TGF-β plays a central role in epithelial-mesenchymal transition (EMT), which is a highly conserved and reversible process that governs tumor development, invasion and metastasis. Through this transition, the epithelial cell acquires a migratory behavior which allows it to move away from the cell community and to integrate into the surrounding tissue. The cells lost epithelial phenotypes including the change of cell polarity and the loss of specialized cell-cell contacts, which related with the shortage of E-cadherin directly. The increasing reports indicated that TGF-β down-regulated the expression of E-cadherin through snail signaling pathway, which played an important role in the development of EMT. In this review, we summarized the contribution of TGF-β in EMT and discussed the molecular mechanism of snail signaling participating in the regulation of E-cadherin triggered by TGF-β.
Laryngeal squamous cell carcinoma (LSCC) is one of the most commonly diagnosed malignancies with high occurrence of tumor metastasis, which usually exposes to fluid shear stress (FSS) in lymphatic channel and blood vessel. Epithelial-mesenchymal transition (EMT) is an important mechanism that induces metastasis and invasion of tumors. We hypothesized that FSS induced a progression of EMT in laryngeal squamous carcinoma. Accordingly, the Hep-2 cells were exposed to 1.4 dyn/cm2 FSS for different durations. Our results showed that most of cells changed their morphology from polygon to elongated spindle with well-organized F-actin and abundant lamellipodia/filopodia in protrusions. After removing the FSS, cells gradually recovered their flat polygon morphology. FSS induced Hep-2 cells to enhance their migration capacity in a time-dependent manner. In addition, FSS down-regulated E-cadherin, and simultaneously up-regulated N-cadherin, translocated β-catenin into the nucleus. These results confirmed that FSS induced the EMT in Hep-2 cells, and revealed a reversible mesenchymal-epithelial transition (MET) process when FSS was removed. We further examined the time-expressions of signaling cascades, and demonstrated that FSS induces the EMT and enhances cell migration depending on integrin-ILK/PI3K-AKT-Snail signaling events. The current study suggests that FSS, an important biophysical factor in tumor microenvironment, is a potential determinant of cell behavior and function regulation.
Loss of gray-white matter discrimination is the primary early imaging finding within of cranial computed tomography in cardiac arrest survivors, and this has been also regarded as a novel predictor for evaluating neurologic outcome. As displayed clearly on computed tomography and based on sensitivity to hypoxia, the gray-white matter ratio at basal ganglia (GWR-BG) region was frequently detected to assess the neurologic outcome by several studies. The specificity of GWR-BG is 72.4 to 100%, while the sensitivity is significantly different. Herein we review the mechanisms mediating cerebral edema following cardiac arrest, demonstrate the determination procedures with respect to GWR-BG, summarize the related researches regarding GWR-BG in predicting neurologic outcomes within cardiac arrest survivors, and discuss factors associated with predicting the accuracy of this methodology. Finally, we describe the effective measurements to increase the sensitivity of GWR-BG in predicting neurologic outcome.
Cerebral ischemia impedes the functional or metabolic demands of the central nervous system (CNS), which subsequently leads to irreversible brain damage. While recanalization of blocked vessels recovers cerebral blood flow, it can also aggravate brain injury, termed as ischemia/reperfusion (I/R) injury. Exosomes, nanometric membrane vesicles, attracted wide attention as carriers of biological macromolecules. In the brain, exosomes can be secreted by almost all types of cells, and their contents can be altered during the pathological and clinical processes of cerebral I/R injury. Herein, we will review the current literature on the possible role of cargos derived from exosomes and exosomes-mediated intercellular communication in cerebral I/R injury. The PubMed and Web of Science databases were searched through January 2015. The studies published in English were identified using search terms including “exosomes”, “cerebral ischemia-reperfusion injury”, “brain ischemia-reperfusion injury”, and “stroke”. We will also focus on the potential therapeutic effects of stem cell-derived exosomes and underlying mechanisms in cerebral I/R injury. Meanwhile, with the advantages of low immunogenicity and cytotoxicity, high bioavailability, and the capacity to pass through the blood–brain barrier, exosomes also attract more attention as therapeutic modalities for the treatment of cerebral I/R injury.
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