1.Effect of urokinase on renal interstitial inflammation in rats with chronic cyclosporine A nephropathy and its possible mechanism.
Yin WANG ; Li MA ; Jun-rong TONG ; Zheng-mao LUO ; Feng HE
Journal of Southern Medical University 2008;28(5):835-838
OBJECTIVETo investigate the protective effect of urokinase on renal interstitial inflammation and fibrosis in rats with chronic cyclosporine A (CsA)-induced nephropathy.
METHODSMale SD rats were fed on low salt diet (0.05% sodium) for 7 days and randomized into 4 groups for treatment with CsA, CsA+continuous low-dose uPA (U2), intermittent CsA+ high-dose uPA (U6) or vehicle (control group). In the former 3 groups, the rats were subjected to daily intragastric administration of CsA (25 mg/kg) for 4 weeks to establish CsA-induced chronic nephropathy model, and those in U2 and U6 groups were given uPA at 2000 U/kg daily or at 6000 U/kg every 3 days, respectively. Four weeks after the treatment, the renal function and 24-h proteinuria were assessed, and Masson staining was used for examining fibrin deposition. Semi-quantitative immunohistochemical staining was employed for evaluation of ED-1-positive cells, urokinase-type plasminogen activator (uPA) and transforming growth factor-beta1 (TGF-beta 1).
RESULTSFour weeks after the treatment, the CsA-treated rats showed significantly elevated serum creatinine (Scr), blood urea nitrogen (BUN) and increased urine proteins. Continuous administration of low-dose uPA resulted in significantly reduced Scr, BUN and 24-h urine protein excretion, while intermittent high-dose uPA treatment did not produce such changes. CsA increased fibrin deposition, total number of macrophages in renal interstitium and TGF-beta1 expression in the renal tissue, which were significantly reduced in U2 group (P<0.05) but not in U6 group (P>0.05).
CONCLUSIONContinuous administration of low-dose uPA may reduce interstitial fibrin deposition and alleviate renal interstitial inflammation in rats with chronic CsA nephropathy, possibly by reducing the number of macrophages and TGF-beta1 expression in the renal tissue.
Animals ; Chronic Disease ; Cyclosporine ; Fibrosis ; Kidney ; drug effects ; metabolism ; pathology ; Macrophages ; drug effects ; metabolism ; pathology ; Male ; Nephritis ; chemically induced ; drug therapy ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; biosynthesis ; Urokinase-Type Plasminogen Activator ; therapeutic use
2.Effects of urokinase on renal interstitial fibrosis and transforming growth factor-beta1 in the kidney of rats with chronic cyclosporine A nephropathy.
Yin WANG ; Jun-rong TONG ; Zheng-mao LUO ; Feng HE ; Li MA
Journal of Southern Medical University 2009;29(12):2449-2452
OBJECTIVETo investigate the effects of urokinase on renal interstitial fibrosis and transforming growth factor-beta1 (TGF-beta1) in the kidney of rats with chronic cyclosporine A nephropathy.
METHODSMale Sprague-Dawley rats on low-salt diet were randomly divided into control (VH), CsA-treated (CsA), CsA+2000 U/kg.day uPA (CsA+U2) and CsA+6000 U.kg.3 days (CsA+U6) groups. The rats were given CsA intragastrically for 4 weeks to prepare CsA-induced chronic nephropathy model. Masson staining was used to examine fibrin deposition. Western blotting and reversal transcription polymerase chain reaction were employed to evaluate urokinase-type plasminogen activator (uPA) and TGF-beta1 protein and gene expressions, respectively.
RESULTSCsA can increase fibrin deposition and the expression of TGF-beta1 in the renal tissue, which were significantly reduced after uPA treatment (P<0.05).
CONCLUSIONContinuous low-dose uPA treatment can reduce renal interstitial fibrosis in rats possibly in association with its inhibitory effect on TGF-beta1 expression.
