The Role of Dietary Phenolic Compounds in Epigenetic Modulation Involved in Inflammatory Processes

A better understanding of the interactions between dietary phenolic compounds and the epigenetics of inflammation may impact pathological conditions and their treatment. Phenolic compounds are well-known for their antioxidant, anti-inflammatory, anti-angiogenic, and anti-cancer properties, with potential benefits in the treatment of various human diseases. Emerging studies bring evidence that nutrition may play an essential role in immune system modulation also by altering gene expression. This review discusses epigenetic mechanisms such as DNA methylation, post-translational histone modification, and non-coding microRNA activity that regulate the gene expression of molecules involved in inflammatory processes. Special attention is paid to the molecular basis of NF-κB modulation by dietary phenolic compounds. The regulation of histone acetyltransferase and histone deacetylase activity, which all influence NF-κB signaling, seems to be a crucial mechanism of the epigenetic control of inflammation by phenolic compounds. Moreover, chronic inflammatory processes are reported to be closely connected to the major stages of carcinogenesis and other non-communicable diseases. Therefore, dietary phenolic compounds-targeted epigenetics is becoming an attractive approach for disease prevention and intervention.

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The Role of miRNA-7 in the Biology of Cancer and Modulation of Drug Resistance

Pharmaceuticals ◽

10.3390/ph14020149 ◽

2021 ◽

Vol 14 (2) ◽

pp. 149

Author(s):

Ewa Gajda ◽

Małgorzata Grzanka ◽

Marlena Godlewska ◽

Damian Gawel

Keyword(s):

Gene Expression ◽

Drug Resistance ◽

Multidrug Resistance ◽

Cancer Progression ◽

Cancer Therapies ◽

Pathological Conditions ◽

Non Coding Rna ◽

Anti Cancer ◽

Cellular Pathways

MicroRNAs (miRNAs, miRs) are small non-coding RNA (ncRNA) molecules capable of regulating post-transcriptional gene expression. Imbalances in the miRNA network have been associated with the development of many pathological conditions and diseases, including cancer. Recently, miRNAs have also been linked to the phenomenon of multidrug resistance (MDR). MiR-7 is one of the extensively studied miRNAs and its role in cancer progression and MDR modulation has been highlighted. MiR-7 is engaged in multiple cellular pathways and acts as a tumor suppressor in the majority of human neoplasia. Its depletion limits the effectiveness of anti-cancer therapies, while its restoration sensitizes cells to the administered drugs. Therefore, miR-7 might be considered as a potential adjuvant agent, which can increase the efficiency of standard chemotherapeutics.

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Tackling Chronic Pain and Inflammation through the Purinergic System

Current Medicinal Chemistry ◽

10.2174/0929867324666170710110630 ◽

2018 ◽

Vol 25 (32) ◽

pp. 3830-3865 ◽

Cited By ~ 8

Author(s):

Giulia Magni ◽

Daniele Riccio ◽

Stefania Ceruti

Keyword(s):

Membrane Transporters ◽

Receptor Subtypes ◽

Physiological Conditions ◽

Purinergic System ◽

Inflammatory Conditions ◽

Pathological Conditions ◽

Inflammatory Processes ◽

Clear Identification ◽

The Many

The purinergic system is composed of purine and pyrimidine transmitters, the enzymes that modulate the interconversion of nucleotides and nucleosides, the membrane transporters that control their extracellular concentrations, and the many receptor subtypes that are responsible for their cellular responses. The components of this system are ubiquitously localized in all tissues and organs, and their involvement in several physiological conditions has been clearly demonstrated. Moreover, extracellular purine and pyrimidine concentrations rise several folds under pathological conditions like tissue damage, ischemia, and inflammation, which suggest that this signaling system might contribute both to disease outcome and, possibly, to its tentative resolution. The complexity of this system has greatly impaired the clear identification of the mediators and receptors that are actually involved in a given pathology, also due to the often opposite roles played by the various receptor subtypes. Nevertheless, this knowledge is fundamental for the possible exploitation of these molecular entities as targets for the development of new pharmacological approaches. In this review, we aim at highlighting what is currently known on the role of the purinergic system in various pain conditions and during inflammatory processes. Although some confusion may arise from conflicting results, literature data clearly show that targeting specific purinergic receptors may represent an innovative approach to various pain and inflammatory conditions, and that new purine-based drugs are now very close to reach the market with these indications.

