PMID: 

J Microbiol Biotechnol. 2019 Nov 22. Epub 2019 Nov 22. PMID: 31752064

Abstract Title: 

Neuroprotective Effects of Phlorotannin-Rich Extract from Brown Seaweedon Neuronal PC-12 and SH-SY5Y Cells with Oxidative Stress.

Abstract: 

Neurodegenerative disorders in the elderly are characterized by gradual loss of memory and cognitive function. Oxidative stress caused by reactive oxygen species is associated with progressive neuronal cell damage and death in Alzheimer's disease, one of the most common neurodegenerative disorders. An edible brown seaweed,, contains a variety of biologically active compounds such as phlorotannins. In this study, we comparatively evaluated total phenolic content, antioxidant capacity, and neuroprotective effects of the phlorotannin-rich extract from(PEEC). The total phenolic content of PEEC and dieckol was 810.8 mg gallic acid equivalents (GAE)/g and 996.6 mg GAE/g, respectively. Antioxidant capacity of PEEC was 1,233.8 mg vitamin C equivalents (VCE)/g and 392.1 mg VCE/g determined using ABTS and DPPH assays, respectively, while those of dieckol were 2,238.4 mg VCE/g and 817.7 mg VCE/g. High-performance liquid chromatography results revealed 48.08± 0.67 mg dieckol/g of PEEC. PEEC had neuroprotective effects in pheochromocytoma (PC-12) and human neuroblastoma (SH-SY5Y) cells against HO- and AAPH-induced oxidative damage, partly due to reduced intracellular oxidative stress. PEEC treatment inhibited acetylcholinesterase and butyrylcholinesterase in a dose-dependent manner. Taken together, these findings suggest that PEEC is a good source of antioxidants and neuroprotective materials.

read more

PMID: 

Theranostics. 2019 ;9(26):8109-8126. Epub 2019 Oct 18. PMID: 31754384

Abstract Title: 

Hepatomas are exquisitely sensitive to pharmacologic ascorbate (P-AscH).

Abstract: 

Ascorbate is an essential micronutrient known for redox functions at normal physiologic concentrations. In recent decades, pharmacological ascorbate has been found to selectively kill tumour cells. However, the dosing frequency of pharmacologic ascorbate in humans has not yet been defined.We determined that among five hepatic cell lines, Huh-7 cells were the most sensitive to ascorbate. The effects of high-dose ascorbate on hepatoma were therefore assessed using Huh-7 cells and xenograft tumour mouse model.In Huh-7 cells, ascorbate induced a significant increase in the percentage of cells in thephase, apoptosis and intracellular levels of ROS. High doses of ascorbate (4.0 pmol cell), but not low doses of ascorbate (1.0 pmol cell), also served as a pro-drug that killed hepatoma cells by altering mitochondrial respiration. Furthermore, in a Huh-7 cell xenograft tumour mouse model, intraperitoneal injection of ascorbate (4.0 g/kg/3 days) but not a lower dose of ascorbate (2.0 g/kg/3 days) significantly inhibited tumour growth. Gene array analysis of HCC tumour tissue from xenograft mice given IP ascorbate (4.0 g/kg/3 days) identified changes in the transcript levels of 192 genes/ncRNAs involved in insulin receptor signalling, metabolism and mitochondrial respiration. Consistent with the array data, gene expression levels of, andwere increased 2.05-11.35 fold in HCC tumour tissue samples from mice treated with high-dose ascorbate, and IHC staining analysis also verified that AGER/RAGE and DGKK proteins were up-regulated, which implied thatandactivation might be related to oxidative stress, leading to hepatoma cell death.Our studies identified multiple mechanisms are responsible for the anti-tumour activity of ascorbate and suggest high doses of ascorbate with less frequency will act as a novel therapeutic agent for liver cancer.

read more

PMID: 

Dose Response. 2019 Oct-Dec;17(4):1559325819885782. Epub 2019 Nov 19. PMID: 31798354

Abstract Title: 

Vitamin C and Turmeric Attenuate Bax and Bcl-2 Proteins' Expressions and DNA Damage in Lead Acetate-Induced Liver Injury.

