PMID: 

Postepy Biochem. 2019 09 30 ;65(3):163-172. Epub 2019 Sep 30. PMID: 31643163

Abstract Title: 

Anticancer properties of probiotic yogurt bacteria

Abstract: 

The intestinal microflora plays a key role in maintaining homeostasis in the human body. Microbes affect, among others, energy conversion and absorption of nutrients, regulate immune system and help to protect the host organism from pathogenic microorganisms. The balanced composition of the intestinal microflora can be easily disturbed and any changes caused by diet, stress, obesity, diseases of the digestive system or medication may lead to pro-inflammatory immune responses and initiation of disease processes, including cancer. Maintaining intestinal microflora homeostasis is therefore extremely important for human health. In order to restore it, it is most often used to take specimens with appropriate bacterial cultures, i. e. probiotics. Due to the fact that yoghurts are a source of probiotic bacteria, their regular consumption may be a strong point in the prevention of various types of diseases, including civilization diseases and cancer. This article reviews the literature in the area of using yogurt bacteria in the prevention of cancer. Issues addressed in the article relate to the characteristics of yogurt bacteria, beneficial effects of probiotics on human health, anti-cancer properties of yogurt bacteria and their metabolites, i. e. immunoregulation, prevention of bacterial infections, maintenance of cellular connections in the intestine and anti-cancer activity of bacterial metabolites.

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PMID: 

JAMA Oncol. 2019 Oct 24. Epub 2019 Oct 24. PMID: 31647500

Abstract Title: 

Association of Dietary Fiber and Yogurt Consumption With Lung Cancer Risk: A Pooled Analysis.

Abstract: 

Importance: Dietary fiber (the main source of prebiotics) and yogurt (a probiotic food) confer various health benefits via modulating the gut microbiota and metabolic pathways. However, their associations with lung cancer risk have not been well investigated.Objective: To evaluate the individual and joint associations of dietary fiber and yogurt consumption with lung cancer risk and to assess the potential effect modification of the associations by lifestyle and other dietary factors.Design, Setting, and Participants: This pooled analysis included 10 prospective cohorts involving 1 445 850 adults from studies that were conducted in the United States, Europe, and Asia. Data analyses were performed between November 2017 and February 2019. Using harmonized individual participant data, hazard ratios and 95% confidence intervals for lung cancer risk associated with dietary fiber and yogurt intakes were estimated for each cohort by Cox regression and pooled using random-effects meta-analysis. Participants who had a history of cancer at enrollment or developed any cancer, died, or were lost to follow-up within 2 years after enrollment were excluded.Exposures: Dietary fiber intake and yogurt consumption measured by validated instruments.Main Outcomes and Measures: Incident lung cancer, subclassified by histologic type (eg, adenocarcinoma, squamous cell carcinoma, and small cell carcinoma).Results: The analytic sample included 627 988 men, with a mean (SD) age of 57.9 (9.0) years, and 817 862 women, with a mean (SD) age of 54.8 (9.7) years. During a median follow-up of 8.6 years, 18 822 incident lung cancer cases were documented. Both fiber and yogurt intakes were inversely associated with lung cancer risk after adjustment for status and pack-years of smoking and other lung cancer risk factors: hazard ratio, 0.83 (95% CI, 0.76-0.91) for the highest vs lowest quintile of fiber intake; and hazard ratio, 0.81 (95% CI, 0.76-0.87) for high vs no yogurt consumption. The fiber or yogurt associations with lung cancer were significant in never smokers and were consistently observed across sex, race/ethnicity, and tumor histologic type. When considered jointly, high yogurt consumption with the highest quintile of fiber intake showed more than 30% reduced risk of lung cancer than nonyogurt consumption with the lowestquintile of fiber intake (hazard ratio, 0.67 [95% CI, 0.61-0.73] in total study populations; hazard ratio 0.69 [95% CI, 0.54-0.89] in never smokers), suggesting potential synergism.Conclusions and Relevance: Dietary fiber and yogurt consumption was associated with reduced risk of lung cancer after adjusting for known risk factors and among never smokers. Our findings suggest a potential protective role of prebiotics and probiotics against lung carcinogenesis.

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PMID: 

Front Genet. 2019 ;10:885. Epub 2019 Sep 27. PMID: 31611907

Abstract Title: 

Glyphosate Primes Mammary Cells for Tumorigenesis by Reprogramming the Epigenome in a TET3-Dependent Manner.

