21 research outputs found
Association between arsenic exposure and plasma cholinesterase activity: a population based study in Bangladesh
Worldwide trends in underweight and obesity from 1990 to 2022: a pooled analysis of 3663 population-representative studies with 222 million children, adolescents, and adults
Background Underweight and obesity are associated with adverse health outcomes throughout the life course. We
estimated the individual and combined prevalence of underweight or thinness and obesity, and their changes, from
1990 to 2022 for adults and school-aged children and adolescents in 200 countries and territories.
Methods We used data from 3663 population-based studies with 222 million participants that measured height and
weight in representative samples of the general population. We used a Bayesian hierarchical model to estimate
trends in the prevalence of different BMI categories, separately for adults (age ≥20 years) and school-aged children
and adolescents (age 5–19 years), from 1990 to 2022 for 200 countries and territories. For adults, we report the
individual and combined prevalence of underweight (BMI <18·5 kg/m2) and obesity (BMI ≥30 kg/m2). For schoolaged children and adolescents, we report thinness (BMI <2 SD below the median of the WHO growth reference)
and obesity (BMI >2 SD above the median).
Findings From 1990 to 2022, the combined prevalence of underweight and obesity in adults decreased in
11 countries (6%) for women and 17 (9%) for men with a posterior probability of at least 0·80 that the observed
changes were true decreases. The combined prevalence increased in 162 countries (81%) for women and
140 countries (70%) for men with a posterior probability of at least 0·80. In 2022, the combined prevalence of
underweight and obesity was highest in island nations in the Caribbean and Polynesia and Micronesia, and
countries in the Middle East and north Africa. Obesity prevalence was higher than underweight with posterior
probability of at least 0·80 in 177 countries (89%) for women and 145 (73%) for men in 2022, whereas the converse
was true in 16 countries (8%) for women, and 39 (20%) for men. From 1990 to 2022, the combined prevalence of
thinness and obesity decreased among girls in five countries (3%) and among boys in 15 countries (8%) with a
posterior probability of at least 0·80, and increased among girls in 140 countries (70%) and boys in 137 countries (69%)
with a posterior probability of at least 0·80. The countries with highest combined prevalence of thinness and
obesity in school-aged children and adolescents in 2022 were in Polynesia and Micronesia and the Caribbean for
both sexes, and Chile and Qatar for boys. Combined prevalence was also high in some countries in south Asia, such
as India and Pakistan, where thinness remained prevalent despite having declined. In 2022, obesity in school-aged
children and adolescents was more prevalent than thinness with a posterior probability of at least 0·80 among girls
in 133 countries (67%) and boys in 125 countries (63%), whereas the converse was true in 35 countries (18%) and
42 countries (21%), respectively. In almost all countries for both adults and school-aged children and adolescents,
the increases in double burden were driven by increases in obesity, and decreases in double burden by declining
underweight or thinness.
Interpretation The combined burden of underweight and obesity has increased in most countries, driven by an
increase in obesity, while underweight and thinness remain prevalent in south Asia and parts of Africa. A healthy
nutrition transition that enhances access to nutritious foods is needed to address the remaining burden of
underweight while curbing and reversing the increase in obesit
Heterogeneous contributions of change in population distribution of body mass index to change in obesity and underweight NCD Risk Factor Collaboration (NCD-RisC)
From 1985 to 2016, the prevalence of underweight decreased, and that of obesity and severe obesity increased, in most regions, with significant variation in the magnitude of these changes across regions. We investigated how much change in mean body mass index (BMI) explains changes in the prevalence of underweight, obesity, and severe obesity in different regions using data from 2896 population-based studies with 187 million participants. Changes in the prevalence of underweight and total obesity, and to a lesser extent severe obesity, are largely driven by shifts in the distribution of BMI, with smaller contributions from changes in the shape of the distribution. In East and Southeast Asia and sub-Saharan Africa, the underweight tail of the BMI distribution was left behind as the distribution shifted. There is a need for policies that address all forms of malnutrition by making healthy foods accessible and affordable, while restricting unhealthy foods through fiscal and regulatory restrictions
Screening and Druggability Analysis of Some Plant Metabolites Against SARS-CoV-2
The sudden outbreak of novel corona virus at
the end of 2019 has caused a global threat to mankind due to its extreme
infection rate and mortality. Despite extensive research, still there is no an
