Hong-Lin Chen

Curcumin Attenuates Cardiopulmonary Bypass-Induced Lung Oxidative Damage in Rats

Objective: Acute lung injury is a common complication after cardiopulmonary bypass (CPB). Oxidative damage greatly impacts CPB-induced lung ischemic pathogenesis and may represent a target for treatment. We aimed to investigate whether curcumin upregulates heme oxygenase 1 (HO-1) expression and ameliorates lung injury in a rat CPB model. Methods: A total of 80 male Sprague-Dawley rats were divided into 2 sets of 5 groups (n = 8 per group): sham; control (CPB); vehicle; low-dose curcumin (L-Cur); and high-dose curcumin (H-Cur). Animals were pretreated with a single intraperitoneal injection of vehicle, L-Cur (50 mg/kg), or H-Cur (200 mg/kg) 2 hours prior to CPB. Lung tissue, serum, and bronchoalveolar lavage fluid was harvested 2 or 24 hours postoperatively. In the control group, CPB-induced lung injury was confirmed by histopathologic examination and a significantly increased wet-to-dry lung weight ratio and pulmonary permeability index value was observed (P < .05 vs sham group). Cardiopulmonary bypass was associated with a marked rise in the level of malondialdehyde and myeloperoxidase and a fall in superoxide dismutase 2 and 24 hours after surgery (P < .05 vs sham group). Administration of curcumin ameliorated lung damage and reversed the oxidative stress markers in a partially dose-dependent manner (P < .05 vs vehicle group). Furthermore, HO-1 gene transcription and protein expression were elevated to a greater extent in the lungs after curcumin pretreatment compared with the vehicle pretreatment. Conclusions: Curcumin has the potential to provide protection from CPB-induced lung damage reflected in the expression of oxidative stress markers. The antioxidant effect of curcumin may be partly related to upregulation of HO-1.

The siRNA cocktail targeting VEGF and HER2 inhibition on the proliferation and induced apoptosis of gastric cancer cell

The aim of this study was to investigate the inhibitory effect of a siRNA cocktail targeting Vascular endothelial growth factor (VEGF) and Human epidermal growth factor receptor 2 (HER2) on cell proliferation, induced apoptosis and the expression of VEGF and HER2 in human gastric carcinoma cell. The silencing rate of pre-designed siRNAs that targeted VEGF and HER2 was detected by Real-time Quantitative PCR (RT-QPCR) analysis. Furthermore, the best silencing siRNA that targeted VEGF and HER2 was prepared as a cocktail to co-knockdown VEGF and HER2 expression at both mRNA and protein levels which were detected by RT-QPCR and Western blot analysis. Cell proliferation inhibition rates were determined by CCK8 assay. The effect of siRNA cocktail on cell apoptosis was determined by flow cytometry. The migration inhibition of siRNA cocktail was analyzed by wound-healing assay. The ability of VEGF to induce endothelial cells to proliferate was examined in HUVECs by the method of tube formation assay. The pre-designed siRNAs could inhibit VEGF and HER2 mRNA level. siRNA cocktail, and co-downregulation of VEGF and HER2 result in significant inhibition of gastric cancer growth and migration in vitro. The inhibition of VEGF and HER2 expressions can induce apoptosis of SGC-7901 cells.

NOB1 in Non-small-cell Lung Cancer: Expression Profile and Clinical Significance

Nin one binding (NOB1) gene has been reported up-regulated in several types of cancer. The aim of this study was to investigate the expression profile of NOB1 in non-small-cell lung cancer (NSCLC) and assess the clinical significance. qRT-PCR was used in the detection of NOB1 mRNA expression both in NSCLC tissue and in adjacent normal lung tissue. Western blot analysis and immunohistochemistry were used in the detection of NOB1 protein expression. The clinicopathological implications of NOB1 were analyzed statistically. It was confirmed by RT-qPCR that expression of NOB1 mRNA in NSCLC cells was higher than in human lung cells (P < 0.05), and NOB1 mRNA was also over-expressed in NSCLC tissue when compared with adjacent tissue and normal lung tissue (P < 0.05). Western blot analysis showed that NOB1 protein was significant increased in NSCLC cell lines compared with human lung cell line. Western blot analysis and immunohistochemistry showed that NOB1 protein was significant increased in NSCLC tissue compared with adjacent tissue and normal lung tissue (P < 0.05). There were significant associations between NOB1 expression and TNM stage, lymph node metastasis, and histopathological grade (P < 0.05), but not gender, age, smoke, or tumor diameter (P > 0.05). Our results suggest that enhanced expression of NOB1 gene plays an important role in the occurrence and development of NSCLC. NOB1 may be a potential therapeutic target in NSCLC.