Abstract: 

Background: Lead is a common environmental and occupational pollutant which induced multiorgans dysfunction. The present study was designed to investigate the hepatoprotective effects of turmeric (TUR) and/or vitamin C (Vit-C) alone or together against lead acetate toxicity and to explore novel molecular pathways.Method: Acute hepatotoxicity was induced by lead acetate (100 mg/kg/day, i.p.) in male rats, and the effect of TUR (200 mg/kg/day, orally) and/or Vit-C (250 mg/kg/day, orally) along with lead acetate for 7 days was studied.Results: Lead acetate increased serum alanine transaminase, aspartate transaminase, lactate dehydrogenase, hepatic lipid peroxidation and nitric oxide; while, hepatic superoxide dismutase and glutathione activities were downregulated. Hepatic Bcl-2-associated X (Bax) and B-cell lymphoma-2 (Bcl-2) proteins expressions were altered and hepatic DNA damaged was increased as well. Liver/body weight ratio was decreased. Hematoxylin and eosin demonstrated that lead acetate induced focal areas of massive hepatic degeneration of the hepatocytes. Treatment with both antioxidants ameliorated all the altered parameters and induced marked improvement of liver architecture.Conclusion: The combination of TUR and Vit-C has shown the most protective effects against lead acetate-induced hepatotoxicity.

read more

PMID: 

BMJ Open Ophthalmol. 2019 ;4(1):e000326. Epub 2019 Nov 10. PMID: 31799410

Abstract Title: 

Omega-3 fatty acids supplementation protects the retina from age-associated degeneration in aged C57BL/6J mice.

Abstract: 

Objective: To evaluate the therapeutic effects of omega-3 (ω3) fatty acids in the retina of aged mice when the blood arachidonic acid (AA)/eicosapentaenoic acid (EPA) ratio is maintained between 1.0 and 1.5.Methods and analysis: Aged (24-month-old) wild-type C57BL/6J mice were allocated to two groups:ω3 treated and untreated. Treatment with ω3 was by daily gavage administration of EPA and docosahexaenoic acid for 60 days. Gas chromatography was used to identify and quantify fatty acids in the blood and retina. To count lipofuscin granules and measure the photoreceptor layer, eyecups were examined histologically using transmission electron microscopy and light microscopy. We also analysed eyecups using mass spectrometry-based proteomics.Results: AA levels were lower, and EPA levels were higher, in the blood and retinas of theω3-treated group than in the untreated group, resulting in a lower AA/EPA ratio. The ω3-treated group also showed significantly fewer lipofuscin granules and a thicker outer nuclear layer than the untreated group. Proteomic analysis revealed significantly greater expression of myelin basic protein, myelin regulatory factor-like protein, myelin proteolipid protein and glial fibrillar acidic protein in the ω3-treated group than in the untreated group. Three different pathways were significantly affected by ω3 treatment: fatty acid elongation, biosynthesis of unsaturated fatty acids and metabolic pathways.Conclusion: Two months ofω3 supplementation (when the blood AA/EPA~1.0-1.5) in aged mice reduced lipofuscin granule formation in the retina and protected the photoreceptor layer, suggesting that ω3 supplementation slows normal age-related retinal degeneration.

read more

PMID: 

Eur Rev Med Pharmacol Sci. 2019 Nov ;23(22):10151-10160. PMID: 31799687

Abstract Title: 

Omega-3 polyunsaturated fatty acids prevent progression of liver fibrosis and promote liver regeneration after partial hepatectomy in cirrhotic rats.

