A new investigative report reveals that Google has been classifying searches such as “do vaccines cause autism” as “fringe queries” alongside searches that include holocaust denial, Pizzagate, the Vatican’s knowledge of aliens, and so-called “false flag” shootings. 

The new report by James O’ Keefe features the video testimony of a Google insider by the name of Zachary Vorhies who reveals that Google has been actively censoring certain search queries and websites that contain information that runs counter to Google’s singular narrative of truth. 

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PMID: 

Indian J Clin Biochem. 2019 Jul ;34(3):296-303. Epub 2018 Feb 26. PMID: 31391719

Abstract Title: 

Caffeic Acid Modulates miR-636 Expression in Diabetic Nephropathy Rats.

Abstract: 

We investigated the action of caffeic acid in regulating miR-636 expression level in kidney of streptozotocin-induced diabetic rats. Streptozotocin-induced diabetic rats were orally treated with caffeic acid at 40 mg/kg/day for 8 weeks. At the end of the treatment, body and kidney weight and blood glucose levels were determined, blood, urine, and kidneys were collected for biochemical and histological examination. Expression levels of miR-636 were determined in liver by qRT-PCR. Induction of diabetic nephropathy by streptozotocin was evidenced by displayed elevated levels of serum creatinine, blood urea nitrogen, microalbuminuria and urinary albumin/creatinine ratio in addition to renal hypotrophy. Caffeic acid (CA) can ameliorate renal damage and significantly decreased the fasting blood glucose, cholesterol and triglyceride in diabetic rats. CA treatment improved histological architecture in the diabetic kidney. CA significantly down regulate miR-636 expression level in the kidney of diabetic rats in comparison to healthy group. Overall, caffeic acid down regulates miR-636 expression level which is involved in development of diabetic nephropathy and might therefore be potential attractive therapeutic agent to pursue in DN.

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PMID: 

Int J Mol Sci. 2019 Jun 22 ;20(12). Epub 2019 Jun 22. PMID: 31234539

Abstract Title: 

Caffeic Acid Phenethyl Ester Inhibits UV-Induced MMP-1 Expression by Targeting Histone Acetyltransferases in Human Skin.

Abstract: 

Caffeic acid phenethyl ester (CAPE), a naturally occurring bioactive compound, displays anti-inflammatory, anti-carcinogenic, and anti-microbial effects. However, the effect of CAPE on skin photoaging is unknown. Herein, we investigated the inhibitory effect of CAPE against ultraviolet (UV) irradiation-mediated matrix metalloproteinase (MMP)-1 expression and its underlying molecular mechanism. CAPE treatment suppressed UV-induced MMP-1 levels in both human dermal fibroblasts (HDF) and human skin tissues. While CAPE did not display any significant effects against the upstream regulatory pathways of MMP-1, CAPE was capable of reversing UV-mediated epigenetic modifications. CAPE suppressed UV-induced acetyl-histone H3 (Lys9) as well as total lysine acetylation in HDF cells. Similarly, CAPE also attenuated UV-induced lysine acetylations in human skin tissues, suggesting that the CAPE-mediated epigenetic alterations can be recapitulated in ex vivo conditions. CAPE was found to attenuate UV-induced histone acetyltransferase (HAT) activity in HDF. Notably, CAPE was able to directly inhibit the activity of several HATs including p300, CREP-binding protein (CBP), and p300/CBP-associated factor (PCAF), further confirming that CAPE can function as an epigenetic modulator. Thus, our study suggests that CAPE maybe a promising agent for the prevention of skin photoaging via targeting HATs.

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PMID: 

J Food Drug Anal. 2019 Jul ;27(3):736-748. Epub 2019 Jan 8. PMID: 31324289

Abstract Title: 

Nelumbo nucifera leaves extract attenuate the pathological progression of diabetic nephropathy in high-fat diet-fed and streptozotocin-induced diabetic rats.

