Association of Chronic Toxoplasma gondii Infection with Pro-Inflamatory Cytokine Interleukin (IL)-12 Responses in Type-2 Diabetes Mellitus Patients of Bangladesh.

Toxoplasma gondii is an intracellular protozoan parasite that causes toxoplasmosis in around one-third of the world population, particularly in pregnant women and immunocompromised individuals. Diabetes mellitus (DM) is one of the most severe global health challenges in the 21st century, and especially, type-2 diabetes mellitus (T2DM) accounts for 90% of the diabetes cases diagnosed globally. In Bangladesh, the rate of T2DM is rising gradually with the improvement in living standards. The aim of this study is to find out the correlation between latent toxoplasmosis and T2DM, emphasizing the pro-inflammatory cytokine immunity. For this, 100 (N = 100) patients with T2DM and 100 (N = 100) healthy controls were enrolled to determine the seroprevalence of toxoplasmosis using enzyme-linked immunosorbent assay (ELISA). In addition, ELISA was also performed to determine the level of pro-inflammatory cytokine, interleukin (IL)-12, to understand its role in the development of toxoplasmosis. In our study, 39.39% of the T2DM patients were positive with anti-T. gondii Immunoglobulin G by ELISA, whereas the rate of seropositivity in healthy controls was 39.73%. We did not find significant association between T. gondii infection and T2DM, but our data confirmed a high prevalence of chronic toxoplasmosis in Bangladeshi population. From hematology tests, it was found that the T2DM patients had significantly lower levels of total white blood cells (P = 0.0015), circulating eosinophils (P = 0.0026), and neutrophils (P = 0.0128) than the healthy controls. On the other hand, the levels of lymphocytes (P = 0.0204) and monocytes (P = 0.0067) were significantly higher in patients. Furthermore, T. gondii infected T2DM patients had significantly higher levels of IL-12 than the healthy controls (P = 0.026), suggesting a link between parasitic infection and IL-12 secretion. Further studies are to be performed to find out the exact cause of high prevalence of chronic T. gondii infection in Bangladeshi population.

Most frequently harboured missense variants of hACE2 across different populations exhibit varying patterns of binding interaction with spike glycoproteins of emerging SARS-CoV-2 of different lineages.

Since the emergence of SARS-CoV-2 at Wuhan in the Hubei province of China in 2019, the virus has accumulated various mutations, giving rise to many variants. According to the combinations of mutations acquired, these variants are classified into lineages and greatly differ in infectivity and transmissibility. In 2021 alone, a variant of interest (VoI) Mu (B.1.621), as well as, variants of concern (VoC) Delta (B.1.617.2) and Omicron (BA.1, BA.2) and later in 2022, BA.4, BA.5, and BA.2.12.1 have emerged. Since then, the world has seen prominent surges in the rate of infection during short periods of time. However, not all populations have suffered equally, which suggests a possible role of host genetic factors. Here, we investigated the strength of binding of the spike glycoprotein receptor-binding domain (RBD) of the SARS-CoV-2 variants: Mu, Delta, Delta Plus (AY.1), Omicron sub-variants BA.1, BA.2, BA.4, BA.5, and BA.2.12.1 with the human angiotensin-converting enzyme 2 (hACE2) missense variants prevalent in major populations. In this purpose, molecular docking analysis, as well as, molecular dynamics simulation was performed of the above-mentioned SARS-CoV-2 RBD variants with the hACE2 containing the single amino acid substitutions prevalent in African (E37K), Latin American (F40L), non-Finnish European (D355 N), and South Asian (P84T) populations, in order to predict the effects of the lineage-defining mutations of the viral variants on receptor binding. The effects of these mutations on protein stability were also explored. The protein-protein docking and molecular dynamics simulation analyses have revealed variable strength of attachment and exhibited altered interactions in the case of different hACE2-RBD complexes. In vitro studies are warranted to confirm these findings which may enable early prediction regarding the risk of transmissibility of newly emerging variants across different populations in the future.

