The effect of mother's age on the neonatal cord serum's oxidative stress index and maternal and neonatal outcomes: a case control study.

BACKGROUND: One of the main challenges of many societies in reducing and ageing of the population is marriage at an advanced age in women and decrease of producing offspring due to the concern of increasing the probability of maternal and neonatal outcomes. The mother's oxidative stress conditions during pregnancy affect mothers and their baby's health. Aging is one of the increasing factors of oxidants in the body. Aim of this study is the compartion total antioxidant capacity (TAC), total oxidants status (TOS), oxidative stress index (OSI) values, and maternal and neonatal outcomes in three groups of mothers with different age ranges from 20 to 29, 30 to 34, and 35 to 45 years old. METHODS: 164 pregnant women were grouped according to age into three groups: 25 to 30 (group I), 30 to 35 (group II), and 35 to 45 years old (group III). The umbilical cord blood samples were taken to the assay TAC, TOS, and OSI (TOS/TAC). The Kolmogorov-Smirnov test was employed to assess the normal distribution of countinus variables. The one-way ANOVA and Kruskal-Wallis test were used to compare anthropometric and biochemical factors between groups. RESULTS: TAC levels decreased non-significantly (438.2 ± 102; 431.7 ± 99.8; and 428.2 ± 100.26 for groups I, II, and III respectively, P value = 0.99), TOS levels increased significantly (23.93 ± 11.7; 25.4 ± 12.3; and 28.2 ± 12.7 for groups I, II, and III respectively, P value = 0.034), and OSI increased non-significantly with increasing maternal age (0.055 ± 0.044; 0.091 ± 0.031; 0.069 ± 0.005, for groups I, II, and III respectively, P value = 0.14). Increasing age did not significantly affects the maternal and infant birth outcomes. CONCLUTION: The results showed that the increasing the age of the mother up to 45 doesn't have a significant effects on the value of OSI and the maternal and infant outcomes.

Protective effects of paraoxonase-1, vitamin E and selenium, and oxidative stress index on the susceptibility of low density lipoprotein to oxidation in diabetic patients with/without coronary artery disease.

BACKGROUND: The oxidative modification of low density lipoprotein (LDL) is closely associated with an increased risk for coronary artery disease (CAD) in diabetic patients. The purpose of this study is to investigate the relation between serum vitamin E and selenium, paraoxonase-1 (PON1) activity, total antioxidant capacity (TAC), total oxidant status (TOS), malondialdehyde (MDA), and oxidative stress index (OSI) values with the susceptibility of LDL to oxidative modification and the possibility of CAD in diabetic patients. METHOD: This study was designed as a case control survey of 82 diabetes patients divided into two groups including T2DM alone (as group I) and both T2DM and CAD (as group II). Fasting blood samples were taken to the assay of fasting blood glucose (FBG), HbA1c, total cholesterol (TC), TAC, TOS, MDA, OSI, vitamin E, selenium, oxidized low density lipoprotein (Ox-LDL), and activity of PON1. RESULTS: Ox-LDL, MDA, TOS, and OSI values in groups II were significantly higher compared with group I (all with P value = 0.000). TAC, vitamin E, selenium, and PON1 activity values were significantly lower in group II compared with groups I (P value = 0.000; P value = 0.000; P value = 0.007; P value = 0.003, respectively). There were significant relationships between the amounts of TAC, TOS, OSI, and vitamin E with the amounts of PON1 activity and Ox-LDL (p < 0.05). But Ox-LDL and PON1 activity correlated weakly with together (p = 0.094). CONCLUSION: Results of this study support the belief that oxidative stress might be an important etiologic factor which makes some diabetics more susceptible to CAD. Increased oxidative stress may be a potential therapeutic target in the prevention and management of CAD in diabetic patients.

Total Antioxidant Capacity and Total Oxidant Status and Disease Severity in a Cohort Study of COVID-19 Patients.

