ABSTRACT
Objective To determine whether store-operated Ca2+ entry (SOCE) is involved in chronic hypoxia-induced alteration of intracellular Ca2 + concentration ([Ca2+] i) and proliferation in pulmonary arterial smooth muscle cells (PASMC).Methods Rat PASMCs were cultured and treated in normoxia (21％O2) or hypoxia (4％ O2) condition.The proliferation of PASMC was detected by cell counting kit-8 (CCK-8) assay.[Ca2 +] i,SOCE and the effects of store-operated Ca2 + channel (SOCC) inhibitors,SKF96365 and NiCl2,on SOCE in hypoxic PASMCs were tested by InCyte [Ca2 +] i measurement system.Results Hypoxia for 24-60 h augmented PASMC proliferation (1.12 ± 0.09 vs 0.71 ± 0.05,P ＜ 0.05) and [Ca2 +] i [(214.8 ± 20.4) nmol/L vs (115.2 ± 13.2) nmol/L,P ＜ 0.05] in a time-dependent manner with the maximum effect at 60 h.Perfusion of Ca2+-free Krebs solution containing nifedipine (5 μ mol/L),cyclopiazonic acid (CPA,10 μmol/L) in PASMCs caused a small transient increase of [Ca2+]i with peak [Ca2+]i (113.3 ± 49.3) nmol/L.Chronic hypoxia (4％ O2,60 h) enhanced [Ca2+]i level with peak value of (193.2 ± 22.7) nmol/L (P ＜ 0.05) in PASMC.After restoration of extracellular Ca2+,CPA caused marked increase of [Ca2+]i with peak value of (328.0 ± 56.7) nmol/L.Chronic hypoxia strengthened CPA-induced increase of [Ca2 +] i with peak value of (526.0 ± 33.7) nmol/L (P ＜ 0.05) in PASMCs.Either SKF96365 50 μmol/L or NiCl2 500 μmol/L distinctly attenuated CPA-induced enhancement of [Ca2 +] i,the peak value of which dropped from (526.0 ± 33.7) nmol/L to (170.4 ± 26.4) nmol/L (P＜0.05) or (177.4±45.9) nmol/L (P＜0.05) respectively.Conclusion Chronic hypoxia boosts the release of Ca2+ from sarcoplasmic reticulum and promotes the activity of SOCC and SOCE,leading to [Ca2 +] i elevation and proliferation of rat PASMCs.
ABSTRACT
Objective To explore the predictive value of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level in anthracycline-based chemotherapy-related cardiotoxicity of breast cancers.Methods A total of 135 breast cancer patients was analyzed if NT-proBNP was associated with chemotherapy-related cardiotoxicity.The level of NT-proBNP in the diagnosis of cardiotoxicity was assessed.Results A total of 22 patients (16.29％) had subsequent claims for cardiotoxicity events.NT-proBNP in cardiotoxicity group was significantly higher than that non-cardiotoxicity group (P ＜ 0.05).According to receiver operating characteristic (ROC) curve, the cut-off value of NT-proBNP was set at 350 pg/ml, specificity and sensitivity were 70.32％ and 82.58％ , respectively.Positive and negative predictive values were 78.12％ and 65.45％, respectively.Conclusions The present study is to confirm excellent clinical value of NTproBNP on cardiotoxicity.The level of NT-proBNP for early detection of cardiotoxicity has good prospects for high risk patients.
ABSTRACT
Objective To investigate the expression of paired amino acid cleaving enzyme 4 (PACE4) protein in non-small-cell lung cancer (NSCLC), analyze the correlation of its clinicopathologic characteristics, and investigate its significance in the process of occurrence, development, and metastasis of NSCLC.Methods Between January 2006 and May 2009, the First Affiliated Hospital of Guangzhou Medical College, 172 patients with NSCLC and 15 patients with non-neoplastic tissues were chosen.Immunohistochemistry was used to detect the expression of PACE4, and clinicopathologic characteristics of NSCLC were analyzed.Results (1)The positive expression rate of PACE4 protein in NSCLC was significantly higher than that in non-tumor tissues (P ＜ 0.05).PACE4 expression was observed in 111 of 172 (64.5％) NSCLC.PACE4 had cytoplasmic expression.(2)Clinicopathologically, PACE4 expression was significantly associated with lymph node metastasis (N stage) (P =0.007), and clinical stage (P =0.024).Conclusions High expression of PACE4 indicates that PACE4 may be involved in the processes of occurrence,development, and metastasis of NSCLC.
