scholarly journals Diet-Derived Exogenous miRNAs As Functional Food Components: Facts and New Perspectives

2021 ◽  
Author(s):  
Pankaj Khurana ◽  
Apoorv Gupta ◽  
Rajeev Varshney
Keyword(s):  
Gene Expression ◽  
Cellular Uptake ◽  
Peripheral Blood ◽  
Functional Food ◽  
Mammalian Cells ◽  
Structural Characteristics ◽  
Unique Sequence ◽  
Food Components ◽  
Extracellular Transport ◽  
Mammalian System

Exogenous miRNAs derived from dietary substances have been shown to be orally transferred to the mammalian system and proven to remain active to regulate host-gene expression. This way they have become an active area of research as functional food components and aspects for dietary supplementation. They are being studied as a new class of metabolically targeted therapeutics that work through diet manipulation and may hold promise for a therapeutic approach in reducing the risk of life-threatening diseases. However, a substantial amount of evidence also defies this dietary miRNA concept in terms of their absorption, bioavailability, cellular uptake and its physiological effects in the mammalian system. But recent advances in the identification of some unique sequence and structural characteristics of dietary miRNAs and a deeper understanding of their stability in host peripheral blood for its cellular uptake have strengthened the whole concept. The review comprehensively summarizes the mechanism for miRNA extracellular transport, absorption through the gastrointestinal tract (GI), stability in peripheral blood, and cellular uptake in mammalian cells. It recapitulates the shreds of evidence, related to the influence of dietary miRNAs on gene expression based on the source of the origin (plant vs animal), and compares their cross-kingdom behaviour in terms of their unique sequence and stem-loop structure properties that help them to get stabilized in the mammalian system. The review also summarizes the parameters required for maintaining the sustainable uptake and bioavailability of the dietary miRNAs with existing examples of successful in-vivo and in-vitro delivery of dietary miRNA for augmented therapy. Lastly, it provides an overview of the available and required databases, webserver, and tools that can be used for the successful identification of potential dietary miRNA candidates.

scholarly journals Three Structural Features of Functional Food Components and Herbal Medicine with Amyloid β42 Anti-Aggregation Properties

Molecules ◽  
2019 ◽  
Vol 24 (11) ◽  
pp. 2125 ◽  
Author(s):  
Kazuma Murakami ◽  
Kazuhiro Irie
Keyword(s):  
Amino Acid ◽  
Functional Food ◽  
Structural Characteristics ◽  
Salt Bridge ◽  
Basic Amino Acid ◽  
Structural Features ◽  
Amino Acid Residues ◽  
Treatment And Prevention ◽  
Food Components ◽  
Underlying Mechanisms

Aggregation of amyloid β42 (Aβ42) is one of the hallmarks of Alzheimer’s disease (AD). There are numerous naturally occurring products that suppress the aggregation of Aβ42, but the underlying mechanisms remain to be elucidated. Based on NMR and MS spectroscopic analysis, we propose three structural characteristics found in natural products required for the suppressive activity against Aβ42 aggregation (i.e., oligomerization by targeting specific amino acid residues on this protein). These characteristics include (1) catechol-type flavonoids that can form Michael adducts with the side chains of Lys16 and 28 in monomeric Aβ42 through flavonoid autoxidation; (2) non-catechol-type flavonoids with planarity due to α,β-unsaturated carbonyl groups that can interact with the intermolecular β-sheet region in Aβ42 aggregates, especially aromatic rings such as those of Phe19 and 20; and (3) carboxy acid derivatives with triterpenoid or anthraquinoid that can generate a salt bridge with basic amino acid residues such as Lys16 and 28 in the Aβ42 dimer or trimer. Here, we summarize the recent body of knowledge concerning amyloidogenic inhibitors, particularly in functional food components and Kampo medicine, and discuss their application in the treatment and prevention of AD.

scholarly journals Anti-Rheumatic Effect of Antisense Oligonucleotide Cytos-11 Targeting TNF-α Expression

2021 ◽  
Vol 22 (3) ◽  
pp. 1022
Author(s):  
Tatyana P. Makalish ◽  
Ilya O. Golovkin ◽  
Volodymyr V. Oberemok ◽  
Kateryna V. Laikova ◽  
Zenure Z. Temirova ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Gene Expression ◽  
Rat Model ◽  
Peripheral Blood ◽  
Antisense Oligonucleotide ◽  
Joint Inflammation ◽  
Blood Concentrations ◽  
Tnf Α ◽  
Effective Drugs ◽  
First Time