BACKGROUND: Previous reports have suggested the role of oxidative stress in progression of COVID-19 infection, but there is limited information regarding the effect of antioxidant capacity and total oxidant status of patients with COVID-19 on disease severity. In the present study, we aimed to investigate the relationship between total antioxidant capacity (TAC), total oxidant status (TOS), TAC/TOS levels, and disease severity in hospitalized patients with COVID-19. METHODS: This cohort study was carried out at Masih Daneshvari Hospital in Tehran, Iran, from September 2020 to October 2020. Clinical data of 331 patients with COVID-19 admitted to the hospital were analyzed and divided into mild, moderate, and severe groups (needed oxygen, intubation, and mechanical ventilation). The patients' TAC, TOS, and TAC/TOS levels were assessed using the serum samples by colorimetric assay kit. RESULTS: We found no significant difference in serum levels of TAC, TOS, and TAC/TOS in terms of the disease severity. CONCLUSIONS: These results indicated that total antioxidant capacity and total oxidant status may not be the determining factor on the disease severity.

The effects of asthma on the oxidative stress, inflammation, and endothelial dysfunction in children with pneumonia.

BACKGROUND: In community-acquired pneumonia (CAP), pulmonary vascular endothelial dysfunction, inflammation, and oxidative stress (OS) are prominent and interesting as the unfavorable clinical outcomes of it. Asthma as a common chronic respiratory disease may affect the clinical outcomes of pneumonia, but the exact mechanism of this effect remains unclear. The present study aimed to assess the effects of asthma on the OS, inflammation, and endothelial dysfunction biomarkers in the children pneumonia. METHODS: A cross-sectional study designed with a total of 75 children including both severe CAP and asthma (as group I), severe CAP alone (as group II), and healthy children (as group III) was conducted. Fasting blood samples were taken to the assay of serum malondialdehyde (MDA), total antioxidant capacity (TAC), tumor necrosis factor-alpha (TNF-α), soluble vascular cell adhesion molecule-1 (sVCAM-1), and plasminogen activator inhibitor-1 (PAI-1). The mean of anthropometric and biochemical parameters was compared by ANOVA and Tukey post-hoc test between groups. RESULTS: We observed TAC levels in groups I and II (0.997 ± 0.22 and 1.23 ± 0.21 mmol/l, respectively) were significantly lower compared with group III (1.46 ± 0.19 mmol/l, P value < 0.001). It was significantly higher in group II than in group I (P value < 0.001). Also, we observed MDA and TNF-α levels in groups I (6.94 ± 1.61 µmol/l, 7.34 ± 2.23 pg/ml, respectively) and II (2.57 ± 0.40 µmol/l, 5.54 ± 1.84 pg/ml, respectively) were significantly higher compared with group III (1.89 ± 0.27 µmol/l, 3.42 ± 1.32 pg/ml, P value < 0.001, P value < 0.001, respectively). VCAM-1 and PAI-1 levels as the endothelial dysfunction biomarkers were significantly higher in group I (1.5 ± 0.62 mmol/l, 10.52 ± 3.2 AU/ml, respectively) compared with groups II (1.06 ± 0.53 mmol/l and 8.23 ± 3.4 AU/ml; P value < 0.001, P value < 0.001, respectively) and III (0.6 ± 0.35 mmol/l and 2.39 ± 0.83 AU/ml; P value < 0.001, P value < 0.001, respectively). Also, VCAM-1 and PAI-1 levels were significantly higher in group II compared with groups III (P value < 0.001, P value < 0.001). CONCLUSIONS: Asthma can exacerbate the vascular dysfunction of pneumonia in children by increasing oxidative stress, inflammation, and endothelial dysfunction.

Patients with severe COVID-19 have reduced circulating levels of angiotensin-(1-7): A cohort study.

Background and Aims: Angiotensin-converting enzyme 2 (ACE2) acts as a functional receptor for the entry of severe acute respiratory syndrome coronavirus 2 into host cells. Angiotensin (1-7) (Ang (1-7)) obtained from the function of ACE2 improves heart and lung function. We investigated the relationship between Ang (1-7) level and disease severity in patients with coronavirus disease 2019 (COVID-19). Methods: This cohort study was carried out at Masih Daneshvari Hospital in Tehran, Iran from September 2020 to October 2020. To do so, the Ang (1-7) levels of 331 hospitalized COVID-19 patients with and without underlying disease were measured by ELISA kit. The need for oxygen, intubation, and mechanical ventilation were recorded for all the patients. Results: Results showed a significant inverse relationship between the levels of Ang 1-7 and the severity of the disease (needed oxygen, intubation, and mechanical ventilation). According to the results, median (interquartile range) of Ang (1-7) levels was significantly lower in patients who needed oxygen versus those who needed no oxygen (44.50 (91) vs. 82.25 (68), p = 0.002), patients who needed intubation and mechanical ventilation versus those who did not (9.80 (62) vs. 68.70 (102), p < 0.000) and patients hospitalized in an intensive care unit (ICU) than people hospitalized in other wards. We also found that the older patients were more in need of ICU and mechanical ventilation than younger patients. Conclusions: Higher levels of Ang (1-7) have been associated with decreased disease severity. Besides this, we perceived that synthetic Ang 1-7 peptides may be useful to treat and reduce the complications of COVID-19.

