The role of non-coding RNAs in neuroprotection and angiogenesis following ischemic stroke.

Stroke is the leading cause of death and physical disability worldwide. Non-coding RNAs (ncRNAs) are endogenous molecules that play key roles in the pathophysiology and retrieval processes following ischemic stroke. The potential of ncRNAs, especially microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) in neuroprotection and angiogenesis highlights their potential as targets for therapeutic intervention. In this review, we document the miRNAs and lncRNAs that have been reported to exert regulatory actions in neuroprotective and angiogenic processes through different mechanisms involving their interaction with target coding genes. We believe that exploration of the expression profiles and the possible functions of ncRNAs during the recovery processes will help comprehension of the molecular mechanisms responsible for neuroprotection and angiogenesis, and may also contribute to find biomarkers and targets for future stroke intervention.

Long non-coding RNAs and cell death following ischemic stroke.

Stroke is a major cause of morbidity and mortality worldwide, and extensive efforts have focused on the improvement of therapeutic strategies to reduce cell death following ischemic stroke. Uncovering the cellular and molecular pathophysiological processes in ischemic stroke have been a top priority. Long noncoding RNAs (lncRNAs) are endogenous molecules that play key roles in the pathophysiology of cerebral ischemia, and involved in the neuronal cell death during ischemic stroke. In recent years, a bulk of aberrantly expressed lncRNAs have been screened out in ischemic stroke insulted animals. LncRNAs along with their targets could affect the genetic machinery at molecular levels, and exploring their functions and mechanisms may be a promising option for ischemic stroke treatment. In this review, we summarize the current knowledge for lncRNAs in ischemic stroke, focusing on the role of specific lncRNAs that may underlie cell death to find possible therapeutic targets.

Human Mesenchymal Stem Cells for Spinal Cord Injury.

Spinal Cord Injury (SCI), as a devastating and life-altering neurological disorder, is one of the most serious health issues. Currently, the management of acute SCI includes pharmacotherapy and surgical decompression. Both the approaches have been observed to have adverse physiological effects on SCI patients. Therefore, novel therapeutic targets for the management of SCI are urgently required for developing cell-based therapies. Multipotent stem cells, as a novel strategy for the treatment of tissue injury, may provide an effective therapeutic option against many neurological disorders. Mesenchymal stem cells (MSCs) or multipotent stromal cells can typically self-renew and generate various cell types. These cells are often isolated from bone marrow (BM-MSCs), adipose tissues (AD-MSCs), umbilical cord blood (UCB-MSCs), and placenta (PMSCs). MSCs have remarkable potential for the development of regenerative therapies in animal models and humans with SCI. Herein, we summarize the therapeutic potential of human MSCs in the treatment of SCI.

Paracrine Mechanisms Involved in Mesenchymal Stem Cell Differentiation into Cardiomyocytes.

Cardiovascular Disease (CVD) is one of the world-wide healthcare problem that involves the heart or blood vessels. CVD includes myocardial infarction and coronary artery diseases (CAD). Dysfunctional myocardial cells are leading causes of low cardiac output or ventricular dysfunction after cardiac arrest and may contribute to the progression of CVD which could not generate new cardiomyocytes in human adult heart. The mesenchymal stem cells (MSCs) which are present in adult marrow can self-renew and have the capacity of differentiation into multiple types of cells including cardiomyocytes. Recent biochemical analyses greatly revealed that several regulators of MSCs, such as HGF, PDGF, Wnt, and Notch-1 signaling pathways have been shown to be involved in the proliferation and differentiation into cardiomyocytes. Preclinical studies are paving the way for further applications of MSCs in the repair of myocardial infarction. In this study, we discuss and summarize the paracrine mechanisms involved in MSCs differentiation into cardiomyocytes.

The Expression and Functional Roles of miRNAs in Embryonic and Lineage-Specific Stem Cells.

The discovery of small non-coding RNAs began an interesting era in cellular and molecular biology. To date, miRNAs are the best recognized non-coding RNAs for maintenance and differentiation of pluripotent stem cells including embryonic stem cells (ES), induced pluripotent stem cells (iPSC), and cancer stem cells. ES cells are defined by their ability to self-renew, teratoma formation, and to produce numerous types of differentiated cells. Dual capacity of ES cells for self-renewal and differentiation is controlled by specific interaction with the neighboring cells and intrinsic signaling pathways from the level of transcription to translation. The ES cells have been the suitable model for evaluating the function of non-coding RNAs and in specific miRNAs. So far, the general function of the miRNAs in ES cells has been assessed in mammalian and non-mammalian stem cells. Nowadays, the evolution of sequencing technology led to the discovery of numerous miRNAs in human and mouse ES cells that their expression levels significantly changes during proliferation and differentiation. Several miRNAs have been identified in ectoderm, mesoderm, and endoderm cells, as well. This review would focus on recent knowledge about the expression and functional roles of miRNAs in embryonic and lineage-specific stem cells. It also describes that miRNAs might have essential roles in orchestrating the Waddington's landscape structure during development.

NLRP3 inflammasome in ischemic stroke: As possible therapeutic target.

Inflammation is a devastating pathophysiological process during stroke, a devastating disease that is the second most common cause of death worldwide. Activation of the NOD-like receptor protein (NLRP3)-infammasome has been proposed to mediate inflammatory responses during ischemic stroke. Briefly, NLRP3 inflammasome activates caspase-1, which cleaves both pro-IL-1 and pro-IL-18 into their active pro-inflammatory cytokines that are released into the extracellular environment. Several NLRP3 inflammasome inhibitors have been promoted, including small molecules, type I interferon, micro RNAs, nitric oxide, and nuclear factor erythroid-2 related factor 2 (Nrf2), some of which are potentially efficacious clinically. This review will describe the structure and cellular signaling pathways of the NLRP3 inflammasome during ischemic stroke, and current evidence for NLRP3 inflammasome inhibitors.