ABSTRACT
Purpose To investigate the expression and significance of epiderma1 growth factor receptor( EGFR)mutation-specific anti-bodies in 1ung adenocarcinoma. Methods Immunohistochemica1( IHC)technique was used to detect the expression of EGFR muta-tion-specific antibodies(EGFR-19,EGFR-21)and EGFR tota1 protein antibody(EGFR-P)in 171 cases of 1ung adenocarcinoma with resected specimens,and EGFR gene mutation was a1so performed by amp1ification refractory mutation aystem-PCR( ARMS-PCR). The expression of EGFR-19,EGFR-21 and EGFR-P mutant proteins was compared with EGFR gene mutation and their re1ationship with histo1ogica1 c1assification and c1inica1 characteristics were ana1yzed. Results The expression of EGFR mutant protein was corre1ated with the poor differentiation group inc1uding micropapi11ary and so1id predominant types( P=0. 021 ). EGFR-21 high expression was re1ated to p1eura1 invasion(P=0. 005). The coherence of IHC(with EGFR-19/21 antibodies)and ARMS-PCR was existed(Kappa>0. 4 ). Taking ARMS-PCR as a standard,the sensitivity and specificity of EGFR-19 and EGFR-21 were 65. 0% and 89. 4%, 70. 0% and 97. 6%,respective1y. Conclusions Expression of EGFR mutation-specific antibodies is associated with poor differentia-tion and p1eura1 invasion. It suggests a worse prognosis indicator in 1ung adenocarcinoma. Because of the coherence with ARMS-PCR, using IHC with mutation-specific antibodies to detect the mutant proteins of EGFR-19/21 may act as a pre1iminary screening method of EGFR gene mutation.
ABSTRACT
Objective To investigate the relationship between high sensitive C reactive protein(hsCRP) and monocyte chemotactic protein-1 (MCP-1) in patients with metabolic syndrome(MS).Methods Sixty-two patients with MS and 52 normal healthy individuals (NS) were recruited in the study.And the levels of hs-CRP and MCP-1 were detected by ELISA.The severity of Insulin resistance was calculated by homeostasismodel assessment of insulin resistance(HOMA-IR).The monocytes in blood were isolated,cultured and stimulated by different concentrations of CRP.MCP-lexpression of monocytes was measured by real-time PCR.Results Patients with MS displayed significantly higher serum levels of hs-CRP and MCP-1 compared with healthy control group [(80.26 ±35.52) nmol/L vs (3.12 ±2.55) nmol/L for hs-CRP,P ＜0.01 ; (15.35 ± 10.12) nmol/L vs (9.76 ± 6.15) nmol/L for MCP-1,P ＜ 0.05].There was significantly positive correlation between hs-CRP and MCP-1.Serum hs-CRP,MCP-1and insulin resistance index were positively correlated,respectively.In vitro experiments indicated that CRP could up-regulate MCP-1 expression of monocytes in a concentration-dependent way.When the concentration of CRP was 176nmol/L,the expression of MCP-1 could reach 105％ compared with non-stimulated group.Conclusion With the severity of the inflammatory response and enhanced insulin resistance,elevated serum CRP level may result in MCP-1 expression in patients with metabolic syndrome.
ABSTRACT
<p><b>OBJECTIVE</b>To study the treatment effects of cultured Cordyceps sinensis combined with glucocorticosteroid on experimental pulmonary fibrosis in rats induced by bleomycin.</p><p><b>METHOD</b>Fifty rats were randomly divided into five groups, including control group, model group, cultured C. sinensis groups, prednisone group, cultured C. sinensis combined with prednisone group. On experimental day 0, the rats were respectively intratracheally instilled with bleomycin, and rats in the control group and model group with the same volume of normal saline. One day after the injection, cultured C. sinensis and glucocorticosteroid was respectively given to rats daily by gastric gavage, while the same volume of normal saline was given to those in the control group and model group. On 28th d, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Histological changes of the lungs were evaluated by HE stain, Masson's trichrome stain. Collagen content of the lung tissue was assessed by hydroxyprolin concentration. Lung expression of CTGF protein was assessed by immunohistochemistry. The level of TGF-beta1 protein was measured by ELISA.</p><p><b>RESULT</b>Compared to model group, pulmonary fibrosis were alleviated in cultured C. sinensis and prednisone group, and CTGF expression, Hydroxyproline concentrations and protein TGF-beta1 were decreased. The combination effect of C. sinensis and prednisone group is augmented compared with using C. sinensis or prednisone group alone.</p><p><b>CONCLUSION</b>The cultured C. sinensis and prednisone alleviates pulmonary fibrosis, and the combination use of both drugs has synergia effects in anti-fibrous degeneration.</p>