Improving the endothelial dysfunction in type 2 diabetes with chromium and vitamin D3 byreducing homocysteine and oxidative stress: A randomized placebo-controlled trial.

BACKGROUND: Chromium picolinate (CrPic) and vitamin D3 are known as two antioxidant micronutrients. Through inducing endothelial dysfunction, oxidants such as homocysteine (Hct) and malondialdehyde (MDA) lead to cardiovascular disease in type 2 diabetes mellitus (T2DM). No published data has directly examined the effects of these two antioxidants on improving the endothelial dysfunction in T2DM throughreducing homocysteine and oxidative stress. METHODS: Subjects (n = 92) in this randomized, double blind, placebo-control study were randomly assigned to receive oral placebo (group I), D3 (group II: 50,000 IU/ week), chromium picolinate (CrPic) (group III: 500 µg/day), and both vitamin D3 and CrPic (group IV) for four months. Fasting blood samples were drawn at study baseline and following intervention to determine Hct, MDA, total antioxidant capacity (TAC), total thiol groups (SHs), vascular cell adhesion molecule- 1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1). RESULTS: After intervention, MDA significantly decreased in groups II and IV; TAC significantly increased in group IV, and SHs significantly augmented in group III; Hct was significantly reduced in groups II, III, and IV; and VCAM-1 significantly decreased in groups III and IV and PAI-1 was significantly reduced in groups II, III, and IV. CONCLUSION: Our findings suggest that through reducing homocysteine and oxidative stress and improving endothelial dysfunction, chromium and vitamin D3 co-supplementation might be predictive and preventive of cardiovascular diseasesassociated with T2DM. IRCT, IRCT20190610043852N1, registered 21 October 2019, https://fa.irct.ir/user/trial/42293/view.

The effects of chromium and vitamin D3 co-supplementation on insulin resistance and tumor necrosis factor-alpha in type 2 diabetes: a randomized placebo-controlled trial.

The current study was conducted to assess the effects of simultaneous usage with vitamin D3 and chromium picolinate (CrPic) supplementations on homeostasis model assessment of insulin resistance (HOMA-IR), fasting blood glucose (FBS), hemoglobin A1c (HbA1c), tumor necrosis factor-α (TNF-α), and lipid profile in type 2 diabetes mellitus (T2DM). Ninety-two patients with T2DM were randomly allocated to the following 4 groups for 4 months: (I) placebo of vitamin D3 (n = 23); (II) vitamin D3 supplement at a dose of 50 000 IU/week (n = 23); (III) CrPic supplement at a dose of 500 µg/day (n = 23); and (IV) both vitamin D3 at a dose of 50 000 IU/week and CrPic at a dose of 500 µg/day (n = 23). HOMA-IR levels increased significantly in groups I and II after the intervention. However, this increase in group I was significantly higher than that in group II after the treatment. HOMA-IR levels were controlled in groups III and IV during the intervention. TNF-α decreased significantly in groups II, III, and IV after the intervention. FBS, HbA1c, and lipid profile did not change significantly in total groups after the intervention. It seems that chromium and vitamin D3 co-supplementation are probably effective in controlling HOMA-IR by decreasing TNF-α in T2DM. Novelty Chromium alone and/or in simultaneous pretreatment with vitamin D3 is more effective than vitamin D3 in controlling HOMA-IR in T2DM. Chromium and vitamin D3 alone and/or in simultaneous pretreatment decrease TNF-α in T2DM.

Evaluation of targeted curcumin (CUR) loaded PLGA nanoparticles for in vitro photodynamic therapy on human glioblastoma cell line.

