ABSTRACT
Atrial fibrillation ( AF) is the most common arrhythmia in clinical practice .Mitochondrial oxidative stress is supposed to contribute to development , progression and self-perpetuation of AF .Reactive oxygen species ( ROS) is the major molecule mediating mitochondrial oxidative stress damage .ROS can alter the redox status of various molecular targets, which quite specifically leads to functional alterations of ion channel activity or activation of a variety of redox sensi -tive signal transduction pathways .Eventually , it leads to atrial electrical remodeling and promotes the development of AF . Therefore, mitochondrial oxidative stress pathways may be a new target for the therapy of atrial fibrillation .
ABSTRACT
AIM:To investigate the change of late sodium current (INaL) and the effect of Ca2+/calmodulin-dependent protein kinaseⅡ (CaMKⅡ) inhibitor KN-93 on INaLin the cardiomyocytes after isoproterenol-induced heart fai-lure (HF) in rabbits. METHODS:The rabbit model of HF was induced by injecting isoproterenol (300 μg·kg-1· d-1) for 15 d. One month later, all rabbits received by echocardiography and HE staining to observe the morphological changes of myocardium for evaluating the HF model. The protein expression of NaV1.5, CaMKⅡδ and phosphorylated CaMKⅡδ was determined by Western blot. The ventricular myocytes were isolated from the rabbits of normal saline(NS) group and HF group by Langendorff perfusion, and the whole-cell patch-clamp technique was used to record INaL. RE-SULTS:Compared with NS group,the heart rate in HF group was increased (P<0.01), the ventricular cavity was en-larged (P<0.05),and the cardiac function was decreased(P<0.01). Compared with NS group,the cardiomyocytes in HF group arranged in disorder, vacuolar degeneration and myocardial interstitial edema were observed, and fibrous tissue increased. The protein levels of NaV1.5,CaMKⅡδ and phosphorylated CaMKⅡδ in HF group were higher than those in NS group(P<0.01). INaLin HF group significantly increased compared with NS group (P<0.01). After adding sea anemone toxin Ⅱ (ATXⅡ), the density of INaLin HF group and NS group was significantly increased, but that in HF group increased more obviously than that in NS group (P<0.01). After ATXⅡ had induced stable current, we added KN-93 into NS group and HF group,and we found that the ATXⅡ-increased INaLin NS group and HF group was signifi-cantly decreased(P<0.05).CONCLUSION:CaMKⅡinhibitor KN-93 inhibits the increase in INaLin HF rabbits,which may be related to the activity of CaMKⅡδ and the regulation of CaMKⅡ δ on INaL.
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AIM:To investigate the effects of xeroderma pigmentosum group D ( XPD) gene on the prolifera-tion of human umbilical arterial smooth muscle cells ( HUASMCs) induced by oxidized low-density lipoprotein ( Ox-LDL) . METHODS:The recombinant plasmid pEGFP-N2/XPD was transfected into HUASMCs by liposome .The cells were di-vided into blank control group , pEGFP-N2 group, pEGFP-N2/XPD group, Ox-LDL group, Ox-LDL+pEGFP-N2 group and Ox-LDL+pEGFP-N2/XPD group.The proliferation rate of the cells was detected by MTT and EdU assays .The apop-totic rate and cell cycle distribution were analyzed by flow cytometry .The protein levels of XPD, caspase-3, Bcl-2 and Bax were determined by Western blot .RESULTS:Compared with blank control group , the expression of XPD was increased in pEGFP-N2/XPD group (P<0.05).According to the results of MTT and EdU assays , the cell proliferation in pEGFP-N2/XPD group was reduced compared with blank control group (P<0.05).Compared with Ox-LDL group, the cell prolifera-tion in Ox-LDL+pEGFP-N2/XPD group was significantly inhibited (P<0.05).According to the results of flow cytome-try, the cell proportion of S phase decreased and the G 0/G1-phase cell proportion increased significantly in pEGFP-N2/XPD group and Ox-LDL+pEGFP-N2/XPD group compared with blank control group and Ox-LDL group, repectively (P<0.05).Compared with blank control group and Ox-LDL group, the protein level of Bcl-2 decreased and the protein levels of Bax and cleaved caspase-3 increased in pEGFP-N2/XPD group and Ox-LDL +pEGFP-N2/XPD group, respectively (P<0.05).CONCLUSION:XPD inhibits the proliferation of HUASMCs and promotes their apoptosis , and reduces the promoting effect of Ox-LDL on the proliferation of HUVSMCs .XPD may be the target for treatment of atherosclerosis .
