Meta-analysis Identifies Serum C-Reactive Protein as an Indicator of Atrial Fibrillation Risk After Coronary Artery Bypass Graft.

A meta-analysis-based study was conducted to examine the clinical value of serum C-reactive protein (CRP) levels in predicting postoperative atrial fibrillation (POAF) in patients with coronary artery disease (CAD) who underwent coronary artery bypass graft. Computer-based search of scientific literature databases was performed to identify relevant studies in strict accordance with our inclusion and exclusion criteria. Data extracted from the selected studies were used to perform meta-analysis using the STATA 12.0 statistical software. Standardized mean differences (SMDs) with their 95% confidence interval (95% CI) were calculated. The database search strategy initially identified 62 articles (Chinese = 17, English = 45). After multiple levels of screening and validation, 15 case-control studies (Chinese = 1, English = 14), containing of a total of 3110 atrial fibrillation patients (POAF = 925, non-POAF = 2185), were selected for our meta-analysis. The meta-analysis results confirmed that serum CRP level was remarkably higher in patients with POAF compared with non-POAF (SMD = 1.36; 95% CI, 0.44-2.28; P = 0.004). Ethnicity-stratified analysis revealed that elevated serum CRP levels were associated with an increased risk of POAF in white patients with CAD (SMD = 0.85; 95% CI, 0.12-1.58; P = 0.022), but not Asian patients with CAD (SMD = 3.31, 95% CI, -0.04 to 6.66; P = 0.053). Elevated CRP levels, indicating profound inflammation, may be associated with significantly increased risk of POAF in patients with CAD who underwent coronary artery bypass graft. Thus, serum CRP levels are important for early diagnosis and monitoring of POAF in high-risk patients.

TERT promoter mutated WHO grades II and III gliomas are located preferentially in the frontal lobe and avoid the midline.

The promoter region of telomerase reverse transcriptase (TERTp) and isocitrate dehydrogenase (IDH) have been regarded as biomarkers with distinct clinical and phenotypic features. Investigated the possible correlations between tumor location and genetic alterations would enhance our understanding of gliomagenesis and heterogeneity of glioma. We examined mutations of TERTp and IDH by direct sequencing and fluorescence in-situ hybridization in a cohort of 225 grades II and III diffuse gliomas. Correlation analysis between molecular markers and tumor locations was performed by Chi-square tests/Fisher's exact test and multivariate logistic regression analysis. We found gliomas in frontal lobe showed higher frequency of TERTp mutation (P=0.0337) and simultaneously mutations of IDH and TERTp (IDH (mut)-TERTp(mut)) (P=0.0281) than frequency of biomarkers mutation of tumors in no-Frontal lobes, while lower frequency of TERTp mutation (P<0.0001) and simultaneously wild type of IDH and TERTp (IDH (wt)-TERTp(wt)) (P<0.0001) in midline than no-midline lobes. Logistic regression analysis indicated that locations of tumors associated with TERTp mutation (OR=0.540, 95% CI 0.324-0.900, P=0.018) and status of combinations of IDH and TERTp (IDH (mut)-TERTp (mut) vs. IDH (wt)-TERTp (wt) OR=0.162, 95% CI 0.075-0.350, P<0.001). In conclusion, grades II and III gliomas harboring TERTp mutation were located preferentially in the frontal lobe and rarely in midline. Association of IDH-TERTp status and tumor location suggests their potential values in molecular classification of grades II and III gliomas.

Protective effect of microRNA-30b on hypoxia/reoxygenation-induced apoptosis in H9C2 cardiomyocytes.

