scholarly journals Microbial Metabolites of Flavan-3-Ols and Their Biological Activity

Nutrients ◽  
2019 ◽  
Vol 11 (10) ◽  
pp. 2260 ◽  
Author(s):  
Campos ◽  
Stehle ◽  
Simon
Keyword(s):  
Biological Activity ◽  
Scientific Literature ◽  
Current Status ◽  
Microbial Metabolites ◽  
Potential Health ◽  
In Vivo Animal Models ◽  
Polyphenol Intake

Flavan-3-ols are the main contributors to polyphenol intake. Many varying beneficial health effects in humans have been attributed to them, including the prevention of cardiovascular disease and cancer. Nevertheless, the mechanisms by which these flavonoids could exert beneficial functions are not entirely known. Several in vitro studies and in vivo animal models have tried to elucidate the role of the specific colonic metabolites on the health properties that are attributed to the parent compounds since a larger number of ingested flavan-3-ols reach the colon and undergo there microbial metabolism. Many new studies about this topic have been performed over the last few years and, to the best of our knowledge, no scientific literature review regarding the bioactivity of all identified microbial metabolites of flavan-3-ols has been recently published. Therefore, the aim of this review is to present the current status of knowledge on the potential health benefits of flavan-3-ol microbial metabolites in humans while using the latest evidence on their biological activity.

scholarly journals The Role of Pre-Clinical 3-Dimensional Models of Osteosarcoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5499
Author(s):  
Hannah L. Smith ◽  
Stephen A. Beers ◽  
Juliet C. Gray ◽  
Janos M. Kanczler
Keyword(s):  
Three Dimensional ◽  
Chorioallantoic Membrane ◽  
3D Models ◽  
In Ovo ◽  
Future Directions ◽  
3 Dimensional ◽  
In Vivo Animal Models

Treatment for osteosarcoma (OS) has been largely unchanged for several decades, with typical therapies being a mixture of chemotherapy and surgery. Although therapeutic targets and products against cancer are being continually developed, only a limited number have proved therapeutically active in OS. Thus, the understanding of the OS microenvironment and its interactions are becoming more important in developing new therapies. Three-dimensional (3D) models are important tools in increasing our understanding of complex mechanisms and interactions, such as in OS. In this review, in vivo animal models, in vitro 3D models and in ovo chorioallantoic membrane (CAM) models, are evaluated and discussed as to their contribution in understanding the progressive nature of OS, and cancer research. We aim to provide insight and prospective future directions into the potential translation of 3D models in OS.

scholarly journals The gut microbial metabolite trimethylamine N-oxide aggravates GVHD by inducing M1 macrophage polarization in mice

Blood ◽  
2020 ◽  
Vol 136 (4) ◽  
pp. 501-515 ◽  
Author(s):  
Kunpeng Wu ◽  
Yan Yuan ◽  
Huihui Yu ◽  
Xin Dai ◽  
Shu Wang ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Macrophage Polarization ◽  
Short Chain Fatty Acids ◽  
Inflammasome Activation ◽  
Microbial Metabolites ◽  
M1 Macrophage ◽  
The Impact

Abstract The diversity of the human microbiome heralds the difference of the impact that gut microbial metabolites exert on allogenic graft-versus-host (GVH) disease (GVHD), even though short-chain fatty acids and indole were demonstrated to reduce its severity. In this study, we dissected the role of choline-metabolized trimethylamine N-oxide (TMAO) in the GVHD process. Either TMAO or a high-choline diet enhanced the allogenic GVH reaction, whereas the analog of choline, 3,3-dimethyl-1-butanol reversed TMAO-induced GVHD severity. Interestingly, TMAO-induced alloreactive T-cell proliferation and differentiation into T-helper (Th) subtypes was seen in GVHD mice but not in in vitro cultures. We thus investigated the role of macrophage polarization, which was absent from the in vitro culture system. F4/80+CD11b+CD16/32+ M1 macrophage and signature genes, IL-1β, IL-6, TNF-α, CXCL9, and CXCL10, were increased in TMAO-induced GVHD tissues and in TMAO-cultured bone marrow–derived macrophages (BMDMs). Inhibition of the NLRP3 inflammasome reversed TMAO-stimulated M1 features, indicating that NLRP3 is the key proteolytic activator involved in the macrophage’s response to TMAO stimulation. Consistently, mitochondrial reactive oxygen species and enhanced NF-κB nuclear relocalization were investigated in TMAO-stimulated BMDMs. In vivo depletion of NLRP3 in GVHD recipients not only blocked M1 polarization but also reversed GVHD severity in the presence of TMAO treatment. In conclusion, our data revealed that TMAO-induced GVHD progression resulted from Th1 and Th17 differentiation, which is mediated by the polarized M1 macrophage requiring NLRP3 inflammasome activation. It provides the link among the host choline diet, microbial metabolites, and GVH reaction, shedding light on alleviating GVHD by controlling choline intake.