Abstract: 

Diabetic nephropathy is not only a common and severe microvascular complication of diabetes mellitus but also the leading cause of renal failure. Lotus (Nelumbo nucifera) possesses antioxidative and anticancer properties. The present study aimed to investigate the antidiabetic and renoprotective effects of N. nucifera leaf extract (NLE) in a rat model of type 2 diabetic mellitus. Male Sprague-Dawley rats with type 2 diabetes induced by a high-fat diet (HFD)/streptozotocin (STZ) were treated with NLE at dosages of 0.5% and 1% (w/w) daily for 6 weeks. At the end of the experimental period, body weight, serum glucose levels, insulin levels, and kidney function were assessed. Furthermore, antioxidant enzyme and lipid peroxide levels were determined in the kidney, and histopathological examination was performed using hematoxylin and eosin staining, periodic acid Schiff staining, and Masson trichrome staining. To shed light on the molecular mechanism underlying the functioning of NLE, mouse glomerular mesangial cells (MES-13) treated with high glucose (HG, 25 mM glucose) were chosen as a model for an examination of the signal transduction pathway of NLE. The results revealed that NLE improved diabetic kidney injury by reducing blood glucose, serum creatinine, and blood urea nitrogen levels and enhanced antioxidant enzyme activities in kidney tissue. Treatment with NLE significantly reduced the malondialdehyde and 8-hydroxy-2-deoxyguanosine levels and increased serum insulin levels; expression of renal superoxide dismutase, catalase, and glutathione peroxidase activities; and glutathione content. Histological studies have also demonstrated that NLE treatment inhibited the dilation of Bowman's capsule, which confirmed its renoprotective action in diabetes. In addition, treatment with NLE and its major component quercetin 3-glucuronide attenuated 25 mM HG-induced suppressed nuclear factor erythroid 2-related factor 2 and antioxidant enzyme expression in MES-13 cells. Collectively, these findings indicate that NLE may have antidiabetic and renoprotective effects against HFD/STZ-induced diabetes, at least in part, through antioxidative pathways.

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PMID: 

J Microbiol Biotechnol. 2019 Aug 1. Epub 2019 Aug 1. PMID: 31370119

Abstract Title: 

Anti-biofilm Activity of Grapefruit Seed Extract againstand.

Abstract: 

Grapefruit seed extract (GSE) is a safe and effective preservative that is used widely in the food industry. However, there are few studies addressing the anti-biofilm effect of GSE. In this study, the anti-biofilm effect of GSE was investigated against biofilm-forming strains ofand. The GSE minimum inhibitory concentration (MIC) forandwere 25μg/ml and 250 μg/ml, respectively. To investigate biofilm inhibition and degradation effect, crystal violet assay and stainless-steel were used. Biofilm formation rates of four strains (7, and8,ATCC 25922, andO157:H4 FRIK 125) were 55.8%, 70.2%, 55.4%, and 20.6% at 1/2× MIC of GSE, respectively. The degradation effect of GSE on biofilms attached to stainless-steel coupons was observed (≥1 log CFU/coupon) after exposure to concentrations above the MIC for all strains and 1/2 × MIC for7. In addition, the specific mechanisms of this anti-biofilm effect were investigated by evaluating hydrophobicity, auto-aggregation, exopolysaccharide (EPS) production rate, and motility. Significant changes in EPS production rate and motility were observed in bothandin the presence of GSE, while changes in hydrophobicity were observed only in. No relationship was seen between auto-aggregation and biofilm formation. Therefore, our results suggest that GSE might be used as an anti-biofilm agent that is effective againstand.

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PMID: 

Acta Biochim Biophys Sin (Shanghai). 2019 Jan 1 ;51(1):31-40. PMID: 30544155

Abstract Title: 

Lotus seed skin proanthocyanidin extract exhibits potent antioxidant property via activation of the Nrf2-ARE pathway.

