Curcumin chitosan nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone.

PMID: 

Int J Nanomedicine. 2020 ;15:2699-2715. Epub 2020 Apr 22. PMID: 32368050

Abstract Title: 

Antiviral Activity of Chitosan Nanoparticles Encapsulating Curcumin Against Hepatitis C Virus Genotype 4a in Human Hepatoma Cell Lines.

Abstract: 

Purpose: Current direct-acting antiviral agents for treatment of hepatitis C virus genotype 4a (HCV-4a) have been reported to cause adverse effects, and therefore less toxic antivirals are needed. This study investigated the role of curcumin chitosan (CuCs) nanocomposite as a potential anti-HCV-4a agent in human hepatoma cells Huh7.Methods: Docking of curcumin and CuCs nanocomposite and binding energy calculations were carried out. Chitosan nanoparticles (CsNPs) and CuCs nanocomposite were prepared with an ionic gelation method and characterized with TEM, zeta size and potential, and HPLC to calculate encapsulation efficiency. Cytotoxicity studies were performed on Huh7 cells using MTT assay and confirmed with cellular and molecular assays. Anti-HCV-4a activity was determined using real-time PCR and Western blot.Results: The strength of binding interactions between protein ligand complexes gave scores with NS3 protease, NS5A polymerase, and NS5B polymerase of -124.91, -159.02, and -129.16, for curcumin respectively, and -68.51, -54.52, and -157.63 for CuCs nanocomposite, respectively. CuCs nanocomposite was prepared at sizes 29-39.5 nm and charges of 33 mV. HPLC detected 4% of curcumin encapsulated into CsNPs. IC50 was 8µg/mL for curcumin and 25 µg/mL for the nanocomposite on Huh7 but was 25.8 µg/mL and 34 µg/mL on WISH cells. CsNPs had no cytotoxic effect on tested cell lines. Apoptotic genes' expression revealed the caspase-dependent pathway mechanism. CsNPs and CuCs nanocomposite demonstrated 100% inhibitionof viral entry and replication, which was confirmed with HCV core protein expression.Conclusion: CuCs nanocomposite inhibited HCV-4a entry and replication compared to curcumin alone, suggesting its potential role as an effective therapeutic agent.

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Epigallocatechin gallate inhibits hepatitis B virus infection in human liver chimeric mice.

PMID: 

BMC Complement Altern Med. 2018 Sep 6 ;18(1):248. Epub 2018 Sep 6. PMID: 30189898

Abstract Title: 

Epigallocatechin gallate inhibits hepatitis B virus infection in human liver chimeric mice.

Abstract: 

BACKGROUND: Persistent hepatitis B virus (HBV) infection causes liver cirrhosis and hepatocellular carcinoma and constitutes a major worldwide health problem. Currently, anti-HBV drugs are limited to peginterferon and nucleos(t)ide analogs, which are costly and have considerable side effects; the development of novel, effective anti-HBV agents is crucial.METHODS: Catechins are a major group of compounds found in green tea extract and epigallocatechin gallate (EGCG) has been shown to have antiviral properties, including inhibition of cellular entry by HBV. FRG (Fah/ Rag2/ IL-2Rγ) mice were used in this study to generate chimeras carrying human primary hepatocytes, to facilitate investigation of the inhibitory effect of EGCG on HBV infection.RESULTS: Here, we show the inhibitory effect of EGCG on HBV infection and replication in HuS-E/2 cells. The inhibitory effect of EGCG on HBV infection in vivo was confirmed by monitoring HBV DNA and HBsAg in serum and immunostaining the liver tissues of the human liver chimeric mice.CONCLUSIONS: The effects of EGCG suggest a robust strategy for the treatment of HBV infection and EGCG may have therapeutic potential for the treatment of HBV-associated liver diseases.

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This reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

PMID: 

Nutrients. 2020 Mar 17 ;12(3). Epub 2020 Mar 17. PMID: 32192175

Abstract Title: 

Pathophysiological Role and Therapeutic Implications of Vitamin D in Autoimmunity: Focus on Chronic Autoimmune Diseases.

Abstract: 

Vitamin D is a pleiotropic secosteroid yielding multiple actions in human physiology. Besides the canonical regulatory activity on bone metabolism, several non-classical actions have been described and the ability of vitamin D to partake in the regulation of the immune system is particularly interesting, though far stronger and convincing evidence has been collected in in vitro as compared to in vivo studies. Whether vitamin D is able to regulate at physiological concentrations the human immune system remains unproven to date. Consequently, it is not established if vitamin D status is a factor involved in the pathogenesis of immune-mediated diseases and if cholecalciferol supplementation acts as an adjuvant for autoimmune diseases. The development of autoimmunity is a heterogeneous process, which may involve different organs and systems with a wide range of clinical implications. In the present paper, we reviewed the current evidences regarding vitamin D role in the pathogenesis and management of different autoimmune diseases.