Animals ; Cyclosporine ; Fibrosis ; prevention & control ; Kidney ; pathology ; Kidney Diseases ; chemically induced ; drug therapy ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Transforming Growth Factor beta1 ; metabolism ; Urokinase-Type Plasminogen Activator ; pharmacology ; therapeutic use
3. Outcomes of splenectomy in relapsed/refractory autoimmune hemolytic anemia
Sibin FAN ; Zhijun WANG ; Qiang MAO ; Chunfan TONG ; Weitao ZHAI ; Yizhou ZHENG ; Chaoxia SUN ; Jun SHI
Chinese Journal of Hematology 2019;40(2):132-136
Objective:
To evaluate the outcomes of splenectomy in the treatment of relapsed/refractory autoimmune hemolytic anemia (AIHA).
Methods:
Retrospective analysis was performed in 30 cases with relapsed/refractory AIHA who were treated with splenectomy in our hospital. The pre- and post-operative blood routine indexes and responses were followed up.
Results:
Among the 30 relapsed/refractory AIHA patients, 20 were pure AIHA (including 13 patients with warm antibody AIHA, 2 with warm-cold double antibody AIHA and 5 with Coombs negative AIHA) and 10 were Evans syndrome. The short-term response was evaluated 10-14 days after operation, and the overall response rate (ORR) of short-term response was 90% [12 cases in complete response (CR), 6 cases in partial response (PR)] in 20 therapeutic evaluable cases. Among 13 patients with long-term follow-up data, except 3 patients with Evans syndrome died (2 cases were refractory to splenectomy, 1 case relapsed after surgery), the ORR of 10 patients with relapsed/refractory pure AIHA at 6 months and 12 months were 90% (9/10) and 70% (7/10), respectively, with a median follow-up of 14 (4-156) months. At the end of follow-up, 3 cases had maintained CR for more than 3 years.
Conclusion
The short-term response of splenectomy as a second-line treatment for relapsed/refractory AIHA is satisfactory, and long-term outcome of splenectomy is up to 70% at 1 year. Approximately one-third of patients could maintain sustained remission.
4.Outcomes of splenectomy in relapsed/refractory autoimmune hemolytic anemia.
Si Bin FAN ; Zhi Jun WANG ; Qiang MAO ; Chun Fan TONG ; Wei Tao ZHAI ; Yi Zhou ZHENG ; Chao Xia SUN ; Jun SHI
Chinese Journal of Hematology 2019;40(2):132-136
Objective: To evaluate the outcomes of splenectomy in the treatment of relapsed/refractory autoimmune hemolytic anemia (AIHA). Methods: Retrospective analysis was performed in 30 cases with relapsed/refractory AIHA who were treated with splenectomy in our hospital. The pre- and post-operative blood routine indexes and responses were followed up. Results: Among the 30 relapsed/refractory AIHA patients, 20 were pure AIHA (including 13 patients with warm antibody AIHA, 2 with warm-cold double antibody AIHA and 5 with Coombs negative AIHA) and 10 were Evans syndrome. The short-term response was evaluated 10-14 days after operation, and the overall response rate (ORR) of short-term response was 90% [12 cases in complete response (CR), 6 cases in partial response (PR)] in 20 therapeutic evaluable cases. Among 13 patients with long-term follow-up data, except 3 patients with Evans syndrome died (2 cases were refractory to splenectomy, 1 case relapsed after surgery), the ORR of 10 patients with relapsed/refractory pure AIHA at 6 months and 12 months were 90% (9/10) and 70% (7/10), respectively, with a median follow-up of 14 (4-156) months. At the end of follow-up, 3 cases had maintained CR for more than 3 years. Conclusion: The short-term response of splenectomy as a second-line treatment for relapsed/refractory AIHA is satisfactory, and long-term outcome of splenectomy is up to 70% at 1 year. Approximately one-third of patients could maintain sustained remission.
Anemia, Hemolytic, Autoimmune
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Antibodies, Monoclonal, Murine-Derived
;
Humans
;
Retrospective Studies
;
Rituximab
;
Splenectomy
5.A rare case of spontaneous renal cholesterol crystallization embolism.
Ling-Yun CHEN ; Yan-Ping HUANG ; Shao-Jun LIU ; Pei-Jyu MAO
Chinese Medical Journal 2019;132(3):367-369
Aged
;
Creatinine
;
blood
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Crystallization
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Embolism, Cholesterol
;
blood
;
diagnosis
;
drug therapy
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Humans
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Kidney
;
metabolism
;
pathology
;
Male
6.Potential Antitumor Activity of SIM-89 in Non-Small Cell Lung Cancer Cells.
