Anthocyanins are colored water-soluble pigments belonging to the phenolic group. The pigments are in glycosylated forms. Anthocyanins responsible for the colors, red, purple, and blue, are in fruits and vegetables. Berries, currants, grapes, and some tropical fruits have high anthocyanins content. Red to purplish blue-colored leafy vegetables, grains, roots, and tubers are the edible vegetables that contain a high level of anthocyanins. Among the anthocyanin pigments, cyanidin-3-glucoside is the major anthocyanin found in most of the plants. The colored anthocyanin pigments have been traditionally used as a natural food colorant. The color and stability of these pigments are influenced by pH, light, temperature, and structure. In acidic condition, anthocyanins appear as red but turn blue when the pH increases. Chromatography has been largely applied in extraction, separation, and quantification of anthocyanins. Besides the use of anthocyanidins and anthocyanins as natural dyes, these colored pigments are potential pharmaceutical ingredients that give various beneficial health effects. Scientific studies, such as cell culture studies, animal models, and human clinical trials, show that anthocyanidins and anthocyanins possess antioxidative and antimicrobial activities, improve visual and neurological health, and protect against various non-communicable diseases. These studies confer the health effects of anthocyanidins and anthocyanins, which are due to their potent antioxidant properties. Different mechanisms and pathways are involved in the protective effects, including free-radical scavenging pathway, cyclooxygenase pathway, mitogen-activated protein kinase pathway, and inflammatory cytokines signaling. Therefore, this review focuses on the role of anthocyanidins and anthocyanins as natural food colorants and their nutraceutical properties for health. Abbreviations: CVD: Cardiovascular disease VEGF: Vascular endothelial growth factor.

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Anthocyanidins and anthocyanins: colored pigments as food, pharmaceutical ingredients, and the potential health benefits.

MicroRNAs (miRNAs) are endogenous ∼23 nt RNAs that play important gene-regulatory roles in animals and plants by pairing to the mRNAs of protein-coding genes to direct their posttranscriptional repression. This review outlines the current understanding of miRNA target recognition in animals and discusses the widespread impact of miRNAs on both the expression and evolution of protein-coding genes.

MicroRNAs: Target Recognition and Regulatory Functions

Genetics and epigenetics of NAFLD and NASH: Clinical impact

Allergic asthma is caused by the aberrant expansion in the lung of T helper cells that produce type 2 (TH2) cytokines and is characterized by infiltration of eosinophils and bronchial hyperreactivity. This disease is often triggered by mast cells activated by immunoglobulin E (IgE)-mediated allergic challenge. Activated mast cells release various chemical mediators, including prostaglandin D2 (PGD2), whose role in allergic asthma has now been investigated by the generation of mice deficient in the PGD receptor (DP). Sensitization and aerosol challenge of the homozygous mutant (DP-/-) mice with ovalbumin (OVA) induced increases in the serum concentration of IgE similar to those in wild-type mice subjected to this model of asthma. However, the concentrations of TH2 cytokines and the extent of lymphocyte accumulation in the lung of OVA-challenged DP-/- mice were greatly reduced compared with those in wild-type animals. Moreover, DP-/- mice showed only marginal infiltration of eosinophils and failed to develop airway hyperreactivity. Thus, PGD2 functions as a mast cell-derived mediator to trigger asthmatic responses.

Prostaglandin D_2 as a Mediator of Allergic Asthma.

Cancer remains to be one of the leading causes of death in the United States and around the world. The advent of modern drug-targeted therapies has undeniably improved cancer patients' cares. However, advanced metastasized cancer remains untreatable. Hence, continued searching for a safer and more effective chemoprevention and treatment is clearly needed for the improvement of the efficiency and to lower the treatment cost for cancer care. Cancer chemoprevention with natural phytochemical compounds is an emerging strategy to prevent, impede, delay, or cure cancer. This review summarizes the latest research in cancer chemoprevention and treatment using the bioactive components from natural plants. Relevant molecular mechanisms involved in the pharmacological effects of these phytochemicals are discussed. Pharmaceutical developmental challenges and opportunities in bringing the phytochemicals into the market are also explored. The authors wish to expand this research area not only for their scientific soundness, but also for their potential druggability.

Plants vs. cancer: a review on natural phytochemicals in preventing and treating cancers and their druggability.

MicroRNAs (miRNAs) are small non-coding RNAs with the capability of modulating gene expression at the post-transcriptional level either by inhibiting messenger RNA (mRNA) translation or by promoting mRNA degradation. The outcome of a myriad of physiological processes and pathologies, including cancer, cardiovascular and metabolic diseases, relies highly on miRNAs. However, deciphering the precise roles of specific miRNAs in these pathophysiological contexts is challenging due to the high levels of complexity of their actions. Indeed, regulation of mRNA expression by miRNAs is frequently cell/organ specific; highly dependent on the stress and metabolic status of the organism; and often poorly correlated with miRNA expression levels. Such biological features of miRNAs suggest that various regulatory mechanisms control not only their expression, but also their activity and/or bioavailability. Several mechanisms have been described to modulate miRNA action, including genetic polymorphisms, methylation of miRNA promoters, asymmetric miRNA strand selection, interactions with RNA-binding proteins (RBPs) or other coding/non-coding RNAs. Moreover, nucleotide modifications (A-to-I or C-to-U) within the miRNA sequences at different stages of their maturation are also critical for their functionality. This regulatory mechanism called “RNA editing” involves specific enzymes of the adenosine/cytidine deaminase family, which trigger single nucleotide changes in primary miRNAs. These nucleotide modifications greatly influence a miRNA’s stability, maturation and activity by changing its specificity towards target mRNAs. Understanding how editing events impact miRNA’s ability to regulate stress responses in cells and organs, or the development of specific pathologies, e.g., metabolic diseases or cancer, should not only deepen our knowledge of molecular mechanisms underlying complex diseases, but can also facilitate the design of new therapeutic approaches based on miRNA targeting. Herein, we will discuss the current knowledge on miRNA editing and how this mechanism regulates miRNA biogenesis and activity.

