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Polyphenols Modulating Effects of PD-L1/PD-1 Checkpoint and EMT-Mediated PD-L1 Overexpression in Breast Cancer.
Messeha, SS, Zarmouh, NO, Soliman, KFA
Nutrients. 2021;(5)
Abstract
Investigating dietary polyphenolic compounds as antitumor agents are rising due to the growing evidence of the close association between immunity and cancer. Cancer cells elude immune surveillance for enhancing their progression and metastasis utilizing various mechanisms. These mechanisms include the upregulation of programmed death-ligand 1 (PD-L1) expression and Epithelial-to-Mesenchymal Transition (EMT) cell phenotype activation. In addition to its role in stimulating normal embryonic development, EMT has been identified as a critical driver in various aspects of cancer pathology, including carcinogenesis, metastasis, and drug resistance. Furthermore, EMT conversion to another phenotype, Mesenchymal-to-Epithelial Transition (MET), is crucial in developing cancer metastasis. A central mechanism in the upregulation of PD-L1 expression in various cancer types is EMT signaling activation. In breast cancer (BC) cells, the upregulated level of PD-L1 has become a critical target in cancer therapy. Various signal transduction pathways are involved in EMT-mediated PD-L1 checkpoint overexpression. Three main groups are considered potential targets in EMT development; the effectors (E-cadherin and Vimentin), the regulators (Zeb, Twist, and Snail), and the inducers that include members of the transforming growth factor-beta (TGF-β). Meanwhile, the correlation between consuming flavonoid-rich food and the lower risk of cancers has been demonstrated. In BC, polyphenols were found to downregulate PD-L1 expression. This review highlights the effects of polyphenols on the EMT process by inhibiting mesenchymal proteins and upregulating the epithelial phenotype. This multifunctional mechanism could hold promises in the prevention and treating breast cancer.
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A polyphenol-rich dietary pattern improves intestinal permeability, evaluated as serum zonulin levels, in older subjects: The MaPLE randomised controlled trial.
Del Bo', C, Bernardi, S, Cherubini, A, Porrini, M, Gargari, G, Hidalgo-Liberona, N, González-Domínguez, R, Zamora-Ros, R, Peron, G, Marino, M, et al
Clinical nutrition (Edinburgh, Scotland). 2021;(5):3006-3018
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Abstract
BACKGROUND & AIM: Increased intestinal permeability (IP) can occur in older people and contribute to the activation of the immune system and inflammation. Dietary interventions may represent a potential strategy to reduce IP. In this regard, specific food bioactives such as polyphenols have been proposed as potential IP modulator due to their ability to affect several critical targets and pathways that control IP. The trial aimed to test the hypothesis that a polyphenol-rich dietary pattern can decrease serum zonulin levels, an IP surrogate marker involved in tight junction modulation, and can beneficially alter the intestinal microbiota, and IP-associated biochemical and clinical markers in older subjects. METHODS A randomised, controlled, cross-over intervention trial was performed. Sixty-six subjects (aged ≥ 60 y) with increased IP based on serum zonulin levels, were randomly allocated to one of the two arms of the intervention consisting of a control diet (C-diet) vs. a polyphenol-rich diet (PR-diet). Each intervention was 8-week long and separated by an 8-week wash out period. At the beginning and at the end of each intervention period, serum samples were collected for the quantification of zonulin and other biological markers. Faecal samples were also collected to investigate the intestinal microbial ecosystem. In addition, anthropometrical/physical/biochemical parameters and food intake were evaluated. RESULTS Fifty-one subjects successfully completed the intervention and a high compliance to the dietary protocols was demonstrated. Overall, polyphenol intake significantly increased from a mean of 812 mg/day in the C diet to 1391 mg/day in the PR-diet. Two-way analysis of variance showed a significant effect of treatment (p = 0.008) and treatment × time interaction (p = 0.025) on serum zonulin levels, which decreased after the 8-week PR-diet. In addition, a treatment × time interaction was observed showing a reduction of diastolic blood pressure (p = 0.028) following the PR-diet, which was strongest in those not using antihypertensive drugs. A decrease in both diastolic (p = 0.043) and systolic blood pressure (p = 0.042) was observed in women. Interestingly, a significant increase in fibre-fermenting and butyrate-producing bacteria such as the family Ruminococcaceae and members of the genus Faecalibacterium was observed following the PR intervention. The efficacy of this dietary intervention was greater in subjects with higher serum zonulin at baseline, who showed more pronounced alterations in the markers under study. Furthermore, zonulin reduction was also stronger among subjects with higher body mass index and with insulin resistance at baseline, thus demonstrating the close interplay between IP and metabolic features. CONCLUSIONS These data show, for the first time, that a PR-diet can reduce serum zonulin levels, an indirect marker of IP. In addition, PR-diet reduced blood pressure and increased fibre-fermenting and butyrate-producing bacteria. These findings may represent an initial breakthrough for further intervention studies evaluating possible dietary treatments for the management of IP, inflammation and gut function in different target populations. THIS STUDY WAS REGISTERED AT WWW.ISRCTN. ORG AS ISRCTN10214981.
