Biomedicine & pharmacotherapy = Biomédecine & pharmacothérapie
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Biomed. Pharmacother. · Sep 2017
Dexmedetomidine preconditioning plays a neuroprotective role and suppresses TLR4/NF-κB pathways model of cerebral ischemia reperfusion.
Dexmedetomidine has been reported to play an efficient role on multi-organ protection. Our study aims to investigate the neuroprotective of dexmedetomidine preconditioning on cerebral ischemic reperfusion (I/R) injury and investigate the underlining signaling mechanisms. ⋯ The results of this study suggest that dexmedetomidine preconditioning plays a neuroprotective role against I/R injury. Dexmedetomidine might suppress TLR4/NF-??B pathway and drive TLR4/TRIF signaling pathway to reduce the inflammatory injury.
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Biomed. Pharmacother. · Sep 2017
Effect of microRNA-129-5p targeting HMGB1-RAGE signaling pathway on revascularization in a collagenase-induced intracerebral hemorrhage rat model.
This study aimed at exploring the effect of microRNA-129-5p (miR-129-5p) targeting high mobility group box-1 (HMGB1)-receptor for advanced glycation end-products (RAGE) signaling pathway on the revascularization in a collagenase-induced intracerebral hemorrhage (ICH) rat model. ⋯ Our study proved that up-regulation of miR-129-5p might suppress the HMGB1-RAGE signaling pathway to restrain the revascularization of rats with ICH.
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Biomed. Pharmacother. · Sep 2017
Activation of the PI3K-Akt pathway promotes neuroprotection of the δ-opioid receptor agonist against cerebral ischemia-reperfusion injury in rat models.
The central objective was to identify the role of the PI3K-Akt activation pathway on the neuroprotection of δ-opioid receptor agonist (DADLE) against cerebral ischemia-reperfusion (I/R) injury in a rat model. Fifty-five male Sprague-Dawley (SD) rats were included to establish a middle cerebral artery occlusion (MCAO) model which were then divided into the sham, MCAO, LY294002 (MCAO+DADLE+LY294002 [inhibitor of PI3K-Akt pathway]), DADLE (MCAO+DADLE) and DMSO (MCAO+DADLE+DMSO [dimethyl sulphoxide]) groups. The cerebral infarction (CI) volume and nerve cell apoptosis was determined using TTC and TUNEL staining. ⋯ Compared with the MCAO group, the mRNA and protein expressions of PI3K and Bcl-2, and the protein expressions of p-Akt and p-Bad were elevated, while the mRNA and protein expressions of Bax were decreased in the DADLE and DMSO groups. Decreased mRNA and protein expressions of PI3K and Bcl-2, reduced protein expressions of p-Akt and p-Bad and elevated mRNA and protein expressions of Bax exhibited in the LY294002 group than the DADLE group. These results indicate that activation of PI3K-Akt pathway promotes the neuroprotection of DADLE against cerebral I/R injury in a rat model by decreasing nerve cells apoptosis.
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Biomed. Pharmacother. · Aug 2017
Overexpression of long noncoding RNA H19 indicates a poor prognosis for cholangiocarcinoma and promotes cell migration and invasion by affecting epithelial-mesenchymal transition.
Cholangiocarcinoma (CCA) is a deadly disease that poorly responds to chemotherapy and radiotherapy and whose incidence has increased worldwide. Furthermore, long noncoding RNAs (lncRNAs) play important roles in multiple biological processes, including tumorigenesis. Specifically, H19, the first discovered lncRNA, has been reported to be overexpressed in diverse human carcinomas, but the overall biological role and clinical significance of H19 in CCA remains unknown. ⋯ Moreover, knockdown of H19 followed by RNA silencing restrained cell proliferation and promoted apoptosis. In addition, H19 suppression impaired migration and invasion potential by reversing EMT. Overall, our findings may help to develop diagnostic biomarkers and therapeutics that target H19 for the treatment of CCA.
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Biomed. Pharmacother. · Aug 2017
MicroRNA-494 improves functional recovery and inhibits apoptosis by modulating PTEN/AKT/mTOR pathway in rats after spinal cord injury.
Multiple cellular, molecular, and biochemical changes contribute to the etiology and treatment outcome of contusion spinal cord injury (SCI). MicroRNAs (miRNAs) aberrant expression have been found after SCI in recent studies. However, little is known about the functional significance of the unique role of miRNAs in SCI. ⋯ Moreover, our data showed that miR-494 suppresses phosphatase and tensin homolog (PTEN), a negative regulator of AKT/mTOR pathway, through directly targeting its 3'-UTR in BV-2 cells. Most importantly, we demonstrated that overexpression of miR-494 activates AKT/mTOR signaling pathway via inhibiting PTEN expression in rat SCI model. These findings suggested that miR-494 harbored the protective effect after SCI by modulating PTEN/AKT/mTOR pathway in rats and it is a potential candidate for SCI therapeutics.