ABSTRACT
Objective@#To investigate the role of microRNA-96-5p in the proliferation and invasion of gastric cancer cells and its molecular mechanism.@*Methods@#From June 2015 to January 2017, 53 resected specimens were collected. The transcriptional levels of microRNA-96-5p and forkhead box Q1 (FoxQ1) in gastric cancer tissues and the matched para-cancerous tissues were quantified by quantitative real-time PCR (qRT-PCR). The expression of FoxQ1 protein was also detected by immunohistochemistry (IHC). The relationship between microRNA-96-5p expression and the clinicopathological features of gastric cancer and its correlation with FoxQ1 expression were analyzed. The expressions of miRNA-96-5p in gastric cancer tissue and adjacent normal tissue were detected by qRT-PCR. miRNA-96-5p mimics was transfected to BGC-823 gastric cancer cells. The effects of miRNA-96-5p on cell proliferation and invasion were detected by cell counting kit-8 (CCK-8) assay and Transwell assay, respectively. The protein expressions of FoxQ1, E-cadherin and vimentin were determined by western blot. The relationship between FoxQ1 and miRNA-96-5p expressed in BGC-823 cells was detected by dual-luciferase reporter assay.@*Results@#The median expression of miRNA-96-5p in gastric cancer tissue was 1.05, significantly lower than 3.23 of para-cancerous tissues (P<0.05). The positive rate of FoxQ1 expression in gastric cancer tissue was 71.7%, significantly higher than 28.3% of para-cancerous tissues (P<0.05). The expression of FoxQ1 was negatively corelated with the level of miRNA-96-5p (r=-0.613, P=0.006). The expression of miRNA-96-5p in gastric cancer cell BGC-823 was significantly decreased compared with normal gastric epithelial cell (0.96±0.08 vs 2.84±0.15, P<0.05). The results of CCK-8 assay and Transwell assay showed that overexpression of miRNA-96-5p significantly reduced the proliferation and invasion abilities of gastric cancer cells (P<0.05). Overexpression of miRNA-96-5p decreased the protein level of FoxQ1. Moreover, it upregulated the expression of E-cadherin and downregulated the expression of vimentin. The result of dual-luciferase-3′-UTR reporter assay confirmed that miRNA-96-5p binds to the 3′UTR of FoxQ1.@*Conclusion@#miRNA-96-5p may suppress the proliferation, migration and epithelial-mesenchymal transition (EMT) of gastric cancer cell by down-regulation of FoxQ1.
ABSTRACT
Fucoidan has been reported to exhibit various beneficial activities ranging from to antivirus and anticancer properties. However, little information is available about the effects of fucoidan on cerebral ischemia-reperfusion injury (IRI). Our study aimed to explore the effects of fucoidan on cerebral IRI, as well as the underlying mechanisms. Sprague-Dawley (SD) rats were randomly subjected to four groups: Sham, IRI+saline (IRI+S), IRI+80 mg/kg fucoidan (IRI+F80), and IRI+160 mg/kg fucoidan (IRI+F160). Fucoidan (80 mg/kg or 160 mg/kg) was intraperitoneally injected from 7 days before the rats were induced to cerebral IRI model with middle cerebral artery occlusion (MCAO) method. At 24 h after reperfusion, neurological deficits and the total infarct volume were determined. The levels of inflammation-associated cytokines (interleukin (IL)-1β, IL-6, myeloperoxidase (MPO), and tumor necrosis factor (TNF)-α), oxidative stress-related proteins (malondialdehyde (MDA) and superoxide dismutase (SOD)) in the ischemic brain were measured by enzyme-linked immunosorbent assay (ELISA). Besides, the levels of apoptosis-related proteins (p-53, Bax, and B-cell lymphoma (Bcl)-2) and mitogen-activated protein kinase (MAPK) pathway (phosphorylation-extracellular signal-regulated kinase (p-ERK), p-c-Jun N-terminal kinase (JNK), and p-p38) were measured. Results showed that administration of fucoidan significantly reduced the neurological deficits and infarct volume compared to the IRI+S group in a dose-dependent manner. Also, fucoidan statistically decreased the levels of inflammation-associated cytokines, and oxidative stress-related proteins, inhibited apoptosis, and suppressed the MAPK pathway. So, Fucoidan plays a protective role in cerebral IRI might be by inhibition of MAPK pathway.