We examined the protective role of microRNA-30b (miR-30b) in ischemia-reperfusion (I/R)-induced injury in rat H9C2 cardiomyocytes. H9C2 cells were subjected to hypoxia-reoxygenation (H/R) treatment to simulate ischemia-reperfusion (I/R) injury. H9C2 cells were divided into: vehicle control (VC) group; scrambled inhibitors (INC) group; scrambled mimics (MNC) group; H/R+VC group; H/R+INC group; H/R+mimics group. H/R induced apoptosis was detected by flow cytometry and the pathways involved in miR-30b-mediated protection were examined by analyzing the expression of miR-30b, Bcl-2, Bax, Caspase-3, KRAS, p-AKT and total AKT in H9C2 cells. Overexpression of miR-30b mimic (H/R+mimics group) significantly increased Bcl-2 and Bcl-2/Bax levels and decreased Bax and Caspase-3 levels, compared with the H/R+VC group (all P<0.05). Consistent with this, the apoptosis rate was significantly decreased in the H/R+mimics group (P<0.05) compared with the H/R+VC group. Western blot analysis revealed that overexpression of miR-30b mimic resulted in significantly increase in AKT activation and decreased KRAS, compared to the H/R+VC group (both P<0.05). In conclusion, the H/R induced apoptosis decreased miR-30b expression, but over-expression of miR-30b inhibited H/R induced apoptosis. The observed miR-30b-mediated protection against H/R induced apoptosis involved the upregulation of Ras-PI3K-Akt pathway.

Serum fetuin-A levels in patients with cardiovascular disease: a meta-analysis.

BACKGROUND: Fetuin-A (FA) suppresses arterial calcification, promotes insulin resistance, and appears to be elevated in patients with cardiovascular diseases (CVD), but the data is still inconsistent. To clarify the correlation between serum FA levels and the presence and severity of CVDs, we performed this meta-analysis. METHOD: Potential relevant studies were identified covering the following databases: PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, China BioMedicine (CBM), and China National Knowledge Infrastructure (CNKI) databases. Data from eligible studies were extracted and included in the meta-analysis using a random-effects model. RESULTS: Ten case-control studies, including 1,281 patients with CVDs and 2,663 healthy controls, were included. The results showed significant differences in serum levels of FA between the CVDs patients and the healthy controls (SMD=1.36, 95%CI: 0.37-2.36, P=0.007). Ethnicity-subgroup analysis implied that low serum FA levels are related to CVDs in Caucasians (SMD=1.73, 95%CI: 0.20-3.26, P=0.026), but not in Asians (SMD=1.04, 95%CI: -0.33-2.40, P=0.138). CONCLUSION: The data indicated that decreased serum FA level is correlated with the development of CVDs. FA might be clinically valuable for reflecting the progression of CVDs.

[Association between differentiation potential of immortalized human mesenchymal stem cells and cluster of differentiation antigens].

OBJECTIVE: To explore the relationship between multi-differentiation potential of monoclonal immortalized human mesenchymal stem cells (hMSC-TERT) in vivo and their cluster of differentiation antigens (CD). METHODS: Monoclonal hMSC-TERT were isolated using limiting dilution. Direct immunofluorescence staining flow cytometry was used to detect the cluster of differentiation antigens (CD44, CD45, CD105) of these cell lines. Their adipocytic, osteogenic, neuronal differentiation potential in vitro were determined by Oil Red O staining, Von Kossa staining and immunocytochemistry for tubulin-ß III antibody. Then hMSC-TERTs were transplanted subcutaneously into severe combined immunodeficiency (SCID) mice. The cell grafts were removed and analyzed by immunohistochemistry for pathologic tissue markers for multi-differentiation potential of hMSC-TERT cells in vivo. RESULTS: CD105+ cell was 84.68% positive in hMSC-TERT-C19 while <5% in other monoclonal cell lines. The positive rate of cytokeratin in grafts formed by hMSC-TERT-C19 cell line in SCID mice was much higher than the others (P < 0.01). CONCLUSION: The positive CD105 of monoclonal hMSC-TERTs may be directly correlated with its epithelial differentiation potential.

[Effects of high plating densities on in vitro and in vivo differentiation capability of immortalized human mesenchymal stem cells].

OBJECTIVE: To determine whether different cell plating densities could influence the potential differentiation of immortalized human mesenchymal stem cells (hMSC-TERT). METHODS: Extensive characterization was performed for two independent cell lines derived from parental hMSC-TERT cell line based on different plating densities during expansion in culture: 1: 2 (hMSC-TERT2) and 1: 20 (hMSC-TERT20). Their adipocytic, osteogenic, neuronal differentiation potential in vitro and multidirectional differentiation potential in vivo were analyzed by immunohistochemistry for pathologic tissue markers. RESULTS: hMSC-TERT2 formed cellular adipose foci and mineralized tuberculum after in vitro induction while hMSC-TERT20 showed adipocytes but no adipose foci or mineralized tuberculum. The positive rate of hMSC-TERT2 formed tissues on VIM, GFAP and LCA (89.17% ± 5.97%, 72.5% ± 10.11% and 76.67% ± 11.15%) under SCID murine skin were more than that of hMSC-TERT20 formed tissues (0.33% ± 0.65%, 9.58% ± 4.29% and 22.08% ± 6.95%). CONCLUSION: The cell lines derived at high plating density may have more powerful differentiation potential in vitro and in vivo than those derived at low cell plating density.

