COVID-19, is a disease resulting from the SARS-CoV-2 global pandemic. Due to the current global emergency and the length of time required to develop specific antiviral agent(s) and a vaccine for SARS-CoV-2, the world health organization (WHO) adopted the strategy of repurposing existing medications to treat COVID-19. Iron oxide nanoparticles (IONPs) were previously approved by the US food and drug administration (FDA) for anemia treatment and studies have also demonstrated its antiviral activity in vitro. Therefore, we performed a docking study to explore the interaction of IONPs (Fe 2 O 3 and Fe 3 O 4) with the spike protein receptor binding domain (S1-RBD) of SARS-CoV-2 that is required for virus attachment to the host cell receptors. A similar docking analysis was also performed with hepatitis C virus (HCV) glycoproteins E1 and E2. These studies revealed that both Fe 2 O 3 and Fe 3 O 4 interacted efficiently with the SARS-CoV-2 S1-RBD and to HCV glycoproteins, E1 and E2. Fe 3 O 4 formed a more stable complex with S1-RBD whereas Fe 2 O 3 favored HCV E1 and E2. These interactions of IONPs are expected to be associated with viral proteins conformational changes and hence, viral inactivation. Therefore, we recommend FDA-approved-IONPs to proceed for COVID-19 treatment clinical trials.
Serum omentin-1 levels were found to be significantly decreased in patients with Type 2 diabetes (19.7 ± 1 ng/ml) and in patients with Type 2 diabetes with ischaemic heart disease (18.5 ± 1.6 ng/ml) compared with healthy control subjects (27.4 ± 2.6 ng/ml) at P < 0.01. Moreover, serum chemerin levels were found to be significantly increased in patients with Type 2 diabetes (347 ± 14 ng/ml) and in patients with Type 2 diabetes with ischaemic heart disease (341 ± 16.5 ng/ml) compared with healthy control subjects (281 ± 13 ng/ml) at P < 0.01. Interestingly, omentin-1 and chemerin levels were found to be significantly correlated negatively with each other as well as being individually correlated with some selected anthropometric, biochemical and clinical variables. In conclusion, both omentin-1 and chemerin might play as a pivotal role in obesity and its associated disorders as Type 2 diabetes; however, their role in cardiovascular diseases needs to be fully elucidated.
We examined whether Nigella sativa (NS) oil and its active constituent thymoquinone (TQ) attenuate oxidative stress in the heart and brain in an experimental model of diabetes mellitus using streptozotocin (STZ). Oxidative stress was assessed by measuring cardiac and brain nitric oxide (NO), lipid peroxide levels, glutathione (GSH) and antioxidant enzyme activities, i.e. glutathione-S-transferase (GST) and catalase. Cardiac metabolic damage was estimated by measuring cardiac creatine kinase muscle and brain types (CK-MB). Brain monoamine levels were also evaluated. STZ diabetes induced a significant increase in heart and brain NO and malondialdehyde concentrations compared with the control group. These changes were attenuated by posttreatment of rats with NS oil and TQ. STZ diabetes induced oxidative stress via a significant decrease in GST, GSH and catalase. These lowered levels were improved by either NS oil or TQ administration. Serum CK-MB was decreased in the diabetic rats, which recovered with NS oil and TQ administration. During the course of diabetes, there was a marked increase in norepinephrine and dopamine concentrations and a marked decrease in serotonin concentration compared to the control group. These findings were partly reversed by oral administration of either NS oil or TQ. It is concluded that NS and TQ correct STZ-diabetes-induced alterations in CK-MB and brain monoamines due to their antioxidant properties.
This study compared lipids, the product of lipid peroxidation malondialdehyde (MDA), the acute phase reactant high-sensitive C-reactive protein (hsCRP), endothelin-1 (ET-1), P-selectin, intercellular adhesion molecule-1 (ICAM-1), and vascular cell adhesion molecule-1 (VCAM-1) between healthy controls, subjects with ischemic heart disease (IHD) and type 2 diabetes mellitus (DM) subjects who did not perform coronary artery bypass graft (CABG) surgery as well as type 2 DM subjects who performed CABG. HbA1c, lipids, MDA, hsCRP, ET-1, P-selectin, ICAM-1, and VCAM-1 levels were significantly higher in the diabetic groups than in either healthy controls or IHD subjects. In the diabetic groups, there was a negative association among hsCRP and HDL-C. ET-1, ICAM-1 levels, and TAG were positively correlated, as do the association between P-selectin, VCAM-1, and HbA1c%. Also a positive relation was found among hsCRP levels and ICAM-1, as well as MDA and ET-1. P-selectin and ICAM-1 were significantly positively correlated. This study indicates that increased level of oxidative stress marker, proinflammatory markers, and their downstream effectors adhesion molecules occur in type 2 DM.
Aspirin and clopidogrel are the mainstay oral antiplatelet regimens, yet a substantial number of major adverse cardiac events (MACE) still occur. Herein, we investigated genetic and nongenetic factors associated with clopidogrel response in Egyptians. In all, 190 Egyptians with acute coronary syndrome (ACS) and/or percutaneous coronary intervention (PCI), treated with clopidogrel (75 mg/day) for at least a month, were genotyped for CYP2C19 *2, *3, *6, *8, *10, and *17, CES1 G143E and ABCB1*6 and *8. These variants along with nongenetic factors were tested for association with the risk of having MACE in clopidogrel‐treated patients. CYP2C19 loss‐of‐function (LOF) alleles carriers had increased risk of MACE vs. noncarriers (odds ratio 2.52; 95% confidence interval 1.23–5.15, P = 0.011). In a logistic regression, CYP2C19 LOF variants (P = 0.011), age (P = 0.032), and body mass index (BMI, P = 0.039) were significantly associated with the incidence of MACE in patients taking clopidogrel. CYP2C19 genetic variants, age, and BMI are potential predictors associated with variability to clopidogrel response in Egyptians.
Soluble forms of the receptor for advanced glycation end product could be an endogenous protection factor against occurrence of DF, hence may be of therapeutic value in the treatment of DF.
Chronic inflammation and insulin resistance form hallmarks of type 2 diabetes mellitus (T2DM). An increased circulating level of the serine protease granzyme B (GzmB) is observed during prolonged inflammation and is implicated in the pathogenesis of several chronic inflammatory diseases. Moreover, insulin receptor cleavage by unknown proteases, yielding elevated levels of insulin receptor α-subunit (IRα), was observed in T2DM and was proposed as a new mechanism of insulin resistance. Therefore, a possible association between GzmB and IRα is suggested. Accordingly, this study was set to explore whether GzmB and IRα levels are altered in T2DM patients with the impact of obesity. Furthermore, we aimed to identify if GzmB contributes towards inflammation and insulin resistance through its suggested extracellular activities. All subjects were assessed for anthropometric and metabolic parameters related to obesity and T2DM. In addition, fasting plasma insulin, GzmB, interleukin-1β (IL-1β), and IRα levels were estimated by enzyme linked immunosorbent assay. Levels of GzmB and IRα were found to be significantly elevated in T2DM patients compared to nondiabetic subjects. In addition, GzmB levels were positively correlated with measures of obesity and insulin resistance, IL-1β, IRα, and other metabolic parameters. While multiple linear regression analysis revealed that both T2DM and central obesity were predicting factors for GzmB, our findings reveal a possible role of GzmB in T2DM.
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