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1.
Int J Mol Sci ; 23(15)2022 Jul 27.
Article in English | MEDLINE | ID: mdl-35955411

ABSTRACT

Ageing is associated with changes in body composition, such as low muscle mass (sarcopenia), decreased grip strength or physical function (dynapenia), and accumulation of fat mass. When the accumulation of fat mass synergistically accompanies low muscle mass or reduced grip strength, it results in sarcopenic obesity and dynapenic obesity, respectively. These types of obesity contribute to the increased risk of cardiovascular disease and mortality in the elderly, which could increase the damage caused by COVID-19. In this review, we associated factors that could generate a higher risk of COVID-19 complications in dynapenic obesity and sarcopenic obesity. For example, skeletal muscle regulates the expression of inflammatory cytokines and supports metabolic stress in pulmonary disease; hence, the presence of dynapenic obesity or sarcopenic obesity could be related to a poor prognosis in COVID-19 patients.


Subject(s)
COVID-19 , Sarcopenia , Aged , Body Composition , COVID-19/complications , Hand Strength , Humans , Muscle Strength/physiology , Muscle, Skeletal , Obesity/complications , Sarcopenia/etiology
2.
Sci Rep ; 11(1): 22288, 2021 11 15.
Article in English | MEDLINE | ID: mdl-34782703

ABSTRACT

Numerous repositioned drugs have been sought to decrease the severity of SARS-CoV-2 infection. It is known that among its physicochemical properties, Ursodeoxycholic Acid (UDCA) has a reduction in surface tension and cholesterol solubilization, it has also been used to treat cholesterol gallstones and viral hepatitis. In this study, molecular docking was performed with the SARS-CoV-2 Spike protein and UDCA. In order to confirm this interaction, we used Molecular Dynamics (MD) in "SARS-CoV-2 Spike protein-UDCA". Using another system, we also simulated MD with six UDCA residues around the Spike protein at random, naming this "SARS-CoV-2 Spike protein-6UDCA". Finally, we evaluated the possible interaction between UDCA and different types of membranes, considering the possible membrane conformation of SARS-CoV-2, this was named "SARS-CoV-2 membrane-UDCA". In the "SARS-CoV-2 Spike protein-UDCA", we found that UDCA exhibits affinity towards the central region of the Spike protein structure of - 386.35 kcal/mol, in a region with 3 alpha helices, which comprises residues from K986 to C1032 of each monomer. MD confirmed that UDCA remains attached and occasionally forms hydrogen bonds with residues R995 and T998. In the presence of UDCA, we observed that the distances between residues atoms OG1 and CG2 of T998 in the monomers A, B, and C in the prefusion state do not change and remain at 5.93 ± 0.62 and 7.78 ± 0.51 Å, respectively, compared to the post-fusion state. Next, in "SARS-CoV-2 Spike protein-6UDCA", the three UDCA showed affinity towards different regions of the Spike protein, but only one of them remained bound to the region between the region's heptad repeat 1 and heptad repeat 2 (HR1 and HR2) for 375 ps of the trajectory. The RMSD of monomer C was the smallest of the three monomers with a value of 2.89 ± 0.32, likewise, the smallest RMSF was also of the monomer C (2.25 ± 056). In addition, in the simulation of "SARS-CoV-2 membrane-UDCA", UDCA had a higher affinity toward the virion-like membrane; where three of the four residues remained attached once they were close (5 Å, to the centre of mass) to the membrane by 30 ns. However, only one of them remained attached to the plasma-like membrane and this was in a cluster of cholesterol molecules. We have shown that UDCA interacts in two distinct regions of Spike protein sequences. In addition, UDCA tends to stay bound to the membrane, which could potentially reduce the internalization of SARS-CoV-2 in the host cell.


Subject(s)
Antiviral Agents/metabolism , Drug Repositioning/methods , Lipid Bilayers/metabolism , Molecular Docking Simulation/methods , Phospholipids/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Ursodeoxycholic Acid/metabolism , Antiviral Agents/chemistry , COVID-19/metabolism , COVID-19/virology , Humans , Hydrogen Bonding , Membrane Fusion , Molecular Dynamics Simulation , Protein Binding , Protein Conformation, alpha-Helical , SARS-CoV-2/metabolism , Spike Glycoprotein, Coronavirus/chemistry , Ursodeoxycholic Acid/chemistry , Virion/metabolism
3.
Biomolecules ; 11(11)2021 10 20.
Article in English | MEDLINE | ID: mdl-34827548

ABSTRACT

SARS-CoV-2 contains certain molecules that are related to the presence of immunothrombosis. Here, we review the pathogen and damage-associated molecular patterns. We also study the imbalance of different molecules participating in immunothrombosis, such as tissue factor, factors of the contact system, histones, and the role of cells, such as endothelial cells, platelets, and neutrophil extracellular traps. Regarding the pathogenetic mechanism, we discuss clinical trials, case-control studies, comparative and translational studies, and observational studies of regulatory or inhibitory molecules, more specifically, extracellular DNA and RNA, histones, sensors for RNA and DNA, as well as heparin and heparinoids. Overall, it appears that a network of cells and molecules identified in this axis is simultaneously but differentially affecting patients at different stages of COVID-19, and this is characterized by endothelial damage, microthrombosis, and inflammation.