[Associativity between differentiation potential and VEGF secretory capability of immortalized human mesenchymal stem cells].

OBJECTIVE: To investigate the multi-differentiation potential and VEGF secretory volume of monoclonal immortalized human mesenchymal stem cells (hMSC-TERT) and to determine the relationship between them. METHODS: Monoclonal hMSC-TERT were isolated using limiting dilution. The growth curves of them were detected by method of MTT. ELISA was used to detect the concentration of VEGF in the supernatant of those monoclonal hMSC-TERT. Their adipocytic, osteogenic, neuronal differentiation potential in vitro were determined by Oil Red O staining, Von Kossa staining and immunocytochemistry for Tubulin-ßIII antibody. Those Monoclonal hMSC-TERT were transplanted into the subcutaneously of severe combined immunodeficiency (SCID) mice. The grafts of those cells were removed and analyzed by immunohistochemistry for pathologic tissue markers to discover the multi-differentiation potential of those monoclonal hMSC-TERT in vivo. RESULTS: There was statistically significant difference between different monoclonal hMSC-TERT in mult differentiation potential and the decreased concentration of VEGF in the supernatant of those monoclonal hMSC-TERT from the 3(rd) day to the 5(th) day. The positive rates of CK in grafts formed by those monoclonal hMSC-TERT in SCID mice were direct correlation with the decreased concentration of VEGF in the supernatant of those cells. CONCLUSION: The secretory capability of VEGF of those monoclonal hMSC-TERT may direct correlation with the epithelial differentiation potential of those cells.

[Effect of monoclonal or different cell seeding densities on the differentiation potential of immortalized human mesenchymal stem cells in vitro and in vivo].

OBJECTIVE: To determine whether monoclonality or different cell seeding densities could influence the differentiation potential of immortalized human mesenchymal stem cells (hMSC-TERT) and to find an effective cultural method of hMSC-TERT in vitro. METHODS: From the parental hMSC-TERT cell line, we derived 30 monoclonal cell lines and two independent cell lines based on different plating densities during expansion in culture. Their adipocytic, osteogenic, neuronal differentiation potential in vitro and multidirectional differentiation potential in vivo were analyzed by immunohistochemistry for pathologic tissue markers. RESULTS: Monoclonal cell lines and the cell line derived at low seeding density had a lower differentiation potential in vitro than the cell line derived at higher cell seeding density. The differentiation potential of monoclonal hMSC-TERT cells were dissimilar. Some of monoclonal hMSC-TERT lines expressed epithelial differentiation potential in vivo while the parental hMSC-TERT cells line did not. CONCLUSION: Multiclonal hMSC-TERT cells cultured in high seeding density can keep the differentiation potential, cloning the hMSC-TERT cells before transplantation to find the special clones for special purpose of transplantation.

Antitumor activity of F90, an epidermal growth factor receptor tyrosine kinase inhibitor, on glioblastoma cell line SHG-44.