ABSTRACT
Atrial fibrillation ( AF) is the most common arrhythmia in clinical practice .Mitochondrial oxidative stress is supposed to contribute to development , progression and self-perpetuation of AF .Reactive oxygen species ( ROS) is the major molecule mediating mitochondrial oxidative stress damage .ROS can alter the redox status of various molecular targets, which quite specifically leads to functional alterations of ion channel activity or activation of a variety of redox sensi -tive signal transduction pathways .Eventually , it leads to atrial electrical remodeling and promotes the development of AF . Therefore, mitochondrial oxidative stress pathways may be a new target for the therapy of atrial fibrillation .
ABSTRACT
<p><b>OBJECTIVE</b>To study the cytopathologic features of transbronchial needle aspiration (TBNA) samples and to evaluate the role of cytopathology in the diagnosis and staging of lung carcinomas, as compared to histopathology.</p><p><b>METHODS</b>Three hundred seventy-four cytology specimens were collected by TBNA using 21-gauge needle, including 65 lung masses and 309 lymph nodes. Direct smears and liquid-based thin-layer preparations were performed for each case. The correlation between cytology and histopathologic diagnoses were analyzed.</p><p><b>RESULTS</b>The sensitivity, specificity, false positive rate, false negative rate and accuracy of cytopathology in diagnosing lung carcinomas by TBNA was 95.7% (88/92) (266/278), 100% (96/96), 0 (0/96), 4.3% (12/278) and 96.8% (362/374), respectively. Overall 62.8% (167/266) of the cases were precisely typed, including 95.7% (88/92) of small cell carcinoma, 73.5% (25/34) of squamous cell carcinoma and 67.9% (53/78) of adenocarcinoma. There was no statistical difference in the diagnostic accuracy of cytopathology between lung mass aspiration and mediastinal lymph node aspiration, as well as between subcarinal lymph node aspiration and other lymph node aspiration (all P > 0.05). There was also no statistical difference in the diagnostic accuracy between direct smears and liquid-based preparations (χ(2) = 0.11, P > 0.05).</p><p><b>CONCLUSIONS</b>Cytopathology of TBNA specimens is accurate and sensitive for diagnosing pulmonary carcinomas. In most cases, the lung carcinoma can be precisely typed. TBNA is useful for diagnosing and staging lung carcinomas.</p>
Subject(s)
Adult , Aged , Aged, 80 and over , Female , Humans , Male , Middle Aged , Young Adult , Adenocarcinoma , Diagnosis , Pathology , Biopsy, Needle , Methods , Bronchoscopy , Methods , Carcinoma, Small Cell , Diagnosis , Pathology , Carcinoma, Squamous Cell , Diagnosis , Pathology , Lung Neoplasms , Diagnosis , Pathology , Lymph Nodes , Pathology , Lymphatic Metastasis , Neoplasm Staging , Sensitivity and SpecificityABSTRACT
<p><b>OBJECTIVE</b>To determine the diagnostic value of B72.3, BerEP4 and calretinin in differentiating metastatic carcinoma cells from reactive mesothelial cells (RMC) in serous effusions by using immunocytochemical method (ICC), and to investigate the feasibility of ThinPrep (TP) preparation for ICC.</p><p><b>METHODS</b>One hundred fifty eight serous effusion specimens were examined by ICC on cell block (CB) sections (CB-ICC) using antibodies against of B72.3, BerEP4 and calretinin. Fourty-nine of the samples, ICC on ThinPrep slides (TP-ICC) and CB-ICC were performed concurrently.</p><p><b>RESULTS</b>The sensitivities of B72.3 and Ber-EP4 for detecting carcimoma cells were 76.9% and 69.2% respectively, and when combined the sensitivity was increased to 89.7%. The sensitivity and specificity of Calretinin for detecting mesothelial cells were 90.9% and 87.2% respectively. The sensitivity of B72.3 in differentiating cancer cells from reactive mesothelial cells by CB-ICC and TP-ICC was 78.9% and 68.4%. It was 78.9% and 68.4% of BerEP4 respectively. No statistical significance was observed between CB-ICC and TP-ICC in differentiating metastatic carcinoma cells from reactive mesothelial cells.</p><p><b>CONCLUSION</b>The combination of antibodies of B72.3, Ber-EP4 and calretinin is quite helpful as an auxiliary in differentiating metastatic carcinoma cells from reactive mesothelial cells. ThinPrep preparation slides may effectively replace the cell block sections for ICC in differential diagnosis of serous effusions.</p>