Abstract: 

Lotus seed is well known as traditional food and medicine, but its skin is usually discarded. Recent studies have shown that lotus seed skin contains a high concentration of proanthocyanidins that have multi-functions, such as antioxidation, anti-inflammation, and anti-cancer effects. In the present study, we aimed to isolate and purify the proanthocyanidins from lotus seed skin by acetone extraction and rotary evaporation, identify their chemical structures by HPLC-MS-MS and NMR, and further investigate the antioxidant properties of the extract purified by macroporous resin (PMR) from lotus seed skin both in vitro and in vivo. The results showed that PMR mainly contained oligomeric proanthocyanidins, especially dimeric procyanidin B1 (PB1), procyanidin B2 and procyanidin B4. Although it had limited ability to directly scavenge radicals in vitro, PMR could significantly enhance the expressions of antioxidant proteins via activation of nuclear factor-E2-related factor 2 (Nrf2)-antioxidant response element (ARE) pathway in HepG2 cells. Molecular data revealed that PB1, a major component in PMR, stabilized Nrf2 by inhibiting the ubiquitination of Nrf2, which led to subsequent activation of the Nrf2-ARE pathway, including the enhancements of Nrf2 nuclear translocation, Nrf2-ARE binding and ARE transcriptional activity. Moreover, the in vivo results in high fat diet-induced mice further verified the powerful antioxidant property of PMR. These results revealed that lotus seed skin is a promising resource for functional food development.

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PMID: 

J Agric Food Chem. 2019 Jan 9 ;67(1):229-235. Epub 2018 Dec 28. PMID: 30562012

Abstract Title: 

Lipophilic Grape Seed Proanthocyanidin Exerts Anti-Proliferative and Pro-Apoptotic Effects on PC3 Human Prostate Cancer Cells and Suppresses PC3 Xenograft Tumor Growth in Vivo.

Abstract: 

The in vitro antiprostate cancer activity of lipophilic grape seed proanthocyanidin (LGSP) against the PC3 cell line was evaluated by MTT assay, flow cytometry, and immunoblot analysis, and the in vivo antiprostate cancer effect was evaluated by a PC3-derived mouse xenograft model via oral gavage LGSP. Ki67 and cleaved caspase 3 immunostaining experiments were performed in tumor tissues. LGSP exhibited a strong inhibitory effect on PC3 cell proliferation by inducing apoptosis. Treatment with LGSP resulted in a G1 phase cell cycle arrest in PC3 cells, which was further confirmed by decreasing the expression of cyclin D1 and CDK 4 and increasing the expression of the tumor suppressors p21 and p27. Furthermore, activation of cleaved fragments of caspases 3, caspases 9, and PARP indicated that LGSP-induced apoptosis is caspase-dependent. Upstream of caspase cascade, LGSP increased the cytochrome c release in cytoplasm. After treatment with LGSP, the Bcl-2/Bax ratio also decreased in PC3 cells. In tumor studies, LGSP inhibited the growth of PC3-derived mouse xenografts by inhibiting tumor cell proliferation and inducing apoptosis. Our findings suggest that LGSP is an effective antiprostate cancer component and deserves further study.

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PMID: 

J Exp Clin Cancer Res. 2019 May 17 ;38(1):204. Epub 2019 May 17. PMID: 31101057

Abstract Title: 

PKM2 is the target of proanthocyanidin B2 during the inhibition of hepatocellular carcinoma.

Abstract: 

BACKGROUND: The treatment for advanced primary hepatocellular carcinoma (HCC) is sorafenib (SORA), while HCC has become increasingly drug resistant with enhanced aerobic glycolysis. The present study aimed to examine the chemotherapeutic effects of a flavonoid proanthocyanidin B2 (PB2) on HCC.METHODS: Five kinds of HCC cell lines and LO2 were used to test the effect of PB2 on aerobic glycolysis. The proliferation, cell cycle, apoptosis and a xenograft mouse model were analyzed. Lentivirus overexpressed pyruvate kinase M2 (PKM2) or sh-PKM2 was used to verify the target of PB2. The detailed mechanism was investigated by immunofluorescence, co-immunoprecipitation, and western blotting.RESULTS: PB2 inhibited the proliferation, induced cell cycle arrest, and triggered apoptosis of HCC cells in vivo and in vitro. PB2 also suppressed glucose uptake and lactate levels via the direct inhibition of the key glycolytic enzyme, PKM2. In addition, PKM2 inhibited the nuclear translocation of PKM2 and co-localization of PKM2/HIF-1α in the nucleus, leading to the inhibition of aerobic glycolysis. Co-treatment with PB2 was also effective in enhancing the chemosensitivity of SORA.CONCLUSIONS: PB2 inhibited the expression and nuclear translocation of PKM2, therefore disrupting the interaction between PKM2/HSP90/HIF-1α, to suppress aerobic glycolysis and proliferation, and trigger apoptosis in HCC via HIF-1α-mediated transcription suppression.