approved drug or vaccine to combat SARS-CoV-2 infections. Hence, the study was
designed to evaluate some plant-based active compounds for drug candidacy against
SARS-CoV-2 by using virtual screening methods and various computational
analysis. A total of 27 plant metabolites were screened against SARS-Cov-2 main
protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding
domain, spike ecto-domain and HR2 domain using molecular docking approach. Four
metabolites i.e. asiatic acid, avicularin, guajaverin and withaferin showed
maximum binding affinity with all key proteins in terms of lowest global
binding energy. The top candidates were further employed for ADME (absorption, distribution, metabolism, and excretion) analysis to investigate their drug
profiles. Results suggest that none of the compounds render any undesirable
consequences that could reduce their drug likeness properties. The analysis of
toxicity pattern revealed no significant tumorigenic, mutagenic, irritating or
reproductive effects by the compounds. However, witheferin was comparatively
toxic among the top four candidates with considerable cytotoxicity and
immunotoxicity. Most of the target class by top drug candidates belonged to
enzyme groups (e.g. oxidoreductases hydrolases, phosphatases). Moreover, results of drug similarity prediction
identified two approved structural analogs of Asiatic acid from DrugBank,
Hydrocortisone (DB00741) (previously used for SARS-CoV-1 and MERS) and
Dinoprost-tromethamine (DB01160). In addition, two other biologically active
compounds, Mupirocin (DB00410) and Simvastatin (DB00641) could be an
alternative choice to witheferin for the treatment of viral infections. The
study may pave the way to develop effective medications and preventive measure
against SARS-CoV-2 in the future. However, the results were based solely on
computational tools and algorithms. Due to the encouraging results, we highly
recommend further in vivo trials for the experimental validation of our
findings. </p
Comprehensive genome based analysis of Vibrio parahaemolyticus for identifying novel drug and vaccine molecules: Subtractive proteomics and vaccinomics approach.
Multidrug-resistant Vibrio parahaemolyticus has become a significant public health concern. The development of effective drugs and vaccines against Vibrio parahaemolyticus is the current research priority. Thus, we aimed to find out effective drug and vaccine targets using a comprehensive genome-based analysis. A total of 4822 proteins were screened from V. parahaemolyticus proteome. Among 16 novel cytoplasmic proteins, 'VIBPA Type II secretion system protein L' and 'VIBPA Putative fimbrial protein Z' were subjected to molecular docking with 350 human metabolites, which revealed that Eliglustat, Simvastatin and Hydroxocobalamin were the top drug molecules considering free binding energy. On the contrary, 'Sensor histidine protein kinase UhpB' and 'Flagellar hook-associated protein of 25 novel membrane proteins were subjected to T-cell and B-cell epitope prediction, antigenicity testing, transmembrane topology screening, allergenicity and toxicity assessment, population coverage analysis and molecular docking analysis to generate the most immunogenic epitopes. Three subunit vaccines were constructed by the combination of highly antigenic epitopes along with suitable adjuvant, PADRE sequence and linkers. The designed vaccine constructs (V1, V2, V3) were analyzed by their physiochemical properties and molecular docking with MHC molecules- results suggested that the V1 is superior. Besides, the binding affinity of human TLR-1/2 heterodimer and construct V1 could be biologically significant in the development of the vaccine repertoire. The vaccine-receptor complex exhibited deformability at a minimum level that also strengthened our prediction. The optimized codons of the designed construct was cloned into pET28a(+) vector of E. coli strain K12. However, the predicted drug molecules and vaccine constructs could be further studied using model animals to combat V. parahaemolyticus associated infections
Major Insights in Dynamics of Host Response to SARS-CoV-2:Impacts and Challenges
The coronavirus disease 2019 (COVID-19), a pandemic declared by the World Health Organization on March 11, 2020, is caused by the infection of highly transmissible species of a novel coronavirus called severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). As of July 25, 2021, there are 194,372,584 cases and 4,167,937 deaths with high variability in clinical manifestations, disease burden, and post-disease complications among different people around the globe. Overall, COVID-19 is manifested as mild to moderate in almost 90% of the cases and only the rest 10% of the cases need hospitalization. However, patients with older age and those having different comorbidities have made worst the pandemic scenario. The variability of pathological consequences and clinical manifestations of COVID-19 is associated with differential host–SARS-CoV-2 interactions, which are influenced by the factors that originated from the SARS-CoV-2 and the host. These factors usually include the genomic attributes and virulent factors of the SARS-CoV-2, the burden of coinfection with