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Hox Genes in Reptile Development, Epigenetic Regulation, and Teratogenesis

Cytogenetic and Genome Research ◽

10.1159/000495712 ◽

2018 ◽

Vol 157 (1-2) ◽

pp. 34-45 ◽

Cited By ~ 2

Author(s):

Rodolfo Martín-del-Campo ◽

Itzel Sifuentes-Romero ◽

Alejandra García-Gasca

Keyword(s):

Gene Expression ◽

Cell Fate ◽

Epigenetic Regulation ◽

Hox Genes ◽

Present Information ◽

Modulation Of Gene Expression ◽

Body Shapes ◽

Epigenetic Modulation ◽

Genetic Pool

Reptiles are ancestral organisms presenting a variety of shapes, from the elongated vertebral column of the snake to the turtle dorsalized ribs or retractile neck. Body plans are specified by a conserved group of homeobox-containing genes (Hox genes), which encode transcription factors important in cell fate and vertebral architecture along the anteroposterior axis during embryonic development; thus, dysregulation of these genes may cause congenital malformations, from mild-sublethal to embryonic-lethal. The genetic pool, maternal transfer, and environmental conditions during egg incubation affect development; environmental factors such as temperature, moisture, oxygen, and pollution may alter gene expression by epigenetic mechanisms. Thus, in this review, we present information regarding Hox genes and development in reptiles, including sex determination and teratogenesis. We also present some evidence of epigenetic regulation of Hox genes and the role of the environment in epigenetic modulation of gene expression. So far, the evidence suggests that the molecular instructions encoded by Hox genes to build a snake, a lizard, or a turtle represent the interplay between genome and epigenome after years of evolution, with occasional environmentally induced molecular mistakes leading to abnormal body shapes.

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The Challenging Riddle about the Janus-Type Role of Hsp60 and Related Extracellular Vesicles and miRNAs in Carcinogenesis and the Promises of Its Solution

Applied Sciences ◽

10.3390/app11031175 ◽

2021 ◽

Vol 11 (3) ◽

pp. 1175

Author(s):

Sabrina David ◽

Alessandra Maria Vitale ◽

Alberto Fucarino ◽

Federica Scalia ◽

Giuseppe Vergilio ◽

...

Keyword(s):

Cell Membrane ◽

Extracellular Vesicles ◽

Cancer Development ◽

Cancer Therapies ◽

Ongoing Research ◽

Pathological Conditions ◽

Anti Cancer ◽

Evolutionarily Conserved ◽

The Impact

Hsp60 is one of the most ancient and evolutionarily conserved members of the chaperoning system. It typically resides within mitochondria, in which it contributes to maintaining the organelle’s proteome integrity and homeostasis. In the last few years, it has been shown that Hsp60 also occurs in other locations, intracellularly and extracellularly, including cytosol, plasma-cell membrane, and extracellular vesicles (EVs). Consequently, non-canonical functions and interacting partners of Hsp60 have been identified and it has been realized that it is a hub molecule in diverse networks and pathways and that it is implicated, directly or indirectly, in the development of various pathological conditions, the Hsp60 chaperonopathies. In this review, we will focus on the multi-faceted role of this chaperonin in human cancers, showing the contribution of intra- and extracellular Hsp60 in cancer development and progression, as well as the impact of miRNA-mediated regulation of Hsp60 in carcinogenesis. There are still various aspects of this intricate biological scenario that are poorly understood but ongoing research is steadily providing new insights and we will direct attention to them. For instance, we will highlight the possible applications of the Hsp60 involvement in carcinogenesis not only in diagnosis, but also in the development of specific anti-cancer therapies centered on the use of the chaperonin as therapeutic target or agent and depending on its role, pro- or anti-tumor.

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DNA Methylation Signatures of Bone Metabolism in Osteoporosis and Osteoarthritis Aging-Related Diseases: An Updated Review

International Journal of Molecular Sciences ◽

10.3390/ijms22084244 ◽

2021 ◽

Vol 22 (8) ◽

pp. 4244

Author(s):

Virginia Veronica Visconti ◽

Ida Cariati ◽

Simona Fittipaldi ◽

Riccardo Iundusi ◽

Elena Gasbarra ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Late Onset ◽

Bone Diseases ◽

Epigenetic Mechanisms ◽

Crucial Point ◽

Pathological Conditions ◽

New Findings ◽

Late Onset Disorders

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.