scholarly journals Role of Key Micronutrients from Nutrigenetic and Nutrigenomic Perspectives in Cancer Prevention

Medicina ◽  
2019 ◽  
Vol 55 (6) ◽  
pp. 283 ◽  
Author(s):  
Alexandra Irimie ◽  
Cornelia Braicu ◽  
Sergiu Pasca ◽  
Lorand Magdo ◽  
Diana Gulei ◽  
...  
Keyword(s):  
Scientific Literature ◽  
Inhibitory Effect ◽  
General View ◽  
Molecular Alteration ◽  
Gene Level ◽  
Effective Doses ◽  
Cancer Inhibition

Regarding cancer as a genetic multi-factorial disease, a number of aspects need to be investigated and analyzed in terms of cancer’s predisposition, development and prognosis. One of these multi-dimensional factors, which has gained increased attention in the oncological field due to its unelucidated role in risk assessment for cancer, is diet. Moreover, as studies advance, a clearer connection between diet and the molecular alteration of patients is becoming identifiable and quantifiable, thereby replacing the old general view associating specific phenotypical changes with the differential intake of nutrients. Respectively, there are two major fields concentrated on the interrelation between genome and diet: nutrigenetics and nutrigenomics. Nutrigenetics studies the effects of nutrition at the gene level, whereas nutrigenomics studies the effect of nutrients on genome and transcriptome patterns. By precisely evaluating the interaction between the genomic profile of patients and their nutrient intake, it is possible to envision a concept of personalized medicine encompassing nutrition and health care. The list of nutrients that could have an inhibitory effect on cancer development is quite extensive, with evidence in the scientific literature. The administration of these nutrients showed significant results in vitro and in vivo regarding cancer inhibition, although more studies regarding administration in effective doses in actual patients need to be done.

scholarly journals THE BIOLOGICAL ACTIVITY OF EUROPEAN MISTLETOE (Viscum album) EXTRACTS AND THEIR PHARMACEUTICAL IMPACT

1970 ◽  
Vol 63 ◽  
Author(s):  
Simona Ioana Vicaş ◽  
Carmen Socaciu
Keyword(s):  
Biological Activity ◽  
Mechanism Of Action ◽  
Viscum Album ◽  
Cancer Therapies ◽  
Main Principle ◽  
Mistletoe Extracts ◽  
Comparison Of The Results

Extracts of Viscum album (mistletoe) are widely used as complementary cancer therapies in Europe. The mistletoe lectins and viscotoxins have been identified as the main principle of mistletoe extracts that participating in biological activity of V. album. These compounds were isolated and studied in vitro and in vivo for their biological activity and mechanism of action. A comparison of the results to those using whole extracts indicated that lectins and viscotoxins are not the only bioactive compounds present in the mistletoe. In this paper, we review the recent studies regarding with cytotoxic activity on tumor cells of mistletoe extracts, as well as, the role of this semiparasitic plant in diabetics and hypertension illness.

scholarly journals Identification of peptides interfering the lrrk2/pp1 interaction

2019 ◽  
Author(s):  
Chang Zhi Dong ◽  
Heriberto Bruzzoni-Giovanell ◽  
Yanhua Yu ◽  
Karim Dorgham ◽  
Christophe Parizot ◽  
...  
Keyword(s):  
Biological Activity ◽  
Elisa Test ◽  
Short Peptides ◽  
Cell Penetrating Peptide ◽  
Original Sequence ◽  
Pathological Conditions ◽  
Cell Penetrating

