PMID: 

Mult Scler J Exp Transl Clin. 2019 Oct-Dec;5(4):2055217319892291. Epub 2019 Dec 6. PMID: 31839980

Abstract Title: 

High serum concentration of vitamin D may protect against multiple sclerosis.

Abstract: 

Background: High 25-hydroxyvitamin D concentrations have been associated with a reduced risk of multiple sclerosis, with indications of a stronger effect among young individuals.Objective: Investigate the 25-hydroxyvitamin D association with multiple sclerosis and test if this association is age dependent.Methods: Prospectively drawn blood samples from individuals later developing relapsing-remitting multiple sclerosis and controls matched for biobank, sex, age and date of sampling, were analysed with liquid chromatography tandem mass spectrometry.Results: High levels of 25-hydroxyvitamin D (top quintile) were associated with a reduced multiple sclerosis risk (odds ratio 0.68, 95% confidence interval 0.50-0.93).Conclusion: These findings further support a role for vitamin D in MS aetiology.

read more

PMID: 

J Neurol. 2019 Dec 17. Epub 2019 Dec 17. PMID: 31844981

Abstract Title: 

Low sun exposure increases multiple sclerosis risk both directly and indirectly.

Abstract: 

OBJECTIVE: We aimed to study (1) to what extent the influence of low sun exposure on multiple sclerosis (MS) risk is mediated by low vitamin D levels; (2) whether low sun exposure or vitamin D deficiency act synergistically with HLA-DRB1*15:01 and absence of HLA-A*02:01.METHODS: We used two population-based case-control studies (7069 cases, 6632 matched controls). Subjects with different HLA alleles, sun exposure habits and vitamin D status were compared regarding MS risk, by calculating odds ratios (OR) with 95% confidence intervals (CI) employing logistic regression. Mediation analysis was used to identify the potential mediation effect of vitamin D on the relationship between low sun exposure and MS risk.RESULTS: Low sun exposure increased MS risk directly as well as indirectly, by affecting vitamin D status. The direct effect, expressed as OR, was 1.26 (95% CI 1.04-1.45) and the indirect effect, mediated by vitamin D deficiency, was 1.10 (95% CI 1.02-1.23). Of the total effect, nearly 30% was mediated by vitamin D deficiency. There was a significant interaction between low sun exposure and vitamin D deficiency (attributable proportion due to interaction 0.3, 95% CI 0.04-0.5) accounting for about 12% of the total effect. Further, both factors interacted with HLA-DRB1*15:01 to increase MS risk.INTERPRETATION: Our findings indicate that low sun exposure acts both directly on MS risk as well as indirectly, by leading to low vitamin D levels. The protective effect of sun exposure thus seems to involve both vitamin D and non-vitamin D pathways, which is of relevance for prevention, in particular for those with a genetic susceptibility to MS.

read more

PMID: 

Food Chem Toxicol. 2019 Nov 30:111012. Epub 2019 Nov 30. PMID: 31794802

Abstract Title: 

Anti-proliferation activities of Oryza sativa L. anthocyanins-Hohenbuehelia serotina polysaccharides complex after in vitro gastrointestinal digestion.

Abstract: 

In order to improve the bioavailability of Oryza sativa L. anthocyanins, we fabricated Oryza sativa L. anthocyanins-Hohenbuehelia serotina polysaccharides (OSA-HSP) complex and investigated its anti-proliferation activities taking into account its changes along simulated gastrointestinal digestion in vitro. Results showed that OSA mainly composed by delphinidin, cyanidin, petunidin, malvidin and their derivatives was combined with HSP through electrostatic interaction. OSA-HSP complex belonged to non-crystalline substance, and had compact and laminar structural characteristics. Under simulated gastrointestinal digestion, OSA-HSP complex significantly prevented the degradation of anthocyanins, and presented sustain release effect. However, the anti-proliferation activities of OSA-HSP complex digested by different gastrointestinal process were remarkably changed, especially after small intestinal digestion. HeLa cells treated with OSA-HSP complex exhibited pro-apoptosis characteristics by triggering endogenous mitochondrial apoptosis pathway through activating the expressions of Bax, cytochrome c and Caspase-3 as well as inhibiting the expression of Bcl-2. These findings provided new insight to improve the bioavailability of anthocyanins in functional foods and tumor therapy.

read more

PMID: 

Nutr Rev. 2019 Dec 4. Epub 2019 Dec 4. PMID: 31800057

Abstract Title: 

Effect of vitamins C and E on recovery of motor function after spinal cord injury: systematic review and meta-analysis of animal studies.