Deciphering miRNAs’ Action through miRNA Editing

It is well admitted that the link between chronic inflammation and cancer involves cytokines and mediators of inflammatory pathways, which act during the different steps of tumorigenesis. The cyclooxygenases (COXs) are a family of enzymes, which catalyze the rate-limiting step of prostaglandin biosynthesis. This family contains three members: ubiquitously expressed COX-1, which is involved in homeostasis; the inducible COX-2 isoform, which is upregulated during both inflammation and cancer; and COX-3, expressed in brain and spinal cord, whose functions remain to be elucidated. COX-2 was described to modulate cell proliferation and apoptosis mainly in solid tumors, that is, colorectal, breast, and prostate cancers, and, more recently, in hematological malignancies. These findings prompt us to analyze here the effects of a combination of COX-2 inhibitors together with different clinically used therapeutic strategies in order to further improve the efficiency of future anticancer treatments. COX-2 modulation is a promising field investigated by many research groups.

https://downloads.hindawi.com/journals/ijcb/2010/215158.pdf

The Role of cyclooxygenase-2 in Cell Proliferation and Cell Death in Human Malignancies

Non-alcoholic fatty liver disease (NAFLD) is associated with a thorough reprogramming of hepatic metabolism. Epigenetic mechanisms, in particular those associated with deregulation of the expressions and activities of microRNAs (miRNAs), play a major role in metabolic disorders associated with NAFLD and their progression towards more severe stages of the disease. In this review, we discuss the recent progress addressing the role of the many facets of complex miRNA regulatory networks in the development and progression of NAFLD. The basic concepts and mechanisms of miRNA-mediated gene regulation as well as the various setbacks encountered in basic and translational research in this field are debated. miRNAs identified so far, whose expressions/activities are deregulated in NAFLD, and which contribute to the outcomes of this pathology are further reviewed. Finally, the potential therapeutic usages in a short to medium term of miRNA-based strategies in NAFLD, in particular to identify non-invasive biomarkers, or to design pharmacological analogues/inhibitors having a broad range of actions on hepatic metabolism, are highlighted.

https://gut.bmj.com/content/gutjnl/68/11/2065.full.pdf

miRNAs and NAFLD: from pathophysiology to therapy.

Targeting COX-2 expression by natural compounds: a promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy.

Objective miR-21 is an oncomir highly upregulated in hepatocellular carcinoma and in early stages of liver diseases characterised by the presence of steatosis. Whether upregulation of miR-21 contributes to hepatic metabolic disorders and their progression towards cancer is unknown. This study aims at investigating the role of miR-21/miR-21* in early stages of metabolic liver disorders associated with diet-induced obesity (DIO). Design Constitutive miR-21/miR-21* knockout (miR21KO) and liver-specific miR-21/miR-21* knockout (LImiR21KO) mice were generated. Mice were then fed with high-fat diet (HFD) and alterations of the lipid and glucose metabolism were investigated. Serum and ex vivo explanted liver tissue were analysed. Results Under normal breeding conditions and standard diet, miR-21/miR-21* deletion in mice was not associated with any detectable phenotypic alterations. However, when mice were challenged with an obesogenic diet, glucose intolerance, steatosis and adiposity were improved in mice lacking miR-21/miR-21* . Deletion of miR-21/miR-21* specifically in hepatocytes led to similar improvements in mice fed an HFD, indicating a crucial role for hepatic miR-21/miR-21* in metabolic disorders associated with DIO. Further molecular analyses demonstrated that miR-21/miR-21* deletion in hepatocytes increases insulin sensitivity and modulates the expression of multiple key metabolic transcription factors involved in fatty acid uptake, de novo lipogenesis, gluconeogenesis and glucose output. Conclusions Hepatic miR-21/miR-21* deficiency prevents glucose intolerance and steatosis in mice fed an obesogenic diet by altering the expression of several master metabolic regulators. This study points out miR-21/miR-21 * as a potential therapeutic target for non-alcoholic fatty liver disease and the metabolic syndrome.

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Cyril Sobolewski

Papers

Deciphering miRNAs’ Action through miRNA Editing

The Role of cyclooxygenase-2 in Cell Proliferation and Cell Death in Human Malignancies

miRNAs and NAFLD: from pathophysiology to therapy.

Targeting COX-2 expression by natural compounds: a promising alternative strategy to synthetic COX-2 inhibitors for cancer chemoprevention and therapy.

Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption