Diabetes mellitus has become a serious and chronic metabolic disorder that results from a complex interaction of genetic and environmental factors, principally characterized by hyperglycemia, polyuria, and polyphagia. Uncontrolled high blood sugar can result in a host of diabetic complications. Prolonged diabetes leads to serious complications some of which are life-threatening. The prevalence of diabetes patients is rising at epidemic proportions throughout the world. Every year, a major portion of the annual health budget is spent on diabetes and related illnesses. Multiple risk factors are involved in the etiopathogenesis of the disease and turning the disease into an epidemic. Diabetes, for which there is no cure, apparently can be kept under control by maintaining self-care in daily living, effective diabetes education, with comprehensive improvements in knowledge, attitudes, skills, and management. In this review, we focused on the biochemical aspects of diabetes, risk factors including both environmental and genetic, disease complications, diagnosis, management, and currently available medications for the treatment of diabetes.

The dengue-infected patients with or without hemorrhagic manifestations, typically exhibit moderate to severe thrombocytopenia. A thrombopoietin receptor agonist – eltrombopag has been efficacious in correcting thrombocytopenia in patients with various pathological conditions including immune thrombocytopenia, chronic liver disease, and severe aplastic anemia. This study investigated the efficacy and safety of eltrombopag to correct dengue-mediated thrombocytopenia. In this open-label, randomized controlled phase-II trial, patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) having platelet (PLT) count lower than 100 × 109/L without comorbidity, pregnancy, and liver abnormalities were enrolled in Dhaka Medical College Hospital, Better Life Hospital and AMZ hospital, Dhaka, Bangladesh. Between October 10, 2019, and December 30, 2019, 123 DF and DHF patients were assessed for eligibility to be enrolled in the trial. Fourteen patients were excluded as they failed to fulfill the inclusion criteria (N = 6) or refused to participate in the trial (N = 8). Finally, 109 patients were randomly assigned to either Group 1, (N = 36), Group 2 (N = 37), or Control-group (N = 36) in a 1:1:1 ratio. Two doses of eltrombopag - 25 mg/day and 50 mg/day were administered to Group-1 and Group-2 patients, respectively whereas the control-group patients received standard dengue treatment without eltrombopag. The management of all enrolled patients was according to WHO guidelines. The randomization procedure was performed by using a computerized system (STATA Inc.). CBC and immature platelet fraction (IPF) were monitored from Day-0 to Day-7. Absolute immature platelet count (A-IPC) was calculated from PLT count and IPF for each patient. Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were measured on Day-0 and Day-4 and an Ultrasonogram (USG) of the abdomen was performed on Day-4 and Day-7 for each patient. The efficacy of eltrombopag as the primary outcome of the trial was investigated by the proportion of patients with recovered platelet count receiving eltrombopag with corrected platelet count (platelet count above the lower normal limit: 150 × 109/L) on Day-7 of the enrollment as compared to the Control-group. As the secondary outcomes, the reduction of bleeding tendency in response to eltrombopag as well as the safety of eltrombopag in dengue patients were assessed. The safety was evaluated in case of adverse events, liver function enzymes AST/ALT levels and USG. This trial is registered with the international clinical trial registry, number SLCTR/2019/037. A total of 101 patients including 77 DF and 24 DHF patients completed the trial as eight patients left the trial without completing the follow-up. Patients of the different groups were compared with respect to mean age (26±8, 30±10 and 30±9 years for, Group-1,-2 and Control-group, respectively) (p-value= 0.23) and basal PLT count (Group-1: 58±24 × 109; Group-2: 52±29 × 109 and control-group: 55±30 × 109) (p-value= 0.63). The mean PLT counts for Group-1 (332 × 109/L ± 92) and Group-2 (371 × 109/L ± 111) were significantly higher than control-group (194 × 109/L ± 96) on Day-7 (adjusted p-value= 1.15 × 10−06 for Group-1 vs. Control-group, and adjusted p-value= 1.82 × 10−08 for Group-2 vs. Control-group).). On Day-7, 91% of Group-1 (N = 30) and Group-2 (N = 32) patients who received eltrombopag achieved primary endpoint of PLT count above than lower normal limit (150 × 109/L) (Group-1: 91%, OR: 8.33, 95% CI: 2.11 to 32.80, p-value: 0.0024 and Group-2: 91%, OR: 8.89, 95% CI: 2.26 to 34.89, p-value: 0.0017) compared to 55% (N = 18) of control-group patients who did not receive eltrombopag. The bleeding manifestations for thirteen out of fourteen grade-II DHF patients were subsided within Day-7 who received eltrombopag, whereas four out of ten grade-II DHF patients with PLT counts lower than the lower normal limit in the control group showed intermittent bleeding symptoms throughout the trial period. Mean A-IPC but not IPF was significantly higher for eltrombopag-treated groups in comparison to the Control-group. The frequency of the most common adverse events (vomiting and diarrheal tendencies) was similar in the treated-and control-groups (N = 5, 15%, and N = 3, 9% for Group-1 and -2, respectively vs. N = 4, 12% in the Control-group). Ten (30%) patients of Group-1 and, fourteen (40%) patients of Group-2 showed increased AST (U/L) as opposed to nine patients (27%) in the Control-group. Increased ALT levels were observed for three (9%), nine (26%), and seven (21%) patients belonging to the Group-1, -2, and Control-group, respectively. PLT counts higher than the upper normal limit (450 × 109/L) on Day-7 were observed for seven patients who were administered the higher dose (50 mg/day) in contrast to the three patients receiving the lower dose (25 mg/day). USG reports did not show thrombosis events in any of the patients. The trial revealed that the administration of eltrombopag in a short regimen for three days was efficacious to restore the PLT count in DF and DHF patients. The higher number of A-IPCs in eltrombopag treated patients underscored the possible mode of action of eltrombopag through stimulating megakaryopoiesis in dengue patients. The trial hints toward the positive effect of eltrombopag in the cessation of bleeding manifestation. Administration of the lower dose (25 mg/day) of eltrombopag was shown to be safer and equally efficacious to the higher dose (50 mg/day) in treating dengue-infected patients.