Abstract: 

The acknowledgment that pollutants might influence the epigenome raises serious concerns regarding their long-term impact on the development of chronic diseases. The herbicide glyphosate has been scrutinized for an impact on cancer incidence, but reports demonstrate the difficulty of linking estimates of exposure and response analysis. An approach to better apprehend a potential risk impact for cancer is to follow a synergistic approach, as cancer rarely occurs in response to one risk factor. The known influence of glyphosate on estrogen-regulated pathway makes it a logical target of investigation in breast cancer research. We have used nonneoplastic MCF10A cells in a repeated glyphosate exposure pattern over 21 days. Glyphosate triggered a significant reduction in DNA methylation, as shown by the level of 5-methylcytosine DNA; however, in contrast to strong demethylating agent and cancer promoter UP peptide, glyphosate-treated cells did not lead to tumor development. Whereas UP acts through a DNMT1/PCNA/UHRF1 pathway, glyphosate triggered increased activity of ten-eleven translocation (TET)3. Combining glyphosate with enhanced expression of microRNA (miR) 182-5p associated with breast cancer induced tumor development in 50% of mice. Culture of primary cells from resected tumors revealed a luminal B (ER+/PR-/HER2-) phenotype in response to glyphosate-miR182-5p exposure with sensitivity to tamoxifen and invasive and migratory potentials. Tumor development could be prevented either by specifically inhibiting miR 182-5p or by treating glyphosate-miR 182-5p-cells with dimethyloxallyl glycine, an inhibitor of TET pathway. Looking for potential epigenetic marks of TET-mediated gene regulation under glyphosate exposure, we identifiedandgenes, the hypomethylation of which was sustained even after stopping glyphosate exposure for 6 weeks. Our findings reveal that low pressure but sustained DNA hypomethylation occurringthe TET pathway primes cells for oncogenic response in the presence of another potential risk factor. These results warrant further investigation of glyphosate-mediated breast cancer risk.

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PMID: 

Endocr Metab Immune Disord Drug Targets. 2019 Oct 15. Epub 2019 Oct 15. PMID: 31613732

Abstract Title: 

The Herbicide Glyphosate and Its Apparently Controversial Effect on Human Health: An Updated Clinical Perspective.

Abstract: 

Glyphosate (G) is the most common weed-killer in the world. Every year tons and tons of G are applied on crop fields. G was first introduced in the mid 1970s and since then its usage has gradually increased to reach a peak since 2005. Now G usage is approximately 100 -fold what it was in 1970. Its impact on human health was considered benign at the beginning. But over the years evidence of a pervasive negative effect of this pesticide on humans has been mounting. Nonetheless, G usage is allowed by government health control agencies (both in the United States and Europe), that rely upon the evidence produced by the G producer. However, the IARC (International Agency for Research on Cancer) in 2015 has stated that G is probable carcinogenic (class 2A), the second highest class in terms of risk.Objective. In this review we explore the effect of G on human health, focusing in particular on more recent knowledge.Results. We have attempted to untangle the controversy about the dangers of the product for human beings in view of a very recent development, when the so -called Monsanto Papers, consisting of Emails and memos from Monsanto came to light, revealing a coordinated strategy to manipulate the debate about the safety of glyphosate to the company's advantage.Conclusions. The story of G is a recurrent one (see the tobacco story), that seriously jeopardizes the credibility of scientific study in the modern era..

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PMID: 

Insects. 2019 Oct 18 ;10(10). Epub 2019 Oct 18. PMID: 31635293

Abstract Title: 

Effects of the Herbicide Glyphosate on Honey Bee Sensory and Cognitive Abilities: Individual Impairments with Implications for the Hive.

Abstract: 

The honeybeeis an important pollinator in both undisturbed and agricultural ecosystems. Its great versatility as an experimental model makes it an excellent proxy to evaluate the environmental impact of agrochemicals using current methodologies and procedures in environmental toxicology. The increase in agrochemical use, including those that do not target insects directly, can have deleterious effects if carried out indiscriminately. This seems to be the case of the herbicide glyphosate (GLY), the most widely used agrochemical worldwide. Its presence in honey has been reported in samples obtained from different environments. Hence, to understand its current and potential risks for this pollinator it has become essential to not only study the effects on honeybee colonies located in agricultural settings, but also its effects under laboratory conditions. Subtle deleterious effects can be detected using experimental approaches. GLY negatively affects associative learning processes of foragers, cognitive and sensory abilities of young hive bees and promotes delays in brood development. An integrated approach that considers behavior, physiology, and development allows not only to determine the effects of this agrochemical on this eusocial insect from an experimental perspective, but also to infer putative effects in disturbed environments where it is omnipresent.

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PMID: 

BMC Complement Altern Med. 2019 Jul 11 ;19(1):171. Epub 2019 Jul 11. PMID: 31296214

Abstract Title: 

Evaluation of the anti-malarial activity of crude extract and solvent fractions of the leaves of Olea europaea (Oleaceae) in mice.