Association study of leukocyte telomere length and genetic polymorphism within hTERT promoter with type 2 diabetes in Bangladeshi population.

Telomeres are protective cap on the ends of DNA of non-coding tandem repeats of TTAGGG. Human telomerase reverse transcriptase (hTERT) is a catalytic subunit of telomerase that maintains the structure of telomeres. Type 2 diabetes (T2D) affects multi-organ and telomere length by altering telomerase activity. We aimed to evaluate the relative telomere length (RTL) and risk association of rs2853669 with T2D in Bangladeshi population. RTL was measured in 408 unrelated Bangladeshi (224 T2D and 184 healthy) using primers for target gene and reference gene albumin. Genotypic frequencies for rs2853669 were determined using TaqMan® probes. The mean level of age adjusted RTL (AARTL) varied significantly between the healthy and individuals with T2D for all the genotypes with respect to rs2853669. Moreover, healthy individuals had significantly higher AARTL than T2D. Similar findings were observed when study participants were stratified based on their gender. Association studies revealed that under codominant model of inheritance, TC genotype showed protective role against development of type 2 diabetes. This study suggests a possible role of telomere biology in T2DM, but their association needs to be evaluated further with a larger series and matched healthy controls.

Genetic variation of the transcription factor GATA3, not STAT4, is associated with the risk of type 2 diabetes in the Bangladeshi population.

Type 2 diabetes mellitus is a multifactorial metabolic disorder caused by environmental factors and has a strong association with hereditary issues. These hereditary issues result in an imbalance in CD4+T cells and a decreased level of naïve CD4+T cells, which may be critical in the pathogenesis of type 2 diabetes. Transcription factors GATA3 and STAT4 mediate the cytokine-induced development of naïve T cells into Th1 or Th2 types. In the present study, genetic analyses of GATA3 SNP rs3824662 and STAT4 SNP rs10181656 were performed to investigate the association of allelic and genotypic variations with the risk of T2D in the Bangladeshi population. A total of 297 unrelated Bangladeshi patients with type 2 diabetes and 247 healthy individuals were included in the study. The allelic and genotypic frequencies of rs10181656 located in the STAT4 gene were not found to be associated with risk of type 2 diabetes. The GATA3 rs3824662 T allele and mutant TT genotype had a significant association with the risk of T2D [OR: 1.52 (1.15-2.02), X2 = 8.66, p = 0.003 and OR: 2.98 (1.36-6.55), X2 = 7.98, p = 0.04, respectively]. Thus, the present study postulates that the genetic variation of the transcription factor GATA3, not STAT4, is associated with the risk of type 2 diabetes in the Bangladeshi population.

Prediction of epitope-based peptides for the utility of vaccine development from fusion and glycoprotein of nipah virus using in silico approach.

This study aims to design epitope-based peptides for the utility of vaccine development by targeting glycoprotein G and envelope protein F of Nipah virus (NiV) that, respectively, facilitate attachment and fusion of NiV with host cells. Using various databases and tools, immune parameters of conserved sequence(s) from G and F proteins of different isolates of NiV were tested to predict probable epitope(s). Binding analyses of the peptides with MHC class-I and class-II molecules, epitope conservancy, population coverage, and linear B cell epitope prediction were analyzed. Predicted peptides interacted with seven or more MHC alleles and illustrated population coverage of more than 99% and 95%, for G and F proteins, respectively. The predicted class-I nonamers, SLIDTSSTI and EWISIVPNF, superimposed on the putative decameric B cell epitopes, were also identified as core sequences of the most probable class-II 15-mer peptides GPKVSLIDTSSTITI and EWISIVPNFILVRNT. These peptides were further validated for their binding to specific HLA alleles using in silico docking technique. Our in silico analysis suggested that the predicted epitopes, either GPKVSLIDTSSTITI or EWISIVPNFILVRNT, could be a better choice as universal vaccine component against NiV irrespective of different isolates which may elicit both humoral and cell-mediated immunity.

