ABSTRACT
BACKGROUND: Diabetic encephalopathy(DE) is a neurological complication of diabetes, and its pathogenesis is unclear. Current studies indicate that insulin receptors and downstream signaling pathways play a key role in the occurrence and development of DE. Additionally, CLC-3, a member of the CLC family of anion channels and transporters, is closely related to the secretion and processing of insulin. Here, we investigated the changes and putative roles of CLC-3 in diabetic encephalopathy. RESULTS: To this aim, we combined lentivirus and adeno-associated virus gene transfer to change the expression level of CLC-3 in the HT-22 hippocampal cell line and hippocampal CA1. We studied the role of CLC-3 in DE through the Morris water maze test.CLC-3 expression increased significantly in HT-22 cells cultured with high glucose and STZ-induced DE model hippocampus. Moreover, Insulin receptor(IR) and downstream PI3K/AKT/GSK3ß signaling pathways were also dysfunctional. After knocking down CLC-3, impaired cell proliferation, apoptosis, IR and the downstream PI3K/AKT/GSK3ß signaling pathways were significantly improved. However, when CLC-3 was overexpressed, the neurotoxicity induced by high glucose was further aggravated. Rescue experiments found that through the use of inhibitors such as GSK3ß, the PI3K/AKT/GSK3ß signaling pathways pathway changes with the use of inhibition, and the expression of related downstream signaling molecules such as Tau and p-Tau also changes accordingly. Using adeno-associated virus gene transfer to knock down CLC-3 in the hippocampal CA1 of the DE model, the IR caused by DE and the dysfunction of the downstream PI3K/AKT/GSK3ß signaling pathway were significantly improved. In addition, the impaired spatial recognition of DE was partially restored. CONCLUSION: Our study proposes that CLC-3, as a key molecule, may regulate insulin receptor signaling and downstream PI3K/AKT/GSK3ß signaling pathways and affect the pathogenesis of diabetic encephalopathy.
Subject(s)
Brain Diseases , Chloride Channels , Cognitive Dysfunction , Diabetes Mellitus , Animals , Chloride Channels/genetics , Cognitive Dysfunction/genetics , Gene Knockdown Techniques , Glucose , Glycogen Synthase Kinase 3 beta/genetics , Mice , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Receptor, Insulin/geneticsABSTRACT
Teaching mode of modem distance medical education mainly includes teacher-centered teaching mode and the student-centered teaching model,while the latter derivatives autonomous planning learning,collaborative learning and case learning,etc.Student-centered teaching mode embodies the teaching characteristics and advantages of modem distance medical education.In view of the diversity of teaching objects,we should give full play to the advantages of various teaching models and ieasonably apply these teaching modes.To strengthen the construction of practical training courses,improve all kinds of teaching resources and the safeguard,train a contingent of qualified teachers is the important factor to improve teaching quality.
ABSTRACT
BACKGROUND: Human cytomegalovirus (HCMV) is a virus which has the potential to alter cellular gene expression through multiple mechanisms. OBJECTIVE: With the application of DNA microarrays, we could monitor the effects of pathogens on host-cell gene expression programmes in great depth and on a broad scale. METHODS: Changes in mRNA expression levels of human endothelial-like ECV304 cells following infection with human cytomegalovirus AD169 strain was analyzed by a microarray system comprising 21073 60-mer oligonucleotide probes which represent 18716 human genes or transcripts. RESULTS: The results from cDNA microarray showed that there were 559 differential expressed genes consisted of 471 upregulated genes and 88 down-regulated genes. Real-time qPCR was performed to validate the expression of 6 selected genes (RPS24, MGC8721, SLC27A3, MST4, TRAF2 and LRRC28), and the results of which were consistent with those from the microarray. Among 237 biology processes, 39 biology processes were found to be related significantly to HCMV-infection. The signal transduction is the most significant biological process with the lowest p value (p=0.005) among all biological process which involved in response to HCMV infection. CONCLUSION: Several of these gene products might play key roles in virus-induced pathogenesis. These findings may help to elucidate the pathogenic mechanisms of HCMV caused diseases.
Subject(s)
Cytomegalovirus Infections/genetics , Cytomegalovirus/genetics , Endothelial Cells/virology , Gene Expression Profiling , China , Cytomegalovirus Infections/pathology , Female , Humans , Male , Polymerase Chain Reaction , Tissue Array AnalysisABSTRACT
Objective To observe the injury of some chief organ induced by paraquat (PQ) poisoning in rats, and to explore the mechanism. Method A total of 60 inbred line SD rats were randomly divided into experimental group (n = 30) and control group (n = 30), and each group was further divided into 6 subgroups (n =5) as per the sacrifice of rats at different intervals. The rats of experimental group received the intra-abdominal injection of paraquat (1 mg/mL, 18 mg/kg), and the rats of control group were treated with the same amount of saline solution instead. The rats of each subgroup were sacrificed separately 2 h,6 h, 12 h,24 h,72 h and 120 h after administration of PQ or saline. Lungs, livers and kidneys were taken for histopathological study. Results There was noticeable exudate in lung tissue of rats in experimental group in the early stage. And then the cystic changes in the liver of rats in experimental group were found. A noticeable hemoglobin was found in the renal tubules 24 h after modeling. But the exudation in lung decreased 24 h later, and in the mean time, the disorganization of pulmonary alveoli was obvious and some remarkable collagen appeared in the interstitial tissue of lung, and it was significantly obvious 72 h after modeling. In the liver of rats in experimental group, the injured tissue had some extent of repair in 72 h after modeling, and recovered gradually. But the injury of kidney was exacerbated 72 h after modeling. In the control group, the lung, liver and kidney were not changed in all stages after modeling.Conclusions The paraquat could induce failure of some chief organs in SD rats. The injury was most remarkable in the lung in a progressive way. The kidney injury was not more severe than that of lung tissue, but the pathological changes of the kidney became worse and worse as time taken. The injury of liver induced by paraquat was slight, and the injury could heal up gradually.