ABSTRACTSerine/threonine phosphatases are responsible for counteracting the effect of the protein kinases implicated in the development of several pathologies. Here we identified by PEP-scan approach the sequence of a fragment of LRRK2, a Parkinson’s disease associated protein, interacting with the phosphatase PP1. The fragment, that is located in a LRRK2 domain of undefined function, was associated in N-terminal to an optimized cell penetrating peptide in order to study their in vitro and in vivo biological activity. From this original sequence, we developed and studied five interfering peptides (IPs) and identified two peptides able to disrupt the LRRK2/PP1 interaction by in vitro competition in anti-LRRK2 immunoprecipitates. Using FITC-labelled peptides, we confirmed the internalization of the peptides in cell lines as well as in and primary human normal and pathological cells. Finally, we have confirmed by ELISA test the association of Mut3DPT-LRRK2-Long and Mut3DPT-LRRK2-Short peptides to purified PP1 protein in a selective manner. The shortest peptides, MuteDPT-LRRK2-5 to 8 with either N or C-terminal deletions are not able neither disrupt the association LRRK2/PP1 nor to associate to purified PP1 protein. The peptides Mut3DPT-LRRK2-Long and Mut3DPT-LRRK2-Short may be new tools to study the role of LRRK2/PP1 interaction in normal and pathological conditions.

Epigenetics in Neurodegenerative Diseases: The Role of Histone Deacetylases

2019 ◽  
Vol 18 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Sorabh Sharma ◽  
K.C. Sarathlal ◽  
Rajeev Taliyan
Keyword(s):  
Neurodegenerative Diseases ◽  
Histone Acetylation ◽  
Histone Deacetylases ◽  
Hdac Inhibitors ◽  
Beneficial Effects ◽  
In Vivo Animal Models ◽  
Preclinical And Clinical Studies

Background & Objective: Imbalance in histone acetylation levels and consequently the dysfunction in transcription are associated with a wide variety of neurodegenerative diseases. Histone proteins acetylation and deacetylation is carried out by two opposite acting enzymes, histone acetyltransferases and histone deacetylases (HDACs), respectively. In-vitro and in-vivo animal models of neurodegenerative diseases and post mortem brains of patients have been reported overexpressed level of HDACs. In recent past numerous studies have indicated that HDAC inhibitors (HDACIs) might be a promising class of therapeutic agents for treating these devastating diseases. HDACs being a part of repressive complexes, the outcome of their inhibition has been attributed to enhanced gene expression due to heightened histone acetylation. Beneficial effects of HDACIs has been explored both in preclinical and clinical studies of these diseases. Thus, their screening as future therapeutics for neurodegenerative diseases has been widely explored. Conclusion: In this review, we focus on the putative role of HDACs in neurodegeneration and further discuss their potential as a new therapeutic avenue for treating neurodegenerative diseases.

Decorin in atherosclerosis

2011 ◽  
Vol 5 (6) ◽  
pp. 305-314 ◽  
Author(s):  
Sandeep Singla ◽  
Changping Hu ◽  
Adam Mizeracki ◽  
Jawahar L. Mehta
Keyword(s):  
Western World ◽  
Atherosclerotic Cardiovascular Disease ◽  
Cellular Interactions ◽  
Coronary Syndrome ◽  
Clinical Syndromes ◽  
In Vivo Animal Models ◽  
Cellular Components

Atherosclerotic cardiovascular disease is a major cause of morbidity and mortality in the Western world. Despite tremendous strides in understandings its pathogenesis, it still remains a challenge because of gaps in our understanding of its initiation, progression and complications leading to the clinical syndromes of angina, acute coronary syndrome, cerebrovascular disease and peripheral vascular disease. Recent studies have provided impetus on the shift from models of atherosclerosis based on cellular interactions to models where the important role of extracellular matrix is recognized. Proteoglycans, especially those belonging to the small leucine-rich proteoglycan family of which decorin is a representative example, have come under close scrutiny for their role in atherogenesis. There is evidence from in vitro and in vivo animal models as well as humans to suggest an important role of decorin in attenuating progression of atherosclerosis. Decorin distribution in different blood vessels has been shown to inversely correlate with the tendency to develop atherosclerosis. Decorin seems to interact closely with different cellular components of the plaque milieu, thereby suggesting its role in influencing atherogenesis at different steps. Here we review the current understanding of the role of decorin in the pathogenesis of atherosclerosis.

