scholarly journals Introducing Gordonibacter urolithinfaciens into Gut Ecosystems to Study Its Role in Mediating the Metabolic Benefits of Dietary Polyphenols

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 1594-1594
Author(s):  
Ashley Toney ◽  
Yibo Xian ◽  
Jing Shao ◽  
Robert Schmaltz ◽  
Virginia Chaidez ◽  
...  
Keyword(s):  
Drinking Water ◽  
Ellagic Acid ◽  
Improve Insulin Sensitivity ◽  
Microbial Conversion ◽  
Dietary Polyphenols ◽  
Funding Sources ◽  
Host Metabolism

Abstract Objectives Dietary polyphenols such as ellagitannins undergo microbial conversion to yield urolithins, which improve insulin sensitivity. However, feeding ellagic acid-containing foods sometimes yields variable levels of metabolic improvements in humans, suggesting that some individuals may not harbor the specific microbes responsible for transforming ellagic acid (EA) into urolithins. One species of gut bacteria, Gordonibacter urolithinfaciens (G. uro), has been shown to convert EA into urolithins in vitro. However, the specific role of G. uro in mediating the metabolic benefits of EA-containing foods in vivo is unknown, in part, because of challenges associated with its engraftment in mouse models. This study aimed to determine whether G. uro could be introduced into an established microbiota as a single dose or daily probiotic to facilitate future studies regarding its role in improving host metabolism via conversion of EA to urolithins. Methods Germ-free (GF) C57BL/6 mice were either: (1) mono-associated with G. uro for 2 wks prior to introduction of one of three conventional mouse microbiotas naturally deficient for G. uro, (2) colonized with both G. uro and a conventional G. uro-deficient microbiota together, (3) colonized with a conventional G. uro-deficient microbiota for 2 wks and then given a single oral gavage of G. uro, or (4) colonized with a conventional G. uro-deficient microbiota for 2 wks and then administered G. uro fresh daily in drinking water. Results G. uro successfully monocolonized a previously GF mouse but was not detectable following introduction of a complex G. uro-deficient microbiota. G. uro also failed to persist when GF mice were first colonized with a conventional G. uro-deficient microbiota and then given a single gavage of G. uro. However, ex-GF mice colonized with a complex G. uro-deficient microbiota and given daily doses of G. uro in their drinking water were able to maintain this organism throughout the study. Conclusions Our studies demonstrate the challenges associated with introducing G. uro into a microbiota even when G. uro is provided prior to microbiota establishment and the microbiota is naturally devoid of G. uro. These results suggest that G. uro may need to be administered as a daily probiotic to provide health benefits to individuals unable to convert ellagic acid foods into beneficial urolithins. Funding Sources USDA NIFA.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

scholarly journals Interactions between CYP3A4 and Dietary Polyphenols

2015 ◽  
Vol 2015 ◽  
pp. 1-15 ◽  
Author(s):  
Loai Basheer ◽  
Zohar Kerem
Keyword(s):  
Critical Role ◽  
Negative Consequences ◽  
Cytochrome P450 Enzymes ◽  
Dietary Polyphenols ◽  
Complex Interactions ◽  
Human Cytochrome ◽  
Clinical Consequences

The human cytochrome P450 enzymes (P450s) catalyze oxidative reactions of a broad spectrum of substrates and play a critical role in the metabolism of xenobiotics, such as drugs and dietary compounds. CYP3A4 is known to be the main enzyme involved in the metabolism of drugs and most other xenobiotics. Dietary compounds, of which polyphenolics are the most studied, have been shown to interact with CYP3A4 and alter its expression and activity. Traditionally, the liver was considered the prime site of CYP3A-mediated first-pass metabolic extraction, butin vitroandin vivostudies now suggest that the small intestine can be of equal or even greater importance for the metabolism of polyphenolics and drugs. Recent studies have pointed to the role of gut microbiota in the metabolic fate of polyphenolics in human, suggesting their involvement in the complex interactions between dietary polyphenols and CYP3A4. Last but not least, all the above suggests that coadministration of drugs and foods that are rich in polyphenols is expected to stimulate undesirable clinical consequences. This review focuses on interactions between dietary polyphenols and CYP3A4 as they relate to structural considerations, food-drug interactions, and potential negative consequences of interactions between CYP3A4 and polyphenols.

