The entire vaccine debate can scarcely even be labeled a debate. It is an exercise in social shaming, shouting down opposing views. . .

PMID: 

Mol Nutr Food Res. 2019 Dec 1:e1900995. Epub 2019 Dec 1. PMID: 31786828

Abstract Title: 

Red Raspberry Polyphenols Attenuate High-Fat Diet-Driven Activation of NLRP3 Inflammasome and its Paracrine Suppression of Adipogenesis via Histone Modifications.

Abstract: 

SCOPE: The authors aim to investigate the mechanisms by which red raspberry (RR) polyphenolic fractions regulate obesity and inflammation with an emphasis on the crosstalk between adipose tissue macrophages (ATM) and adipocyte progenitors.METHODS AND RESULTS: C57BL/6 male mice are fed either a high-fat (HF) diet or an HF diet supplemented with a RR polyphenolic fraction from whole fruit, pulp, or seed. Supplementation with pulp significantly increases energy expenditure and reduces HF-diet-induced obesity and insulin resistance. The pulp, and to a lesser extent, whole polyphenols, decreases the recruitment of ATM, activation of the nod-like receptor protein 3 (NLRP3) inflammasome, and adipocyte hypertrophy, which is associated with epigenetic modulation of adipogenesis (e.g., H3K27Ac, H3K9Ac). Results from an IL-1β reporter assay in J774 macrophages recapitulate the inhibitory role of RR polyphenols on NLRP3 inflammasome activation. Using conditioned media from macrophages, it is demonstrated that RR polyphenols reverse the IL-1β-mediated epigenetic suppression of H3K27Ac in adipocyte progenitor cells.CONCLUSIONS: RR polyphenols from pulp and whole fruit serve as an inhibitor for NLRP3 inflammasome activation and an epigenetic modifier to regulate adipogenesis, which confers resistance against diet-induced obesity and metabolic dysfunction.

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Nutrition. 2019 Sep 13 ;70:110579. Epub 2019 Sep 13. PMID: 31743815

Abstract Title: 

Blueberry extract decreases oxidative stress and improves functional parameters in lungs from rats with pulmonary arterial hypertension.

Abstract: 

OBJECTIVES: Pulmonary arterial hypertension (PAH) is a condition characterized by an increased resistance of pulmonary vasculature, culminating in an increase in pulmonary pressure. This process involves disturbances in lung redox homeostasis, causing progressive right heart failure. In this context, the use of natural antioxidants, such as those found in blueberries, may represent a therapeutic approach. The aim of this study was to evaluate the effect of blueberry extract (BB) on functional parameters and oxidative stress levels in rat lungs with induced PAH.METHODS: Forty-eight male Wistar rats (weighing 200± 20 g) were randomized into five groups: control, monocrotaline, monocrotaline + BB 50, monocrotaline + BB 100, and monocrotaline + BB 200. PAH was induced by the administration of monocrotaline (60 mg/kg, intraperitoneal). Rats were treated with BB at doses of 50, 100, and 200 mg/kg via gavage for 5 wk (2 wk before monocrotaline and 3 wk after monocrotaline injection). At day 35, rats were submitted to echocardiography and catheterization. They were then sacrificed and lungs were harvested for biochemical analyses.RESULTS: BB increased the E/A ratio of blood flow across the tricuspid valve and tricuspid annular phase systolic excursion, as wells as decreased the mean pulmonary artery pressure of animals compared with the PAH group. Moreover, BB decreased total reactive species concentration and lipid oxidation, reduced activity of nicotinamide adenine dinucleotide phosphate oxidase and expression of xanthine oxidase, increased the activity of superoxide dismutase and restored sulfhydryl content in the animal lungs compared with those in the PAH group. Additionally, BB restored expression of the antioxidant transcriptional factor Nrf2 in the lungs of the animal subjects. Finally, BB normalized the endothelin receptor (ETA/ETB) expression ratio in the animal lungs, which were increased in the PAH group.CONCLUSION: Intervention with BB mitigated functional PAH outcomes through improvement of the pulmonary redox state. Our results provide a basis for future research on natural antioxidant interventions as a novel treatment strategy in PAH.

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PMID: 

Food Funct. 2019 Dec 11 ;10(12):7707-7713. PMID: 31746877

Abstract Title: 

The effects of blueberry and strawberry serum metabolites on age-related oxidative and inflammatory signaling in vitro.

Abstract: 

Berry fruits contain a variety of bioactive polyphenolic compounds that exhibit potent antioxidant and anti-inflammatory activities. We have shown that consumption of freeze-dried whole berry powder, equivalent to 1 cup per day of blueberry (BB) or 2 cups per day of strawberry (SB), can differentially improve some aspects of cognition in healthy, older adults, compared to placebo-supplemented controls. We investigated whether fasting and postprandial serum from BB- or SB-supplemented older adults (60-75 years), taken at baseline or after 45 or 90 days of supplementation, would reduce the production of inflammatory and oxidative stress markers compared to serum from a placebo group, in LPS-stressed HAPI rat microglial cells, in vitro. Serum from both BB- and SB-supplemented participants reduced nitrite production, iNOS and COX-2 expression, and TNF-alpha release relative to serum from placebo controls (p

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PMID: 

Arch Biochem Biophys. 2019 Nov 15 ;676:108153. Epub 2019 Oct 14. PMID: 31622587

Abstract Title: 

Brahmi (Bacopa monnieri): An ayurvedic herb against the Alzheimer's disease.