In this study, antibody-conjugated biodegradable polymeric nanoparticles were developed to enhance the photodaynamic efficiency of curcumin (CUR) on glioblastoma tumor cells. Poly (D, l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) were synthesized and stabilized by polyvinyl alcohol (PVA). Poly(ethylene-alt-maleic anhydride) (PEMA) was used to provide carboxyl groups on the surface of NPs. The CUR or FITC (fluorescein isothiocyanate) was encapsulated in PLGA NPs using the nanoprecipitation method. The carboxylic groups on the surface of the PLGA NPs were covalently conjugated to the amino groups of a monoclonal antibody against EGFRvIII (A-EGFRvIII-f). The prepared NPs were fully characterized by Zetasizer, scanning electron microscope (SEM), differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR), and then entrapment efficiency (EE), drug loading efficiency (DLE), CUR release, cell internalization, intrinsic cytotoxicity, and phototoxicity were evaluated. Furthermore, the effect of monoclonal antibody (MAb) on the tyrosine phosphorylation of EGFRvIII after photodynamic therapy (PDT) was assessed. The immunoreactivity of the antibody in MAb-PLGA NPs was preserved during the process of conjugation. The selective cellular internalization of MAb-PLGA NPs (FITC or CUR loaded) into the DKMG/EGFRvIII cells (EGFRvIII overexpressed human glioblastoma cell line) in comparison with DK-MGlow (human glioblastoma cell line with low level of EGFRvIII) was also confirmed. MAb-CUR-PLGA NPs were able to show more effective photodynamic toxicity (56% vs. 24%) on the DKMG/EGFRvIII cells compared to CUR-PLGA NPs. These results suggest that the anti-EGFRvIII MAb-CUR-PLGA NPs have potential of targeted drug delivery system for PDT in the overexpressed EGFRvIII tumor cells.

Evaluation of a novel biocompatible magnetic nanomedicine based on beta-cyclodextrin, loaded doxorubicin-curcumin for overcoming chemoresistance in breast cancer.

Codelivery of chemo-sensitizers with chemotherapeutics using combo nanomedicine is a promising platform for overcoming chemoresistance in breast cancer. However, tumor accumulation of nano-carriers based on enhanced permeability and retention (EPR) effect is confounded by heterogeneity in tumor microenvironment. Adsorption of protein corona on surface of nanoparticle boost up clearance by reticulo-endothelial system. In this study, a surface functionalized magnetic nanocomposite (NC) for codelivery of doxorubicin (DOX) and curcumin (CUR) is developed. NCs were coated with hydroxyapatite and were also cross linked with ß-cyclodextrin. NCs efficiently encapsulated DOX and CUR. Release of CUR and DOX were in a sustained pH-depended pattern. ß-cyclodextrin functionalization reduced protein corona according sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) analysis. As shown by flowcytometric and confocal microscopy analyses, NCs internalized efficiently by human breast carcinoma cells MCF-7 and adriamycin resistant MCF-7 (MCF-7/adr) cells. 3-(4,5-Dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) test demonstrated superior cytotoxicity of DOX-CUR loaded NCs. Anti-tumor efficacy analyses confirmed reduction in relative tumor volume size (RTV%) compared to control group. Western blot analyses demonstrated marginal CUR mediated P-glycoprotein (P-gp) down regulation. DOX-CUR loaded NCs efficiently accumulated into the tumor via external magnet guidance. Nevertheless, the increased tumor accumulation did not correlate with pharmacologic responses such as RTV% and significant superiority over free DOX was not observed.

Zinc and Selenium Co-supplementation Reduces Some Lipid Peroxidation and Angiogenesis Markers in a Rat Model of NAFLD-Fed High Fat Diet.