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Grapevine as a Rich Source of Polyphenolic Compounds.
Šikuten, I, Štambuk, P, Andabaka, Ž, Tomaz, I, Marković, Z, Stupić, D, Maletić, E, Kontić, JK, Preiner, D
Molecules (Basel, Switzerland). 2020;(23)
Abstract
Grapes are rich in primary and secondary metabolites. Among the secondary metabolites, polyphenolic compounds are the most abundant in grape berries. Besides their important impacts on grape and wine quality, this class of compounds has beneficial effects on human health. Due to their antioxidant activity, polyphenols and phenolic acids can act as anti-inflammatory and anticancerogenic agents, and can modulate the immune system. In grape berries, polyphenols and phenolic acids can be located in the pericarp and seeds, but distribution differs considerably among these tissues. Although some classes of polyphenols and phenolic acids are under strict genetic control, the final content is highly influenced by environmental factors, such as climate, soil, vineyard, and management. This review aims to present the main classes of polyphenolic compounds and phenolic acids in different berry tissues and grape varieties and special emphasis on their beneficial effect on human health.
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Interaction of dietary compounds, especially polyphenols, with the intestinal microbiota: a review.
Duda-Chodak, A, Tarko, T, Satora, P, Sroka, P
European journal of nutrition. 2015;(3):325-41
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Abstract
The intestinal microbiome plays an important role in the metabolism of chemical compounds found within food. Bacterial metabolites are different from those that can be generated by human enzymes because bacterial processes occur under anaerobic conditions and are based mainly on reactions of reduction and/or hydrolysis. In most cases, bacterial metabolism reduces the activity of dietary compounds; however, sometimes a specific product of bacterial transformation exhibits enhanced properties. Studies on the metabolism of polyphenols by the intestinal microbiota are crucial for understanding the role of these compounds and their impact on our health. This review article presents possible pathways of polyphenol metabolism by intestinal bacteria and describes the diet-derived bioactive metabolites produced by gut microbiota, with a particular emphasis on polyphenols and their potential impact on human health. Because the etiology of many diseases is largely correlated with the intestinal microbiome, a balance between the host immune system and the commensal gut microbiota is crucial for maintaining health. Diet-related and age-related changes in the human intestinal microbiome and their consequences are summarized in the paper.
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Role of fatty acids and polyphenols in inflammatory gene transcription and their impact on obesity, metabolic syndrome and diabetes.
Sears, B, Ricordi, C
European review for medical and pharmacological sciences. 2012;(9):1137-54
Abstract
Obesity, metabolic syndrome and diabetes represent multi-factorial conditions resulting from improper balances of hormones and gene expression. In addition, these conditions have a strong inflammatory component that can potentially be impacted by the diet. The purpose of this review is to discuss the molecular targets that can be addressed by anti-inflammatory nutrition. These molecular targets range from reduction of pro-inflammatory eicosanoids that can alter hormonal signaling cascades to the modulation of the innate immune system, via toll-like receptors and gene transcription factors. Working knowledge of the impact of nutrients, especially dietary fatty acids and polyphenols, on these various molecular targets makes it possible to develop a general outline of an anti-inflammatory diet that offers a unique, non-pharmacological approach for treating obesity, metabolic syndrome and diabetes.