Abstract: 

OBJECTIVE: To assess the effect of omega-3 polyunsaturated fatty acids (n-3 PUFA) on liver regeneration of rats with liver cirrhosis after hepatectomy and antifibrosis.MATERIALS AND METHODS: Omega-3 polyunsaturated fatty acids were intravenously injected in n-3 PUFA group 3 days before the operation to 1 day after partial hepatectomy. 70% hepatectomy was performed in rats, which were subsequently divided into 4 groups, namely normal and hepatectomy group (PH); liver cirrhosis and hepatectomy group (LC+PH); liver cirrhosis, n-3 PUFA (1 mL/kg), and hepatectomy group (LC+n-3 PUFA+PH); liver cirrhosis, n-3 PUFA (2 mL/kg) and hepatectomy group (LC+n-3PUFA*+PH). Body/liver weight ratios, serum parameters, histopathological examination, immunostaining, inflammatory cytokine and quantification of mRNA expression were also investigated.RESULTS: Liver regeneration was significantly delayed compared with PH group 7 days after hepatectomy (PH) in LC+PH group. Besides, liver regeneration of LC+n-3 PUFA*+PH group increased significantly compared with LC+PH group 7 days after PH. In LC+PH group, liver cirrhotic was significantly higher compared with LC+n-3 PUFA+PH group 7 days after PH. In the meantime, liver cirrhosis of LC+n-3 PUFA*+PH group was significantly reduced compared with LC+n-3 PUFA+PH group 7 days after PH. Anti-inflammatory cytokine IL-10 was increased and pro-inflammatory cytokine IL-6 was decreased in LC+n-3 PUFA*+PH group compared with LC+PH group. N-3 PUFA also suppressed increments in mRNA expression for transforming growth factor-β and up-regulated the expression of matrix metalloproteinase-9 and matrix metalloproteinase-1 in the liver.CONCLUSIONS: The mentioned results clearly show that n-3 PUFA reduces liverfibrosis and promotes liver regeneration, even under cirrhotic conditions. This could be a potentially useful treatment for liver cirrhosis.

read more

PMID: 

Nutrients. 2019 11 22 ;11(12). Epub 2019 Nov 22. PMID: 31766714

Abstract Title: 

Dietary Omega-3 Fatty Acid Dampens Allergic Rhinitis via Eosinophilic Production of the Anti-Allergic Lipid Mediator 15-Hydroxyeicosapentaenoic Acid in Mice.

Abstract: 

The metabolism and generation of bioactive lipid mediators are key events in the exertion of the beneficial effects of dietary omega-3 fatty acids in the regulation of allergic inflammation. Here, we found that dietary linseed oil, which contains high amounts of alpha-linolenic acid (ALA) dampened allergic rhinitis through eosinophilic production of 15-hydroxyeicosapentaenoic acid (15-HEPE), a metabolite of eicosapentaenoic acid (EPA). Lipidomic analysis revealed that 15-HEPE was particularly accumulated in the nasal passage of linseed oil-fed mice after the development of allergic rhinitis with the increasing number of eosinophils. Indeed, the conversion of EPA to 15-HEPE was mediated by the 15-lipoxygenase activity of eosinophils. Intranasal injection of 15-HEPE dampened allergic symptoms by inhibiting mast cell degranulation, which was mediated by the action of peroxisome proliferator-activated receptor gamma. These findings identify 15-HEPE as a novel EPA-derived, and eosinophil-dependent anti-allergic metabolite, and provide a preventive and therapeutic strategy against allergic rhinitis.

read more

PMID: 

Vaccine. 2009 Apr 28 ;27(19):2540-7. Epub 2009 Jan 3. PMID: 19124057

Abstract Title: 

Safety and immunogenicity of a hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 3, 4, and 12-14 months of age.

Abstract: 

Combination vaccines improve parental and provider satisfaction and schedule compliance by decreasing the number of injections. In a Phase 2, randomized, double-blind, multicenter study, we compared four formulations of a liquid, hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B virus (DTaP-IPV-Hib-HBV) vaccine in 708 infants immunized at 2, 3, 4, and 12-14 months of age. The formulations contained identical DTaP and IPV components, differing in the contents of Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus-toxoid [PRP-T, 12microg] or Neisseria meningitidis outer-membrane-protein-complex [PRP-OMPC, 3microg or 6microg]), and in hepatitis B surface antigen (HBsAg, 10microg or 15microg). A minimum acceptable postdose 3 antibody response rate was defined by the lower limit of the 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited injection-site reactions (pain, redness, swelling) with increasing PRP-OMPC and HBsAg concentration. Serious AEs reported by eight subjects were not considered to be vaccine related. All PRP-OMPC formulations met prespecified acceptability criteria for postdose 3 immunogenicity for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and polio. Apart from the Hib response, the postdose 3 responses obtained with the PRP-T formulation met the acceptability criterion for each antigen. Postdose 4 responses were acceptable for all antigens in all formulations. All vaccine formulations were well tolerated. The three PRP-OMPC formulations met prespecified immunogenicity criteria, and the one with the lowest PRP-OMPC concentration was selected for further optimization of immunogenicity.