Abstract: 

Ayurveda is the medicinal science, dealing with utilization of naturally available plant products for treatment. A wide variety of neuroprotective herbs have been reported in Ayurveda. Brahmi, Bacopa monnieri is a nootropic ayurvedic herb known to be effective in neurological disorders from ancient times. Numerous approaches including natural and synthetic compounds have been applied against Alzheimer's disease. Amyloid-β and Tau are the hallmarks proteins of several neuronal dysfunctions resulting in Alzheimer's disease. Tau is a microtubule-associated protein known to be involved in progression of Alzheimer's disease. The generation of reaction oxygen species, increased neuroinflammation and neurotoxicity are the major physiological dysfunctions associated with Tau aggregates, which leads to dementia and behavioural deficits. Bacoside A, Bacoside B, Bacosaponins, Betulinic acid, etc; are the bioactive component of Brahmi belonging to various chemical families. Each chemical component known have its significant role in neuroprotection. The neuroprotective properties of Brahmi and its bioactive components including reduction of ROS, neuroinflammation, aggregation inhibition of Amyloid-β and improvement of cognitive and learning behaviour. Here on basis of earlier studies we hypothesize the inhibitoryrole of Brahmi against Tau-mediated toxicity. The overall studies have concluded that Brahmi can be used as a lead formulation for treatment of Alzheimer's disease and other neurological disorders.

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PMID: 

Metab Brain Dis. 2019 Dec 13. Epub 2019 Dec 13. PMID: 31834548

Abstract Title: 

Neuroprotective effects of Bacopa monnieri in Parkinson's disease model.

Abstract: 

Parkinson's disease (PD) is a common neurodegenerative disorder characterized by loss of dopaminergic neurons in substantia nigra region and the presence ofα-synuclein aggregates in the striatum and surrounding areas of brain. Evidences suggest that neuroinflammation plays a role in the progression of PD. We examined the neuro-protective effects of Bacopa monnieri (BM) in regulating neuroinflammation. Administration of BM suppressed the level of pro-inflammatory cytokines, decreased the levels of α-synuclein, and reduced reactive oxygen species (ROS) generation in PD animal model. Pre-treatment of BM showed more prominent results as compare to co- and post-treatment. Results suggest that Bacopa can limit inflammation in the different areas of brain, thus, offers a promising source of novel therapeutics for the treatment of many CNS disorders.

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PMID: 

Biomolecules. 2019 Dec 9 ;9(12). Epub 2019 Dec 9. PMID: 31835306

Abstract Title: 

Transthyretin Anti-Amyloidogenic and Fibril Disrupting Activities of(L.) Wettst (Brahmi) Extract.

Abstract: 

The homotetrameric plasma protein transthyretin (TTR), is responsible for a series of debilitating and often fatal disorders in humans known as transthyretin amyloidosis. Currently, there is no cure for TTR amyloidosis and treatment options are rare. Thus, the identification and development of effective and safe therapeutic agents remain a research imperative. The objective of this study was to determine the effectiveness ofextract (BME) in the modulation of TTR amyloidogenesis and disruption of preformed fibrils. Using aggregation assays and transmission electron microscopy, it was found that BME abrogated the formation of human TTR aggregates and mature fibrils but did not dis-aggregate pre-formed fibrils. Through acid-mediated and urea-mediated denaturation assays, it was revealed that BME mitigated the dissociation of folded human TTR and L55P TTR into monomers. ANS binding and glutaraldehyde cross-linking assays showed that BME binds at the thyroxine-binding site and possibly enhanced the quaternary structural stability of native TTR. Together, our results suggest that BME bioactives prevented the formation of TTR fibrils by attenuating the disassembly of tetramers into monomers. These findings open up the possibility of further exploration of BME as a potential resource of valuable anti-TTR amyloidosis therapeutic ingredients.

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Eur J Gastroenterol Hepatol. 2019 Nov 25. Epub 2019 Nov 25. PMID: 31789949

Abstract Title: 

Vitamin D-related immunomodulation in patients with liver cirrhosis.

