PMID: 

Molecules. 2018 Jan 18 ;23(1). Epub 2018 Jan 18. PMID: 29346317

Abstract Title: 

Liposomal TriCurin, A Synergistic Combination of Curcumin, Epicatechin Gallate and Resveratrol, Repolarizes Tumor-Associated Microglia/Macrophages, and Eliminates Glioblastoma (GBM) and GBM Stem Cells.

Abstract: 

Glioblastoma (GBM) is a deadly brain tumor with a current mean survival of 12-15 months. Despite being a potent anti-cancer agent, the turmeric ingredient curcumin (C) has limited anti-tumor efficacy in vivo due to its low bioavailability. We have reported earlier a strategy involving the use two other polyphenols, epicatechin gallate (E) from green tea and resveratrol (R) from red grapes at a unique, synergistic molar ratio with C (C:E:R: 4:1:12.5, termed TriCurin) to achieve superior potency against HPV+ tumors than C alone at C:E:R (μM): 32:8:100 (termed 32 μM+ TriCurin). We have now prepared liposomal TriCurin (TrLp) and demonstrated that TrLp boosts activated p53 in cultured GL261 mouse GBM cells to trigger apoptosis of GBM and GBM stem cells in vitro. TrLp administration into mice yielded a stable plasma concentration of 210 nM C for 60 min, which, though sub-lethal for cultured GL261 cells, was able to cause repolarization of M2-like tumor (GBM)-associated microglia/macrophages to the tumoricidal M1-like phenotype and intra-GBM recruitment of activated natural killer cells. The intratumor presence of such tumoricidal immune cells was associated with concomitant suppression of tumor-load, and apoptosis of GBM and GBM stem cells. Thus, TrLp is a potential onco-immunotherapeutic agent against GBM tumors.

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PMID: 

Crit Rev Food Sci Nutr. 2019 ;59(13):2136-2143. Epub 2018 Apr 12. PMID: 29565637

Abstract Title: 

Curcuminoids from: New adjuvants for the treatment of crohn's disease and ulcerative colitis?

Abstract: 

Crohn's Disease (CD) and Ulcerative Colitis (UC) result from an overreaction of the bowel to multifactorial stimuli leading to discomfort, pain, and it is associated with high morbidity and lethality. The medications commonly used are expensive and associated with multiple side effects. Curcuma longa exerts anti-inflammatory and antioxidant actions and has shown positive effects on CD and UC treatment, possibly due to the presence of curcuminoids. The objective of this review was to evaluate the role of curcuminoids in the treatment of IBD. A search for articles associating curcuminoids and CD and UC was performed using MEDLINE-PubMed. It has been found that curcumin can reduce oxidative stress and inhibit the migration of neutrophils and inducible nitric oxide synthase in the intestine. It may also improve micro and macroscopic lesions, prevent apoptosis of intestinal cells and also induce the restoration of the mitogen-activated protein kinase immune reaction. As the incidence of CD and UC is growing in many populations, there is an urgency to find an appropriate and accessible therapeutic approach to improve quality of life of patients. The use of curcumin is cheap, efficient and associated with no side effects, and may become an alternative to the IBD treatment.

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PMID: 

Eur J Pharmacol. 2020 Apr 8 ;878:173098. Epub 2020 Apr 8. PMID: 32275908

Abstract Title: 

Selenium may suppress peripheral blood mononuclear cell apoptosis by modulating HSP70 and regulate levels of SIRT1 through reproductive hormone secretion and oxidant stress in women suffering fluorosis.

Abstract: 

Excessive taking fluoride (F) causes severe damage to reproductive system through stimulation of apoptosis and oxidant stress. Selenium (Se) may promote anti-oxidant enzymes and invert cell apoptosis. The aim of this study was to investigate the effect of Se on peripheral blood mononuclear cell (PBMC) apoptosis and oxidant stress in women with fluorosis. Sixty women were divided into three groups according to serum and urine fluoride and hair Se as High F + high Se group, High F group and Control group. The activities of anti-oxidant enzymes, malondialdehyde (MDA) and Se were measured. The levels of sirtuin type 1 (SIRT1), estradiol (E), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured by enzyme-linked immune sorbent assay (ELISA) kits. The expression of protein and apoptosis rate were detected by Western blot and Flow cytometry. The levels of E, anti-oxidant enzymes in High F group were significantly lower than that in Control group, while the levels of SIRT1 and MDA were significantly higher. The levels of anti-oxidant enzymes and heat shock protein 70 (HSP70) were significantly increased in High Se + high F group while the expression of caspase-3 was significantly increased in high F group. The levels of LH and FSH in serum were significantly increased in High F group and High Se + high F group. Therefore, Se alleviates apoptosis induced by F through improving the expression of HSP70 andreduces oxidative stress by regulating levels of SIRT1 and anti-oxidant enzymes, and the secretion of certain reproductive hormones.

