Mohiuddin Ahmed Bhuiyan

X-linked inhibitor of apoptosis protein (XIAP) is a member of inhibitor of apoptosis protein (IAP) family responsible for neutralizing the caspases-3, caspases-7, and caspases-9. Overexpression of the protein decreased the apoptosis process in the cell and resulting development of cancer. Different types of XIAP antagonists are generally used to repair the defective apoptosis process that can eliminate carcinoma from living bodies. The chemically synthesis compounds discovered till now as XIAP inhibitors exhibiting side effects, which is making difficulties during the treatment of chemotherapy. So, the study has design to identifying new natural compounds that are able to induce apoptosis by freeing up caspases and will be low toxic. To identify natural compound, a structure-based pharmacophore model to the protein active site cavity was generated following by virtual screening, molecular docking and molecular dynamics (MD) simulation. Initially, seven hit compounds were retrieved and based on molecular docking approach four compounds has chosen for further evaluation. To confirm stability of the selected drug candidate to the target protein the MD simulation approach were employed, which confirmed stability of the three compounds. Based on the finding, three newly obtained compounds namely Caucasicoside A (ZINC77257307), Polygalaxanthone III (ZINC247950187), and MCULE-9896837409 (ZINC107434573) may serve as lead compounds to fight against the treatment of XIAP related cancer, although further evaluation through wet lab is necessary to measure the efficacy of the compounds.

BACKGROUND: Epilepsy is one of the most common serious neurological disorders and affects individuals of all ages across the globe. The aim of this study is to provide estimates of the epilepsy burden on the global, regional, and national levels for 1990-2021. METHODS: Using well established Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) methodology, we quantified the prevalence of active idiopathic (epilepsy of genetic or unknown origin) and secondary epilepsy (epilepsy due to an underlying abnormality of the brain structure or chemistry), as well as incidence, death, and disability-adjusted life-years (DALYs) by age, sex, and location (globally, 21 GBD regions and seven super-regions, World Bank country income levels, Socio-demographic Index [SDI], and 204 countries) and their trends from 1990 to 2021. Vital registrations and verbal autopsies provided information about deaths, and data on the prevalence and severity of epilepsy, largely came from population representative surveys. All estimates were calculated with 95% uncertainty intervals (UIs). FINDINGS: In 2021, there were 51·7 million (95% UI 44·9-58·9) people with epilepsy (idiopathic and secondary combined) globally, with an age-standardised prevalence of 658 per 100 000 (569-748). Idiopathic epilepsy had an age-standardised prevalence of 307 per 100 000 (235-389) globally, with 24·2 million (18·5-30·7) prevalent cases, and secondary epilepsy had a global age-standardised prevalence of 350 per 100 000 (322-380). In 2021, 0·7% of the population had active epilepsy (0·3% attributed to idiopathic epilepsy and 0·4% to secondary epilepsy), and the age-standardised global prevalence of epilepsy from idiopathic and secondary epilepsy combined increased from 1990 to 2021 by 10·8% (1·1-21·3), mainly due to corresponding changes in secondary epilepsy. However, age-standardised death and DALY rates of idiopathic epilepsy reduced from 1990 to 2021 (decline of 15·8% [8·8-22·8] and 14·5% [4·2-24·2], respectively). There were three-fold to four-fold geographical differences in the burden of active idiopathic epilepsy, with the bulk of the burden residing in low-income to middle-income countries: 82·1% (81·1-83·4) of incident, 80·4% prevalent (79·7-82·7), 84·7% (83·7-85·1) fatal epilepsy, and 87·9% (86·2-89·2) epilepsy DALYs. INTERPRETATION: Although the global trends in idiopathic epilepsy deaths and DALY rates have improved in the preceding decades, in 2021 there were almost 52 million people with active epilepsy (24 million from idiopathic epilepsy and 28 million from secondary epilepsy), with the bulk of the burden (>80%) residing in low-income to middle-income countries. Better treatment and prevention of epilepsy are required, along with further research on risk factors of idiopathic epilepsy, good-quality long-term epilepsy surveillance studies, and exploration of the possible effect of stigma and cultural differences in seeking medical attention for epilepsy. FUNDING: Bill and Melinda Gates Foundation.