Abstract: 

OBJECTIVE(S): Increasing evidence indicates that vitamin D status is linked to severity of liver cirrhosis and patients' survival. However, the potential role of vitamin D-related immunomodulation in hepatic decompensation and patients' mortality in relation to vitamin D deficiency remains unknown. The aim of the current study is to evaluate the association between vitamin D status and vitamin D binding protein (VDBP) levels with serum cytokine and lipopolysaccharide binding protein (LBP) and to examine their role on disease severity and cirrhotics' mortality.METHODS: One hundred consecutive Caucasian patients with liver cirrhosis were enrolled in the study. 25(OH)D, VDBP, and LBP concentrations were assessed by ELISA. Cytokine tumor necrosis factor-a (TNF-a), interleukin 6 (IL-6), IL-1β, IL-8, IL-10, and IL-12 levels were determined by Cytometric Bead Array.RESULTS: 25(OH)D levels were inversely correlated with CP score, MELD, IL-6, and CP stage and VDBP levels with CP score, MELD, IL-6, IL-8, LBP, and CP stage. Cirrhotics with 25(OH)D deficiency and severe deficiency had significantly higher CP score, increased IL-6 levels and lower VDBP levels. In the multivariate analysis, the independent prognostic factors associated with patients' survival were CP stage B [hazard ratio = 6.75; 95% confidence interval (CI) 1.32, 34.43; P = 0.022], CP stage C (hazard ratio = 7.39; 95% CI 1.41, 38.81; P = 0.018), the presence of hepatocellular carcinoma (hazard ratio = 4.50; 95% CI 1.54, 13.13; P = 0.006) and 25(OH)D levels (hazard ratio = 0.87; 95% CI 0.80, 0.95; P = 0.002).CONCLUSION: The results show that vitamin D status and VDBP levels are associated with liver cirrhosis severity and patients' mortality, possibly through a proinflammatory immune response.

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PMID: 

J Steroid Biochem Mol Biol. 2019 Dec 3 ;198:105561. Epub 2019 Dec 3. PMID: 31809869

Abstract Title: 

The effects of correction of vitamin D deficiency on arterial stiffness: A systematic review and updated meta-analysis of randomized controlled trials.

Abstract: 

It is unclear whether nutritional vitamin D supplementation in vitamin d-deficient persons improves arterial stiffness. To conduct a meta-analysis of the effects of the nutritional vitamin D therapy on arterial stiffness in adults with vitamin D deficiency, the Scopus, PUBMED, EMBASE, and Cochrane databases were searched for systematic reviews conducted up to October 5, 2018. Randomized clinical trials that compared nutritional vitamin D therapy with placebo in adults with vitamin D deficiency were eligible. Two reviewers independently evaluated eligibility of all retrieved studies based on titles and abstracts. Meta-analysis was performed using random effect or fixed effects model and inverse variance method was used to calculate the effect using standardized mean difference (SMD) and weighted mean difference. A leave-one-out method was used for sensitivity analysis. The main outcome was arterial stiffness, indicated by the carotid-femoral pulse wave velocity (PWV). We identified 237 records, of which 9 satisfied the inclusion criteria of the study. Our meta-analysis included relatively high-quality placebo-controlled randomized trials. In a random-effects model, nutritional vitamin D was associated with significant reductions in the pooled difference of PWV [(SMD: -0.29; 95 % CI: -0.51 to -0.06), p = 0.01; Cochran's Q test: chi = 21.85; df = 9; p = 0.009; I = 59 %; n = 909 from 9 studies]. All sensitivity analyses yielded similar results. Nutritional vitamin D supplementation significantly improved arterial stiffness (PWV) in several subgroups by correcting vitamin D deficiency, for a study duration of ≥4 months and a daily dose of vitamin D3 ≥ 2000 IU. The study indicated that the correction of vitamin D deficiency by nutritional vitamin D supplementation may improve arterial stiffness in vitamin d-deficient persons, especially by the correction of vitamin D deficiency with a daily dose of vitamin D3 ≥ 2000 IU. However, further studies are required to confirm this.

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PMID: 

Clin Res Hepatol Gastroenterol. 2019 Dec 3. Epub 2019 Dec 3. PMID: 31810868

Abstract Title: 

Active vitamin D impedes the progression of non-alcoholic fatty liver disease by inhibiting cell senescence in a rat model.

Abstract: 

OBJECTIVE: Non-alcoholic fatty liver disease (NAFLD) refers to an accumulation of excess fat in liver due to causes other than alcohol use. The relationship between vitamin D (VD) and NAFLD has been previously studied. Therefore, we aimed to explore the mechanism involved active VD regulating the progression of NAFLD by inhibiting cell senescence and to provide a potential approach for further nutritional treatment of NAFLD.METHODS: Following the induction with high-fat diet and intraperitoneal injection of corn oil, the successfully established NAFLD rat models were treated with 1,25(OH)Dat 1μg/kg, 5μg/kg or 10μg/kg. Meanwhile, the levels of factors related to oxidative stress, cell senescence, the p53-p21 signaling pathway and inflammation in liver were determined. Then, cell senescence was also measured by using senescence-associated β-galactosidase (SAβ-gal) staining.RESULTS: It was also found that active VD increased the concentration of VD in serum and VDR in liver of NAFLD rats, and alleviated hepatic fibrosis. Besides, treatment of 1,25(OH)Dat 1μg/kg, 5μg/kg or 10μg/kg reduced oxidative stress and inflammation, inhibited the p53-p21 signaling pathway and consequent cell senescence. Furthermore, treatment of 1,25(OH)Dat a dosage of 5μg/kg made the most impact on these factors.CONCLUSION: Collectively, the evidences from this study demonstrated that active VD could alleviate the development of NAFLD through blocking the p53-p21 signaling pathway, which provided a novel nutritional therapeutic insight for NAFLD.

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