Molecular Docking and Thermodynamic Studies of the Interactions between Aspirinate Complexes of Transition metals and Cyclooxygenase-2 Enzyme: Quantum Chemical Calculations based on the ONIOM method

In the present research, molecular docking and thermodynamic properties of the transition metal complexes of aspirin were calculated against Cyclooxygenase-2 (COX-2) enzyme.  Density functional theory with dispersion function (DFT-D) using LANL2DZ basis set calculation was carried out to study the structural and thermodynamic properties of the interaction between aspirinate complexes of transition metals and COX-2. The ONIOM2 (wB97X-D/LANL2DZ:UFF) method was applied to the interaction of transition metal complexes with COX-2 binding site. The Interaction enthalpies and the Gibbs free energies between aspirinate complexes of Cu(II), Zn(II), Fe(III), and In(III) as anti-inflammatory complexes and COX-2  enzyme in the gas phase were calculated. The structure as well as the thermodynamics of optimized metal complexes was debated from the biological point of view. In the gas phase, the interaction was relatively strong and transition metal complexes could be used as potential anti-inflammatory drugs.</p

Profile of Cigarette and Drug Use Status in Population of Tabari Cohort Study

Background: The study of the smoking and drug use profile of the Tabari cohort enrolment phase, the outcomes of which will be evaluated in the coming years, has proper comprehensiveness. Therefore, the present study aimed to determine the cigarette and drug use status in the population of the Tabari cohort study (TCS).Methods: In this study, the profile of cigarette and drug use in the TCS was evaluated. Data analysis was performed in SPSS version 24 using percentage, mean, and standard deviation, chi-square, and independent t test.Findings: The frequency of daily smoking in the entire population was 9.1%, and the frequencies in men and women were 21.5% and 0.6%, respectively (P<0.001). The frequency of exposure to smoking in the home, at present or in the past, in the entire population was 30.5%, and in the populations living in urban and mountainous areas were 35.4% and 19.8%, respectively (P<0.001). The mean age at first use of cigarettes in the entire population was 20.50±7.61, whereas the mean age of regular smoking was 23.19±8.02. Furthermore, the frequency of experiencing drug abuse in the total population was 6.1%, and the frequencies in men and women were 14.1% and 0.7%, respectively.Conclusion: According to the results of this study, cigarette smoking and drug use are significant in men, and overall exposure of the Tabari cohort population to tobacco and drugs in the home is high. If effective prevention is not on the agenda, a significant proportion of the future outcomes in this population may be attributable to these risk factors

Levels of Blood Biomarkers among Patients with Myocardial Infarction in Comparison to Control Group

BACKGROUND: Myocardial infarction (MI) as a term for a heart attack happens due to reduced blood flow to heart myocardium and lack of oxygen supply caused by plaques inthe interior walls of coronary arteries. With respect to the importance of MI etiology, we aimed to study the relationship of MI and blood examination variables.METHODS: This study was conducted in Mazandaran Heart Center as a hospital-based case-control Comprising 894 participants including 465 cases and 429 controls, individually matched by sex and age. Considered blood markers were analyzed using routine laboratory methods and equipment.RESULTS: Of all participants, 64.3% of the cases and 51.0% of the controls were males with a mean age of 61.2 (±13.8) in cases and 62.4 (±14.) in controls. We could not find any differences between cases and controls for total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), and alkaline-phosphatase (ALP) (P&gt;0.05). However, levels of creatine-kinase-muscle/brain (CK-MB) (P&lt;0.0001), fasting-blood-sugar (FBS) (P&lt;0.0001), aspartateaminotransferase (AST) (P&lt;0.0001), alanine-transferase (ALT) (P&lt;0.0001) and erythrocyte sedimentation rate (ESR) (P=0.001) were significantly higher in cases compared to the controls (P&lt;0.05). Multivariable analyses revealed that the risk of MI was associated with high levels of AST (adjusted OR=24.3, 95%CI=3.5±165.6, P=0.001) and LDL (adjusted OR=7.4, 95%CI=1.0±51.8, P=0.001).CONCLUSION: Our investigation indicated that the levels of CK-MB, FBS, AST, ALT and ESR were significantly higher in patients with MI. Besides, our findings showed that the risk of MI in cases with high levels of AST and LDL was about 24 and 7 times more than the control group respectively

