ABSTRACT
Short-stranded miRNAs are single-stranded RNA molecules involved in the regulation of gene expression. miRNAs are involved in a variety of cellular physiological processes, including cell proliferation, differentiation, and apoptosis. miR-23b have been identified to act both as oncogenes and as tumor suppressors. In addition, miR-23b is related to inflammation resistance to various autoimmune diseases and restrained inflammatory cell migration. The characterization of the specific alterations in the patterns of miR-23b expression in cancer and autoimmune disease has great potential for identifying biomarkers for early disease diagnosis, as well as for potential therapeutic intervention in various diseases. In this review, we summarize the ever-expanding role of miR-23b and its target genes in different models and offer insight into how this multifunctional miRNA modulates tumor cell proliferation and apoptosis or inflammatory cell activation, differentiation, and migration.
ABSTRACT
A random-pattern skin flap plays an important role in the field of wound repair; the mechanisms that influence the survival of random-pattern skin flaps have been extensively studied but little attention has been paid to endogenous counterinjury substances and mechanism. Previous reports reveal that the apelin-APJ axis is an endogenous counterinjury mechanism that has considerable function in protecting against infection, inflammation, oxidative stress, necrosis, and apoptosis in various organs. As an in vivo study, our study proved that the apelin/APJ axis protected the skin flap by alleviating vascular oxidative stress and the apelin/APJ axis works as an antioxidant stress factor dependent on CaMKK/AMPK/GSK3ß signaling. In addition, the apelin/APJ-manipulated CaMKK/AMPK/GSK3ß-dependent mechanism improves HUVECs' resistance to oxygen and glucose deprivation/reperfusion (OGD/R), reduces ROS production and accumulation, maintained the normal mitochondrial membrane potential, and suppresses oxidative stress in vitro. Besides, activation of the apelin/APJ axis promotes vascular migration and angiogenesis under relative hypoxia condition through CaMKK/AMPK/GSK3ß signaling. In a word, we provide new evidence that the apelin/APJ axis is an effective antioxidant and can significantly improve the vitality of random flaps, so it has potential be a promising clinical treatment.
Subject(s)
AMP-Activated Protein Kinases/metabolism , Apelin/pharmacology , Calcium-Calmodulin-Dependent Protein Kinase Kinase/metabolism , Glycogen Synthase Kinase 3 beta/metabolism , Signal Transduction , Skin/pathology , Wound Healing , Animals , Cell Movement/drug effects , Cell Survival/drug effects , Glucose , Human Umbilical Vein Endothelial Cells/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Humans , Mice, Inbred C57BL , Models, Biological , NF-E2-Related Factor 2/metabolism , Neovascularization, Physiologic/drug effects , Oxygen , Phosphorylation/drug effects , Phosphoserine/metabolism , Pyrazoles/pharmacology , Pyrimidines/pharmacology , Reperfusion Injury/pathology , Signal Transduction/drug effects , Skin/drug effects , Superoxide Dismutase/metabolism , Wound Healing/drug effectsABSTRACT
Multiple sclerosis (MS) is a CNS autoimmune disease characterized by demyelination and inflammatory infiltration with a high disability rate. Increasing evidence has demonstrated the importance of gut microbiota as an environmental risk factor in MS and its animal model experimental autoimmune encephalomyelitis (EAE). Diet is the main determinant of gut microbiota composition and function, which greatly affects the shaping of microbial structure. Pomegranate peel, a waste product in the production of juice, is rich in health-promoting compounds. However, its individual constituents, immunoregulatory activities, and action associated with bacterial diversity in the gut microbiota are largely unknown. Here, the main nutrient ingredients of pomegranate peel extract (PPE) were identified as phenols, flavonoids, amino acids, carbohydrates, fatty acids, lipids, nucleotides, organic acids, alcohols, and vitamins via metabolomics evaluation. We found, for the first time, oral PPE (100 mg/kg/day) not only effectively relieves EAE, inhibits CNS inflammatory factor infiltration and myelin loss, but also reshapes gut microbiota. Furthermore, recipient EAE mice with fecal transplantation from the PPE-treated donor delayed the disease development significantly. 16S rRNA gene sequencing revealed the increased gut microbiota richness in PPE-treated group. Among them, Lactobacillaceae enriched significantly, while Alcaligenaceae and Acidaminococcacea decreased remarkably. In conclusion, our data demonstrated that gut microbiota mediated the beneficial effects of oral PPE on EAE, and provided new ideas for developing the prebiotic value of pomegranate peel for the treatment of autoimmune diseases.