PMID: 

Nutrients. 2019 Feb 15 ;11(2). Epub 2019 Feb 15. PMID: 30781364

Abstract Title: 

(-)-Oleocanthal Combined with Lapatinib Treatment Synergized against HER-2 Positive Breast Cancer In Vitro and In Vivo.

Abstract: 

Dysregulation of epidermal growth factor receptor (EGFR)/human epidermal growth factor-2 (HER2) family is a hallmark of aggressive breast cancer. Small-molecule tyrosine kinase inhibitors are among the most effective cancer targeted treatments. (-)-Oleocanthal (OC) is a naturally occurring phenolic secoiridoid lead from extra-virgin olive oil with documented anti-cancer activities via targeting mesenchymal epithelial transition factor (c-Met). Dysregulation of c-Met promotes aggressiveness to breast cancer-targeted therapies. Lapatinib (LP) is an FDA-approved dual EGFR/HER2 inhibitor for HER2-amplified breast cancer. HER2-Positive tumor cells can escape targeted therapies like LP effects by overexpressing c-Met. Combined OC-LP treatment is hypothesized to be mechanistically synergistic against HER2-overexpressing breast cancer. Combined sub-effective treatments of OC-LP resulted in synergistic anti-proliferative effects against the HER2-positive BT-474 and SK-BR-3 breast cancer cell lines, compared to OC or LP monotherapy. Antibody array and Western blot analysis showed that combined OC-LP treatment significantly inhibited EGFR, HER2, and c-Met receptor activation, as well as multiple downstream signaling proteins, compared to individual OC or LP treatment. OC-LP Combination significantly inhibited invasion and migration of breast cancer cells through reduced activation of focal adhesion kinase (FAK) and paxillin. Combined treatment of OC-10 mg/kg with LP-12.5 mg/kg suppressed more than 90% of BT-474 tumor cells growth in a nude mouse xenograft model, compared to individual OC or LP treatment. Activated c-Met, EGFR, HER2, and protein kinase B (AKT) were significantly suppressed in combination-treated mice tumors, compared to OC or LP monotherapy. This study reveals the OC future potential as combination therapy to sensitize HER2-overexpressing breast cancers and significantly reduce required doses of targeted HER family therapeutics.

read more

PMID: 

J Agric Food Chem. 2019 May 15 ;67(19):5552-5559. Epub 2019 May 1. PMID: 31042377

Abstract Title: 

Oleocanthal Modulates LPS-Induced Murine Peritoneal Macrophages Activation via Regulation of Inflammasome, Nrf-2/HO-1, and MAPKs Signaling Pathways.

Abstract: 

The present study was designed to investigate the role of the canonical and noncanonical inflammasome, MAPKs and NRF-2/HO-1, signaling pathways involved in the antioxidant and anti-inflammatory activities of oleocanthal in lipopolysaccharide (LPS)-stimulated murine peritoneal macrophages. Isolated cells were treated with oleocanthal in the presence or absence of LPS (5μg mL) for 18 h. Oleocanthal showed a potent reduction of reactive oxygen species (ROS) (25μM, 50. 612 ± 0.02; 50 μM, 53. 665 ± 0.09; 100 μM, 52. 839 ± 0.02), nitrites (25 μM, 0.631 ± 0.07; 50 μM, 0.652 ± 0.07; 100 μM, 0.711 ± 0.08), and pro-inflammatory cytokines levels when compared with LPS-DMSO-treated control cells. In terms of enzymes protein expression, oleocanthal was able to downregulate iNOS (25 μM, 0.173 ± 0.02; 50 μM, 0.149 ± 0.01; 100 μM, 0.150 ± 0.01; p

read more

PMID: 

ACS Chem Neurosci. 2019 Aug 21 ;10(8):3543-3554. Epub 2019 Jun 25. PMID: 31244050

Abstract Title: 

Oleocanthal-Rich Extra-Virgin Olive Oil Restores the Blood-Brain Barrier Function through NLRP3 Inflammasome Inhibition Simultaneously with Autophagy Induction in TgSwDI Mice.

Abstract: 

Alzheimer's disease (AD) is a complex neurodegenerative disorder characterized by multiple hallmarks including extracellular amyloid (Aβ) plaques, neurofibrillary tangles, dysfunctional blood-brain barrier (BBB), neuroinflammation, and impaired autophagy. Thus, novel strategies that target multiple disease pathways would be essential to prevent, halt, or treat the disease. A growing body of evidence including our studies supportsa protective effect of oleocanthal (OC) and extra-virgin olive oil (EVOO) at early AD stages before the onset of pathology. In addition, we reported previously that OC and EVOO exhibited such effect by restoring the BBB function; however, the mechanism(s) by which OC and EVOO exert such an effect and whether this effect extends to a later stage of AD remain unknown. In this work, we sought first to test the effect of OC-rich EVOO consumption at an advanced stage of the disease in TgSwDI mice, an AD mouse model, starting at the age of 6 months for 3 months treatment, and then to elucidate the mechanism(s) by which OC-rich EVOO exerts the observed beneficial effect. Overall findings demonstrated that OC-rich EVOO restored the BBB function and reduced AD-associated pathology by reducing neuroinflammation through inhibition of NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome and inducing autophagy through activation of AMP-activated protein kinase (AMPK)/Unc-51-like autophagy activating kinase 1 (ULK1) pathway. Thus, diet supplementation with OC-rich EVOO could provide beneficial effect to slow or halt the progression of AD.

read more

PMID: 

Biotech Histochem. 2019 Nov 6:1-9. Epub 2019 Nov 6. PMID: 31691588

Abstract Title: 

Inhibiting effect of oleocanthal on neuroblastoma cancer cell proliferation in culture.

Abstract: 

We investigated the potential anticancer effects of oleocanthal (OC) on neuroblastoma cells. Cells were divided into four groups: group 1, neuroblastoma cells were treated with OC; group 2, neurons that differentiated from neuroblastoma cells were treated with phosphate-buffered saline(PBS); group 3, bone marrow derived neuronal (BMDN) cells that were differentiated from bone marrow derived mesenchymal stem cells (BMSCs) were treated with OC; group 4, BMDN cells that were differentiated from BMSCs were treated with PBS. Groups 2 and 4 were control groups. The effects of OC on cell viability, oxidative stress, neurite inhibition and apoptosis at ICdose were investigated using MTT analysis, i-NOS and e-NOS measurement, neurotoxicity screening test (NST) and TUNEL staining, respectively. MTT analysis demonstrated that cells were significantly less viable in group 1 than in group 3. i-NOS and e-NOS staining intensity was significantly greater in group 1 than in group 3. NST revealed that OC inhibited neurite growth in both neuroblastoma and BMND cells; inhibition was significantly less in group 3 than in group 1. Significantly more TUNEL labeled cells were found in group 1 than in group 3. We found that OC prevented growth and proliferation of neuroblastoma cells in culture by increasing oxidative stress and apoptosis. We also found that the cytotoxicity of OC is negligible in BMDN cells.

read more

PMID: 

Nutrients. 2019 Nov 21 ;11(12). Epub 2019 Nov 21. PMID: 31766503

Abstract Title: 

The Extra-Virgin Olive Oil Polyphenols Oleocanthal and Oleacein Counteract Inflammation-Related Gene and miRNA Expression in Adipocytes by Attenuating NF-κB Activation.

Abstract: 

Inflammation of the adipose tissue plays an important role in the development of several chronic diseases associated with obesity. Polyphenols of extra virgin olive oil (EVOO), such as the secoiridoids oleocanthal (OC) and oleacein (OA), have many nutraceutical proprieties. However, their roles in obesity-associated adipocyte inflammation, the NF-κB pathway and related sub-networks have not been fully elucidated. Here, we investigated impact of OC and OA on the activation of NF-κB and the expression of molecules associated with inflammatory and dysmetabolic responses. To this aim, fully differentiated Simpson-Golabi-Behmel syndrome (SGBS)adipocytes were pre-treated with OC or OA before stimulation with TNF-α. EVOO polyphenols significantly reduced the expression of genes implicated in adipocyte inflammation (IL-1β, COX-2), angiogenesis (VEGF/KDR, MMP-2), oxidative stress (NADPH oxidase), antioxidant enzymes (SOD and GPX), leukocytes chemotaxis and infiltration (MCP-1, CXCL-10, MCS-F), and improved the expression of the anti-inflammatory/metabolic effector PPARγ. Accordingly, miR-155-5p, miR-34a-5p and let-7c-5p, tightly connected with the NF-κB pathway, were deregulated by TNF-α in both cells and exosomes. The miRNA modulation and NF-κB activation by TNF-α was significantly counteracted by EVOO polyphenols. Computational studies suggested a potential direct interaction between OC and NF-κB at the basis of its activity. This study demonstrates that OC and OA counteract adipocyte inflammation attenuating NF-κB activation. Therefore, these compounds could be novel dietary tools for the prevention of inflammatory diseases associated with obesity.

read more

PMID: 

Nutrients. 2019 Nov 27 ;11(12). Epub 2019 Nov 27. PMID: 31783578

Abstract Title: 

The Effects of Probiotic Supplementation on the Incidence of Diarrhea in Cancer Patients Receiving Radiation Therapy: A Systematic Review with Meta-Analysis and Trial Sequential Analysis of Randomized Controlled Trials.