scholarly journals Modulation of Autophagy in Cancer Cells by Dietary Polyphenols

Antioxidants ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 123
Author(s):  
Claudia Musial ◽  
Kamila Siedlecka-Kroplewska ◽  
Zbigniew Kmiec ◽  
Magdalena Gorska-Ponikowska
Keyword(s):  
Cell Death ◽  
Cancer Cells ◽  
Polyphenolic Compounds ◽  
In Vivo Studies ◽  
Cancer Disease ◽  
Protective Function ◽  
Dietary Polyphenols

The role of autophagy is to degrade damaged or unnecessary cellular structures. Both in vivo and in vitro studies suggest a dual role of autophagy in cancer—it may promote the development of neoplasms, but it may also play a tumor protective function. The mechanism of autophagy depends on the genetic context, tumor stage and type, tumor microenvironment, or clinical therapy used. Autophagy also plays an important role in cell death as well as in the induction of chemoresistance of cancer cells. The following review describes the extensive autophagic cell death in relation to dietary polyphenols and cancer disease. The review documents increasing use of polyphenolic compounds in cancer prevention, or as agents supporting oncological treatment. Polyphenols are organic chemicals that exhibit antioxidant, anti-inflammatory, anti-angiogenic, and immunomodulating properties, and can also initiate the process of apoptosis. In addition, polyphenols reduce oxidative stress and protect against reactive oxygen species. This review presents in vitro and in vivo studies in animal models with the use of polyphenolic compounds such as epigallocatechin-3-gallate (EGCG), oleuropein, punicalgin, apigenin, resveratrol, pterostilbene, or curcumin and their importance in the modulation of autophagy-induced death of cancer cells.

scholarly journals The Microbial Biotransformation of Soy Genistein Significantly Enhances Its Trapping Capacities of Reactive Carbonyl Metabolites

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 467-467
Author(s):  
Shengmin Sang ◽  
Yingdong Zhu
Keyword(s):  
Active Phase ◽  
The Body ◽  
Carbonyl Stress ◽  
Mouse Urine ◽  
Dietary Polyphenols ◽  
Funding Sources ◽  
Abnormal Accumulation ◽  
Reactive Carbonyl

Abstract Objectives Carbonyl stress is the abnormal accumulation of carbonyl metabolites, such as methylglyoxal (MGO) and acrolein (ACR) that leads to increased modification of protein, lipids and DNA, and contributes to cell and tissue dysfunction resulting in aging and diseases, such as diabetes, cardiovascular diseases and neurodegenerative diseases. Carbonyl stress is caused by an imbalance in the formation and metabolism of carbonyl metabolites and also by increased exposure to exogenous carbonyl species. In vitro studies have shown that dietary flavonoids have the capacities to detoxify reactive carbonyl metabolites. However, whether flavonoids can trap carbonyl metabolites in vivo and whether biotransformation especially microbial metabolism limits the trapping capacities of flavonoids remain virtually unknown. The objective of this study is to use soy genistein as an example to test the impacts of bioavailability and biotransformation on the in vivo trapping capacities of RCS by genistein. Methods Chemically, we synthesized the MGO and ACR conjugates of genistein as authentic standards. In mice, we oral gavaged 200 mg/kg genistein or vehicle to mice. Urine and feces were collected in metabolic cages for 24 h. The urine samples from genistein treated mice were also used to prepare the RCS conjugates of genistein metabolites. Using LC tandem mass and the high-resolution accurate mass, we searched and identified the formation of genistein metabolites and their corresponding RCS conjugates. The RCS conjugates of genistein and its metabolites were also quantified using the synthetic standards. Results We found that 1) absorbed genistein trapped endogenous MGO and ACR by forming mono-RCS adducts and eventually be excreted into mouse urine; 2) absorbed genistein could produce active phase I metabolite, orobol, to scavenge endogenous MGO and ACR; and 3) considerable amounts of microbial metabolites of genistein displayed enhanced anti-RCS capacity both in the body and in the gut, compared to genistein. Conclusions Our findings demonstrate that in vivo anti-RCS ability of dietary polyphenols cannot be reflected solely based on their in vitro ability. The bioavailability and biotransformation of individual polyphenols especially gut microbiome contribute to in vivo anti-RCS ability of dietary polyphenols. Funding Sources N/A.