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PMID: 

PLoS One. 2019 ;14(5):e0216726. Epub 2019 May 16. PMID: 31095617

Abstract Title: 

Short-term fish oil supplementation applied in presymptomatic stage of Alzheimer's disease enhances microglial/macrophage barrier and prevents neuritic dystrophy in parietal cortex of 5xFAD mouse model.

Abstract: 

Dystrophic neurites and activated microglia are one of the main neuropathological characteristics of Alzheimer's disease (AD). Although the use of supplements with omega-3 fatty acids has been associated with reduced risk and lessened AD pathology, it still remains elusive whether such a treatment could affect dystrophic neurites (DNs) formation and microglia/macrophage behavior in the early phase of disease. We analyzed the effects of short-term (3 weeks) fish oil supplementation on DNs formation, tau hyperphosphorylation, Amyloid-beta peptide 1-42 (Aβ42) levels and microglial/macrophage response to AD pathology in the parietal cortex of 4-month-old 5xFAD mice, a mouse model of AD. The present study shows for the first time that short-term FO supplementation applied in presymptomatic stage of AD, alters the behaviour of microglia/macrophages prompting them to establish a physical barrier around amyloid plaques. This barrier significantly suppresses DNs formation through the reduction of both Aβ content and tau hyperphosphorylation. Moreover, the short-term FO treatment neither suppresses inflammation nor enhances phagocytic properties ofmicroglia/macrophages in the response to Aβ pathology, the effects most commonly attributed to the fish oil supplementation. Our findings suggest that fish oil consumption may play an important role in modulating microglial/macrophage response and ameliorating the AD pathology in presymptomatic stage of Alzheimer's disease.

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PMID: 

PLoS One. 2019 ;14(7):e0219405. Epub 2019 Jul 23. PMID: 31335861

Abstract Title: 

Dendritic cells mediate the anti-inflammatory action of omega-3 long-chain polyunsaturated fatty acids in experimental autoimmune uveitis.

Abstract: 

We previously showed that dietary omega (ω)-3 long-chain polyunsaturated fatty acids (LCPUFAs) suppress inflammation in mice with experimental autoimmune uveitis (EAU). We have now investigated the role of antigen presenting cells (APCs) in this action of ω-3 LCPUFAs. C57BL/6 mice were fed a diet supplemented with ω-3 or ω-6 LCPUFAs for 2 weeks, after which splenocytes were isolated from the mice and cocultured with CD4+ T cells isolated from mice with EAU induced by injection of a human interphotoreceptor retinoid-binding protein peptide together with complete Freund's adjuvant. The proliferation of and production of interferon-γ and interleukin-17 by T cells from EAU mice in vitro were attenuated in the presence of splenocytes from ω-3 LCPUFA-fed mice as compared with those from mice fed ω-6 LCPUFAs. Splenocyte fractionation by magnetic-activated cell sorting revealed that, among APCs, dendritic cells (DCs) were the target of ω-3 LCPUFAs. Adoptive transfer of DCs from mice fed ω-3 LCPUFAs attenuated disease progression in EAU mice as well as the production of pro-inflammatory cytokines by T cells isolated from these latter animals. The proliferation of T cells from control Balb/c mice was also attenuated in thepresence of DCs from ω-3 LCPUFA-fed mice as compared with those from ω-6 LCPUFA-fed mice. Furthermore, T cell proliferation in such a mixed lymphocyte reaction was inhibited by prior exposure of DCs from mice fed an ω-6 LCPUFA diet to ω-3 LCPUFAs in vitro. Our results thus suggest that DCs mediate the anti-inflammatory action of dietary ω-3 LCPUFAs in EAU.

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PMID: 

Mar Drugs. 2019 Jun 22 ;17(6). Epub 2019 Jun 22. PMID: 31234533

Abstract Title: 

Effects of Fish n-3 PUFAs on Intestinal Microbiota and Immune System.

Abstract: 

Studies over several decades have documented the beneficial actions of n-3 polyunsaturated fatty acids (PUFAs), which are plentiful in fish oil, in different disease states. Mechanisms responsible for the efficacy of n-3 PUFAs include: (1) Reduction of triglyceride levels; (2) anti-arrhythmic and antithrombotic effects, and (3) resolution of inflammatory processes. The human microbiota project and subsequent studies using next-generation sequencing technology have highlighted that thousands of different microbial species are present in the human gut, and that there has been a significant variability of taxa in the microbiota composition among people. Several factors (gestational age, mode of delivery, diet, sanitation and antibiotic treatment) influence the bacterial community in the human gastrointestinal tract, and among these diet habits play a crucial role. The disturbances in the gut microbiota composition, i.e., gut dysbiosis, have been associated with diseases ranging from localized gastrointestinal disorders to neurologic, respiratory, metabolic, ocular, and cardiovascular illnesses. Many studies have been published about the effects of probiotics and prebiotics on the gut microbiota/microbioma. On the contrary, PUFAs in the gut microbiota have been less well defined. However, experimental studies suggested that gut microbiota, n-3 PUFAs, and host immune cells work together to ensure the intestinal wall integrity. This review discussed current evidence concerning the links among gut microbiota, n-3 PUFAs intake, and human inflammatory disease.