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Higher neonatal vitamin D concentration may reduce the risk of developing childhood asthma at ages 3-9 years.

PMID: 

Nutrients. 2020 Mar 21 ;12(3). Epub 2020 Mar 21. PMID: 32245170

Abstract Title: 

Neonatal Vitamin D Status and Risk of Asthma in Childhood: Results from the D-Tect Study.

Abstract: 

BACKGROUND: low vitamin D status in pregnancy can influence the offspring's lung function and contribute to childhood asthma development. The objective of this study was to examine the influence of neonatal vitamin D status on the development of asthma among children age 3-9 years in a large population sample.METHOD: in a case-cohort study utilizing a Danish biobank and register data we examined the association between neonatal 25-hydroxyvitamin D(25(OH)D) concentrations and incidence of asthma among children aged 3-9 years. Cases of asthma (= 911) were randomly selected among all cases of asthma in the Danish National Patient Register from children born between 1992 and 2002. The sub-cohort (= 1423) was randomly selected among all children born in the same period. We used a weighted Cox proportional hazard model assessing the hazard of first asthma diagnoses by quintiles of 25(OH)D.RESULTS: the median 25(OH)D3 (interquartile range) for asthma cases was 23 nmol/L (14-35) and the sub-cohort 25 nmol/L (14-40). The hazard ratio for developing asthma between ages 3 and 9 years was lower for children in the fifth quintile of neonatal 25(OH)Dcompared to children in the first quintile, both in the unadjusted (0.61 95% CI: 0.46-0.80) and adjusted (0.55 95% CI: 0.39-0.77) analyses.CONCLUSION: the results from our study suggest that higher neonatal vitamin D concentration may reduce the risk of developing childhood asthma at ages 3-9 years, indicating that neonatal vitamin D status as a proxy of vitamin D status during the prenatal period is important for normal immune- and lung development.

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Addition of selenium improves immunomodulative effects of glucan.

PMID: 

N Am J Med Sci. 2016 Feb ;8(2):88-92. PMID: 27042606

Abstract Title: 

Addition of Selenium Improves Immunomodulative Effects of Glucan.

Abstract: 

BACKGROUND: Selenium (Se) is an established essential nutrient that plays a role in various biological processes including cancer development. Similarly, stimulation of immune reactions byβ-glucans is well-documented.AIMS: In the current study, we focused on the stimulation of phagocytosis and interleukin (IL)-2 production and on potentiation of anticancer immunity by a combination of glucan with two types of Se.MATERIALS AND METHODS: Phagocytosis was evaluated using synthetic microspheres; cancer development was measured either using breast cancer cells or using lung cancer cells.RESULTS: Using two different murine models of cancer, we showed that the Se/glucan combination strongly suppressed the growth of cancer, mostly probably via stimulation of immunity.CONCLUSIONS: A combination of glucan with Se offers superior stimulation of immunity and inhibition of cancer growth.

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The effect of coenzyme Q10 supplementation on oxidative stress.

PMID: 

Food Sci Nutr. 2020 Apr ;8(4):1766-1776. Epub 2020 Mar 19. PMID: 32328242

Abstract Title: 

The effect of coenzyme Q10 supplementation on oxidative stress: A systematic review and meta-analysis of randomized controlled clinical trials.

Abstract: 

Some evidence exists in supporting the beneficial effects of coenzyme Q10 (CoQ10) on oxidative stress. Since the findings of studies over the impact of CoQ10 supplementation on oxidative stress are contradictory, this study was conducted. The aim was to evaluate CoQ10 supplementation effect on total antioxidant capacity (TAC), malondialdehyde (MDA), glutathione peroxidase (GPx), superoxide dismutase (SOD), and catalase (CAT) levels using data collected from randomized controlled trials (RCTs). Several databases including PubMed, Web of Science, Google Scholar, and Scopus were comprehensively searched up to 23 January 2019 to identify RCTs. A random-effects model, standardized mean difference (SMD), and 95% confidence interval (CI) were applied for data analysis. According to the meta-analysis results on 19 eligible studies, CoQ10 increased the levels of TAC (SMD = 1.29; 95% CI = 0.35-2.23; = .007), GPX (SMD = 0.45; 95% CI = 0.17-0.74; = .002), SOD (SMD = 0.63; 95% CI = 0.29-0.97; 

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Clinical evidence for Q10 coenzyme supplementation in heart failure.

PMID: 

J Clin Med. 2020 Apr 27 ;9(5). Epub 2020 Apr 27. PMID: 32349341

Abstract Title: 

Clinical Evidence for Q10 Coenzyme Supplementation in Heart Failure: From Energetics to Functional Improvement.