Abstract: 

CONTEXT: Many animal studies have evaluated the role of vitamins in the recovery of motor function after spinal cord injury, but their results have been contradictory and no consensus has been reached.OBJECTIVE: This meta-analysis aimed to investigate the effects of vitamin C and vitamin E on recovery of motor function after spinal cord injury in animal models.DATA SOURCES: Two authors independently collected the records of relevant articles published in MEDLINE, Embase, Scopus, and Web of Science through November 2018.STUDY SELECTION: All studies conducted in animal models to evaluate the therapeutic effects of vitamin C or vitamin E or both on recovery of motor function after spinal cord injury were included. Studies that lacked a control group or a standard treatment, lacked an assessment of motor function, included genetically modified/engineered animals, included animals pretreated with vitamin C or vitamin E, or combined vitamin treatment with other methods, such as cell therapies, were excluded.DATA EXTRACTION: Data from 10 articles met the inclusion criteria for meta-analysis, conducted in accordance with PRISMA guidelines.RESULTS: Daily supplementation with vitamin C (P 

read more

PMID: 

Blood Adv. 2019 Dec 23 ;3(24):4187-4201. PMID: 31856270

Abstract Title: 

Vitamin C stabilizes CD8+ iTregs and enhances their therapeutic potential in controlling murine GVHD and leukemia relapse.

Abstract: 

Adoptive transfer of induced regulatory T cells (iTregs) can ameliorate graft-versus-host disease (GVHD) after allogeneic hematopoietic cell transplantation (allo-HCT). CD4+ iTregs can effectively prevent GVHD but impair the graft-versus-leukemia (GVL) effect, whereas CD8+ iTregs preserve the GVL effect but have limited efficacy in GVHD control because of their instability under inflammatory conditions. Thus, we aimed to stabilize CD8+ iTregs via treatment with vitamin C (Vit C) to improve their efficacy in controlling GVHD. We found that addition of Vit C significantly improved the stability of forkhead box P3 (Foxp3) expression in CD8+ iTregs. Moreover, Vit C-treated CD8+ iTregs exhibited high efficacy in attenuating acute and chronic GVHD. The mechanistic study revealed that addition of Vit C to CD8+ iTreg culture markedly increased DNA demethylation in the conserved noncoding sequence 2 region and, hence, maintained higher Foxp3 expression levels compared with untreated controls. In acute GVHD, Vit C-treated CD8+ iTregs were able to inhibit pathogenic T-cell expansion and differentiation while reducing thymus damage and B-cell activation in cGVHD. Importantly, in contrast to CD4+ iTregs, Vit C-treated CD8+ iTregs retained the ability to control tumor relapse. These results provide a strong rationale to use Vit C in the clinic to stabilize CD8+ iTregs for the control of GVHD and preservation of GVL after allo-HCT.

read more

PMID: 

Microb Pathog. 2019 Dec 14:103927. Epub 2019 Dec 14. PMID: 31846743

Abstract Title: 

Anti-virulence activity of polyphenolic fraction isolated from Kombucha against Vibrio cholerae.

Abstract: 

The use of traditional foods and beverages or their bioactive compounds as anti-virulence agents is a new alternative method to overcome the increased global emergence of antimicrobial resistance in enteric pathogens. In the present study, we investigated the anti-virulence activity of a polyphenolic fraction previously isolated from Kombucha, a 14-day fermented beverage of sugared black tea, against Vibrio cholerae O1. The isolated fraction was mainly composed of the polyphenols catechin and isorhamnetin. The fraction, the individual polyphenols and the combination of the individual polyphenols significantly inhibited bacterial swarming motility and expression of flagellar regulatory genes motY and flaC, even at sub-inhibitory concentrations. The polyphenolic compounds also decreased bacterial protease secretion and mucin penetration in vitro. In vivo study revealed that the polyphenolic fraction significantly inhibited V. cholerae induced fluid accumulation in the rabbit ileal loop model and intestinal colonization in suckling mice model. Therefore, the anti-virulence activity of the Kombucha polyphenolic fraction involved inhibition of motility and protease secretion of V. cholerae, thus preventing bacterial penetration through the mucin layer as well as fluid accumulation and bacterial colonization in the intestinal epithelial cells. The overall results implied that Kombucha might be considered as a potential alternative source of anti-virulence polyphenols against V. cholerae. To the best of our knowledge, this is the first report on the anti-virulence activity of Kombucha, mostly attributed to its polyphenolic content.

read more

PMID: 

Int J Mol Sci. 2019 Dec 6 ;20(24). Epub 2019 Dec 6. PMID: 31817750

Abstract Title: 

Astaxanthin Ameliorates Ischemic-Hypoxic-Induced Neurotrophin Receptor p75 Upregulation in the Endothelial Cells of Neonatal Mouse Brains.

Abstract: 

Ischemic stroke is a leading cause of human death in present times. Two phases of pathological impact occur during an ischemic stroke, namely, ischemia and reperfusion. Both periods include individual characteristic effects on cell injury and apoptosis. Moreover, these conditions can cause severe cell defects and harm the blood-brain barrier (BBB). Also, the BBB components are the major targets in ischemia-reperfusion injury. The BBB owes its enhanced protective roles to capillary endothelial cells, which maintain BBB permeability. One of the nerve growth factor (NGF) receptors initiating cell signaling, once activated, is the p75 neurotrophin receptor (p75NTR). This receptor is involved in both the survival and apoptosis of neurons. Although many studies have attempted to explain the role of p75NTR in neurons, the mechanisms in endothelial cells remain unclear. Endothelial cells are the first cells to encounter p75NTR stimuli. In this study, we found the upregulated p75NTR expression and reductive expression of tight junction proteins after in vivo and in vitro ischemia-reperfusion injury. Moreover, astaxanthin (AXT), an antioxidant drug, was utilized and was found to reduce p75NTR expression and the number of apoptotic cells. This study verified that p75NTR plays a prominent role in endothelial cell death and provides a novel downstream target for AXT.

read more

PMID: 

Sci Rep. 2018 08 16 ;8(1):12238. Epub 2018 Aug 16. PMID: 30116003

Abstract Title: 

Investigation of the anti-TB potential of selected propolis constituents using a molecular docking approach.