The urgency of the search for inexpensive and effective drugs with localized action for the treatment of rheumatoid arthritis continues unabated. In this study, for the first time we investigated the Cytos-11 antisense oligonucleotide suppression of TNF-α gene expression in a rat model of rheumatoid arthritis induced by complete Freund’s adjuvant. Cytos-11 has been shown to effectively reduce peripheral blood concentrations of TNF-α, reduce joint inflammation, and reduce pannus development. The results achieved following treatment with the antisense oligonucleotide Cytos-11 were similar to those of adalimumab (Humira®); they also compared favorably with those results, which provides evidence of the promise of drugs based on antisense technologies in the treatment of this disease.

389 Combining transcriptomic- and tissue-based immune biomarkers to evaluate GB1275, a CD11b modulator, as a single agent or with pembrolizumab in patients with advanced solid tumors

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A414-A414
Author(s):  
Wells Messersmith ◽  
Drew Rasco ◽  
Johann De Bono ◽  
Andrea Wang-Gillam ◽  
Wungki Park ◽  
...  
Keyword(s):  
Gene Expression ◽  
Solid Tumors ◽  
Peripheral Blood ◽  
Post Treatment ◽  
Transcriptomic Analysis ◽  
Gene Set Enrichment Analysis ◽  
Cancer Center ◽  
Advanced Solid Tumors ◽  
Core Tissue ◽  
Dose Dependent

BackgroundGB1275 is a first-in-class CD11b modulator in development as monotherapy and in combination with pembrolizumab or chemotherapy for the treatment of advanced solid tumors. Nonclinical data show that GB1275 reduced influx of tumor-associated myeloid-derived suppressor cells (MDSCs) and macrophages (TAMs), and repolarized M2 immuno-suppressive TAMs towards an M1 phenotype. We hypothesize that GB1275 administration can alleviate myeloid cell-mediated immunosuppressive effects and improve cancer treatment outcomes. A phase 1 trial evaluating GB1275 as monotherapy and in combination with pembrolizumab in specified advanced tumors in ongoing (NCT04060342).MethodsBlood gene expression variations as well as core tissue biopsies pre- and post-treatment were assessed following GB1275 monotherapy and combination with pembrolizumab. After obtaining informed consent, peripheral blood for MDSCs was collected from 21 patients pre- and two weeks post-treatment; core tissue biopsies were collected from 13 patients pre- and post-treatment. The frequency of MDSCs in whole blood was measured using the Serametrix MDSC FACS Assay. Gene expression transcriptome profiles were generated using NovaSeq platform. CD8 staining was performed at Neogenomics, and tumor infiltrating lymphocyte (TIL) quantification was performed by an independent pathologist.ResultsPreliminary statistical analysis of MDSC immunophenotyping pre- and post- treatment is consistent with the proposed mechanism of GB1275, showing modulation of peripheral blood MDSCs in some patients. Preliminary gene expression analysis in the blood showed dose-dependent clusters following treatment with GB1275 alone. Moreover, the transcriptomic analysis revealed two unique expression patterns for patients treated with GB1275 monotherapy or in combination with pembrolizumab. Gene Set Enrichment Analysis showed that the CD11b pathway is downregulated in patients treated with GB1275. Analyses of TIL count revealed an increase in lymphocyte trafficking into the tumor after treatment with GB1275 alone or in combination with pembrolizumab. CD8 expression and transcriptomic analysis are underway and will be presented.ConclusionsGB1275 alone or in combination with pembrolizumab demonstrates biological activity, which may be dose dependent. The observed increase in TILs after treatment is supportive of the mechanism of action of GB1275. Further biomarker analyses in blood and tissues are ongoing and will be correlated with clinical activity in a larger number of patients.Ethics ApprovalThis ongoing study is being conducted in accordance with the the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines. The study was approved by the Ethics Boards of University of Colorado Hospital, Washington University School of Medicine - Siteman Cancer Center, Memorial Sloan Kettering Cancer Center, The Sarah Cannon Research Institute/Tennessee Oncology, South Texas Accelerated Research Therapeutics, and The Royal Marsden NHS Foundation Trust.

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