PMID: 

J Basic Clin Physiol Pharmacol. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31730524

Abstract Title: 

Possible therapeutic effect of magnesium in ocular diseases.

Abstract: 

Magnesium (Mg2+) is one of the major elements required to maintain normal metabolism and ionic balances in ocular tissues. The physiological role of Mg2+ is mediated through maintaining the Na+-K+-ATPase on membrane, favoring energy-generating reactions, replication of DNA and protein synthesis. Despite the wide availability of this element, hypomagnesemia has been associated with many human ailments. Recent studies highlighted the association of hypomagnesemia and, thereby, supplementation of Mg2+ in the management of eye diseases. Glaucoma, senile cataract and diabetic retinopathy were associated with low level of extracellular Mg2+. The neurovascular protective effects of Mg2+ mediated through activation of endothelial nitric oxide synthase and inhibition of endothelin-1 eventually result in vasodilatation of retinal vessels. Mg2+ can maintain the lens sodium pump activity and antioxidant status and block the calcium channels and release of glutamate in nerve endings. Furthermore, it can prevent the apoptosis of retinal ganglion cells. All these effects contribute to its being a pharmacological agent against ocular diseases. However, clinical trials are scant. This article discusses the role of Mg2+ as a possible therapeutic agent in the management of glaucoma, cataract and diabetic retinopathy.

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PMID: 

Front Pharmacol. 2019 ;10:1186. Epub 2019 Oct 11. PMID: 31680964

Abstract Title: 

Cytokines Driven Anti-Inflammatory and Anti-Psoriasis Like Efficacies of Nutraceutical Sea Buckthorn () Oil.

Abstract: 

Psoriasis is a chronic inflammatory skin disease characterized by circumscribed, red, thickened plaques with overlying silvery white scales. It is associated with the release of pro-inflammatory mediators that lead to the development of edema and distress. Here we show the anti-inflammatory and anti-psoriatic efficacies of a neutraceutical sea buckthorn oil (SBKT) derived from the fruit pulp of. Chemical analysis of the SBKT showed the presence of 16 major saturated, mono-, and polyunsaturated fatty acids components, imparting significant nutritional values. Efficacy of the SBKT in modulating psoriasis and associated inflammation was first testedusing human monocytic (THP-1) cells. SBKT induced cytotoxicity at a dose of≥25 µl/ml. Treatment of the lipopolysaccharide-stimulated THP-1 cells with SBKT subdued the enhanced release of intracellular reactive nitrogen species and expression of NF-κB protein, in a concentration-dependent manner. This was accompanied by a reduction in the release of downstream pro-inflammatory cytokines: Interleukin-1ß and interleukin-6. Tumor necrosis factor-α released in the stimulated THP-1 cells were also inhibited by SBKT dose of 5 µl/ml.oral and topical treatment with SBKT in the Carrageenan-stimulated paw edema model, showed a significant decrease in paw volume and edema. In the 12-O tetradecanoyl phorbol 13-acetate (TPA) stimulated CD-1 mice psoriasis-like model, concurrent oral and tropical SBKT treatments substantially reduced ear edema and ear biopsy weights. Histopathologically, significant reduction in ear epidermal thickness and skin lesion scores was observed in the SBKT-treated animals. In conclusion, SBKT showed anti-inflammatory and anti-psoriasis-like efficacies in healing chemical-induced inflammation and psoriasis. The possible mode of action of SBKT was found through inhibition of reactive nitrogen species, and downregulation of NF-κB protein and pro-inflammatory cytokines. Thus, the present data suggest that Sea buckthorn oil can be used as an anti-inflammatory and anti-psoriatic nutraceutical.

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PMID: 

Int J Biol Macromol. 2019 Nov 12. Epub 2019 Nov 12. PMID: 31730993

Abstract Title: 

Hippophae rhamnoides polysaccharides protect IPEC-J2 cells from LPS-induced inflammation, apoptosis and barrier dysfunction in vitro via inhibiting TLR4/NF-κB signaling pathway.