Abstract: 

The protective effects of probiotic supplementation against radiation-induced diarrhea (RID) have been reported in previous systematic reviews; however so far, only non-conclusive results have been obtained. The objective of this study was to systematically update and evaluate the available evidence for probiotic supplementation. The protocol of this systematic review has been registered (CRD42018106059) with the International Prospective Register of Systematic Reviews (PROSPERO). The primary efficacy outcome was the incidence of RID. Secondary outcomes were the incidence of watery stool, soft stool, and antidiarrheal medication use. There were eight trials, and a total of 1116 participants were included in the primary analysis. Compared with placebo, probiotics were associated with a lower risk of RID [risk ratio (RR) = 0.62, 95% CI = 0.46, 0.83]. A requisite heterogeneity-adjusted trial sequential analysis indicated conclusive evidence for this beneficial effect. No statistically significant reduction in RID (RR = 0.52, 95% CI = 0.14, 1.91) was observed on subgroup analysis in patients receiving both radiation therapy and chemotherapy. However, those patients receiving only radiation therapy (RT) demonstrated significant benefit (RR = 0.61, 95% CI = 0.48, 0.78). There was a significant difference in the antidiarrheal medication use (RR = 0.54, 95% CI = 0.35, 0.84) observed with the use of probiotics. However, no significant difference was observed for the incidence of soft and watery stool. The use of probiotics is beneficial in preventing RID in patients receiving RT.

read more

PMID: 

Nutrients. 2019 Dec 1 ;11(12). Epub 2019 Dec 1. PMID: 31805673

Abstract Title: 

Vitamin E Supplementation and Mitochondria in Experimental and Functional Hyperthyroidism: A Mini-Review.

Abstract: 

Mitochondria are both the main sites of production and the main target of reactive oxygen species (ROS). This can lead to mitochondrial dysfunction with harmful consequences for the cells and the whole organism, resulting in metabolic and neurodegenerative disorders such as type 2 diabetes, obesity, dementia, and aging. To protect themselves from ROS, mitochondria are equipped with an efficient antioxidant system, which includes low-molecular-mass molecules and enzymes able to scavenge ROS or repair the oxidative damage. In the mitochondrial membranes, a major role is played by the lipid-soluble antioxidant vitamin E, which reacts with the peroxyl radicals faster than the molecules of polyunsaturated fatty acids, and in doing so, protects membranes from excessive oxidative damage. In the present review, we summarize the available data concerning the capacity of vitamin E supplementation to protect mitochondria from oxidative damage in hyperthyroidism, a condition that leads to increased mitochondrial ROS production and oxidative damage. Vitamin E supplementation to hyperthyroid animals limits the thyroid hormone-induced increases in mitochondrial ROS and oxidative damage. Moreover, it prevents the reduction of the high functionality components of the mitochondrial population induced by hyperthyroidism, thus preserving cell function.

read more

This Bill clearly seeks to control speech, and specifically speech about health and wellness, as well as speech about what people eat, a matter impressed with significant privacy interests

PMID: 

J Pediatr. 2004 Dec ;145(6):845-7. PMID: 15580216

Abstract Title: 

Stroke after varicella vaccination.

Abstract: 

Two children presented with acute hemiparesis 5 days and 3 weeks following varicella vaccination. Both showed unilateral infarction of the basal ganglia and internal capsule, a distribution consistent with varicella angiopathy. Both children had small patent foramen ovale (PFO), and one child also had severe iron-deficiency anemia, which may have predisposed the patient to this adverse effect.

read more

PMID: 

Arch Med Sci. 2011 Apr ;7(2):345-8. Epub 2011 May 17. PMID: 22291779

Abstract Title: 

Ischaemic stroke and influenza A H1N1 vaccination: a case report.

Abstract: 

We report a 75-year-old male patient who suffered posterior circulation ischaemia after influenza A/H1N1 vaccination. Vaccination provokes a variable magnitude of inflammatory and immunological response that modifies the risk for ischaemic stroke. Whereas a causal relation between vaccination and ischaemic stroke is still unsettled, an inflammatory/immunological response after vaccination may trigger thrombosis superimposing a pre-existing prothrombotic state. Careful monitoring is strongly suggested for individuals who received H1N1 vaccine, especially those with high ischaemic stroke risk.

read more