Jun PEI ; Tianqing CHU ; Minhua SHAO ; Jiajun TENG ; Huifang SHA ; Aiqing GU ; Rong LI ; Jialin QIAN ; Weifeng MAO ; Ying LI ; Baohui HAN
Yonsei Medical Journal 2017;58(3):581-591
PURPOSE: c-Met and its ligand, hepatocyte growth factor (HGF), play a critical role in oncogenesis and metastatic progression. The aim of this study was to identify inhibited enzymogram and to test the antitumor activity of SIM-89 (a c-Met receptor tyrosine kinase inhibitor) in non-small cell lung cancer. MATERIALS AND METHODS: Z′-LYTE kinase assay was employed to screen the kinase enzymogram, and mechanism of action (MOA) analysis was used to identify the inhibited kinases. Cell proliferation was then analyzed by CCK8 assay, and cell migration was determined by transwell assay. The gene expression and the phosphorylation of c-Met were examined by realtime-PCR and western blotting, respectively. Finally, the secretion of HGF was detected by ELISA assay. RESULTS: c-Met, activated protein kinase (AMPK), and tyrosine kinase A (TRKA) were inhibited by SIM-89 with the IC₅₀ values of 297 nmol/L, 1.31 µmol/L, and 150.2 nmol/L, respectively. SIM-89 exerted adenosine triphosphate (ATP) competitive inhibition on c-Met. Moreover, the expressions of STAT1, JAK1, and c-Met in H460 cells were decreased by SIM-89 treatment, and c-Met phosphorylation was suppressed in A549, H441, H1299, and B16F10 cells by the treatment. In addition, SIM-89 treatment significantly decreased the level of HGF, which accounted for the activation of c-Met receptor tyrosine kinase. Finally, we showed cell proliferation inhibition and cell migration suppression in H460 and H1299 cells after SIM-89 treatment. CONCLUSION: In conclusion, SIM-89 inhibits tumor cell proliferation, migration and HGF autocrine, suggesting it's potential antitumor activity.
Adenosine Triphosphate
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Blotting, Western
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Carcinogenesis
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Carcinoma, Non-Small-Cell Lung*
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Cell Movement
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Cell Proliferation
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Enzyme-Linked Immunosorbent Assay
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Gene Expression
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Hepatocyte Growth Factor
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Lung Neoplasms
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Phosphorylation
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Phosphotransferases
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Protein Kinases
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Protein-Tyrosine Kinases
7.Effect of purple sweet potato on lipid metabolism and oxidative stress in hyperlipidemic rats.
Wei-ping CHEN ; Tong-jun MAO ; Lin FAN ; Yu-han ZHOU ; Jing YU ; Yun JIN ; Peng-chao HOU
Journal of Zhejiang University. Medical sciences 2011;40(4):360-364
OBJECTIVETo investigate the effect of purple sweet potato on lipid metabolism and oxidative stress in hyperlipidemic rats.
METHODSForty male SD rats were randomly divided into 4 groups: normal control group, high-fat control group, high purple sweet potato groups, low purple sweet potato group. The rats were fed with different diets for 6w respectively.
RESULTSSerum TC, TG levels were significantly lower in high dosage group than in high-fat control group; while only serum TG was significantly lower in low dosage group than in high-fat control group, these changes started at the third week and lasted to the end of experiment. Serum LDL-C and AI levels were significantly lower in high and low dosage group than in high-fat control group, whereas, serum HDL-C was significantly higher than that in high-fat control group at w3 and lasted to the end of experiment. Serum SOD was significantly higher in high and low dosage group than in high-fat control group, whereas, serum MDA was significantly lower than that in high-fat control group at w6.
CONCLUSIONPurple sweet potato can decrease serum lipids and reduce hepatic oxidative stress in hyperlipidemic rats.
Animals ; Disease Models, Animal ; Hyperlipidemias ; metabolism ; Ipomoea batatas ; Lipid Metabolism ; Lipids ; blood ; Male ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley
8.Investigation of distribution of bacteria and fungi in severe acute pancreatitis.