The infection mechanism and pathogenicity of Human T-lymphotropic virus 1 (HTLV-1) are ambiguously known for hundreds of years. Our knowledge about this virus is recently emerging. The purpose of the study is to design a vaccine targeting the envelope glycoprotein, GP62, an outer membrane protein of HTLV-1 that has an increased number of epitope binding sites. Data collection, clustering and multiple sequence alignment of HTLV-1 glycoprotein B, variability analysis of envelope Glycoprotein GP62 of HTLV-1, population protection coverage, HLA-epitope binding prediction, and B-cell epitope prediction were performed to predict an effective vaccine. Among all the predicted peptides, ALQTGITLV and VPSSSTPL epitopes interact with three MHC alleles. The summative population protection coverage worldwide by these epitopes as vaccine candidates was found nearly 70%. The docking analysis revealed that ALQTGITLV and VPSSSTPL epitopes interact strongly with the epitope-binding groove of HLA-A*02:03, and HLA-B*35:01, respectively, as this HLA molecule was found common with which every predicted epitope interacts. Molecular dynamics simulations of the docked complexes show they form stable complexes. So, these potential epitopes might pave the way for vaccine development against HTLV-1.

Background: A variety of accessible data, including those of single-nucleotide polymorphisms (SNPs) on the human p53 gene, are made widely available on a global scale. Owing to this, our investigation aimed to deal with the detrimental SNPs in the p53 gene by executing various valid computational tools, including—Filter, SIFT, PredictSNP, Fathmm, UTRScan, ConSurf, SWISS-MODEL, Amber 16 package, Tm-Adjust, I-Mutant, Task Seek, GEPIA2 after practical and basic appraisal, dissolvable openness, atomic progression, analyzing the energy minimization and assessing the gene expression pattern. Results: Out of the total 581 p53 SNPs, 420 SNPs were found to be missense or non-synonymous, 435 SNPs were in the three prime UTR, and 112 SNPs were in the five prime UTR from which 16 non-synonymous SNPs (nsSNPs) were predicted to be non-tolerable while PredictSNP package predicted 14. Concentrating on six bioinformatics tools of various dimensions, a combined output was generated, where 14 nsSNPs could exert a deleterious effect. We found 5 missense SNPs in the DNA binding domain's three crucial amino acid positions, using diverse SNP analyzing tools. The underlying discoveries were fortified by microsecond molecular dynamics (MD) simulations, TM-align, I-Mutant, and Project HOPE. The ExPASy-PROSITE tools characterized whether the mutations were located in the functional part of the protein or not. This study provides a decisive outcome, concluding the accessible SNPs' information by recognizing the five unfavorable nsSNPs—rs28934573 (S241F), rs11540652 (R248Q), rs121913342 (R248W), rs121913343 (R273C), and rs28934576 (R273H). By utilizing Heatmapper and GEPIA2, several visualization plots, including heat maps, box plots, and survival plots, were produced. Conclusions: These plots disclosed differential expression patterns of the p53 gene in humans. The investigation focused on recognizing the detrimental nsSNPs, which augmented the danger posed by various oncogenesis in patients of different populations, including within the genome-wide studies (GWS).

Previous studies showed that prolonged exposure to fluoride (F-) and aluminum (Al3+) ions is associated with numerous diseases including neurological disorders. They don't have any known biological function. But they can bind with proteins that interact with ions similar to them. Such unwanted interactions affect the normal biological function of the target proteins, as well as their downstream protein-protein interactions. Several studies show the detrimental effects posed by them including Alzheimer's disease. However, their target proteins have never been reported. Here, we have screened for the human protein targets subjected to F- and Al3+ interactions by using data-driven prediction tools. We have identified 20 different proteins that directly bind with them (10 interact with fluoride and 10 with aluminum). In addition, protein-protein interaction has been explored to find the proteins that indirectly interact with F- and Al3+. We have found 86 indirect targets for F- and 90 for Al3+. Furthermore, 19 common protein targets have been identified, including proteins (9 out of 19) associated with neurodegenerative disorders. However, wet lab experiments are beyond our scopes to validate the binding networks. Additional studies must be warranted.

Success story of plant-based medicine had been overlooked during the advent of modern pharmaceutical industry. Despite the negligence of the multimillion-dollar drug industry, people entirely rely on medicinal plants in some part of the world. In this study, we have emphasized on going back to those traditional medicinal practices to figure out their underlying mechanism to move forward on phytochemical based drug development. We screened Medicinal Plant Database Bangladesh 1.0 (MPDB1.0) and on-going extension, MPDB2.0, of that database to find traditionally used medicinal plants and their active compounds. Here, Mangiferin, extracted from Mangifera indica, have been demonstrated to interact with cell cycle regulator Cyclin-dependent Kinase 4 (CDK4). CDK4 is differentially expressed during Glioblastoma multiforme (GBM), Brain Lower Grade Glioma (LGG), and Sarcoma (SARC). Expression of CDK4 is interlinked to the patients’ survival rate and its consistent expression throughout different stages have provided the advantage to use it as diagnostic tool and drug target. Altogether, this study demonstrated that simple mango tree extracted active compounds, mangiferin, can work as potential anticancer drug and leveraging the recent advancement of sequencing and gene expression data can accelerate the phytochemical based drug discovery process.