BACKGROUND: Over-expression of epidermal growth factor receptor (EGFR) is thought to be related to cell proliferation, invasion, metastasis, resistance to chemoradiotherapy and poor prognosis of various human cancers. Forty percent to fifty percent of glioblastoma multiforme (GBM) possess deregulated EGFR, which may contribute to the aggressive and refractory course of GBM. Therefore, blockade of EGFR signal transduction may be a promising treatment strategy for GBM. METHODS: MTT assay, cell growth curve assay and tumor xenograft model were used to evaluate the antitumor activity of F90 against SHG-44 in vitro and in vivo. Western blot assay was applied to evaluate the expression of p-EGFR, p-ERK1, p-JNK, p-P38, Bcl2 and P53 proteins. RESULTS: F90 inhibited the cell proliferation in a dose-dependent manner in vitro. The growth of SHG-44 tumor xenografts was suppressed by F90 at a high dose level (100 mg x kg(-1) x d(-1)). Phosphorylation of EGFR and activated downstream signaling proteins, such as ERK1, JNK and P38, were found to be depressed after incubation with F90 for 48 hours in vitro. Down-regulated Bcl2 protein and up-regulated P53 protein were also observed. CONCLUSIONS: The results demonstrate that F90 is effective in inhibiting the proliferation of SHG-44 cells in vitro and tumor growth in vivo, suggesting that F90 may be a new therapeutic option for treatment of GBM.

[Transthoracic echocardiography in transcatheter closure of atrial septal aneurysm combined with secoundum-type atrial septal defect].

OBJECTIVE: To explore the value of transthoracic echocardiography (TTE) in transcatheter closure of atrial septal aneurysm (ASA) combined with secoundum-type atrial septal defect (ASD). METHODS: Fourteen patients (3 males and 11 females) who had ASA combined with secoundum-type ASD were diagnosed by TTE or transesophageal echocardiography. The ASA projected to the right atrium in all patients. The width of basilar part was 13 approximately 24 (18.5+/-3.9) mm, and the vertical extent was 7 approximately 11(9.7+/-1.8) mm. Ten patients combined with single hole ASD and 4 patients with multiple hole ASD. Blood shifting from the left atrium to the right atrium was displayed in color Doppler in all patients. All patients were treated by transcatheter closure under the guiding of X fluoroscopy and TTE, and examined with TTE during the follow-up. RESULTS: Transcatheter closure was successfully performed by 14 occluders in all patients. No residual shunt was detected immediately by TTE after the procedure in all patients. During the 6 approximately 12 month follow-up, no residual shunt or occluder shifting was found, the dimensions of the heart became normal in 11 patients (79%) and were significantly decreased in 4. CONCLUSION: Transcatheter closure is feasible in patients with ASA combined with secoundum-type ASD, and extra attention must be paid to the specialty. TTE is very important in case selection before transcatheter closure, and it may be used to monitor and guide the procedure during transcatheter closure.

Effects of valsartan and indapamide on plasma cytokines in essential hypertension.

OBJECTIVE: investigate and compare the effect of valsartan and indapamide on inflammatory cytokines in hypertension. METHODS: Forty-one untreated patients with mild to moderate hypertension and 20 age and sex-matched normotensives were enrolled in this study. Hypertensives were treated with indapamide 1.5 mg/d (n=20) or valsartan 80 mg/d (n=21) for 4 weeks, and blood samples for determining monocyte chemotactic protein-1 (MCP-1), macrophage inflammatory protein-1 (MIP-1alpha), sP-selectin, asymmetric dimethylarginin (ADMA), angiotensin II (Ang II), and 6-keto-PGF1alpha were collected before the treatment and 4 weeks after the treatment. RESULTS: Hypertensives exhibited significantly higher blood pressure, as well as elevated plasma levels of MCP-1, MIP-1alpha, sP-selectin and serum level of ADMA compared with the normotensives. Nevertheless, there was no significant difference in serum 6-keto-PGF1alpha and Ang II between the hypertensives and the normotensives. After the treatment with indapamide or valsartan for 4 weeks, both the systolic and diastolic blood pressures, though still higher than those of the normotensives, decreased markedly. After the treatment with indapamide for 4 weeks, MCP-1, MIP-1alpha and sP-selectin slightly decreased, but not statistically significant (P>0.05). Those cytokines decreased significantly after being treated with valsartan for 4 weeks [(19.16+/-3.11) pg/mL vs (16.08+/-2.67) pg/mL, P<0.05; (27.74+/-8.36) pg/mL vs (17.64+/-7.59) pg/mL, P<0.05; (2.67+/-3.18) pg/mL vs (6.15+/-2.94) pg/mL, P<0.01]. In the 2 treatment groups, 6-keto-PGF1alpha markedly increased [(61.96+/-20.81) pg/mL vs (96.72+/-25.89) pg/mL, P<0.05; (63.25+/-16.92) pg/mL vs (143.22+/-43.45) pg/mL, P<0.01]; ADMA decreased significantly [(1.35+/-0.74) pg/mL vs (0.98+/-0.56) micromol/L, P<0.05; (1.31+/-0.68) pg/mL vs (0.71+/-0.52) micromol/L, P<0.01]. Though Ang II slightly increased, no statistical significance was found (P>0.05). CONCLUSION: The levels of MCP-1, MIP-1alpha, sP-selectin and ADMA were elevated in mild to moderate hypertensives. Valsartan and indapamide have similar blood pressure lowering effect. Valasartan exerts more significant effect on cytokines than indapamide does.