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PMID: 

Sci Rep. 2018 Jul 16 ;8(1):10706. Epub 2018 Jul 16. PMID: 30013052

Abstract Title: 

Propolis potentiates the effect of cranberry (Vaccinium macrocarpon) against the virulence of uropathogenic Escherichia coli.

Abstract: 

Uropathogenic Escherichia coli (UPEC), the most prevalent bacteria isolated in urinary tract infections (UTI), is now frequently resistant to antibiotics used to treat this pathology. The antibacterial properties of cranberry and propolis could reduce the frequency of UTIs and thus the use of antibiotics, helping in the fight against the emergence of antibiotic resistance. Transcriptomic profiles of a clinical UPEC strain exposed to cranberry proanthocyanidins alone (190 µg/mL), propolis alone (102.4 µg/mL) and a combination of both were determined. Cranberry alone, but more so cranberry + propolis combined, modified the expression of genes involved in different essential pathways: down-expression of genes involved in adhesion, motility, and biofilm formation, and up-regulation of genes involved in iron metabolism and stress response. Phenotypic assays confirmed the decrease of motility (swarming and swimming) and biofilm formation (early formation and formed biofilm). This study showed for the first time that propolis potentiated the effect of cranberry proanthocyanidins on adhesion, motility, biofilm formation, iron metabolism and stress response of UPEC. Cranberry + propolis treatment could represent an interesting new strategy to prevent recurrent UTI.

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PMID: 

Front Microbiol. 2018 ;9:1826. Epub 2018 Aug 7. PMID: 30131793

Abstract Title: 

The Cranberry Extract OximacroExertsVirucidal Activity Against Influenza Virus by Interfering With Hemagglutinin.

Abstract: 

The defense against influenza virus (IV) infections still poses a series of challenges. The current antiviral arsenal against influenza viruses is in fact limited; therefore, the development of new anti-influenza strategies effective against antigenically different viruses is an urgent priority. Bioactive compounds derived from medicinal plants and fruits may provide a natural source of candidates for such broad-spectrum antivirals. In this regard, cranberry (Aiton) extracts on the basis of their recognized anti-adhesive activities against bacteria, may provide potential compounds able to prevent viral attachment to target cells. Nevertheless, only few studies have so far investigated the possible use of cranberry extracts as an antiviral tool. This study focuses on the suitability of a cranberry extract as a direct-acting anti-influenza compound. We show that the novel cranberry extract Oximacroinhibits influenza A and B viruses (IAV, IBV) replicationbecause of its high content of A-type proanthocyanidins (PAC-A) dimers and trimers. Mechanistic studies revealed that Oximacroprevents attachment and entry of IAV and IBV into target cells and exerts a virucidal activity. Oximacrowas observed to interact with the ectodomain of viral hemagglutinin (HA) glycoprotein, thus suggesting the interference with HA functions and a consequent loss of infectivity of IV particles. Fluorescence spectroscopy revealed a reduction in the intrinsic fluorescence of HA protein after incubation with purified dimeric PAC-A (PAC-A2), thus confirming a direct interaction between HA and OximacroPAC-A2.docking simulations further supported theresults and indicated that among the different components of the Oximacrochemical profile, PAC-A2 exhibited the best binding propensity with an affinity below 10 nM. The role of PAC-A2 in the anti-IV activity of Oximacrowas eventually confirmed by the observation that it prevented IAV and IVB replication and caused the loss of infectivity of IV particles, thus indicating PAC-A2 as the major active component of Oximacro. As a whole, these results suggest Oximacroas a potential candidate to create novel antiviral agents of natural origin for the prevention of IV infections.

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