as age, marital status, physical activity, dieting behavior, parental education, and family size. These results suggest that PBI and a desire to be thinner were strongly related to BID and that thinness is becoming more desired in Kuwaiti society than the plump body image of the past.

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.

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.

Activation of p53/ATM-dependent DNA damage signaling pathway by shiga toxin in mammalian cells.

In this report, we studied the role of DNA damage signaling pathway in shiga toxin (STX)-induced mammalian cell death. Shiga toxin 1 exhibited cytotoxic activity in different mammalian cells such as HeLa cells, mouse embryo fibroblasts, and Caco-2 cells (a human intestinal primary fibroblast cell line). STX-1 was found to induce the release of cytochrome c from the mitochondria, nuclear condensation, and fragmentation of chromosomal DNA. STX-1 activated DNA damage signaling as determined by induction of H2AX phosphorylation and cleavage of PARP. Inhibition of caspase-3 reduced STX-1-induced phosphorylation of H2AX and nuclear condensation. It was also found that STX-1-induced p53 expression, and activated ATM in mammalian cells. STX-1-induced nuclear condensation significantly reduced in p53-, and ATM-knockout cells suggesting an involvement of p53 and ATM in transducing signals produced by STX in inducing apoptosis in mammalian cells. This is the first demonstration of involvement of ATM/p53 in STX-inducing mammalian cell death.

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.

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.

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.