[Protective effect of losartan on injury induced by ox-LDL in endothelial cells and the relationship with asymmetric dimethylarginine].

OBJECTIVE: To investigate the protective effect of losartan against on injury induced by ox-LDL in endothelial cells and the relationship with asymmetric dimethylarginine (ADMA). METHODS: Endothelial injury was induced by incubation with ox-LDL 100 mg/L in cultured HUVECs for 24 h, and the levels of ADMA, lactate dehydrogenase (LDH), nitric oxide (NO) and tumor necrosis factor-alpha (TNF-alpha) in the conditioned medium were measured. The activity of dimethylarginine dimethylaminohydrolase (DDAH) of cultured endothelial cells was also determined. RESULTS: Incubation of endothelial cells with ox-LDL 100 mg/L for 24 h induced a marked elevation of the levels of ADMA, LDH and TNF-alpha in the conditioned medium and a significant decrease in the activity of DDAH and the content of NO (P < 0.05). Pretreatment with losartan (10(-8) - 10(-6) mmol/L) significantly inhibited the increased levels of ADMA, LDH and TNF-alpha, attenuated the decreased levels of NO and the decreased activity of DDAH induced by ox-LDL (P < 0.05). CONCLUSION: Losartan may preserve ox-LDL-induced endothelial cell injury by increasing the DDAH activity and decreasing the ADMA level.

Losartan reduces monocyte chemoattractant protein-1 expression in aortic tissues of 2K1C hypertensive rats.

BACKGROUND: Previous study has demonstrated an arterial inflammatory response in aortic tissues in several hypertensive models which can not be fully explained by hemodynamic forces. This study sought to investigate the effect of angiotensin II (Ang II)and its subtype-1 receptor blocker Losartan on the chemokine expression of monocyte chemoattractant protein-1(MCP-1) in aortic tissues of acute stage of 2-kidney-1-clip (2K1C) hypertensive rats. METHODS: 2K1C renovascular hypertension was produced in male Wistar-Kyoto(WKY) rats by placing a silver clip with an internal diameter of 0.2 mm around the left renal artery. The MCP-1 mRNA on aortic wall was detected by in situ hybridization and reverse transcription-polymerase chain reaction(RT-PCR); the levels of Ang II in plasma and aorta were determined by radioimmunoassay. The concentration of MCP-1 in supernatant of cultured endothelial cells (ECV-304) was measured by ELISA. RESULTS: No MCP-1 was exhibited in aortic wall of normotensive rats both by RT-PCR and in situ hybridization; it would be expressed on the aortic wall of rats in 7 days after 2K1C hypertensive model was formed, especially in intima. The expression of MCP-1 in aortic wall was increased with the duration of hypertension and correlated with local Ang II activity (r=0.594, P=0.02) other than those in plasma, it was decreased obviously after being treated by Losartan for 28 days (optical density of MCP-1/GAPDH ratio: 0, 0.58+/-0.10, 1.14+/-0.09, 1.52+/-0.20, 0.66+/-0.07, respectively, P<0.01). Ang II had increased the expression of MCP-1 in endothelial cells; the highest levels had been performed at 1x10(-7)mol/l Ang II or after 4 h, respectively; and losartan markedly reduced the expression of MCP-1. CONCLUSIONS: The expression of MCP-1 significantly increases in aortic tissues of the acute stage 2K1C hypertensive rats and is decreased markedly by treatment of losartan. These findings imply Ang II may be involved in facilitating MCP-1 production in hypertension, and may provide a molecular link between hypertension and the development of atherosclerosis.