1.Gastrin attenuates sepsis-induced myocardial dysfunction by down-regulation of TLR4 expression in macrophages.
Dandong FANG ; Yu LI ; Bo HE ; Daqian GU ; Mingming ZHANG ; Jingwen GUO ; Hongmei REN ; Xinyue LI ; Ziyue ZHANG ; Ming TANG ; Xingbing LI ; Donghai YANG ; Chunmei XU ; Yijie HU ; Hongyong WANG ; Pedro A JOSE ; Yu HAN ; Chunyu ZENG
Acta Pharmaceutica Sinica B 2023;13(9):3756-3769
Myocardial dysfunction is the most serious complication of sepsis. Sepsis-induced myocardial dysfunction (SMD) is often associated with gastrointestinal dysfunction, but its pathophysiological significance remains unclear. The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD. In mice, knockdown of the gastrin receptor, cholecystokinin B receptor (Cckbr), aggravated lipopolysaccharide (LPS)-induced cardiac dysfunction and increased inflammation in the heart, whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury. Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes, 48 h prior to LPS administration, alleviated LPS-induced cardiac injury in Cckbr-deficient mice. The intravenous injection of bone marrow macrophages (BMMs) overexpressing Cckbr reduced LPS-induced myocardial dysfunction. Furthermore, gastrin treatment inhibited toll-like receptor 4 (TLR4) expression through the peroxisome proliferator-activated receptor α (PPAR-α) signaling pathway in BMMs. Thus, our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD, which could be used to develop new treatment modalities for SMD.
2.miR-758-3p inhibits the proliferation and invasion of non-small cell lung cancer cells by targeting NUSAP1
Xiaomin LI ; Zhe YU ; Mei HUAI ; Hongyong HAN ; Shanshan CAO
Chinese Journal of Oncology 2021;43(1):113-117
Objective:To investigate the biological function of miR-758-3p and the underlying mechanism in non-small cell lung cancer (NSCLC).Methods:miR-758-3p mimics was transfected to A549 NSCLC cells, miRNA control was used as a negative control, cells transfected with nucleolar and spindle associated protein 1 (NUSAP1)-overexpression vector indicated as NUSAP1 group, cells co-transfected with miR-758-3p mimics and NUSAP1-overexpression vector indicated as miR-758-3p mimics+ NUSAP1 group. The effects of miR-758-3p on the proliferation, migration and invasion abilities of A549 cells were detected by cell counting kit-8 (CCK-8) and Transwell assays, respectively. Bioinformatics and dual luciferase reporter assay were used to predict and verify the target gene of miR-758-3p.Results:The expressions of miR-758-3p and NUSAP1 in A549 cells were significantly up-regulated at 24 hours after transfection with miR-758-3p mimics ( P<0.05). Compared with the miRNA control group (1.15±0.06), the OD value of miR-758-3p mimic group (0.78±0.06) was significantly decreased at 72 hours after transfection ( P<0.05). The number of migrated cells of miR-758-3p mimic group (119.04±11.49) was significantly lower than that of the control group (271.38±19.05) ( P<0.05). The number of invaded cells of miR-758-3p mimic group (71.33±5.36) was significantly lower than the control group (164.30±8.11) ( P<0.05). The result of dual-luciferase reporter assay showed that NUSAP1 was a direct target of miR-758-3p. Moreover, up-regulation of NUSAP1 abolished the inhibitory effects of miR-758-3p on the proliferation, migration and invasion abilities of A549 cells. Conclusion:miR-758-3p inhibits the proliferation, migration and invasion of NSCLC cells by targeting NUSAP1.