other viruses and bacteria, age and gender of the individuals, different comorbidities, immune suppressions/deficiency, genotypes of major histocompatibility complex, and blood group antigens and antibodies. We herein retrieved and reviewed literatures from PubMed, Scopus, and Google relevant to clinical complications and pathogenesis of COVID-19 among people of different age, sex, and geographical locations; genomic characteristics of SARS-CoV-2 including its variants, host response under different variables, and comorbidities to summarize the dynamics of the host response to SARS-CoV-2 infection; and host response toward approved vaccines and treatment strategies against COVID-19. After reviewing a large number of published articles covering different aspects of host response to SARS-CoV-2, it is clear that one aspect from one region is not working with the scenario same to others, as studies have been done separately with a very small number of cases from a particular area/region of a country. Importantly, to combat such a pandemic as COVID-19, a conclusive understanding of the disease dynamics is required. This review emphasizes on the identification of the factors influencing the dynamics of host responses to SARS-CoV-2 and offers a future perspective to explore the molecular insights of COVID-19
Identification of Potential Phytochemical Inhibitors as Promising Therapeutics Against SARS-CoV-2 and Molecular Dynamics Simulation
The high infectivity and mortality of novel coronavirus has caused a serious concern all over the
world. Still, there is no specific drug or preventive medication to treat SARS-CoV-2 infection
despite comprehensive analysis by the researchers. This study was designed to demonstrate the
efficacy of some phyto-chemical compounds against SARS-CoV-2 by using both structure and
ligand based virtual screening methods. A total of 33 plant metabolites were screened against
SARS-CoV-2 main protease proteins (MPP), Nsp9 RNA binding protein, spike receptor binding
domain and HR2 domain using a molecular docking approach. Results showed that three
metabolites, i.e., Limonin, Isoflavone, and Coumadin conferred maximum binding affinity with
all key proteins of SARS-CoV-2. For each viral protein, the critical binding sites and drug surface
hotspots have been unraveled. ADME analysis indicated that none of the compounds have adverse
effects that could decrease their drug-like properties. Moreover, toxicity pattern analysis also
unmasked the non-toxic nature of the top drug candidates. The RMSD values of top ligandmacromolecule complexes were less than 2 Å, while RMSF values showed regular atomic
fluctuations in the molecular dynamics study. Notably, most of the target class by top drug
candidates belonged to enzyme groups (e.g. oxidoreductases, protease, Kinase). Results of drug
similarity prediction revealed two approved structural analogs of Coumadin named Warfarin
(DB00682) and Phenprocoumon (DB00946) from DrugBank. In addition, Isoformononetin an
experimental drug analog of isoflavone could also be an option for the treatment of viral infections.
For limonin there was no analog found in drugbank. The study can pave the way for the creation
of effective SARS-CoV-2 medications and preventive measures. We highly recommend further in
vivo trials for the experimental validation of our finding
Main Protease Inhibitors and Drug Surface Hotspot for the Treatment of COVID-19: Drug Repurposing and Molecular Docking Approach
The world is facing an unprecedented global pandemic caused by the novel SARS-CoV-2. In the absenceof a specific therapeutic agent to treat COVID-19 patients, the present study aimed to virtually screen outthe effective drug candidates from the approved main protease protein (MPP) inhibitors and theirderivatives for the treatment of SARS-CoV-2. Here, drug repurposing and molecular docking wereemployed to screen approved MPP inhibitors and their derivatives. The approved MPP inhibitors againstHIV and HCV were prioritized, whilst hydroxychloroquine, favipiravir, remdesivir, and alpha-ketoamidewere studied as control. The target drug surface hotspot was also investigated through the moleculardocking technique. ADME analysis was conducted to understand the pharmacokinetics and drug-likenessof the screened MPP inhibitors. The result of this study revealed that Paritaprevir (-10.9 kcal/mol), and itsanalog (CID 131982844)(-16.3 kcal/mol) showed better binding affinity than the approved MPP inhibitorcompared in this study including favipiravir, remdesivir, and alpha-ketoamide. A comparative study amongthe screened putative MPP inhibitors revealed that amino acids T25, T26, H41, M49, L141, N142, G143,C145, H164, M165, E166, D187, R188, and Q189 are at critical positions for becoming the surface hotspotin the MPP of SARS-CoV-2. The study also suggested that paritaprevir and its\u27 analog (CID 131982844),may be effective against SARS-CoV-2 as these molecules had the common drug-surface hotspots on themain protease protein of SARS-CoV-2. Other pharmacokinetic parameters also indicate that paritaprevirand its top analog (CID 131982844) will be either similar or better-repurposed drugs than already approvedMPP inhibitors. </div