Local Application of Rapamycin Inhibits Vein Graft Restenosis in Rabbits

OBJECTIVE The aim of this study was to investigate whether local application of rapamycin reduced neointimal formation in a rabbit model of venous disease. METHODS Each rabbit (n = 30; 2.5-3.5 kg) received a treated and a control graft. For the treated graft, 0.3 rapamycin mg was applied locally in Pluronic gel. The control graft received only the Pluronic gel. Grafts were harvested at 28 days for morphometric, immunohistochemical, and flow cytometry analysis. RESULTS In the control group, the intimal thickness was 63.72 ± 14.0 μm; in treated group, it was 77.76 ± 14.9 μm (P < .05). Immunohistochemically, proliferation cell nuclear antigen-positive cells were present in the control group and in the treatment group but not in normal external jugular veins. The control group showed much stronger expression than the treatment group (P < .05). Flow cytometry showed, among the control group, decreased G(0)G(1)-stage cells and increased S/G(2)M-stage cells. Among the treatment group, S/G(2)M stage cells were decreased compared with the control. The progression indexes of the control and treatment groups were 29.3 ± 7.15 and 20.1 ± 9.48, respectively, a remarkable decrease (P < .05). Proliferating cells in the control group were apparently inhibited by rapamycin. The treatment group showed positive staining for P27(kip1), but neither the control group nor the normal external jugular veins showed positive results (P < .05). The degree of reduction in intimal thickness and inhibition of proliferating cells in the treatment group correlated with the expression of P27(kip1). CONCLUSIONS We observed that perivascular application of rapamycin inhibited neointimal hyperplasia of vein grafts in a rabbit model, an effect that appeared to result from increased P27(kip1) expression.

High Expression of RIOK2 and NOB1 Predict Human Non-small Cell Lung Cancer Outcomes

Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related mortality worldwide. However, there is a shortage of suitable diagnostic markers for early stages of NSCLC, and therapeutic targets are limited. Right open reading frame (Rio) kinase 2 (RIOK2) and Nin one binding (NOB1) protein are important accessory factors in ribosome assembly and are highly expressed in malignant tumours; moreover, they interact with each other. However, the RIOK2 expression profile and its clinical significance as well as NOB1’s mechanism in NSCLC remain unknown. In this study, NSCLC cell lines and 15 NSCLC tumour tissues (paired with adjacent normal lung tissues) were collected for a real-time quantitative PCR (RT-qPCR) analysis. In addition, 153 NSCLC cases and 27 normal lung tissues were used in an immunohistochemical analysis to evaluate the RIOK2 and NOB1 expression profiles, their clinicopathological factors in NSCLC and their correlations with prognoses. RIOK2 and NOB1 were highly expressed in NSCLC cells and tissues, and their expression profiles were significantly associated with the Tumour Node Metastasis (TNM) clinical stage, lymph node metastasis, and differentiation. RIOK2 expression was correlated with NOB1. The results suggested that simultaneously determining the expression of RIOK2 and NOB1 will improve the diagnostic rate in early stages of NSCLC. Moreover, RIOK2 and NOB1 might be potential targets for NSCLC therapy.

Relationship between NOB1 expression and prognosis of resected non-small cell lung cancer

Background The aim of this study was to investigate the relationship between Nin one binding (NOB1) protein expression and prognosis for resected non-small cell lung cancer (NSCLC). Methods A prospective cohort of 70 consecutive patients with resected NSCLC was studied in 2009. Immunohistochemistry was used in the detection of NOB1 protein expression. Prognosis outcomes included overall survival (OS) and progression-free survival (PFS). The log-rank test and Cox hazard model were used to estimate the relationship between NOB1 expression and prognosis. Results In the 70 NSCLC tissue specimens, 14 (20%) stained -, 24 (34%) stained +, 21 (30%) stained ++ and 11 (16%) stained +++. The NOB1 high expression rate was 16%. NOB1 expression was significantly different between TMN stage (p=0.024) and lymph node metastasis (p=0.001), as well as histopathological grades (p=0.037). Median OS was 43 months (95% confidence interval [95% CI], 35-51 months), and median PFS was 37 months (95% CI, 25-49 months). OS and PFS were related to TMN stage and lymph node metastasis, as well as NOB1 expression (p<0.05). After adjustment for TMN stage and lymph node metastasis, the hazard ratio (HR) for high NOB1 expression was 1.7 (95% CI, 1.1-3.0, p=0.027) for OS, and 1.8 (95% CI, 1.3-3.7, p=0.031) for PFS. Conclusions Our results suggest that enhanced expression of NOB1 is related to poor overall survival and progression-free survival in patients with resected NSCLC.

