ObjectiveTo investigate the effect and significance of early coronary artery bypass graft (CABG) on the expression level of ionophorous protein at infracted border zone (IBZ) in dog with acute myocardial infarction. MethodsThe anterior descending coronary artery of all thirty healthy mongrel dogs were ligated into myocardial infarction model, whose successful criteria was that the regional myocardium supplied by ligated coronary artery became darker. Coronary artery bypass surgery performed at different time points after myocardial infarction (in the 1st week, the 2nd week, the 4th week, the 6th week respectively) was as an experimental group. While myocardial infarction without coronary artery bypass surgery was set up as a control group. Myocardial tissue without ligation of coronary artery was as a normal group. After 8 weeks, myocardial specimens were cut out in the experimental group and the control group. The local expression levels of ionophorous proteins such as Cav1.2, Kv4.3 and KchIP2 mRNA were detected by means of reverse transcription- polymerase chain reaction (RT-PCR) at normal myocardium and IBZ of the experimental group and the control group. ResultsFour dogs in every experimental group and all dogs in the control group survived to the end of the study. Three myocardial ion channel proteins expression in the control group were lower than those of the normal group or the experimental group significantly (P<0.01). Cav1.2 mRNA expression in the experimental group in the 4th week or the 6th week was lower than that in the normal group significantly (P<0.05). Kv4.3 and KchIP2 mRNA expression in the experimental group in the 4th week or the 6th week were lower than those in the normal group and the experimental group significantly in the 1st week or the 2nd week (P<0.05). ConclusionEarly CABG surgery for acute myocardial infarction could lessen the changes of expression level of ionophorous protein at infracted border zone (IBZ) of dog with acute myocardial infarction. Especially, CABG surgery among two weeks could improve expression level of ionophorous protein, and reduce the effect of ischemia for ionophorous protein and myocardial electrophysiology at IBZ.
Objective To investigate the feasibility of recombinant lentivirus (LVs) mediated hyperpolarization- activated cyclic nucleotide-gated cation channel 4 (HCN4) gene transfecting rat bone mesenchymal stem cells (BMSCs) so as to construct the biological pacemaker cells. Methods Sprague Dawley rats at the age of 3-5 weeks were selected to isolate and culture BMSCs using modified whole bone marrow adherent culture method. LVs was used as carrier, and enhanced green fluorescent protein (EGFP) as marker to build LVs-HCN4-EGFP virus liquid. The BMSCs at passage 3 were transfected with LVs-HCN4-EGFP virus liquid (experimental group) and LVs-EGFP null virus liquid (control group). Fluorescence microscope was used to observe the green fluorescent protein expression after 24, 48, and 72 hours of transfection; Western blot method was used to detect the HCN4 protein expression. The electrophysiology was used to detect the pacemaker current in the experimental group. Results After transfection, BMSCs in the experimental group showed normal morphology and good growth; scattered green fluorescence could be seen at 48 hours under fluorescence microscope, with a transfection efficiency of about 10%; the fluorescence expression increased slightly, with the transfection efficiency of 20% to 25% at 72 hours. While no expression of green fluorescence was seen in the control group. Western blot results showed that the same band expression as a relative molecular mass of HCN4 protein were found at 72 hours after transfection in the experimental group, only weak expression of protein band was seen in the control group; the gray value of the experimental group (33.75 ± 0.41) was significantly higher than that of the control group (23.39 ± 0.33) (t=17.524, P=0.013). In the experimental group, the pacemaker current was recorded, and it could be blocked by CsCl, in accordance with the characteristics of pacemaker current. Conclusion The recombinant LVs mediated HCN4 gene is successfully transfected into rat BMSCs, and the expression of HCN4 protein and the pacemaker current can be detected.
Ion channels are involved in the mechanism of anesthetic action and side effect. The transcription and expression of ion channel genes can be modulated by general anesthetics. The adverse effect of continuous infusion of etomidate has been concerned. However, the effects of etomidate on mRNA expressions of ion channel genes remain unclear. In this study, we exposed Daphnia pulex in 250 μmol/L of etomidate for 240 min and observed the change of heart rate, phototactic behavior and blood glucose during the period of exposure, as well as the mRNA expressions of 120 ion channel genes at the end of the experiment. Compared to the controls, heart rate, phototactic behavior and blood glucose were not influenced by 250 μmol/L of etomidate. According to the quantitative PCR results, 18 of 120 Daphnia pulex ion channel genes transcripts were affected by persistent 240 min exposure to 250 μmol/L of etomidate: 2 genes were upregulated and 16 genes were down-regulated, suggesting that etomidate showed effects on many different ion channels in transcription level. Systematical exploration of transcriptional changes of ion channels could contribute to understanding of the pharmacological mechanism of etomidate.