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The role of eicosanoids in renal diseases – potential therapeutic possibilities

Acta Biochimica Polonica ◽

10.18388/abp.2018_2609 ◽

2018 ◽

Cited By ~ 1

Author(s):

Maciej Fijałkowski ◽

Joanna Stępniewska ◽

Maciej Domański ◽

Kazimierz Ciechanowski ◽

Edyta Golembiewska

Keyword(s):

Acute Kidney Injury ◽

Kidney Injury ◽

Biologically Active ◽

Renal Diseases ◽

Membrane Phospholipids ◽

Future Studies ◽

Renal Replacement Therapies ◽

Pathological Conditions ◽

Inflammatory Processes

Eicosanoids are biologically active molecules that are created in the process of oxidation of arachidonic acid (AA) which is a constituent of the cell membrane phospholipids. Throughout the years it was evidenced by experiments that the lipid and lipid-derived metabolites play an important role in physiological and pathological processes in the kidneys. They are being considered as biomarkers in detecting acute kidney injury, nephrotoxicity, glomerulonephritis and early stages of diabetic nephropathy because of their participation in inflammatory processes and in oxidative stress. They might be also considered as potential novel targets of therapy. However, the role of eicosanoids is still not fully clear and needs to be explored in future studies. In this brief review, studies on the role of eicosanoids in physiological and pathological conditions, e.g. acute kidney injury (AKI) and chronic kidney disease (CKD), and in different renal replacement therapies, including kidney transplantation, are being discussed.

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Gene Expression Data Mining Reveals the Involvement of GPR55 and Its Endogenous Ligands in Immune Response, Cancer, and Differentiation

International Journal of Molecular Sciences ◽

10.3390/ijms222413328 ◽

2021 ◽

Vol 22 (24) ◽

pp. 13328

Author(s):

Artur Wnorowski ◽

Jakub Wójcik ◽

Maciej Maj

Keyword(s):

Gene Expression ◽

Large Scale ◽

Immune Cell ◽

Cell Lineage ◽

Expression Data ◽

Experimental Conditions ◽

Pathological Conditions ◽

Pituitary Adenylate Cyclase ◽

G Protein Coupled

G protein-coupled receptor 55 (GPR55) is a recently deorphanized lipid- and peptide-sensing receptor. Its lipidic endogenous agonists belong to lysoglycerophospholipids, with lysophosphatidylinositol (LPI) being the most studied. Peptide agonists derive from fragmentation of pituitary adenylate cyclase-activating polypeptide (PACAP). Although GPR55 and its ligands were implicated in several physiological and pathological conditions, their biological function remains unclear. Thus, the aim of the study was to conduct a large-scale re-analysis of publicly available gene expression datasets to identify physiological and pathological conditions affecting the expression of GPR55 and the production of its ligands. The study revealed that regulation of GPR55 occurs predominantly in the context of immune activation pointing towards the role of the receptor in response to pathogens and in immune cell lineage determination. Additionally, it was revealed that there is almost no overlap between the experimental conditions affecting the expression of GPR55 and those modulating agonist production. The capacity to synthesize LPI was enhanced in various types of tumors, indicating that cancer cells can hijack the motility-related activity of GPR55 to increase aggressiveness. Conditions favoring accumulation of PACAP-derived peptides were different than those for LPI and were mainly related to differentiation. This indicates a different function of the two agonist classes and possibly the existence of a signaling bias.

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Adrenomedullin RegulatesIL-1βGene Expression in F4/80+ Macrophages during Synovial Inflammation

Journal of Immunology Research ◽

10.1155/2017/9832430 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 5

Author(s):

Shotaro Takano ◽

Kentaro Uchida ◽

Masayuki Miyagi ◽

Gen Inoue ◽

Jun Aikawa ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Synovial Fibroblasts ◽

Synovial Inflammation ◽

Dislocation Model ◽

Surgical Dislocation ◽

Inflammatory Processes ◽

Receptor Activity Modifying Proteins

Adrenomedullin (AM) plays an important role in the regulation of inflammatory processes; however, the role and expression of AM in synovial inflammation have not been determined. To investigate the expression and role of AM in inflamed synovial tissue (ST), the gene expression profiles of AM in the ST, including synovial macrophages and fibroblasts, of a murine patellar surgical dislocation model were characterized. In addition, the effects of interleukin-(IL-) 1βand AM in cultured synovial cells were also examined. CD11c+macrophages were found to be elevated in ST of the surgically dislocated patella. Higher gene expression ofCD11c,IL-1β,AM, receptor activity-modifying proteins 2(RAMP2), and 3(RAMP3)was also observed in ST obtained from the dislocated side.AMexpression was also significantly increased in synovial fibroblasts and macrophages in response to IL-1βtreatment. Synovial macrophages also highly expressedRAMP3compared to fibroblasts and this expression was further stimulated by exogenously added IL-1β. Further, the treatment of the F4/80-positive cell fraction obtained from ST with AM inhibitedIL-1βexpression. Taken together, these findings demonstrated that AM was produced by synovial fibroblasts and macrophages in inflamed ST and that increased levels of AM may exert anti-inflammatory effects on synovial macrophages.