3.miR-758-3p inhibits the proliferation and invasion of non-small cell lung cancer cells by targeting NUSAP1
Xiaomin LI ; Zhe YU ; Mei HUAI ; Hongyong HAN ; Shanshan CAO
Chinese Journal of Oncology 2021;43(1):113-117
Objective:To investigate the biological function of miR-758-3p and the underlying mechanism in non-small cell lung cancer (NSCLC).Methods:miR-758-3p mimics was transfected to A549 NSCLC cells, miRNA control was used as a negative control, cells transfected with nucleolar and spindle associated protein 1 (NUSAP1)-overexpression vector indicated as NUSAP1 group, cells co-transfected with miR-758-3p mimics and NUSAP1-overexpression vector indicated as miR-758-3p mimics+ NUSAP1 group. The effects of miR-758-3p on the proliferation, migration and invasion abilities of A549 cells were detected by cell counting kit-8 (CCK-8) and Transwell assays, respectively. Bioinformatics and dual luciferase reporter assay were used to predict and verify the target gene of miR-758-3p.Results:The expressions of miR-758-3p and NUSAP1 in A549 cells were significantly up-regulated at 24 hours after transfection with miR-758-3p mimics ( P<0.05). Compared with the miRNA control group (1.15±0.06), the OD value of miR-758-3p mimic group (0.78±0.06) was significantly decreased at 72 hours after transfection ( P<0.05). The number of migrated cells of miR-758-3p mimic group (119.04±11.49) was significantly lower than that of the control group (271.38±19.05) ( P<0.05). The number of invaded cells of miR-758-3p mimic group (71.33±5.36) was significantly lower than the control group (164.30±8.11) ( P<0.05). The result of dual-luciferase reporter assay showed that NUSAP1 was a direct target of miR-758-3p. Moreover, up-regulation of NUSAP1 abolished the inhibitory effects of miR-758-3p on the proliferation, migration and invasion abilities of A549 cells. Conclusion:miR-758-3p inhibits the proliferation, migration and invasion of NSCLC cells by targeting NUSAP1.
4.NUSAP1 promotes lung cancer progression by activating AKT/mTOR signaling pathway
Zhe YU ; Xiaomin LI ; Mei HUAI ; Shanshan CAO ; Hongyong HAN ; Yanhua BI
Chinese Journal of Oncology 2020;42(7):551-555
Objective:To investigate the inhibitory effects of nucleolar and spindle associated protein 1 (NUSAP1) on lung cancer and the related mechanisms.Methods:A549 cells were transfected with NUSAP1 siRNA, the cell proliferation, migration and invasion, and apoptosis were detected by CCK8, Transwell and flow cytometry, respectively. Western blot was used to detect the expressions of apoptosis and AKT/mTOR signal pathway related proteins.Results:Compared with the negative control group, the proliferation [(0.610±0.058) vs (1.724±0.067), P<0.05], migration [(178.267±14.780) vs (272.464±36.232), P<0.05] and invasion [(73.527±6.617) vs (120.585±13.235), P<0.05] of NUSAP1 deleted A549 cells were significantly inhibited, while the apoptosis [(3.572±0.214)% vs (11.358±1.047)%, P<0.05] was significantly increased. The expressions of apoptosis related protein Bax and active-caspase 3 were increased ( P<0.05), while the expressions of anti-apoptosis protein Bcl-2 and proliferation related protein P70, the phosphorylation levels of AKT and mTOR were reduced in NUSAP1 knockdown cells ( P<0.05). Conclusion:NUSAP1 knockdown can inhibit the proliferation, migration and invasion, and promote the apoptosis of tumor cells through suppressing AKT/mTOR signaling pathway in lung cancer cells.
5.NUSAP1 promotes lung cancer progression by activating AKT/mTOR signaling pathway
Zhe YU ; Xiaomin LI ; Mei HUAI ; Shanshan CAO ; Hongyong HAN ; Yanhua BI
Chinese Journal of Oncology 2020;42(7):551-555
Objective:To investigate the inhibitory effects of nucleolar and spindle associated protein 1 (NUSAP1) on lung cancer and the related mechanisms.Methods:A549 cells were transfected with NUSAP1 siRNA, the cell proliferation, migration and invasion, and apoptosis were detected by CCK8, Transwell and flow cytometry, respectively. Western blot was used to detect the expressions of apoptosis and AKT/mTOR signal pathway related proteins.Results:Compared with the negative control group, the proliferation [(0.610±0.058) vs (1.724±0.067), P<0.05], migration [(178.267±14.780) vs (272.464±36.232), P<0.05] and invasion [(73.527±6.617) vs (120.585±13.235), P<0.05] of NUSAP1 deleted A549 cells were significantly inhibited, while the apoptosis [(3.572±0.214)% vs (11.358±1.047)%, P<0.05] was significantly increased. The expressions of apoptosis related protein Bax and active-caspase 3 were increased ( P<0.05), while the expressions of anti-apoptosis protein Bcl-2 and proliferation related protein P70, the phosphorylation levels of AKT and mTOR were reduced in NUSAP1 knockdown cells ( P<0.05). Conclusion:NUSAP1 knockdown can inhibit the proliferation, migration and invasion, and promote the apoptosis of tumor cells through suppressing AKT/mTOR signaling pathway in lung cancer cells.