Pattern of ß-Thalassemia and Other Haemoglobinopathies: A Cross-Sectional Study in Bangladesh.

Thalassemia and other structural haemoglobinopathies are the major erythrocyte formation disorder prevalent in certain parts of the world including Bangladesh. We investigated 600 cases of anaemic patients referred from various parts of the country for diagnosis and counselling during 3 months (April to June 2011) of time. The most common form of haemoglobin (Hb) formation disorder observed in 600 subjects studied was ß-thalassemia minor (21.3%). Two other conditions, such as E-ß-Thalassemia and HbE trait, were also fairly common (13.5 and 12.1%, resp.) in the total subjects studied. Other forms of haemoglobin formation disorders observed were HbE disease (9.2%), Hb D/S trait (0.7%), ß-thalassemia major (0.5%), and δ-ß-thalassemia (0.5%). The majority of the haemoglobinopathies belonged to neonatal to childhood period (0-15 years), followed by reproductive age group (16-45 years). Few old-age (46+ years) cases were also detected in course of clinical complications.

A creeper, Coccinia indica, has anti-hyperglycaemic and anti-ureogenic effects in diabetic rats.

OBJECTIVE: To explore how ethanolic extract of Coccinia indica affects normal and diabetic rats. METHODS: The case-controlled animal study was conducted in June 2008 at the Department of Biochemistry and Molecular Biology, University of Dhaka, Bangladesh. Two groups of 10 male rats each - one streptozotocin-induced diabetics and the other normal - were fed orally aqueous suspension of residue extracted from C. indica leaves with 60% ethanol after 18 hours of fasting. After 90 minutes of oral administration, the rats were sacrificed, and blood level of glucose and free fatty acids and hepatic arginase activity were analysed. RESULTS: The blood sugar level had significantly decreased by 23% (p <0.01) and 28% (p <0.001) in the normal and diabetic rats. Level of blood-free fatty acid was depressed by 15% (p <0.01) and 25% (p <0.001) in the two groups respectively. Moreover, the activity of hepatic arginase, a key urea cycle enzyme, was significantly depressed by 14% (p < 0.05) and 22% (p < 0.02) in the normal and diabetic groups. CONCLUSION: Results suggested that C. indica extract had anti-hyperglycaemic and anti-ureogenic effects on the diabetic rats as judged by the decreased level of blood glucose and fatty acid and hepatic arginase activity.

Gamete membrane microdomains and their associated molecules in fertilization signaling.

Fertilization is the fundamental system of biological reproduction in many organisms, including animals, plants, and algae. A growing body of knowledge has emerged to explain how fertilization and activation of development are accomplished. Studies on the molecular mechanisms of fertilization are in progress for a wide variety of multicellular organisms. In this review, we summarize recent findings and debates about the long-standing questions concerning fertilization: how egg and sperm become competent for their interaction with each other, how the binding and fusion of these gamete cells are made possible, and how the fertilized eggs initiate development to a newborn. We will focus on the structure and function of the membrane microdomains (MDs) of egg and sperm that may serve as a platform or signaling center for the aforementioned cellular functions. In particular, we provide evidence that MDs of eggs from the African clawed frog, Xenopus laevis, play a pivotal role in receiving extracellular signals from fertilizing sperm and then transmitting them to the egg cytoplasm, where the tyrosine kinase Src is present and responsible for the subsequent signaling events collectively called egg activation. The presence of a new signaling axis involving uroplakin III, an MD-associated transmembrane protein, and Src in this system will be highlighted and discussed.

Assessment of impact on health of children working in the garbage dumping site in Dhaka, Bangladesh.

