Effect of hypoxia on metabolic markers and gene expression HIF-1 α in adipocytes

Background: Docosahexaenoic acid (DHA; omega-3 fatty acid) has been reported to have potential anti-obesity properties. Hypoxia is a condition that results from the excessive expansion of white adipose tissue resulting in obesity-related conditions including insulin resistance, inflammation and oxidative stress. Methods: The objective of this study was to test the effects of DHA on the hypoxia responses (1.0 % for 24 hours) of 3T3-L1 adipocytes with a focus on oxidative stress, inflammation, and mitochondrial function, and antioxidant status. Cell viability, reactive oxygen species (ROS) and apoptosis were measured by flow cytometry. The metabolic parameters such as lactate, glycerol release, glucose uptake and adenosine triphosphate (ATP) content were measured by fluorometer. The expression of (hypoxia inducible factor 1 α; HIF-1 α) and the secretion of adipocytokines were evaluated by qPCR (quantitative polymerase chain reaction) and ELISA (enzyme linked immunosorbant assay). Results: Under hypoxia conditions, DHA treatment resulted in significant changes in all critical parameters of adipocyte biology including HIF-1α RNA expression (decreased by 50%), decreased lactate and glycerol release (66% and 25% respectively), and reactive oxygen species (ROS) production (decreased by 15%), while glucose uptake was decreased by 25% accompnied by decreased secretion of pro-inflammatory markers (Interleukin 6 IL-6, 31% reduction) , macrophage chemoattractant protein 1 MCP-1 (38% reduction) and leptin (14% reduction), and increased adiponectin secretion (by 45%). The exposure of adipocytes to 1% hypoxia significantly alters the transcript of hypoxia genes, and other genes involved in glucose (GLUT1, GLUT4) and lipid (PPAR-γ) metabolism, and is also linked to anaerobic metabolism with apoptosis and increased oxidative stress. Conclusion: Data indicate that DHA can exert potential anti-hypoxia effects by reducing the secretion of inflammatory adipocytokines, oxidative stress, lipolysis and apoptosis. This may ameliorate the deleterious effects of excess adiposity

A delayed SIR epidemic model with a general incidence rate

A delayed SIR epidemic model with a generalized incidence rate is studied. The time delay represents the incubation period. The threshold parameter, $R_0(\tau)$ is obtained which determines whether the disease is extinct or not. Throughout the paper, we mainly use the technique of Lyapunov functional to establish the global stability of both the disease-free and endemic equilibrium

Integrated datasets of proteomic and metabolomic biomarkers to predict its impacts on comorbidities of type 2 diabetes mellitus

© 2020 Cheema et al. Objective: The objective of the current study is to accomplish a relative exploration of the biological roles of differentially dysregulated genes (DRGs) in type 2 diabetes mellitus (T2DM). The study aimed to determine the impact of these DRGs on the biological pathways and networks that are related to the associated disorders and complications in T2DM and to predict its role as prospective biomarkers. Methods: Datasets obtained from metabolomic and proteomic profiling were used for investigation of the differential expression of the genes. A subset of DRGs was integrated into IPA software to explore its biological pathways, related diseases, and their regulation in T2DM. Upon entry into the IPA, only 94 of the DRGs were recognizable, mapped, and matched within the database. Results: The study identified networks that explore the dysregulation of several functions; cell components such as degranulation of cells; molecular transport process and metabolism of cellular proteins; and inflammatory responses. Top disorders associated with DRGs in T2DM are related to organ injuries such as renal damage, connective tissue disorders, and acute inflammatory disorders. Upstream regulator analysis predicted the role of several transcription factors of interest, such as STAT3 and HIF alpha, as well as many kinases such as JAK kinases, which affects the gene expression of the dataset in T2DM. Interleukin 6 (IL6) is the top regulator of the DRGs, followed by leptin (LEP). Monitoring the dysregulation of the coupled expression of the following biomarkers (TNF, IL6, LEP, AGT, APOE, F2, SPP1, and INS) highlights that they could be used as potential prognostic biomarkers. Conclusion: The integration of data obtained by advanced metabolomic and proteomic technologies has made it probable to advantage in understanding the role of these biomarkers in the identification of significant biological processes, pathways, and regulators that are associated with T2DM and its comorbidities

The Immunophenotyping Changes of Peripheral CD4+ T Lymphocytes and Inflammatory Markers of Class III Obesity Subjects After Laparoscopic Gastric Sleeve Surgery - A Follow-Up Study

Obesity is a chronic disorder characterized by a low-grade inflammatory state and immune cell irregularities. The study aimed to follow up on the changes in the peripheral CD4+ T lymphocytes and the pro-inflammatory cytokines; IL-6, TNF-alpha, MCP-1, and IL-10 at baseline and 12 weeks post-surgical intervention by the laparoscopic gastric sleeve (LGS) in morbidly obese patients (class III obesity subjects). A prospective longitudinal research included 24 class III obesity subjects with a BMI > 40 kg/m. The subjects were enrolled from the Metabolic/Surgical Department at Hamad Medical Corporation (HMC)-Qatar. Fasting blood samples were collected at admission to LGS for weight loss and after 12 weeks of LGS. The immunophenotype of CD4+ T-cell populations; naïve (CD45RAand CD27), central memory T cells (CD45RO and CD27), and effector memory (CD45ROand CD27) and T-regulatory cell (CD4+CD25+ FoxP3+) were identified using flow cytometry. Plasma pro-inflammatory cytokines and adipokines were evaluated. A control group of lean subjects was used to compare changes of T-regulatory and inflammatory biomarkers with postoperative changes in obese patients. The means (SD) of age and BMI of class III obesity subjects was 32.32 (8.36) years and 49.02 (6.28) kg/m respectively. LGS caused a significant reduction in BMI by 32%, p<0.0001. LGS intervention significantly decreased CD4+ T-lymphocytes and effector memory (TEM) cells but increased T-regulatory (Treg), naïve, and central memory (TCM) cells, with all values < 0.05. The increase of Treg cells postoperative is significantly lower compared to lean subjects, p < 0.05. A significant reduction of plasma IL-6, TNF-α, and MCP-1, but IL-10 significantly increased after LGS, with all <0.05. Adiponectin/leptin ratio improved after LGS by 2.9 folds, <0.0001. Weight loss by LGS accomplished a substantial rise of Treg and decreased EM T-lymphocytes with a shift from pro-inflammatory to the anti-inflammatory pattern.QNR