6. Expression of NUSAP1 and its relationship with prognosis in non-small cell lung cancer
Zhe YU ; Xiaomin LI ; Mei HUAI ; Shanshan CAO ; Hongyong HAN ; Haitao LIU
Chinese Journal of Oncology 2019;41(7):522-526
Objective:
To investigate the expression of nucleolar and spindle-associated protein 1 (NUSAP1) in non-small cell lung cancer (NSCLC) and analyze its relationship with the prognosis of NSCLC patients.
Methods:
Real-time fluorescent quantitative PCR and immunohistochemical staining were performed to determine the expression of NUSAP1 in NSCLC tissues and adjacent tissues collected from hospital. The relationship between NUSAP1 expression and prognosis of NSCLC patients was analyzed by online database.
Results:
The expression level of NUSAP1 mRNA in tumor tissues was significantly higher than that of adjacent tissues (
7.Expression of NUSAP1 and its relationship with prognosis in non?small cell lung cancer
Zhe YU ; Xiaomin LI ; Mei HUAI ; Shanshan CAO ; Hongyong HAN ; Haitao LIU
Chinese Journal of Oncology 2019;41(7):522-526
To investigate the expression of nucleolar and spindle?associated protein 1 (NUSAP1) in non?small cell lung cancer ( NSCLC) and analyze its relationship with the prognosis of NSCLC patients. Methods Real?time fluorescent quantitative PCR and immunohistochemical staining were performed to determine the expression of NUSAP1 in NSCLC tissues and adjacent tissues collected from hospital. The relationship between NUSAP1 expression and prognosis of NSCLC patients was analyzed by online database. Results The expression level of NUSAP1 mRNA in tumor tissues was significantly higher than that of adjacent tissues (P<0.05). The high expression rate of NUSAP1 protein in NSCLC tissues was 58.0%( 29/50), significantly higher than 22.0%( 11/50) of adjacent tissues ( P<0.05). The high expression of NUSAP1 protein in NSCLC tissues was closely correlated with tumor size, lymph node metastasis and TNM stage ( P<0.05), but was not related to age and gender. The data showed that the expression level of NUSAP1 mRNA was inversely associated with the overall survival ( OS) of NSCLC patients ( P<0.001). The expression of NUSAP1 mRNA was significantly correlated with the pathological grade, clinical stage, gender, chemotherapy, smoking history, and histological type of NSCLC patients (P<0.05). Conclusions The expression of NUSAP1 is up?regulated in NSCLC, which is correlated with the growth and development of NSCLC and prognosis of the patients. These results indicate that NUSAP1 can be used as a potential prognostic marker for NSCLC.
8.Expression of NUSAP1 and its relationship with prognosis in non?small cell lung cancer
Zhe YU ; Xiaomin LI ; Mei HUAI ; Shanshan CAO ; Hongyong HAN ; Haitao LIU
Chinese Journal of Oncology 2019;41(7):522-526
To investigate the expression of nucleolar and spindle?associated protein 1 (NUSAP1) in non?small cell lung cancer ( NSCLC) and analyze its relationship with the prognosis of NSCLC patients. Methods Real?time fluorescent quantitative PCR and immunohistochemical staining were performed to determine the expression of NUSAP1 in NSCLC tissues and adjacent tissues collected from hospital. The relationship between NUSAP1 expression and prognosis of NSCLC patients was analyzed by online database. Results The expression level of NUSAP1 mRNA in tumor tissues was significantly higher than that of adjacent tissues (P<0.05). The high expression rate of NUSAP1 protein in NSCLC tissues was 58.0%( 29/50), significantly higher than 22.0%( 11/50) of adjacent tissues ( P<0.05). The high expression of NUSAP1 protein in NSCLC tissues was closely correlated with tumor size, lymph node metastasis and TNM stage ( P<0.05), but was not related to age and gender. The data showed that the expression level of NUSAP1 mRNA was inversely associated with the overall survival ( OS) of NSCLC patients ( P<0.001). The expression of NUSAP1 mRNA was significantly correlated with the pathological grade, clinical stage, gender, chemotherapy, smoking history, and histological type of NSCLC patients (P<0.05). Conclusions The expression of NUSAP1 is up?regulated in NSCLC, which is correlated with the growth and development of NSCLC and prognosis of the patients. These results indicate that NUSAP1 can be used as a potential prognostic marker for NSCLC.