Abstract: 

BACKGROUND: Drug resistance poses a challenge to malaria control measures. This calls for discovery&development of new chemotherapeutic agents. This study therefore was initiated to investigate the antimalarial activity of Olea europaea against Plasmodium berghei infected mice and to further ascertain in which fraction (s) the constituents responsible for anti-malarial activity are concentrated.METHODS: The leaves of Olea europaea were extracted by maceration using 80% methanol and the crude extract was then successively fractionated with solvents of differing polarity (chloroform, n-butanol and water). The anti-malarial activity of various doses of the extract and fractions (200, 400 and 600 mg/kg) was evaluated using chemo-suppressive, curative, and repository tests. Parameters, including parasitemia, rectal temperature, body weight, and packed cell volume were determined to establish the activity.RESULTS: The acute oral toxicity test result revealed that the LD50 values of the extract and fractions were greater than 2000 mg/kg in mice. The crude extract significantly reduced parasitemia (p 

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PMID: 

Pharmacol Res. 2019 Oct 11:104487. Epub 2019 Oct 11. PMID: 31610229

Abstract Title: 

The metabolic and vascular protective effects of Olive (Olea europaea L.) leaf extract in diet-induced obesity in mice are related to the amelioration of gut microbiota dysbiosis and to its immunomodulatory properties.

Abstract: 

INTRODUCTION: Many studies have showed the beneficial effects of the olive (Olea europaea) leaf extract (OLE) in experimental models of metabolic syndrome, which have been ascribed to the presence of phenolic compounds, like oleuropeoside. This study evaluated the effects of a chemically characterized OLE in high fat diet (HFD)-induced obesity in mice, describing the underlying mechanisms involved in the beneficial effects, with special attention to vascular dysfunction and gut microbiota composition.METHODS: C57BL/6 J mice were distributed in different groups: control, control-treated, obese and obese-treated with OLE (1, 10 and 25 mg/kg/day). Control mice received a standard diet, whereas obese mice were fed HFD. The treatment was followed for 5 weeks, and animal body weight periodically assessed. At theend of the treatment, metabolic plasma analysis (including lipid profile) as well as glucose and insulin levels were performed. The HFD-induced inflammatory status was studied in liver and fat, by determining the RNA expression of different inflammatory mediators by qPCR; also, different markers ofintestinal epithelial barrier function were determined in colonic tissue by qPCR. Additionally, flow cytometry of immune cells from adipose tissue, endothelial dysfunction in aortic rings as well as gut microbiota composition were evaluated. Faecal microbiota transplantation (FMT) to antibiotic-treated mice fed with HFD was performed.RESULTS: OLE administration reduced body weight gain, basal glycaemia and insulin resistance, and showed improvement in plasma lipid profile when compared with HFD-fed mice. The extract significantly ameliorated the HFD-induced altered expression of key adipogenic genes, like PPARs, adiponectin and leptin receptor, in adipose tissue. Furthermore, the extract reduced the RNA expression of Tnf-α, Il-1β, Il-6 in liver and adipose tissue, thus improving the tissue inflammatory status associated to obesity. The flow cytometry analysis in adipose tissue corroborated these observations. Additionally, the characterization of the colonic microbiota by sequencing showed that OLE administrationwas able to counteract the dysbiosis associated to obesity. The extract reversed the endothelial dysfunction observed in the aortic rings of obese mice. FMT from donors HFD-OLE to recipient mice fed an HFD prevented the development of obesity, glucose intolerance, insulin resistance and endothelialdysfunction.CONCLUSION: OLE exerts beneficial effects in HFD-induced obesity in mice, which was associated to an improvement in plasma and tissue metabolic profile, inflammatory status, gut microbiota composition and vascular dysfunction.

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PMID: 

Antioxidants (Basel). 2019 Jun 21 ;8(6). Epub 2019 Jun 21. PMID: 31234300

Abstract Title: 

Antidiabetic Effects of Hydroxytyrosol: In Vitro and In Vivo Evidence.

Abstract: 

Insulin resistance, a pathological condition characterized by defects in insulin action leads to the development of Type 2 diabetes mellitus (T2DM), a disease which is currently on the rise that pose an enormous economic burden to healthcare systems worldwide. The current treatment and prevention strategies are considerably lacking in number and efficacy and therefore new targeted therapies and preventative strategies are urgently needed. Plant-derived chemicals such as metformin, derived from the French lilac, have been used to treat/manage insulin resistance and T2DM. Other plant-derived chemicals which are not yet discovered, may have superior properties to prevent and manage T2DM and thus research into this area is highly justifiable. Hydroxytyrosol is a phenolic phytochemical found in olive leaves and olive oil reported to have antioxidant, anti-inflammatory, anticancer and antidiabetic properties. The present review summarizes the current in vitro and in vivo studies examining the antidiabetic properties of hydroxytyrosol and investigating the mechanisms of its action.