Objective To summarize research progress of relationship between chloride intracellular channel protein 1 (CLIC1) and colonic cancer. Method The related literatures in recent years on the relationship between the CLIC1 and the colonic cancer were reviewed and analyzed. Results The CLIC1 could play its physiological function as a chloride ion channel, with a wide tissue distribution and high expression in many tumor tissues. The abnormal expression of CLIC1 could result in many diseases and participate in many processes such as the occurrence, development, metastasis, and treatment of the colonic cancer. Conclusions CLIC1 might be a biomarker for early diagnosis and a target for gene therapy of colonic cancer, key genes regulated its expression, signal transduction pathways involved in occurrence and progression of colonic cancer, and interaction with other related molecules are still unclear, and further study is needed.
Mutations in the BEST1 gene are associated with a range of retinal diseases collectively referred to as "Best diseases", including Best vitelline macular dystrophy. More than 300 mutations at different sites of the BEST1 gene have been found, which may cause a series of functional disorders such as the mistransport of the calcium-activated anion channel protein-1 protein encoded by it, protein oligomerization defects, and abnormal anion channel activity, leading to different clinical phenotypes. Although it has been established that the BEST1 gene mutation is associated with at least one different type of Best disease, the relationship between the specific gene mutation site and the specific clinical phenotype has not been fully defined. For the time being. Drugs and gene therapy for the Best diseases are still in the basic research stage, which provides a broad development space for future treatment exploration. In the future, when selecting gene therapy in clinical applications, it is necessary to combine the clinical phenotype and molecular diagnosis of patients, and clearly define their mutation types and pathogenic mechanisms in order to achieve better personalized treatment effects.
Chloride voltage-gated channel 7 (CLCN7) gene mutations can cause the disorder of acidification in lacunas and osteolysis, leading to osteopetrosis characterized by increased bone density throughout the body and lysosomal storage diseases. Deafness can be caused by nerve injury for bone compression, negative pressure in the middle ear and otosclerosis. This article will introduce structure and function of CLCN7 gene and CLCN7 protein, osteolysis process, including the introduction of osteoclasts and the mechanism of osteolysis, osteopetrosis, mechanism and treatment of osteopetrosis caused by CLCN7 gene mutations, as well as osteopetrosis and syndromic deafness, in order to provide a basis for clinical diagnosis and treatment.
ObjectiveTo explore the expression of chloride intracellular channel protein 1 (CLIC1) protein in the matched colorectal normal mucosa tissue, colorectal adenoma tissue， and colorectal cancer tissue, and its relationship with tumorigenesis, tumor progression， and prognosis of patients with colorectal cancer . MethodsThe expression of CLIC1 protein was detected in 150 cases of colorectal normal mucosa tissues, 62 cases of colorectal adenoma tissues, and 187 cases of colorectal cancer tissues by using immunohistochemistry tissue microarray, and the relationships between the expression of CLIC1 protein and clinicopathologic features, and the survival rate of patients with colorectal cancer were analyzed. ResultsThe positive rate of CLIC1 protein expression in normal mucosa tissues (26.00%, 39/150), colorectal adenoma tissues (66.13%, 41/62), and colorectal cancer tissues (82.89%, 187/155) increased in turn and the difference was statistically significant (Plt;0.001). The expression of CLIC1 protein was related to TNM staging (P=0.007), but it was not related to gender (P=0.553), age (P=0.206), tumor diameter (P=0.185), tumor differentiation (P=0.062), and tumor location (P=0.598). The median survival time after surgery in patients with CLIC1 protein positive expression was 80 months, and it was 111 months in patients with CLIC1 protein negative expression. The survival rate of patients with CLIC1 protein positive expression was lower than that with CLIC1 protein negative expression by log-rank test (66.40% vs. 80.00%, P=0.031). ConclusionsThe expression of CLIC1 protein is related to the tumorigenesis and progression of colorectal cancer as well as the survival of patients with colorectal cancer. CLIC1 is a potential tumor biomarker.