Subject(s)
Alarmins , COVID-19/virology , SARS-CoV-2 , Thromboinflammation/virology , Thrombosis/virology , Angiotensin-Converting Enzyme 2/metabolism , Animals , Blood Coagulation , Blood Platelets/virology , COVID-19/complications , DNA/metabolism , Extracellular Traps , Heparin/metabolism , Histones/metabolism , Humans , Mice , Neuropilin-1/metabolism , RNA/metabolism , Signal Transduction , Thrombin/metabolism , Thromboplastin/metabolism , Thrombosis/complications
4.
Rev Med Chil ; 144(8): 1020-1028, 2016 Aug.
Article in Spanish | MEDLINE | ID: mdl-27905649

ABSTRACT

BACKGROUND: Obesity during childhood is a risk factor for developing cardiovascular diseases during adulthood. AIM: To measure insulin and glucose levels and parameters of insulin resistance in obese, overweight and normal weight Mexican children. MATERIAL AND METHODS: Comparative study of 21 obese children with a body mass index (BMI) over percentile 95, aged 10 ± 1 years (10 males), 14 children aged 10 ± 2 (7 males) with a BMI between percentiles 85 and 94 and 16 children aged 9 ± 2 years (3 males) with a body mass index between percentiles 10 and 84. Body weight, blood pressure and waist circumference were measured and a blood sample was obtained to measure fasting glucose and insulin levels. Homeostasis model of insulin resistance (HOMA) and quantitative insulin sensitivity check index (QUICKI) were calculated. RESULTS: Among obese, overweight and normal weight children, insulin levels were 14.9 (95% CI 10.90-18.99), 7.20 (CI 5.12-9.28) and 4.73 (CI 95% 1.92-7.53) uU/ml, respectively. The figures for HOMA were 3.16 (95% CI 2.20-4.12), 1.49 (95% CI 1.03-1.94) and 0.97 (95% CI 0.35-1.60), respectively. The figures for QUICKI were 0.331 (95% CI 0.319-0.343), 0.371 (95% CI 0.349-0.393) and 0.419 (95% CI 0.391-0.446), respectively. Compared to their normal weight counterparts, the risk of obese children and those with a waist circumference over percentile 90 of having a HOMA over 3.16 was 17 and 10 times higher, respectively. BMI correlated better than waist circumference with insulin levels. CONCLUSIONS: Obese children have higher levels of insulin resistance than their normal weight counterparts.


Subject(s)
Hyperinsulinism/blood , Insulin Resistance , Insulin/blood , Obesity/blood , Biomarkers/blood , Body Mass Index , Child , Female , Humans , Hyperinsulinism/diagnosis , Hyperinsulinism/etiology , Male , Mexico/epidemiology , Obesity/complications , Obesity/epidemiology , Risk Factors , Sex Factors , Waist Circumference
5.
Rev. méd. Chile ; 144(8): 1020-1028, ago. 2016. graf, tab
Article in Spanish | LILACS | ID: biblio-830608

ABSTRACT

Background: Obesity during childhood is a risk factor for developing cardiovascular diseases during adulthood. Aim: To measure insulin and glucose levels and parameters of insulin resistance in obese, overweight and normal weight Mexican children. Material and Methods: Comparative study of 21 obese children with a body mass index (BMI) over percentile 95, aged 10 ± 1 years (10 males), 14 children aged 10 ± 2 (7 males) with a BMI between percentiles 85 and 94 and 16 children aged 9 ± 2 years (3 males) with a body mass index between percentiles 10 and 84. Body weight, blood pressure and waist circumference were measured and a blood sample was obtained to measure fasting glucose and insulin levels. Homeostasis model of insulin resistance (HOMA) and quantitative insulin sensitivity check index (QUICKI) were calculated. Results: Among obese, overweight and normal weight children, insulin levels were 14.9 (95% CI 10.90-18.99), 7.20 (CI 5.12-9.28) and 4.73 (CI 95% 1.92-7.53) uU/ml, respectively. The figures for HOMA were 3.16 (95% CI 2.20-4.12), 1.49 (95% CI 1.03-1.94) and 0.97 (95% CI 0.35-1.60), respectively. The figures for QUICKI were 0.331 (95% CI 0.319-0.343), 0.371 (95% CI 0.349-0.393) and 0.419 (95% CI 0.391-0.446), respectively. Compared to their normal weight counterparts, the risk of obese children and those with a waist circumference over percentile 90 of having a HOMA over 3.16 was 17 and 10 times higher, respectively. BMI correlated better than waist circumference with insulin levels. Conclusions: Obese children have higher levels of insulin resistance than their normal weight counterparts.


Subject(s)
Humans , Male , Female , Child , Insulin Resistance , Hyperinsulinism/blood , Insulin/blood , Obesity/blood , Biomarkers/blood , Body Mass Index , Sex Factors , Risk Factors , Waist Circumference , Hyperinsulinism/diagnosis , Hyperinsulinism/etiology , Mexico/epidemiology , Obesity/complications , Obesity/epidemiology
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