read more

PMID: 

J Neurol. 2011 Mar ;258(3):500-1. Epub 2010 Sep 30. PMID: 20878418

Abstract Title: 

Anti-NMDA receptor encephalitis after TdaP-IPV booster vaccination: cause or coincidence?

Abstract: 

[n/a]

read more

PMID: 

J Med Case Rep. 2018 Nov 30 ;12(1):356. Epub 2018 Nov 30. PMID: 30497512

Abstract Title: 

Optic neuritis following diphtheria, tetanus, pertussis, and inactivated poliovirus combined vaccination: a case report.

Abstract: 

BACKGROUND: Diphtheria, tetanus, pertussis, and inactivated poliovirus combined vaccine is widely used in young children as part of a series of immunizations before they start attending school. Case studies of demyelinating conditions following administration of diphtheria, tetanus, pertussis, and polio vaccine have been reported, but none so far resulting in optic neuritis. This report further contributes to the database of central nervous system demyelinating conditions affiliated with receipt of vaccines.CASE PRESENTATION: A previously healthy 27-year-old Hispanic man presented to an emergency department with headache, periorbital pressure, pain with ocular movements, and intermittent blurred vision that developed 1 day after administration of the diphtheria, tetanus, pertussis, and inactivated poliovirus combined vaccine. A diagnosis of optic neuritis was made via ophthalmic examination with fundus photography and automated Humphrey visual field analysis. His vision recovered following treatment with high-dose intravenously administered methylprednisolone followed by a tapered dose of orally administered prednisolone.CONCLUSIONS: Although the association between immunizations and the onset of central nervous system demyelinating conditions is well documented, this report, to the best of our knowledge, is the first case of optic neuritis following diphtheria, tetanus, pertussis, and inactivated poliovirus combined vaccination. Inclusion of this case report in the medical community will allow for broader understanding of possible conditions that may present shortly after receipt of vaccination.

read more

PMID: 

Nutrients. 2019 Nov 25 ;11(12). Epub 2019 Nov 25. PMID: 31775362

Abstract Title: 

Antitumor Effects of Quercetin in Hepatocarcinoma In Vitro and In Vivo Models: A Systematic Review.

Abstract: 

Quercetin is a flavonoid present in fruits, vegetables and plants with antioxidant, anti-inflammatory and anticancer properties. Its beneficial activities have been demonstrated in different human pathologies, including hepatoprotective effects against liver disorders. High mortality and late diagnosis of the primary liver tumor hepatocarcinoma (HCC) makes this cancer an interesting target for the study of quercetin effects. Our aim was to systematically review antitumor activities of quercetin in HCC preclinical studies employing single, encapsulated, combined or derived quercetin forms. Literature search was conducted in PubMed, Scopus and Web of Science (WOS), and 39 studies were finally included. We found that 17 articles evaluated quercetin effects alone, six used encapsulated strategy, 10 combined this flavonoid, two decided to co-encapsulate it and only four studied effects of quercetin derivatives, highlighting that only nine included in vivo models. Results evidence the quercetin antiproliferative and proapoptotic properties against HCC either alone and with the mentioned strategies; nevertheless, few investigations assessed specific activities on different processes related with cancer progression. Overall, further studies including animal models are needed to deeper investigate the precise mechanisms of action of quercetin as antitumor agent, as well as the potential of novel strategies aimed to improve quercetin effects in HCC.

read more