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019Research in context

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences &amp; Sichuan Provincial People's Hospital (2022QN38)

Global, regional, and national burden of diabetes from 1990 to 2021, with projections of prevalence to 2050: a systematic analysis for the Global Burden of Disease Study 2021

Background: Diabetes is one of the leading causes of death and disability worldwide, and affects people regardless of country, age group, or sex. Using the most recent evidentiary and analytical framework from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD), we produced location-specific, age-specific, and sex-specific estimates of diabetes prevalence and burden from 1990 to 2021, the proportion of type 1 and type 2 diabetes in 2021, the proportion of the type 2 diabetes burden attributable to selected risk factors, and projections of diabetes prevalence through 2050. Methods: Estimates of diabetes prevalence and burden were computed in 204 countries and territories, across 25 age groups, for males and females separately and combined; these estimates comprised lost years of healthy life, measured in disability-adjusted life-years (DALYs; defined as the sum of years of life lost [YLLs] and years lived with disability [YLDs]). We used the Cause of Death Ensemble model (CODEm) approach to estimate deaths due to diabetes, incorporating 25 666 location-years of data from vital registration and verbal autopsy reports in separate total (including both type 1 and type 2 diabetes) and type-specific models. Other forms of diabetes, including gestational and monogenic diabetes, were not explicitly modelled. Total and type 1 diabetes prevalence was estimated by use of a Bayesian meta-regression modelling tool, DisMod-MR 2.1, to analyse 1527 location-years of data from the scientific literature, survey microdata, and insurance claims; type 2 diabetes estimates were computed by subtracting type 1 diabetes from total estimates. Mortality and prevalence estimates, along with standard life expectancy and disability weights, were used to calculate YLLs, YLDs, and DALYs. When appropriate, we extrapolated estimates to a hypothetical population with a standardised age structure to allow comparison in populations with different age structures. We used the comparative risk assessment framework to estimate the risk-attributable type 2 diabetes burden for 16 risk factors falling under risk categories including environmental and occupational factors, tobacco use, high alcohol use, high body-mass index (BMI), dietary factors, and low physical activity. Using a regression framework, we forecast type 1 and type 2 diabetes prevalence through 2050 with Socio-demographic Index (SDI) and high BMI as predictors, respectively. Findings: In 2021, there were 529 million (95% uncertainty interval [UI] 500-564) people living with diabetes worldwide, and the global age-standardised total diabetes prevalence was 6·1% (5·8-6·5). At the super-region level, the highest age-standardised rates were observed in north Africa and the Middle East (9·3% [8·7-9·9]) and, at the regional level, in Oceania (12·3% [11·5-13·0]). Nationally, Qatar had the world's highest age-specific prevalence of diabetes, at 76·1% (73·1-79·5) in individuals aged 75-79 years. Total diabetes prevalence-especially among older adults-primarily reflects type 2 diabetes, which in 2021 accounted for 96·0% (95·1-96·8) of diabetes cases and 95·4% (94·9-95·9) of diabetes DALYs worldwide. In 2021, 52·2% (25·5-71·8) of global type 2 diabetes DALYs were attributable to high BMI. The contribution of high BMI to type 2 diabetes DALYs rose by 24·3% (18·5-30·4) worldwide between 1990 and 2021. By 2050, more than 1·31 billion (1·22-1·39) people are projected to have diabetes, with expected age-standardised total diabetes prevalence rates greater than 10% in two super-regions: 16·8% (16·1-17·6) in north Africa and the Middle East and 11·3% (10·8-11·9) in Latin America and Caribbean. By 2050, 89 (43·6%) of 204 countries and territories will have an age-standardised rate greater than 10%. Interpretation: Diabetes remains a substantial public health issue. Type 2 diabetes, which makes up the bulk of diabetes cases, is largely preventable and, in some cases, potentially reversible if identified and managed early in the disease course. However, all evidence indicates that diabetes prevalence is increasing worldwide, primarily due to a rise in obesity caused by multiple factors. Preventing and controlling type 2 diabetes remains an ongoing challenge. It is essential to better understand disparities in risk factor profiles and diabetes burden across populations, to inform strategies to successfully control diabetes risk factors within the context of multiple and complex drivers. Funding: Bill & Melinda Gates Foundation