Subject(s)
Animals , Rats , Apoptosis , Brain , Cytokines , Enzyme-Linked Immunosorbent Assay , Infarction, Middle Cerebral Artery , Interleukin-6 , Lymphoma, B-Cell , Methods , Peroxidase , Phosphotransferases , Protein Kinases , Rats, Sprague-Dawley , Reperfusion , Reperfusion Injury , Superoxide Dismutase , Tumor Necrosis Factor-alphaABSTRACT
Objective To explore the effects of renal denervation (RDN) on hypothalamus angiotensinⅡ(AngⅡ) and oxidative stress in myocardial infarction (MI) dogs. Methods Eighteen mongrel dogs were randomly divided into MI group (n=6), RDN group (n=6) and sham operation group (n=6). Myocardial infarction model was made in the former two groups by gelatin sponge embolization of the left anterior descending artery. One week after MI, RDN was given to dogs in RDN group. Levels of AngⅡ, malondialdehyde (MDA), superoxide dismutase (SOD) and expression of gp91phox protein were detected four weeks after MI. Results Compared with control group, hypothalamus AngⅡ, MDA and expression of gp91phox protein were increased in MI group (P<0.01), but SOD was decreased (P<0.01). There was a negative correlation between AngⅡand SOD activity in MI group (r=-0.849, P < 0.01). There was a positive correlation between AngⅡ and expression of gp91phox protein in MI group (r=0.950, P<0.01). Compared with MI group, hypothalamus AngⅡ, MDA and expression of gp91phox protein were decreased in RDN group (P<0.01), but SOD was increased (P<0.01). Conclusion RDN can de?crease the level of hypothalamus AngⅡand the level of hypothalamus oxidative stress, and improve heart function of MI dogs.
ABSTRACT
Objective To observe the effect of renal denervation (RDN) on the cardiac oxidative stress and sympathetic nerve remodeling after myocardial infarction (MI) in canine. Methods Canine (n=18) were randomly divided into three groups: Sham operation group (SHAM group, n=6), MI group (n=6), MI+RDN group (n=6). Anterior myocardial infarction was gained by gelatin sponge embolization of the left anterior descending artery. At four weeks post-MI, left ventricular end-diastolic volume (LVEDV), left ventricular end-systolic volume (LVESV) and left ventricular ejection fraction (LVEF) were examined using echocardiography. Immunohistochemical assay was used to analyze the distribution and density of tyrosine hydroxylase (TH) stained nerve fibers at peri-infarct zone. Myocardial superoxide dismutase (SOD) activity and malondialde?hyde (MDA) were also assessed. Results Compared with dogs in SHAM group, LVEF and SOD expression were decreased in MI group and MI+RDN group (P<0.05), but Left ventricular end diastolic pressure (LVEDP), LVEDV, LVESV, MDA and rate of TH positive staining nerve fibers were increased (P<0.05). There was a negative correlation between the rate of TH positive staining nerve fibers and SOD level (rs=-0.818,P<0.05) and a positive correlation between rate of TH positive stain?ing nerve fibers with MDA level (rs=0.900,P<0.05). By contract, compared with MI group, LVEF and SOD in MI +RDN group were increased (P<0.05), while LVEDV, LVESV, MDA and rate of TH positive staining nerve fibers were significant?ly lowered (P<0.05). Conclusion RDN is effective to decrease the level of cardiac oxidative stress and improve cardiac sympathetic nerve remodeling and heart function after myocardial infarction in canine.
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Adoptive cellular immunotherapy (ACI) achieves the elimination and control of tumor by mobilizing the body's immune function.It also has targeted efficacy and mild untoward effects.Cytokineinduced killer cells and tumor-infiltrating lymphocytes have been widely used in clinic and have obtained preliminary efficacy.With the development and clinical application of the specific gene transfer of T cell,it will further increase the efficacy of immunotherapy.At present,improving cell culture technology and cell function and using with other treatment are the key links to improve the efficacy of ACI.
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Herpes simplex viruses (HSV) are human pathogens responsible for a variety of diseases,including localized mucocutaneous lesions,encephalitis,and disseminated diseases.HSV infection leads to rapid induction of innate immune responses.A critical part of this host response is the type I IFN system including the induction of type I IFNs,IFN-mediated signaling and amplification of IFN response.This provides the host with immediate countermeasure during acute infection to limit initial viral replication and to facilitate an appropriate adaptive immune response.However,HSV has devised multiple strategies to evade and interfere with innate immunity.This review will focus on the induction of type I IFN response by HSV during acute infection and current knowledge of mechanisms by which HSV interferes with this induction process.