scholarly journals The m6A methyltransferase METTL3 promotes hypoxic pulmonary arterial hypertension via targeting PTEN

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
Q I N Yuhan ◽  
T A N G Chengchun
Keyword(s):  
Pulmonary Arteries ◽  
Rna Modification ◽  
Funding Sources ◽  
Pten Mrna ◽  
Rna Immunoprecipitation ◽  
M6a Rna Methylation ◽  
And Migration

Abstract Background N6-methyladenosine (m6A) is the most prevalent internal RNA modification in mammal mRNAs. Accumulating evidence has indicated the crucial role of m6A modification in cardiovascular diseases including cardiac hypertrophy, heart failure, ischemic heart disease, vascular calcification, restenosis, and aortic aneurysm. However, the role of m6A methylation in the occurrence and development of hypoxic pulmonary hypertension (HPH) remains largely unknown. Purpose The present study aims to explore the role of key transferase METTL3, in the development of HPH. Methods Hypoxic rat models and pulmonary artery smooth muscle cells (PASMCs) and were used to research the METTL3-mediated m6A in HPH in vivo and in vitro. CCK-8, EdU, PCNA, transwell and TUNEL assay were performed to evaluate the proliferation, migration and apoptosis rates of PASMCs. m6A RNA Methylation Quantification Kit and m6A-qPCR were utilized to measure the total m6A level and m6A-PTEN mRNA expression. RNA immunoprecipitation and RNA pull down were used to detect the interaction between METTL3 and PTEN mRNA. The half-life of mRNA was detected through actinomycin D assay. Results Both METTL3 mRNA and protein were found abnormally upregulated in pulmonary arteries of HPH rats and hypoxia induced PASMCs. Furthermore, downregulation of METTL3 attenuated PASMCs proliferation and migration exposed to hypoxia. In addition, m6A binding protein YTHDF2 was found significantly increased in HPH group in vivo and in vitro. Mechanistically, YTHDF2 recognized METTL3 mediated m6A-PTEN mRNA and promoted the degradation of PTEN. Decreased PTEN led to over-proliferation of PASMCs through activation of PI3K/Akt signaling pathway. Conclusion METTL3/YTHDF2/PTEN axis exerts a significant role in hypoxia induced PASMCs proliferation, providing a novel therapeutic target for HPH. FUNDunding Acknowledgement Type of funding sources: Foundation. Main funding source(s): National Natural Science Foundation of China Figure 1

scholarly journals Role of S100A4 in atherosclerosis development

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
L M Cardoso Dos Santos ◽  
N Ambartsumian ◽  
M Grigorian ◽  
M L Bochaton-Piallat
Keyword(s):  
National Budget ◽  
Funding Sources ◽  
S100a4 Expression ◽  
Marker Expression ◽  
Atherosclerosis Development ◽  
Differentiation Marker ◽  
Public Grant