scholarly journals Phyto-oestrogens through the life cycle

2000 ◽  
Vol 59 (3) ◽  
pp. 489-496 ◽  
Author(s):  
Aedin Cassidy ◽  
Marian Faughnan
Keyword(s):  
Life Cycle ◽  
Human Health ◽  
Intestinal Microflora ◽  
Human Subjects ◽  
Epidemiological Data ◽  
Potential Health ◽  
Wide Range

The growing interest in the role of phyto-oestrogens in human health has prompted scientists to evaluate the risk : benefit which would result from consuming high levels of these compounds at different stages of the life cycle. These compounds have been shown to exert a wide range of hormonal and non-hormonal activities in animals and in vitro, and these activities suggest plausible mechanisms for potential health effects in human subjects consuming phyto-oestrogen-rich diets. In addition, experimental and epidemiological data are available supporting the concept that phyto-oestrogen-rich diets exert physiological effects in vivo; however, their relative importance to human health remains to be elucidated. Our understanding of factors involved in their absorption and metabolism, including the role of intestinal microflora, is limited, and these factors together with dose-related effects may well be important in determining clinical efficacy.

scholarly journals Periodontal and Dental Pulp Cell-Derived Small Extracellular Vesicles: A Review of the Current Status

Nanomaterials ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 1858
Author(s):  
Shu Hua ◽  
Peter Mark Bartold ◽  
Karan Gulati ◽  
Corey Stephen Moran ◽  
Sašo Ivanovski ◽  
...  
Keyword(s):  
Stem Cells ◽  
Extracellular Vesicles ◽  
Dental Pulp ◽  
Therapeutic Potential ◽  
Current Status ◽  
Pulp Cell ◽  
Dental Pulp Cell

Extracellular vesicles (EVs) are membrane-bound lipid particles that are secreted by all cell types and function as cell-to-cell communicators through their cargos of protein, nucleic acid, lipids, and metabolites, which are derived from their parent cells. There is limited information on the isolation and the emerging therapeutic role of periodontal and dental pulp cell-derived small EVs (sEVs, <200 nm, or exosome). In this review, we discuss the biogenesis of three EV subtypes (sEVs, microvesicles and apoptotic bodies) and the emerging role of sEVs from periodontal ligament (stem) cells, gingival fibroblasts (or gingival mesenchymal stem cells) and dental pulp cells, and their therapeutic potential in vitro and in vivo. A review of the relevant methodology found that precipitation-based kits and ultracentrifugation are the two most common methods to isolate periodontal (dental pulp) cell sEVs. Periodontal (and pulp) cell sEVs range in size, from 40 nm to 2 μm, due to a lack of standardized isolation protocols. Nevertheless, our review found that these EVs possess anti-inflammatory, osteo/odontogenic, angiogenic and immunomodulatory functions in vitro and in vivo, via reported EV cargos of EV–miRNAs, EV–circRNAs, EV–mRNAs and EV–lncRNAs. This review highlights the considerable therapeutic potential of periodontal and dental pulp cell-derived sEVs in various regenerative applications.

scholarly journals Edible insects as a source of food bioactives and their potential health effects

2021 ◽  
Vol 14 ◽  
Author(s):  
Klaus Lange ◽  
Yukiko Nakamura
Keyword(s):  
Animal Studies ◽  
Oral Intake ◽  
Edible Insects ◽  
Immune Functions ◽  
Potential Health ◽  
Food Ingredients ◽  
Beneficial Effects

Entomophagy (consumption of insects) is an issue of global nutritional and environmental interest. The nutritional value of insects appears to be high, since they are rich in protein and fat and provide a range of vitamins and minerals. Edible insects contain similar amounts of protein to conventional meat and higher levels of polyunsaturated fatty acids. Due to their high content of protein, micronutrients and fiber, insects could become a valuable alternative to food derived from other animals. The findings of various in vitro and in vivo animal studies suggest beneficial effects of entomophagy with respect to cardiovascular, gastrointestinal and non-communicable diseases as well as immune functions and carcinogenesis. Edible insects appear to be a promising and insufficiently explored source of macronutrients, micronutrients and food bioactives. In the course of time, some edible insects may meet the criteria of functional food ingredients. However, there is a significant lack of research investigating health outcomes in humans. The available evidence in humans, derived from randomized controlled trials, suggests a role of edible insects in the promotion of mineral status and the modulation of gut microbiota, with some prebiotic effects. High-quality clinical studies assessing efficacy, oral intake safety and allergy risk are needed.

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