The relationship between total red blood cells and plasma transfusion and acute lung injury risk after cardiac surgery: A retrospective study

The aim of our study was to determine whether red blood cells (RBCs) and fresh frozen plasma (FFP) transfusion is independently associated with the development of acute lung injury (ALI) in patients after cardiac surgery. In retrospective study, 165 patients were included. The results showed total fresh RBCs transfusion were not significantly increased in patients who developed ALI compared with patients who did not develop ALI (4.7 ± 2.4, 4 [0-12] units VS 4.0 ± 1.9, 3 [0-9] units, P = 0.119). FFP transfusion were also not significantly increased (704.1 ± 832.5, 600 [150-6500] ml VS 533.9 ± 323.6, 400 [125-3100] ml, P = 0.053). Multivariable logistic regression analysis showed that only age and CPB time were independent factors for ALI, but not for total RBCs and FFP transfused, with the adjusted OR 0.952 (95% CI 0.762-1.189, P=0.664), and 1.000 (95% CI 0.999-1.001, P = 0.480), respectively. In subgroup analysis, female patients showed a lower ALI incidence in low RBCs transfused group (23.9% VS 45.0%, OR 0.38, 95% CI 0.15-0.98) and in low FFP transfused group (22.0% VS 44.4%, OR 0.35, 95% CI 0.14-0.90). Our study demonstrates that red blood cells and fresh-frozen plasma transfusion are not related with ALI after cardiac surgery in our institution.

Effects of couple based coping intervention on self-efficacy and quality of life in patients with resected lung cancer

OBJECTIVE We aimed to assess the couple based coping intervention (CBCI) for self-efficacy and quality of life in patients with resected lung cancer, compared with individual coping intervention (ICI). METHODS From October to December 2015, 132 consecutive patients with resected lung cancer who were married/lived in a stable relationship were randomly assigned to the ICI group and the CBCI group. RESULTS The CBCI group had higher GSES compared with the ICI group at 2 month after operation, and at 6 month after operation (P<0.05). The CBCI group had higher VT, SF, RE, and MH score of SF-36 compared with the ICI group at 2 month after operation, and at 6 month after operation (P<0.05), but no significant differences were found in RP, PF, BP, and GH score of SF-36 compared between two groups (P>0.05) in these 2 time points. CONCLUSION Couple based coping intervention is more effective than individual coping intervention for improving the self-efficacy and the quality of life in patients with resected lung cancer. PRACTICE IMPLICATIONS Practitioners might like to consider using couple based coping intervention strategy to improve self-efficacy and quality of life in patients with resected lung cancer.

Curcumin attenuates myocardial ischemia–reperfusion injury

Background Cardiovascular diseases (CVDs) are at a badly high-risk of morbidity and mortality in the world. Methods Our study was attempted to investigate the cardioprotective role of curcumin. Hearts injury was assessed in isolated hearts and the rats of coronary artery ligated. Results and Conclusions The inhibition of pro-inflammatory cytokines was observed by curcumin in coronary artery ligated rats. ST segment was also reduced by curcumin. Triphenyltetrazolium chloride staining (TTC) staining and pathological analysis were also showed that curcumin could dramatically alleviate myocardial injury. Besides, the results in vitro also demonstrated that curcumin could improved the function of isolated hearts. Besides, the expressions of inflammation-related pathway in both rats and isolated hearts treated with curcumin were significantly decreased. The present study investigated the protective effects of curcumin on myocardial injury and its mechanism.

Effects of SDF-1/CXCR4 on Acute Lung Injury Induced by Cardiopulmonary Bypass

Acute lung injury (ALI) is one of the most important complications after cardiopulmonary bypass (CPB) and the complex pathophysiology remains to be resolved incomplete. SDF-1/CXCR4 chemokine axis can chemotactically accumulate inflammatory cell to local tissue and regulate the release of inflammatory factors, and SDF-1 has a strong chemotaxis effect on neutrophils with CXCR4. Since CPB animal model was difficult to establish, there was still no report about the effect of SDF-1/CXCR4 on neutrophil chemotaxis in ALI after CPB. Here, a stable CPB rat model was constructed to clarify the role of SDF-1/CXCR4 axis in the CPB-induced ALI. Real-time quantitative PCR (RT-qPCR), Western blot analysis, and enzyme-linked immunosorbent assay (ELISA) were used to detect the changes of SDF-1 and CXCR4 in lung tissues, blood, bronchoalveolar lavage (BALF), and/or isolated neutrophils. SDF-1/CXCR4 was increased after CPB, both of that were increased in blood; CXCR4 was increased in neutrophils; SDF-1/CXCR4 was also increased in BALF of CPB model. Results indicated that SDF-1/CXCR4 axis played a key role in the process of early ALI after CPB, also showed that lung injury was significantly reduce after blocking SDF-1/CXCR4 axis, suggest that CXCR4 might be a new target for ALI treatment.