Abstract Background Smooth muscle cells (SMCs) accumulate into the intima during the process of atherosclerosis, where they switch from a contractile to a synthetic phenotype. We previously identified S100A4 as being a marker of the synthetic SMCs. Recently we have shown that extracellular S100A4 induces a pro-inflammatory-like SMC phenotype and is causally related to atherosclerotic plaque progression. Aim To study the role of intracellular S100A4 depletion in the SMC phenotypic transition during atherosclerosis. Methods We used a full S100A4 knockout (KO) mouse model, where we performed left common carotid ligation and collected carotid arteries after 4 weeks. Primary SMCs were cultured from wild type (WT) and KO animals. We investigated differentiation marker expression, NFκB activation with extracellular S100A4, proliferation and migratory capacities. Results are given as mean ± SD (Fig. 1A and B). Results In vivo, no difference in intimal thickening (IT) size and SMC differentiation marker expression was observed between WT and S100A4 KO mice. CD68 was absent and S100A4 was only detected in WT animals in the inner layer of the IT. In vitro, no difference in differentiation marker expression, proliferation (Fig. 1A) or NFκB activation (Fig. 1C) was observed. Interestingly, migration was decreased in the absence of S100A4 (Fig. 1B) Conclusion The in vivo abrogation of S100A4 does not interfere with IT progression, suggesting that the lack of inflammation in this model might render S100A4 expression neglectable and disguise a possible effect of S100A4 depletion in IT progression. In vitro, S100A4 plays a role in SMC migration. FUNDunding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Swiss National Science Foundation Figure 1

Anti-obesity role of Aster glehni extract: in vivo and in vitro effects

Planta Medica ◽  
2012 ◽  
Vol 78 (11) ◽  
Author(s):  
HM Lee ◽  
TG Ahn ◽  
CW Kim ◽  
HJ An
Keyword(s):  
In Vitro Effects

A Molecular Approach to Immunoscintigraphy: A Study of the T-Antigen Conformation on the Surface of Tumors

1987 ◽  
Vol 26 (01) ◽  
pp. 1-6 ◽  
Author(s):  
S. Selvaraj ◽  
M. R. Suresh ◽  
G. McLean ◽  
D. Willans ◽  
C. Turner ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Tumor Cell ◽  
T Antigen ◽  
Human Carcinomas ◽  
Animal Tumor ◽  
Synthetic Antigens

The role of glycoconjugates in tumor cell differentiation has been well documented. We have examined the expression of the two anomers of the Thomsen-Friedenreich antigen on the surface of human, canine and murine tumor cell membranes both in vitro and in vivo. This has been accomplished through the synthesis of the disaccharide terminal residues in both a and ß configuration. Both entities were used to generate murine monoclonal antibodies which recognized the carbohydrate determinants. The determination of fine specificities of these antibodies was effected by means of cellular uptake, immunohistopathology and immunoscintigraphy. Examination of pathological specimens of human and canine tumor tissue indicated that the expressed antigen was in the β configuration. More than 89% of all human carcinomas tested expressed the antigen in the above anomeric form. The combination of synthetic antigens and monoclonal antibodies raised specifically against them provide us with invaluable tools for the study of tumor marker expression in humans and their respective animal tumor models.

THYROID STIMULATORS AND THYROID STIMULATION

1971 ◽  
Vol 66 (3) ◽  
pp. 558-576 ◽  
Author(s):  
Gerald Burke
Keyword(s):  
Regulatory System ◽  
Control Site ◽  
Thyroid Cell ◽  
Primary Control ◽  
Physico Chemical ◽  
Site Of Action ◽  
Long Acting

ABSTRACT A long-acting thyroid stimulator (LATS), distinct from pituitary thyrotrophin (TSH), is found in the serum of some patients with Graves' disease. Despite the marked physico-chemical and immunologic differences between the two stimulators, both in vivo and in vitro studies indicate that LATS and TSH act on the same thyroidal site(s) and that such stimulation does not require penetration of the thyroid cell. Although resorption of colloid and secretion of thyroid hormone are early responses to both TSH and LATS, available evidence reveals no basic metabolic pathway which must be activated by these hormones in order for iodination reactions to occur. Cyclic 3′, 5′-AMP appears to mediate TSH and LATS effects on iodination reactions but the role of this compound in activating thyroidal intermediary metabolism is less clear. Based on the evidence reviewed herein, it is suggested that the primary site of action of thyroid stimulators is at the cell membrane and that beyond the(se) primary control site(s), there exists a multifaceted regulatory system for thyroid hormonogenesis and cell growth.

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