Yield of Durum Wheat Cultivar Grown under Different Nitrogen Regimes and Rainfed Conditions

The experiment was conducted in randomized complete block design with three replications in two different locations (Kef and Bousselem). The effect of four nitrogen treatments (0, 75, 100, 120 and 140 kg/ha of N) was assessed for Maali durum wheat variety on five agronomic traits: biological yield, grain yield, harvest index, 1000 kernel weight and nitrogen use efficiency. Analysis of variance revealed significant effect (P&lt; 0.01; P&lt; 0.001) of the nitrogen treatments for all studied traits. However, no nitrogen treatment x site interaction was noted. Except for nitrogen use efficiency, both location exhibited significant variation (p&lt;0.01) for all the traits examined. Biological yield, grain yield, harvest index, 1000 kernel weight and nitrogen use efficiency increased with an increase in nitrogen levels. In comparison to kef site, greatest results were obtained in Bousselem site under all nitrogen levels for all measured traits. Maximum average yield (2157.27 kg/ha) and (3013.11 kg /ha) was unregistered under N4 treatment (140 kg/ha) in Kef and Boussalem site respectively. A significant and positive correlation was noted between nitrogen rates and biological yield (r = 0.74**), grain yield (r = 0.66**), harvest index (r = 0.84**) and 1000 kernel weight (r = 0.85**). In this region, it seems that the application of 140 kg/ha of N fertilization lead to great agronomic performance of Maali durum wheat variety

The Association between Serum LDL Cholesterol and Genetic Variation in Chromosomal Locus 1p13.3 among Coronary Artery Disease Patients

Background. Several polymorphisms of a locus on chromosome 1p13.3 have a significant effect on low-density lipoprotein cholesterol (LDL-C), atherosclerosis, and acute coronary syndrome (ACS). Methods. We aimed to investigate the association between rs599839, rs646776, and rs4970834 of locus 1p13.3 and serum LDL-C and severity of coronary artery stenosis in ACS patients. Genotyping of the rs599839, rs646776, and rs4970834 polymorphisms was performed on Arab patients undergoing coronary angiography for ACS. Patients were divided into group A (ACS with insignificant stenosis (<50%)) and group B (with significant stenosis (≥50%)). Results. Patients carrying the minor G allele in rs599839 had significantly lower mean of LDL-C (2.58 versus 3.44 mM, P=0.026) than homozygous A allele carriers (GG versus AA). Carriers of minor C allele in rs64776 had significantly higher mean of HDL-C (2.16 versus 1.36 mM, P=0.004) than carriers of the T alleles (AA versus GG). The odd ratio and 95% confidence interval for dominant model for G allele carriers of rs599839 were 0.51 (0.30–0.92), P=0.038, among patients with significant stenosis. Conclusions. Polymorphisms rs646776 and rs599839 of locus 1p13.3 were significantly associated with LDL-C and other lipid parameters. In addition, the G-allele carriers of variant rs599839 had a significant protective effect against the atherosclerosis.Qatar National Research Fund (a member of Qatar Foundation) under its Undergraduate Research Experience Program no. UREP: 07-091–3-020

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

Systematic Fault Tolerant Control Based on Adaptive Thau Observer Estimation for Quadrotor Uavs

A systematic fault tolerant control (FTC) scheme based on fault estimation for a quadrotor actuator, which integrates normal control, active and passive FTC and fault parking is proposed in this paper. Firstly, an adaptive Thau observer (ATO) is presented to estimate the quadrotor rotor fault magnitudes, and then faults with different magnitudes and time-varying natures are rated into corresponding fault severity levels based on the pre-defined fault-tolerant boundaries. Secondly, a systematic FTC strategy which can coordinate various FTC methods is designed to compensate for failures depending on the fault types and severity levels. Unlike former stand-alone passive FTC or active FTC, our proposed FTC scheme can compensate for faults in a way of condition-based maintenance (CBM), and especially consider the fatal failures that traditional FTC techniques cannot accommodate to avoid the crashing of UAVs. Finally, various simulations are carried out to show the performance and effectiveness of the proposed method

Systematic Fault Tolerant Control Based on Adaptive Thau Observer Estimation for Quadrotor Uavs

International audienceAbstract A systematic fault tolerant control (FTC) scheme based on fault estimation for a quadrotor actuator, which integrates normal control, active and passive FTC and fault parking is proposed in this paper. Firstly, an adaptive Thau observer (ATO) is presented to estimate the quadrotor rotor fault magnitudes, and then faults with different magnitudes and time-varying natures are rated into corresponding fault severity levels based on the pre-defined fault-tolerant boundaries. Secondly, a systematic FTC strategy which can coordinate various FTC methods is designed to compensate for failures depending on the fault types and severity levels. Unlike former stand-alone passive FTC or active FTC, our proposed FTC scheme can compensate for faults in a way of condition-based maintenance (CBM), and especially consider the fatal failures that traditional FTC techniques cannot accommodate to avoid the crashing of UAVs. Finally, various simulations are carried out to show the performance and effectiveness of the proposed method