Yi-bing PENG ; Jie HUANG ; Shuai QIN ; Jun WU ; En-qiang MAO ; Yao-qing TANG ; Sheng-dao ZHANG
Chinese Journal of Surgery 2010;48(7):496-501
OBJECTIVETo investigate the spectrum of bacteria and fungi in different sites in severe acute pancreatitis (SAP).
METHODSThe prospective study was performed in 205 patients with SAP treated from January 2000 to December 2008. The Infection rate of bacteria and fungi was observed prospectively in pancreatic necrosis and(or) pus form abdomen, body fluids and deep vein catheter in SAP. Body fluids and pancreatic necrosis were cultured twice a week. Central venous catheter was cultured when it had been placed for two weeks. Blood was cultured for bacteria and fungi when body temperature was more than 39 degrees C. Constituent ratio of bacteria and fungi was observed in different sites and in all sites within 28 days after onset of SAP.
RESULTSThere were 937 pathogens, among which infection rates of gram-negative bacteria was higher than gram-positive bacteria and fungi (P < 0.05), the infection rates of gam-positive bacteria and fungi were similar. Infection rates of gram-negative bacteria in pancreatic necrosis (55.2%), bile (55.4%), blood (68.1%) and central venous catheter (44.4%) were increased significantly (P < 0.05) compared with gram-positive bacteria and (30.2%, 33.9%, 23.4%, 38.9%) and fungi (14.6%, 10.7%, 8.5%, 16.7%); however, infection rate of fungi (59.6%) was increased significantly (P < 0.05) compared with gram-negative bacteria (24.0%) and gram-positive bacteria (16.3%) in urine; infection rate of gram-negative bacteria (53.2%) was significantly higher (P < 0.05) than that of fungi (27.1%) and gram-positive bacteria (19.7%) in sputum. Infection rate of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii and Stenotrophomonas maltophilia) in gram-negative bacteria in pancreatic necrosis, bile, blood, central venous catheter and sputum was significantly higher than that of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli and Enterobacter cloacae) (P < 0.01); infection rate of zymogenic bacteria (Klebsiella pneumoniae, Escherichia coli) was higher significantly (P < 0.01) than that of non-zymogenic bacteria (Pseudomonas aeruginosa, Acinetobacter baumannii). Infection rate of staphylococcus aureus, Staphylococcus epidermidis and Staphylococcus haemolyticus was significantly higher (P < 0.05) than that of Enterococcus faecalis and Enterococcus faecium in pancreatic necrosis and sputum;but infection rate of Enterococcus faecium in bile and urine was significantly higher than other gram-positive bacteria (P < 0.05). There was not difference among gram-positive bacteria;however, infection rate of Staphylococcus epidermidis in central venous catheter was increased significantly (P < 0.05). Infection rate of candida mycoderma in pancreatic necrosis, bile, urine and sputum was significantly higher than that of tricho bacteria (P < 0.05). The peak of infection rate of microbes in body fluid was within 2 to 3 weeks.
CONCLUSIONSConstituent ratio in gram-negative, gram-positive bacteria and fungi as well as their species in different sites is diverse. The peak of infection rate of microbes is 2 to 3 weeks after onset of the disease.
Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacteria ; isolation & purification ; Female ; Fungi ; isolation & purification ; Humans ; Male ; Middle Aged ; Pancreatitis ; microbiology ; Prospective Studies ; Young Adult
9.Role of integrin-linked kinase in renal tubular epithelial-mesenchymal transition and the regulatory effect of urokinase on its expression in mice with obstructive nephropathy.
Feng HE ; Lu YU ; Jun-rong TONG ; Zheng-mao LUO ; Qi-zhi ZHU ; Yin WANG ; Jian-lin ZHANG
Journal of Southern Medical University 2009;29(5):909-913
OBJECTIVETo investigate the role of integrin-linked kinase (ILK) on renal tubular epithelial-mesenchymal transition and the regulatory effect of urokinase on LIK expression in mice with obstructive nephropathy.