9.Comparison of the therapeutic effect,safety and quality of life of different operation time on ureteral calculi after extracorporeal shock wave lithotripsy
Hongyong HAN ; Min WEI ; Lihong ZHAO ; Fenmei JIA
Chinese Journal of Primary Medicine and Pharmacy 2017;24(17):2607-2610
Objective To study the effect,safety and quality of life of different operation opportunity on the patients with ureteral calculi after extracorporeal shock wave lithotripsy.Methods From July 2015 to September 2016,45 patients with ureteral calculi who received lithotomy after 2 times of extracorporeal shock wave lithotripsy (ESWL) in our hospital were selected as observation group.Another 45 cases who received more than 3 times of ESWL and turend to lithotomy at the same period were selected as control group.The clinical effect was compared between the two groups.Results The total effective rate of the observation group was 95.56% (43/45),which was significantly higher than 71.11% (32/45) of the control group,the difference was statistically significant (χ2=9.680;P=0.002).The incidence rates of obstruction(17.78%),infection (26.67%) and hydronephrosis (24.44%) in the observation group were significantly lower than those in the control group (42.22%,64.44% and 60.00%),the differences were statistically significant (χ2=6.402,12.947,11.660;P=0.011,0.000,0.001).The scores of diet [(83.2±12.6)points],spirit[(85.6±13.3)points],sleep[(87.3±15.4)points] and psychological score[(85.9±13.6)points] in the observation group were significantly higher than those of the control group [(75.1±11.4)points,(76.2±11.6)points,(77.4±13.2)points and (73.2±10.7)points],the differences were statistically significant (t=3.003,4.038,3.514,4.513;P=0.004,0.000,0.001,0.000).The satisfaction rate of patients(97.78%) of the observation group was significantly higher than 77.78% of the control group,the difference was statistically significant (χ2=8.389;P=0.004).Conclusion Patients with ureteral calculi who received more than 2 times of ESWLand the stones in the body has not been effectively removed,should be accepted as soon as possible stone surgery treatment,it can improve the clinical effect,reduce the incidence of complications,improve the quality of life of patients.
10.Interventional treatment of lower extremity arteriosclerosis obliterans
Qiang GUAN ; Hongyong DUAN ; Ning LIANG ; Xiaofei YANG ; Feng HAN ; Zengqing LIU
Chinese Journal of General Surgery 2014;29(3):203-206
Objective To summarize the clinical efficacy of interventional treatment for lower extremity arteriosclerosis obliterans and its complications.Methods We analyzed sixty-nine patients with lower extremities arteriosclerosis obliterans undergoing interventional treatment from October 2011 to January 2013.During the same period,three patients were referred to us who suffered from the complications of interventional treatment.In these patients,eight were TASC ⅡA type,twenty-one were TASC Ⅱ B,twenty TASC Ⅱ C,and twenty-two TASC Ⅱ D lesions.All patients received CTA or DSA.Seventy patients were treated by interventional treatment,and two who had fractured stent underwent external iliacsuperficial femoral artery bypass grafting using artificial grafts.Results The technique success rate was 100%.The symptoms disappeared after surgery.During interventional treatment,one iliac artery ruptured,one patient suffered from arterial perforation and three patients suffered from distal embolization.Sixty-eight patients were followed-up for 9 ± 4 months.Conclusions Endovascular treatment has good early clinical efficacy.In order to reduce the incidence of complications,indication of interventional treatment should be controlled strictly and manipulation should be careful.

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