Abstract: 

Oxidative stress and mitochondrial dysfunction are hallmarks of heart failure (HF). Coenzyme Q10 (CoQ10) is a vitamin-like organic compound widely expressed in humans as ubiquinol (reduced form) and ubiquinone (oxidized form). CoQ10 plays a key role in electron transport in oxidative phosphorylation of mitochondria. CoQ10 acts as a potent antioxidant, membrane stabilizer and cofactor in the production of adenosine triphosphate by oxidative phosphorylation, inhibiting the oxidation of proteins and DNA. Patients with HF showed CoQ10 deficiency; therefore, a number of clinical trials investigating the effects of CoQ10 supplementation in HF have been conducted. CoQ10 supplementation may confer potential prognostic advantages in HF patients with no adverse hemodynamic profile or safety issues. The latest evidence on the clinical effects of CoQ10 supplementation in HF was reviewed.

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The regulation of pathways of inflammation and resolution in immune cells and cancer stem cells by selenium.

PMID: 

Adv Cancer Res. 2017 ;136:153-172. Epub 2017 Aug 31. PMID: 29054417

Abstract Title: 

The Regulation of Pathways of Inflammation and Resolution in Immune Cells and Cancer Stem Cells by Selenium.

Abstract: 

Cancer is a complex disease where cancer stem cells (CSCs) maintain unlimited replicative potential, but evade chemotherapy drugs through cellular quiescence. CSCs are able to give rise to bulk tumor cells that have the capability to override antiproliferative signals and evade apoptosis. Numerous pathways are dysregulated in tumor cells, where increased levels of prooxidant reactive oxygen and nitrogen species can lead to localized inflammation to exacerbate all three stages of tumorigenesis: initiation, progression, and metastasis. Modulation of cellular metabolism in tumor cells as well as immune cells in the tumor microenvironment (TME) can impact inflammatory networks. Altering these pathways can potentially serve as a portal for therapy. It is well known that selenium, through selenoproteins, modulates inflammatory pathways in addition to regulating redox homeostasis in cells. Therefore, selenium has the potential to impact the interaction between tumor cells, CSCs, and immune cells. In the sections later, we review the current status of knowledge regarding this interaction, with reference to leukemia stem cells, and the importance of selenium-dependent regulation of inflammation as a potential mechanism to affect the TME and tumor cell survival.

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Cyanocobalamin and cholecalciferol synergistically improve functional and histopathological nerve healing.

PMID: 

Ideggyogy Sz. 2020 Mar 30 ;73(3-4):113-120. PMID: 32364338

Abstract Title: 

Cyanocobalamin and cholecalciferol synergistically improve functional and histopathological nerve healing in experimental rat model.

Abstract: 

Background and purpose: Peripheral nerve injury (PNI) is a frequent problem among young adults. Hopefully, regeneration can occur in PNI unlike central nervous system. If nerve cut is complete, gold standard treatment is surgery, but incomplete cuts have been tried to be treated by medicines. The aim of the study was to evaluate and compare clinical and histopathological outcomes of independent treatment of each of Vitamin B12 (B12) and Vitamin D3 (D3) and their combination on sciatic nerve injury in an experimental rat model.Methods: Experimental animal study was performed after the approval of BEH Ethics Committee No. 2015/10. 32 rats were grouped into four (n=8) according to treatment procedures, such as Group 1 (controls with no treatment), Group 2 (intraperitoneal 1 mg/kg/day B12), Group 3 (oral 3500 IU/kg/week D3), Group 4 (intraperitoneal 1 mg/kg/day B12+ oral 3500 IU/kg/week D3). Sciatic Functional Index (SFI) and histopathological analysis were performed.Results: SFIs of Group 2, 3, 4 were statistically significantly higher than controls. Group 2 and 3 were statistically not different, however Group 4 was statistically significantly higher than others according to SFI. Axonal degeneration (AD) in all treatment groups were statistically significantly lower than in Group 1. AD in Group 4 was significantly lower than in Group 2 and 3; there was no significant difference between Group 2 and 3. There was no significant difference between Group 1,2 and 3 in Axonolysis (A). But A of Group 4 was significantly very much lower than all others. Oedema- inflammation (OE-I) in all treatment groups were significantly lower than in Group 1; there was no significant difference between Group 2 and group 4. OE-I in Group 2 and 4 were significantly lower than in Group 3. There were no significant differences between Group 1, 2 and 3 in damage level scores; score of Group 4 was significantly lower than of Group 1.Conclusion: B12 and D3 were found effective with no statistically significant difference. But combined use of B12 and D3 improve nerve healing synergistically. We recommend combined use of B12 and D3 after PNI as soon as possible.

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