Waste dumping is one of the major causes of environment pollution in Bangladesh. This study was designed to assess the impact on health of children working in one of the garbage dumping sites in Dhaka. Blood samples were collected from exposed (n = 20, aged: 8-15 years, exposed to dumped garbage from 6 months to 6 years) and control subjects (n = 15, age matched and never worked in the garbage dumping site). Oxidative stress markers like lipid hydroperoxides, thiobarbituric acid reactive substances and protein carbonyl content were measured. Alkaline comet assay was performed to assess the possible damage in DNA. To check the consequences of possible toxic exposure, we performed liver function tests of the study subjects. Oxidative stress-mediated damage of macromolecules was found to be significantly increased in the exposed children. Liver function tests were found normal. Thus, the children working in garbage dumping site are in severe health risk.

Physiology and gene expression of the rice landrace Horkuch under salt stress.

Good donors in breeding for salt tolerance are a prerequisite for food security under changing climatic conditions. Horkuch, a farmer-popular salt tolerant rice (Oryza sativa L.) variety from the south-west coast of Bangladesh was characterised up to maturity under NaCl stress, together with a modern variety (BRRI dhan41), a sensitive control (BRRI dhan29) and Pokkali, the salt-tolerant benchmark for rice. Horkuch had low reduction in shoot biomass, a low Na:K ratio in flag leaves, a low percent reduction in yield and good partitioning of Na in the older leaves, and maintained high levels of Ca and Mg in the flag leaves. In order to understand the physiology at the molecular level, the expression of salt-responsive genes was investigated using microarray analysis. Salt-stressed cDNA of Horkuch seedlings were hybridised with cDNA probes synthesised mainly from database sequences of Arabidopsis thaliana (L.) Heynh. The upregulated genes included transcription factors, signal transducers, metabolic enzymes, reactive oxygen species (ROS) scavengers, osmoprotectants and some specific salt-induced transcripts. An increase in expression of photosynthesis-related genes as well ROS scavengers suggested that this could be the reason for the better yield performance of Horkuch. The data therefore indicate Horkuch as a potential donor alternative to Pokkali in breeding programs for salt tolerance.

Analysis of serum lipid profiles, metal ions and thyroid hormones levels abnormalities in beta-thalassaemic children of Bangladesh.

OBJECTIVE: To assess the serum lipid profile of cardiovascular disease free male and female children with beta-thalassaemia. Levels of zinc, copper and magnesium in the serum were also determined along with the Thyroid profile. METHODS: From January to December 2007, we enrolled 121 consecutive patients with beta-thalassaemia that visited The Thalassaemia Center at Dhaka Shishu (Children) Hospital, Bangladesh every month for routine examinations. Fasting blood lipid levels were measured in all participants. Zinc, Copper and Magnesium levels in serums were determined. Thyroid function was also assessed by evaluating T3, T4 and TSH levels. RESULTS: Of the 121 patients, 65 were males (10.14 +/- 3.91 years) and 56 were females (9.08 +/- 4.32 years). Data analysis revealed that 2.0% males and 4.35% females had high total serum cholesterol, and 28.57% males and 21.74% females had high triglyceride levels. In addition, mean HDL-cholesterol levels were 21.14 +/- 5.82 mg/dl in males and 21.17 +/- 6.02 mg/dl in females; total-cholesterol to HDL-cholesterol ratios were 5.47 +/- 1.66 and 5.96 +/- 2.81 in males and females respectively. About 60% patients showed low serum level of Zn and Cu. Hypothyroidism was detected in 30% patients and 23% patients had abnormal experimental values of all the study parameters. CONCLUSIONS: The majority of the patients had blood lipid levels (by the exception of HDL-cholesterol) within the normal range, and consequently the prevalence of lipid abnormalities was much lower as compared to the general population of the same age. Interestingly, the total-cholesterol to HDL-cholesterol ratio was high in our patients, and may underline the importance of this index for the prognosis of future cardiac events in these patients. The serum Zn and Cu levels were low in most of the patients which may cause some metabolic abnormalities in future. Most of the patients also showed hypothyroidism indicating the presence of endocrine complications.