Studies have shown that non-alcoholic fatty liver disease (NAFLD) patients are more prone to cardiovascular disease (CVD). Zinc and selenium deficiency are common in NAFLD. But the effects of zinc and selenium co-supplementation before and/or after disease progression on CVD markers are not clear in NAFLD patients. This study aimed to compare the effects of zinc and selenium co-supplementation before and/or after disease progression on some of the CVD markers in an experimental model of NAFLD. Forty male Sprague Dawley rats (197 ± 4 g) were randomly assigned into four dietary groups: control group (C; received 9% of calorie as fat), model group (M; received 82% of calorie as fat), and supplementation before (BS) or after (AS) disease progression. Animals were fed diets for 20 weeks in all groups. Fasting plasma glucose (FPG), insulin, HOMA-IR, ALT, AST, lipid profile, malondialdehyde (MDA) and vascular endothelial growth factor (VEGF) levels were measured as CVD indices. Serum ALT, AST, FPG, insulin, MDA, VEGF and HOMA-IR were significantly higher in the M than C group. Co-supplementation reduced serum ALT and AST levels in the BS and AS groups compared with the M group. FPG, insulin, HOMA-IR, VEGF, MDA, LDL/HDL-c and TC/HDL-c ratio were significantly reduced in the AS compared with the M group. TG/HDL-c ratio was significantly reduced in the BS and AS compared with the M group. Serum MDA, VEGF, Insulin and HOMA-IR were significantly lowered in the AS than BS group (p < 0.05). Zinc and selenium co-supplementation after NAFLD progression reduced CVD risk indices in an experimental model.

mZD7349 peptide-conjugated PLGA nanoparticles directed against VCAM-1 for targeted delivery of simvastatin to restore dysfunctional HUVECs.

Endothelial dysfunction is initial and critical step of atherosclerosis. Impaired bioavailability of endothelial nitric oxide synthase (eNOS) is one of the main reasons of endothelial dysfunction. Improving bioavailability of eNOS by increasing its expression or activity using statins is an effective therapeutic strategy in restoring endothelial dysfunction. In this study, simvastatin (SIM) as a poorly water-soluble drug was loaded in poly (lactic-co-glycolic acid) (PLGA) nanoparticles (SIM-PLGA-NPs). NPs were then conjugated with mZD7349 peptide (mZD7349-SIM-PLGA-NPs) and directed against vascular cell adhesion molecule 1 (VCAM-1). In vitro evaluation of the NPs for targeted delivery of SIM was performed on activated Human Umbilical Cord Vascular Endothelial Cells (HUVECs) by tumor necrosis factor alpha (TNF-α). Effect of mZD7349-SIM-PLGA-NPs and SIM-PLGA-NPs was compared on eNOS phosphorylation (ser-1177). Results of western blot showed SIM post-treatment increased significantly phosphor-eNOS (Ser1177) expression but no total eNOS expression. The study showed that mZD7349-SIM-PLGA-NPs have particle size, zeta potential value, polydispersity index (PDI) and encapsulation efficacy % of 233±18nm, -9.6±1.1mV, 0.59±0.066 and 69±17.3%, respectively. Also phosphor-eNOS (Ser1177) expression in activated HUVECs treated with mZD7349-SIM-PLGA-NPs was significantly (p<0.05) better than treated cells with SIM-PLGA-NPs. The results suggest that mZD7349-SIM-PLGA-NPs may be usable as an appropriate drug carrier for restoring endothelial dysfunction.

Potential of mZD7349-conjugated PLGA nanoparticles for selective targeting of vascular cell-adhesion molecule-1 in inflamed endothelium.

Early diagnosis and restoring normal function of dysfunctional endothelium is an attractive strategy for prevention of inflammatory diseases such as atherosclerosis. Inhibition of cell adhesion in the process of atherosclerosis plaque formation, mediated by peptide antagonists of very late antigen-4 (VLA-4) has already been developed and evaluated both in vitro and in vivo. In this study, for the first time, modified ZD7349 (mZD7349) peptide, as an antagonist for VLA-4, was used for targeting fluorescein isothiocyanate-loaded poly (DL-lactic-co-glycolic acid) nanoparticles (FITC-PLGA NPs). Rate of binding and internalization of mZD7349-NPs to activated human umbilical vein endothelial cells (HUVECs) were compared with that of untargeted. Effects of temperature reduction and clathrin-mediated endocytosis inhibitor (0.45M sucrose) were also studied on the binding and internalization of mZD7349-NPs and NPs. Results showed that binding of the conjugated NPs could be significantly blocked by pre-incubating cells with the free peptide, suggesting that the binding of NPs is mediated by attaching the surface peptide to VCAM-1 on HUVECs. Also, conjugated FITC-loaded NPs were shown to be rapidly endocytosized to a greater extent than the unconjugated ones. The binding and internalization of mZD7349-NPs and NPs were slowed down at low temperature and in the presence of sucrose with greater reductions for mZD7349-NPs. To conclude, the peptide-NPs targeting the VCAM-1 is suggested as a theranostic carrier for lesions upregulating VCAM-1.