Abstract: 

Inflammatory response caused by early weaning stress in piglets is associated with various diseases. The Hippophae rhamnoides polysaccharide (HRP) exhibits anti-inflammatory activity and immunomodulatory properties. The mechanisms for the protective effects of HRP on barrier function, inflammatory damage and apoptosis in intestinal porcine epithelial cells (IPEC-J2) induced by the lipopolysaccharide (LPS) are unknown. In this study, we first demonstrated the cytotoxicity of HRP-induced IPEC-J2 cells by reducing cell viability. IPEC-J2 cells were treated with 0-800 μg/mL doses of HRP, and 0-600 μg/mL doses were used in further experiments. Upon exposure to LPS, the viability of IPEC-J2 cells, ROS production, immunoglobulin levels (immunoglobulin M (IgM), immunoglobulin A (IgA) and immunoglobulin G (IgG)) and tight junction protein level (zonula occludens-1 (ZO-1), occluding, claudin-1) decreased. Inflammatory factors (interleukin-1beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-α)) and apoptosis (Bcl-2, Bax, caspase-3, caspase-8 and caspase-9) were increased. Cell morphology and internal structure were damaged in the LPS treatment. Pre-treating cells with HRP (0-600 μg/mL) reduced inflammatory factors levels, apoptosis rate, increased immunoglobulin, tight junction protein levels and relieved cell surface morphology damage. Pre-treatment with HRP also reduced the levels of the Toll-like receptor 4 (TLR4) and Myeloid differentiation factor 88 (MyD88) and inhibited the phosphorylated NF-κB factor-kappa B (NF-κB) in cells induced by LPS. These results show that pre-treatment with HRP protected against LPS-induced IPEC-J2 cell damage through its anti-inflammatory activity.

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PMID: 

Diabetologia. 2019 Nov 14. Epub 2019 Nov 14. PMID: 31728565

Abstract Title: 

Plasma ascorbic acid and the risk of islet autoimmunity and type 1 diabetes: the TEDDY study.

Abstract: 

AIMS/HYPOTHESIS: We studied the association of plasma ascorbic acid with the risk of developing islet autoimmunity and type 1 diabetes and examined whether SNPs in vitamin C transport genes modify these associations. Furthermore, we aimed to determine whether the SNPs themselves are associated with the risk of islet autoimmunity or type 1 diabetes.METHODS: We used a risk set sampled nested case-control design within an ongoing international multicentre observational study: The Environmental Determinants of Diabetes in the Young (TEDDY). The TEDDY study followed children with increased genetic risk from birth to endpoints of islet autoantibodies (350 cases, 974 controls) and type 1 diabetes (102 cases, 282 controls) in six clinical centres. Control participants were matched for family history of type 1 diabetes, clinical centre and sex. Plasma ascorbic acid concentration was measured at ages 6 and 12 months and then annually up to age 6 years. SNPs in vitamin C transport genes were genotyped using the ImmunoChip custom microarray. Comparisons were adjusted for HLA genotypes and for background population stratification.RESULTS: Childhood plasma ascorbic acid (mean ± SD 10.76 ± 3.54 mg/l in controls) was inversely associated with islet autoimmunity risk (adjusted OR 0.96 [95% CI 0.92, 0.99] per +1 mg/l), particularly islet autoimmunity, starting with insulin autoantibodies (OR 0.94 [95% CI 0.88, 0.99]), but not with type 1 diabetes risk (OR 0.93 [95% Cl 0.86, 1.02]). The SLC2A2 rs5400 SNP was associated with increased risk of type 1 diabetes (OR 1.77 [95% CI 1.12, 2.80]), independent of plasma ascorbic acid (OR 0.92 [95% CI 0.84, 1.00]).CONCLUSIONS/INTERPRETATION: Higher plasma ascorbic acid levels may protect against islet autoimmunity in children genetically at risk for type 1 diabetes. Further studies are warranted to confirm these findings.DATA AVAILABILITY: The datasets generated and analysed during the current study will be made available in the NIDDK Central Repository at https://ift.tt/2CQnCAW.

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PMID: 

Behav Brain Res. 2019 Nov 8:112350. Epub 2019 Nov 8. PMID: 31711893

Abstract Title: 

Vitamin C Attenuates Memory Loss Induced by Post-Traumatic Stress like Behavior in a Rat Model.