Abstract: 

Human tuberculosis (TB), caused by Mycobacterium tuberculosis, is the leading bacterial killer disease worldwide and new anti-TB drugs are urgently needed. Natural remedies have long played an important role in medicine and continue to provide some inspiring templates for drug design. Propolis, a substance naturally-produced by bees upon collection of plant resins, is used in folk medicine for its beneficial anti-TB activity. In this study, we used a molecular docking approach to investigate the interactions between selected propolis constituents and four 'druggable' proteins involved in vital physiological functions in M. tuberculosis, namely MtPanK, MtDprE1, MtPknB and MtKasA. The docking score for ligands towards each protein was calculated to estimate the binding free energy, with the best docking score (lowest energy value) indicating the highest predicted ligand/protein affinity. Specific interactions were also explored to understand the nature of intermolecular bonds between the most active ligands and the protein binding site residues. The lignan (+)-sesamin displayed the best docking score towards MtDprE1 (-10.7 kcal/mol) while the prenylated flavonoid isonymphaeol D docked strongly with MtKasA (-9.7 kcal/mol). Both compounds showed docking scores superior to the control inhibitors and represent potentially interesting scaffolds for further in vitro biological evaluation and anti-TB drug design.

read more

PMID: 

J Nutr Biochem. 2019 02 ;64:61-71. Epub 2018 Oct 25. PMID: 30445417

Abstract Title: 

(+)-Sesamin attenuates chronic unpredictable mild stress-induced depressive-like behaviors and memory deficits via suppression of neuroinflammation.

Abstract: 

Depression is a mood disorder that is related to neuroinflammation and cognition loss. This study is aimed to determine the potential antidepressant effects of (+)-sesamin, a lignan component of sesame, in a mild stress-induced depression mouse model. CD-1 mice were treated with chronic unpredictable mild stress (CUMS) process and orally administrated with sesamin (50 mg/kg/d) for 6 weeks. Behavioral tests including forced swimming test, tail suspension test, open field test, and elevated plus maze test demonstrated that sesamin treatment inhibited CUMS-induced mice depressant-like behaviors and anxiety, without changing immobility. It was found that sesamin prevented stress-induced decease levels of 5-HT and NE in striatum and serum. Cognitive deficits were assessed using Y-maze and Morris water maze test. Sesamin treatment also prevented stressed-induced memory impairments and neuronal damages. Consistently, sesamin also enhanced synapse ultrastructure and improved expressions of PSD-95 in stressed mice hippocampus with improving neurotrophic factors expression including BDNF and NT3. Moreover, sesamin treatment significantly prevented CUMS-induced neuroinflammation by inhibiting over-activation of microglia and expressions of inflammatory mediators including iNOS, COX-2, TNF-α and IL-1β in stressed mice hippocampus and cortex. These results illustrated that sesamin markedly improved CUMS-induced depression and memory loss via inhibiting neuroinflammation, which indicate that as food component, sesamin might be also a novel potential therapeutic for depression.

read more

PMID: 

J Oleo Sci. 2019 ;68(1):79-85. PMID: 30606956

Abstract Title: 

Sesame Extract Attenuates the Degradation of Collagen and Elastin Fibers in the Vascular Walls of Nicotine-administered Mice.

Abstract: 

Abdominal aortic aneurysm (AAA) is a vascular disease characterized by the weakening of the vascular walls and the progressive dilation of the abdominal aorta. Nicotine, a primary component of cigarette smoke, is associated with AAA development and rupture. Nicotine induces AAA development by weakening vascular walls. However, little is known about preventive methods using functional food factors for nicotine-induced vascular destruction. Sesamin and sesamolin are functional food factors that are fat-soluble lignans found in Sesamum indicum seeds. Previous reports indicated that sesamin and sesamolin have anti-oxidative and anti-inflammatory effects. In this study, we evaluated the effects of sesamin and sesamolin-rich sesame extract on the weakening of vascular walls in nicotine-administered mice. Sesame extract attenuated the degradation of collagen and elastin fibers caused by nicotine. In addition, sesame extract decreased the area positive for matrix metalloproteinase 12 (MMP-12) and oxidative stress in the vascular walls. These results suggest that sesame extract may decrease the weakening of vascular walls by suppressing the nicotine-induced degradation of collagen and elastin fibers. Sesame extract may be effective in preventing AAA development by decreasing both, MMP-12 expression and oxidative stress in vascular walls.

read more