OBJECTIVE: We do not have any consistent markers for major depressive disorder (MDD) though various biological factors are involved in the pathophysiology. We aimed to evaluate the serum brain-derived neurotrophic factor (BDNF) levels in MDD patients with or without antidepressant therapy compared to healthy controls (HCs). RESULTS: We assessed serum BDNF levels among three groups: drug-naïve MDD patients (n = 41), drug-treated MDD patients (n = 44), and age-and sex-matched HCs (n = 82). Serum BDNF levels were measured by enzyme-linked immunosorbent assay (ELISA) kit. Serum levels of BDNF were detected significantly lower in drug-naïve MDD patients compared to HCs. No significant alterations of serum BDNF levels between drug-treated patients and HCs were identified. Significant negative correlations between serum BDNF levels and Hamilton depression rating (Ham-D) scores were observed in both drug-naïve and drug-treated MDD patients. Receiver operating characteristic (ROC) analysis showed good diagnostic value for serum BDNF levels in drug-naïve MDD patients with the area under the curve at 0.821. The present study suggests that low serum BDNF levels may be involved in the pathophysiology of MDD. The reduced serum BDNF levels might be used as an early risk assessment marker for major depression.

BACKGROUND: Upper respiratory infections (URIs) are the leading cause of acute disease incidence worldwide and contribute to a substantial health-care burden. Although acute otitis media is a common complication of URIs, the combined global burden of URIs and otitis media has not been studied comprehensively. We used results from the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 to explore the fatal and non-fatal burden of the two diseases across all age groups, including a granular analysis of children younger than 5 years, in 204 countries and territories from 1990 to 2021. METHODS: Mortality due to URIs and otitis media was estimated with use of vital registration and sample-based vital registration data, which are used as inputs to the Cause of Death Ensemble model to separately model URIs and otitis media mortality by age and sex. Morbidity was modelled with a Bayesian meta-regression tool using data from published studies identified via systematic reviews, population-based survey data, and cause-specific URI and otitis media mortality estimates. Additionally, we assessed and compared the burden of otitis media as it relates to URIs and examined the collective burden and contributing risk factors of both diseases. FINDINGS: The global number of new episodes of URIs was 12·8 billion (95% uncertainty interval 11·4 to 14·5) for all ages across males and females in 2021. The global all-age incidence rate of URIs decreased by 10·1% (-12·0 to -8·1) from 1990 to 2019. From 2019 to 2021, the global all-age incidence rate fell by 0·5% (-0·8 to -0·1). Globally, the incidence rate of URIs was 162 484·8 per 100 000 population (144 834·0 to 183 289·4) in 2021, a decrease of 10·5% (-12·4 to -8·4) from 1990, when the incidence rate was 181 552·5 per 100 000 population (160 827·4 to 206 214·7). The highest incidence rates of URIs were seen in children younger than 2 years in 2021, and the largest number of episodes was in children aged 5-9 years. The number of new episodes of otitis media globally for all ages was 391 million (292 to 525) in 2021. The global incidence rate of otitis media was 4958·9 per 100 000 (3705·4 to 6658·6) in 2021, a decrease of 16·3% (-18·1 to -14·0) from 1990, when the incidence rate was 5925·5 per 100 000 (4371·8 to 8097·9). The incidence rate of otitis media in 2021 was highest in children younger than 2 years, and the largest number of episodes was in children aged 2-4 years. The mortality rate of URIs in 2021 was 0·2 per 100 000 (0·1 to 0·5), a decrease of 64·2% (-84·6 to -43·4) from 1990, when the mortality rate was 0·7 per 100 000 (0·2 to 1·1). In both 1990 and 2021, the mortality rate of otitis media was less than 0·1 per 100 000. Together, the combined burden accounted for by URIs and otitis media in 2021 was 6·86 million (4·24 to 10·4) years lived with disability and 8·16 million (4·99 to 12·0) disability-adjusted life-years (DALYs) for all ages across males and females. Globally, the all-age DALY rate of URIs and otitis media combined in 2021 was 103 per 100 000 (63 to 152). Infants aged 1-5 months had the highest combined DALY rate in 2021 (647 per 100 000 [189 to 1412]), followed by early neonates (aged 0-6 days; 582 per 100 000 [176 to 1297]) and late neonates (aged 7-24 days; 482 per 100 000 [161 to 1052]). INTERPRETATION: The findings of this study highlight the widespread burden posed by URIs and otitis media across all age groups and both sexes. There is a continued need for surveillance, prevention, and management to better understand and reduce the burden associated with URIs and otitis media, and research is needed to assess their impacts on individuals, communities, economies, and health-care systems worldwide. FUNDING: Bill & Melinda Gates Foundation.