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PMID: 

Int J Mol Sci. 2019 Sep 12 ;20(18). Epub 2019 Sep 12. PMID: 31547227

Abstract Title: 

Endogenous-3 Polyunsaturated Fatty Acids Are Beneficial to Dampen CD8T Cell-Mediated Inflammatory Response upon the Viral Infection in Mice.

Abstract: 

Omega-3 (-3) polyunsaturated fatty acids (PUFAs) have been known to exert anti-inflammatory effects on various disease states. However, its effect on CD8T cell-mediated immunopathology upon viral infection has not been well elucidated yet. In this study, we investigated the possible implication of-3 PUFAs in CD8T cell responses against an acute viral infection. Infection of FAT-1 transgenic mice that are capable of synthesizing-3 PUFAs from-6 PUFAs with lymphocytic choriomeningitis virus (LCMV) resulted in significant reduction of anti-viral CD8T cell responses. Interestingly, expansion of adoptively transferred wild-type (WT) LCMV-specific T cell receptor (TCR) transgenic CD8(P14) T cells into FAT-1 mice was significantly decreased. Also, activation of anti-viral CD4helper T cells was reduced in FAT-1 mice. Importantly, P14 cells carrying thegene that were adoptively transferred into WT mice exhibited a substantially decreased ability to proliferate and produce cytokines against LCMV infection. Together,-3 PUFAs attenuated anti-viral CD8T cell responses against an acute viral infection and thus could be used to alleviate immunopathology mediated by the viral infection.

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Mental health conditions may not only increase opioid use but also risk of death. Learn how this common pain medication may become deadly when you’re depressed

PMID: 

Environ Sci Pollut Res Int. 2020 Feb ;27(4):3950-3961. Epub 2019 Dec 10. PMID: 31823254

Abstract Title: 

Krill oil alleviates oxidative stress, iron accumulation and fibrosis in the liver and spleen of iron-overload rats.

Abstract: 

Krill oil (KO) is a recent supplement which is rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). These fatty acids are found in both krill oil and fish oil. In krill oil, they esterified to phospholipids, but in fish oil, they are esterified to triacylglycerols. The target of this study was to investigate whether KO could help against iron overload-induced toxicity in liver and spleen. Rats were randomly assigned into 3 categories: control rats, rats received iron in a drinking water for 8 weeks followed by either vehicle or KO (40 mg/kg) treatment for an extra 8 weeks. Extent of hepatic and splenic injury was assessed via biochemical, histopathological and immunohistochemical evaluations. KO effectively improved the microscopic features of liver and spleen. Moreover, it decreased the increased levels of serum transaminases, ALP, LDH, iron, and ferritin and increased albumin serum level as well. In addition, it restored the balance between oxidants and antioxidants in the hepatic and splenic tissues. Furthermore, it decreased HO-1 levels, upregulated the production of Nrf2, and limited the expression of MMP9. These findings altogether suggest that KO might be a new candidate for treatment of iron overload-induced toxicity. Graphical abstract Graphical abstract.

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PMID: 

Biol Pharm Bull. 2020 ;43(3):404-408. PMID: 32115501

Abstract Title: 

Daily Meal Supplemented with Astaxanthin-Enriched Yolk Has Mitigative Effects against Hypertension in Spontaneously Hypertensive Rats.

Abstract: 

The aim of this study was to investigate the effects of egg yolk powder enriched with astaxanthin (ASX-E) on blood pressure in spontaneously hypertensive rats (SHR) and to verify the benefits of ASX-E as a functional food. To investigate the antihypertensive effect, SHR were fed with an ASX-E mixed diet before hypertension development. Blood pressures were determined periodically during the study by the tail-cuff method. At the end of the study, animals were euthanized, and their thoracic aortas were collected to determine vascular conductance. The thoracic aorta tension was measured with a force displacement transducer. Concentration-dependent response relationships were determined by cumulative addition of 10-10M Carbamoylcholine (Cch). Blood pressures of the SHR in the ASX-E mixed diet group were ASX-dose-dependently lower than that of those in the control group. In SHR fed with an ASX-E mixed diet, Cch induced vasorelaxation in the thoracic aorta with endothelium lining but not without endothelium. However, the antihypertensive effect of ASX-E was not observed on blood pressures in SHR that were fed with ASX-E only after the development of hypertension. Results suggest that ASX-E protects endothelial function and thereby prevents the development of hypertension. Hence, the results of our research indicate that daily consumption of ASX-E has a potential benefit on human health.

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