METHODSNormal male mice were randomly divided into sham-operated group (n=20), unilateral ureteral obstruction (UUO) group (n=28), and UUO with urokinase treatment group (uPA, n=28), and UUO was induced surgically in the latter two groups. The mice were sacrificed on days l, 3, 7 and 14 after the surgery, and renal interstitial fibrosis (RIF) was graded according to the result of Masson staining. The expression of ILK in the renal tissues of the rats was examined by immunofluorescence staining and Western blotting, and the expression of E-cadherin was detected by immunohistochemistry. RT-PCR was used to examine the mRNA expressions of ILK, E-cadherin and alpha-smooth muscle actin (alpha-SMA).
RESULTSThe expressions of ILK mRNA and protein were significantly increased in UUO group, but significantly decreased by treatment with uPA (P<0.05). The expression of alpha-SMA mRNA level was significantly increased, while E-cadherin decreased in mice with UUO on day 3 after the surgery. Treatment with uPA significantly inhibited such effects (P<0.05).
CONCLUSIONILK plays an important role in renal interstitial fibrosis by mediating epithelial-mesenchymal transition. Urokinase attenuates renal tubulointerstitial fibrosis in mice with UUO possibly by inhibiting ILK expression and preventing tubular epithelial-mesenchymal transition.
Animals ; Cell Transdifferentiation ; drug effects ; Epithelial Cells ; metabolism ; pathology ; Fibrosis ; Kidney Tubules ; metabolism ; pathology ; Male ; Mesoderm ; pathology ; Mice ; Protein-Serine-Threonine Kinases ; genetics ; metabolism ; physiology ; Ureteral Obstruction ; genetics ; metabolism ; pathology ; Urokinase-Type Plasminogen Activator ; pharmacology
10.Effect of shexiang baoxin pill on the function of vascular endothelium in patients with diabetes mellitus type 2 complicated with angina pectoris.
Hongying YE ; Juan DU ; Dingguo SHEN ; Shujun SHI ; Tong HUANG ; Zhongli HONG ; Yu-Shan MAO ; Fu-Jun LI ; Li-Nuo ZHOU
Chinese Journal of Integrated Traditional and Western Medicine 2004;24(12):1077-1079
OBJECTIVETo study the effect of Shexiang Baoxin pill (SBP) on the vascular endothelial function in patients with diabetes mellitus type 2 (DM2) complicated with angina pectoris.
METHODSTwo weeks after runin, according to the randomizing table, 111 patients were divided into two groups, the XBP group (56 patients) and the control group (55 patients, treated with delayed-released isosorbide mononitrate, DRIM), they were treated for 6 months. In the treatment period, the episodes of angina attack and condition of rescue medication were recorded in the daily card, and brachial arterial changes of endothelium-dependent relaxing function before and after treatment were measured by B-ultrasonography.
RESULTSComparison between the two groups in episodes of angina attack and rescue medication were insignificantly different. In the control group, the basal value of brachial arterial inner diameter before and after treatment was 3.68 +/- 0.56 mm and 3.70 +/- 0.58 mm respectively, those before and after responsive congestion was 5.44 +/- 0.81% vs 5.68 +/- 0.83%, and those before and after taking nitroglycerin was 19.8 +/- 4.9% vs 20. +/- 5.2%, all showed insignificant difference (P > 0.05). In the SBP group, the corresponding basal value was 3.73 +/- 0.62 mm vs 3.71 +/- 0.59 mm, and those after taking nitroglycerin 18.8 +/- 4.5 % vs 19.2 +/- 5.8%, also showed insignificant difference, but those before and after responsive congestion (5.69 +/- 0.79 % vs 9.56 +/- 3.82 %) did show significant difference (P < 0.01).
CONCLUSIONXBP could improve the vascular endothelial function in patients with DM2 complicated with angina pectoris.
Aged ; Angina Pectoris ; complications ; drug therapy ; Angioplasty, Balloon, Coronary ; Diabetes Mellitus, Type 2 ; complications ; drug therapy ; Drugs, Chinese Herbal ; therapeutic use ; Endothelium, Vascular ; drug effects ; physiopathology ; Female ; Humans ; Male ; Middle Aged ; Phytotherapy