Abstract: 

Oxidative stress is associated with neuronal damage in many brain regions including the hippocampus; an area in the brain responsible of memory processing. Oxidative stress is also linked with many psychiatric conditions including post-traumatic stress disorder (PTSD). PTSD is triggered by traumatic experience and many PTSD patients show signs of memory impairment. Vitamin C is a water-soluble vitamin with antioxidant properties. Herein, we hypothesized that memory impairment observed during PTSD could be a result of oxidative stress in hippocampal tissues and that prophylactic vitamin C administration may reduce oxidative stress in the hippocampus and prevent memory impairment. The above hypothesis was tested in a rat model where PTSD-like behavior was induced through single prolonged stress (SPS). Short and long-term memory was tested using a radial arm water maze (RAWM). We found that SPS induced a significant increase in the oxidized glutathione levels of the hippocampus. This reduction was accompanied with a significant decrease in glutathione peroxidase and catalase enzyme activity, and a significant increase in lipid peroxidation. Intriguingly, vitamin C administration successfully attenuated memory impairment and all of the changes observed in oxidative stress markers. Our findings demonstrate that vitamin C could prevent oxidative stress and memory impairment induced by SPS model of PTSD-like behavior in rat.

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PMID: 

Braz J Cardiovasc Surg. 2019 12 1 ;34(5):517-524. Epub 2019 Dec 1. PMID: 31719005

Abstract Title: 

The Effect of High-Dose Vitamin C on Biochemical Markers of Myocardial Injury in Coronary Artery Bypass Surgery.

Abstract: 

OBJECTIVE: To evaluate the effect of high-dose vitamin C on cardiac reperfusion injury and plasma levels of creatine kinase-muscle/brain (CK-MB), troponin I, and lactate dehydrogenase (LDH) in patients undergoing coronary artery bypass grafting (CABG).METHODS: This is a double-blind randomized clinical trial study. Fifty patients (50-80 years old) who had CABG surgery were selected. The intervention group received 5 g of intravenous vitamin C before anesthesia induction and 5 g of vitamin C in cardioplegic solution. The control group received the same amount of placebo (normal saline). Arterial blood samples were taken to determine the serum levels of CK-MB, troponin I, and LDH enzymes. Left ventricular ejection fraction was measured and hemodynamic parameters were recorded at intervals.RESULTS: High doses of vitamin C in the treatment group led to improvement of ventricular function (ejection fraction [EF]) and low Intensive Care Unit (ICU) stay. The cardiac enzymes level in the vitamin C group was lower than in the control group. These changes were not significant between the groups in different time intervals (anesthesia induction, end of bypass, 6 h after surgery, and 24 h after surgery) for CK-MB, LDH, and troponin I. Hemodynamic parameters, hematocrit, potassium, urinary output, blood transfusion, arrhythmia, and inotropic support showed no significant difference between the groups.CONCLUSION: Vitamin C has significantly improved the patients' ventricular function (EF) 72 h after surgery and reduced the length of ICU stay. No significant changes in cardiac biomarkers, including CK-MB, troponin I, and LDH, were seen over time in each group.IRCT CODE: IRCT2016053019470N33.

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PMID: 

Sci Total Environ. 2019 Nov 3 ;703:134681. Epub 2019 Nov 3. PMID: 31715463

Abstract Title: 

Metabonomics reveals bisphenol A affects fatty acid and glucose metabolism through activation of LXR in the liver of male mice.

Abstract: 

Bisphenol-A (BPA) is a representative environmental endocrine disrupting chemical that is widely used in the production of polycarbonate plastics and epoxy resins. Many studies have confirmed BPA to be closely associated with metabolic diseases, reproductive system diseases, and sex hormone-dependent cancers. In this study, we aimed to systematically elucidate the molecular action of BPA on liver fatty acid and glucose metabolism and the reasons for BPA-induced hypoglycemia through a metabonomics approach. C57BL/6 mice were orally treated with BPA (1, 10, 50, 250 μg/kg) for 35 days and the liver metabonomics and histopathology, molecular docking, mRNA expression levels and activities of enzymes were analyzed. Based on the high-resolution mass spectrometry (MS) for metabonomics and on various software and bioinformatic analysis methods, we found that BPA could affect fatty acid and glucose metabolism, block the TCA cycle, and BPA also regulated the nuclear receptor LXR caused hypoglycemia, thereby affecting the normal metabolic functions of the liver.