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Renal gene expression profiling using kinin B1 and B2 receptor knockout mice reveals comparable modulation of functionally related genes

Biological Chemistry ◽

10.1515/bc.2006.004 ◽

2006 ◽

Vol 387 (1) ◽

pp. 15-22 ◽

Cited By ~ 10

Author(s):

Dimcho Bachvarov ◽

Magdalena Bachvarova ◽

Rainelli Koumangaye ◽

Julie Klein ◽

João Bosco Pesquero ◽

...

Keyword(s):

Gene Expression ◽

Biological Effects ◽

Renal Physiology ◽

Null Mouse ◽

Biological Processes ◽

Wild Type ◽

Microarray Experiments ◽

B1 Receptor ◽

Pathological Conditions

Abstract The kinin B2 receptor, which is constitutively expressed in a large number of tissues, mediates most of the known effects of bradykinin (BK). Normally undetectable in healthy tissues, the B1 receptor is strongly over-expressed under pathological conditions. BK is an important mediator in renal homeostasis and is mainly known for its natriuretic and vasodilatory effects. Recent data evidenced a role for BK in many other biological processes, such as apoptosis, development, extracellular matrix regulation and angiogenesis. In a first step to better understand how BK and its receptors could be involved in such a large variety of biological effects, we used microarray analysis to identify, under physiological conditions, the global renal gene expression profile in mice lacking either the kinin B1 or B2 receptor. Microarray experiments were performed using Agilent Mouse Oligonucleotide Microarrays (21 000 genes/microarray). Interestingly, there was a considerable number of mostly downregulated genes in both BK null mouse models compared with wild-type mice. Furthermore, a number of genes that are known to be implicated in renal physiology and/or pathology were differentially expressed in the BK null mice, which is indicative of the important role of both BK receptors in renal function.

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Non-invasively triggered spreading depolarizations induce a rapid pro-inflammatory response in cerebral cortex

Journal of Cerebral Blood Flow & Metabolism ◽

10.1177/0271678x19859381 ◽

2019 ◽

Vol 40 (5) ◽

pp. 1117-1131 ◽

Cited By ~ 5

Author(s):

Tsubasa Takizawa ◽

Tao Qin ◽

Andreia Lopes de Morais ◽

Kazutaka Sugimoto ◽

Joon Yong Chung ◽

...

Keyword(s):

Gene Expression ◽

Intercellular Adhesion Molecule ◽

Intercellular Adhesion Molecule 1 ◽

Inflammatory Gene Expression ◽

Inflammatory Gene ◽

Tnf Α ◽

Inflammatory Processes ◽

Factor Α ◽

The Relationship

Cortical spreading depolarization (CSD) induces pro-inflammatory gene expression in brain tissue. However, previous studies assessing the relationship between CSD and inflammation have used invasive methods that directly trigger inflammation. To eliminate the injury confounder, we induced CSDs non-invasively through intact skull using optogenetics in Thy1-channelrhodopsin-2 transgenic mice. We corroborated our findings by minimally invasive KCl-induced CSDs through thinned skull. Six CSDs induced over 1 h dramatically increased cortical interleukin-1β (IL-1β), chemokine (C-C motif) ligand 2 (CCL2), and tumor necrosis factor-α (TNF-α) mRNA expression peaking around 1, 2 and 4 h, respectively. Interleukin-6 (IL-6) and intercellular adhesion molecule-1 (ICAM-1) were only modestly elevated. A single CSD also increased IL-1β, CCL2, and TNF-α, and revealed an ultra-early IL-1β response within 10 min. The response was blunted in IL-1 receptor-1 knockout mice, implicating IL-1β as an upstream mediator, and suppressed by dexamethasone, but not ibuprofen. CSD did not alter systemic inflammatory indices. In summary, this is the first report of pro-inflammatory gene expression after non-invasively induced CSDs. Altogether, our data provide novel insights into the role of CSD-induced neuroinflammation in migraine headache pathogenesis and have implications for the inflammatory processes in acute brain injury where numerous CSDs occur for days.

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