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PMID: 

Biol Pharm Bull. 2019 ;42(7):1120-1127. PMID: 31257288

Abstract Title: 

Olive-Derived Hydroxytyrosol Shows Anti-inflammatory Effect without Gastric Damage in Rats.

Abstract: 

Hydroxytyrosol (HT) is a simple phenol compound present in olive oil. In a previous in vitro study, we showed that HT downregulated lipopolysaccharide-mediated expression of inducible nitric oxide synthase, cyclooxygenase-2 (COX-2), tumor necrosis factor alpha, and interleukin-1β, resulting in reduced nitric oxide and prostaglandin Eproduction. In the present study, we aimed to determine whether HT suppresses COX-2-induced inflammation in a carrageenan-induced rat paw edema model. Additionally, we compared its activity with those of the selective COX-2 inhibitor, celecoxib for a comparative control, and a representative nonsteroidal anti-inflammatory drug (NSAID), indomethacin for a positive control. HT, celecoxib, and indomethacin significantly suppressed swelling in carrageenan-injected rat paws. Although HT was less effective than celecoxib and indomethacin, it had a delayed onset of action. Moreover, we evaluated whether HT aggravates gastric damage, which is a typical adverse effect associated with NSAIDs and COX-2 inhibitors under low dose aspirin (LDA) treatment, in an aspirin-induced gastric damage rat model. Unlike celecoxib and indomethacin, HT did not cause gastric damage when co-administered with aspirin. Our results indicate that HT exerts a delayed but sustained anti-inflammatory effect against COX-2-mediated inflammation. Finally, the combination of short-acting conventional anti-inflammatory drugs and long-acting HT can be considered a new, safe, and effective anti-inflammatory treatment modality even when continuously administered for a long period under LDA treatment.

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PMID: 

Free Radic Biol Med. 2019 Sep ;141:393-407. Epub 2019 Jul 4. PMID: 31279968

Abstract Title: 

Hydroxytyrosol prevents PM-induced adiposity and insulin resistance by restraining oxidative stress related NF-κB pathway and modulation of gut microbiota in a murine model.

Abstract: 

Exposure to fine particular matter (≤2.5 μM, PM) contributes to increased risk of obesity and type 2 diabetes. Hydroxytyrosol (HT), a simple polyphenol found in virgin olive oil, is considered to be beneficial for cardiovascular and metabolic disorders. The current study determined whether HT could improve PM-induced adiposity and insulin resistance (IR), and explored the underlying mechanisms. Fifteen adult female C57BL/6j mice on a chow diet were randomly divided into three groups receiving (1) sterile PBS, (2) PMsuspended in sterile PBS (1 mg/mL) and (3) PM+HT (50 mg/kg/day). PM/PBS exposure was administered by oropharynx instillation every other day and HT supplementation was achieved by gavage every day. Four-week PMexposure did not affect body weight, but significantly increased visceral fat mass. The abdominal adiposity coincided with adipocyte hypertrophy and proliferation in visceral white adipose tissue (WAT), as well as decreased metabolic activity in brown adipose tissue and subcutaneous WAT. PMenhanced the oxidative stress by diminishing antioxidant enzyme activities in liver and serum, whereas contents of 4-hydroxynonenal (4-HNE), malondialdehyde (MDA) levels in liver and serum were elevated. These changes were accompanied by macrophage infiltration and activation of NF-κB pathway in the liver. Moreover, PMexposure led to glucose intolerance and insulin insensitivity, impaired hepatic glycogenesis, and decreased insulin-stimulated Akt phosphorylation in peripheral tissues. Importantly, HT treatment prevented PM-induced visceral adipogenesis, oxidative stress, hepatic inflammation and NF-κB activation, systemic and peripheral IR. In vitro, after HepG2 cells were incubated with PM(0, 5, 25, 50, 100 and 200 μg/mL), reduced glutathione depletion and 4-HNE, 8-hydroxy-2'-deoxyguanosine, MDA increment in a dose-dependent manner were observed; likewise, insulin-stimulated glucose uptake decreased in a dose-dependent manner. Further, with antioxidant NAC and NF-κB inhibitor PDTC, we confirmed that HT attenuated PM-induced IR through restraining NF-κB activation evoked by oxidative stress. In addition, HT could expand gut microbiota richness, reduce pathogenic bacteria and accommodate the microbial architecture in PM-exposed mice, which were correlated with parameters of adiposity, oxidative stress and glycometabolism. HT could effectively correct imbalanced oxidative stress triggered by PM, in turn ameliorated NF-κB pathway and insulin signaling. Gut microbiota may mediate the actions of HT.

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