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PMID: 

Ecotoxicol Environ Saf. 2019 Nov 1 ;188:109870. Epub 2019 Nov 1. PMID: 31683046

Abstract Title: 

Bisphenol F exposure impairs neurodevelopment in zebrafish larvae (Danio rerio).

Abstract: 

BPF, a substitute of BPA, has been widely detected in environment and human bodies. Although the genotoxicity, endocrine disrupting effects, reproductive toxicity of BPF has been well documented, its neurodevelopmental toxicity still remains nebulous. In our study, zebrafish embryos were exposed to BPF treatment (0, 7, 70 and 700 μg/L) for 3 or 6 days. Our results showed that BPF exposure markedly decreased zebrafish locomotor behavior, increased oxidative stress, promoted apoptosis and altered brain structure in zebrafish. In addition, the expressions of neurodevelopment related genes were also downregulated upon BPF treatment. In conclusion, our results systematically demonstrated the developmental neurotoxicity of BPF in zebrafish.

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PMID: 

Environ Sci Technol. 2019 Nov 8. Epub 2019 Nov 8. PMID: 31702913

Abstract Title: 

Bisphenol F-induced neurotoxicity towards zebrafish embryos.

Abstract: 

In this study, the influence of bisphenol F (BPF) toward central neural system (CNS) was assessed using zebrafish embryos. We found that BPF could induce significant neurotoxicity towards zebrafish embryos, including inhibited locomotion, reduced moving distance and CNS cell apoptosis at an effective concentration of 0.0005 mg/L. Immunofluorescence assay showed that both microglia and astrocyte in zebrafish brain were significantly activated by BPF, indicating the existence of neuroinflammatory response. A motor neuron green fluorescence (MnGF) transgenic zebrafish assay showed that BPF significantly inhibited motor neuron development at 72 hpf. RNA-seq data indicated that neuronal developmental processes and cell apoptosis pathways were significantly affected by BPF exposure, which was consistent with the phenotypic results. Chip-Seq assay implied that the transcriptional changes were not mediated by ERα. Additionally, no significant change was found in neurotransmitter levels (5-hydroxytryptamine, dopamine, acetylcholine) or acetylcholinesterase (ache) enzyme activity after BPF exposure, indicating BPF may not affect neurotransmission. In conclusion, BPF could lead to abnormal neural outcomes during zebrafish early life stage through inducing neuroinflammation and CNS cell apoptosis even at environmentally relevant concentrations.

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PMID: 

Environ Sci Pollut Res Int. 2019 Nov 11. Epub 2019 Nov 11. PMID: 31713131

Abstract Title: 

Role of copeptin as a novel biomarker of bisphenol A toxic effects on cardiac tissues: biochemical, histological, immunohistological, and genotoxic study.

Abstract: 

Copeptin is a precursor for arginine vasopressin which is usually elevated in acute stress and cardiac emergencies. Bisphenol A (BPA) is an ideal plasticizing factor used in manufacturing of plastics and epoxy resins. To evaluate the cardio toxicity of bisphenol A and to assess copeptin as a cardio toxic diagnostic and prognostic biomarker in Wistar rats. Sixty Wistar rats were classified into three groups: group I, naive group received regular diet and water; group II, vehicle group administered corn oil; and group III, each rat received BPA daily with (30 mg/kg/day S.C). After 4 weeks, blood samples were collected for estimating serum copeptin levels. Then, the hearts were subjected to histological, immunohistochemical, and electron microscopic examination. Cell suspensions from the hearts were examined to determine the extent of DNA damage by comet assay. Bisphenol A induced a significant increase in mean values of serum copeptin level, histopathological changes in the form of dilated congested blood vessels and extensive collagen fiber deposition in the myocardium. Ultrastructurally, disturbed indented nuclei, focal lysis of myofibrils, normal cross striations loss, mitochondrial swelling, and intercalated disks distortion were noticed. Immunohistochemical study showed a significant increase in TLR2 immunoreactions in the myocytes of BPA administered rats. In addition, comet assay showed that bisphenol A exposure produced DNA damage in cardiac cells. We concluded that bisphenol A has deleterious effects on cardiac tissues mean, while copeptin is a good diagnostic and prognostic biomarker.

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