3.Effect of hypoxia on the gene profile of human bone marrow-derived mesenchymal stem cells.
En-Hui WU ; Hai-Sheng LI ; Tong ZHAO ; Jun-Die FAN ; Xin MA ; Lei XIONG ; Wu-Ju LI ; Ling-Ling ZHU ; Ming FAN
Acta Physiologica Sinica 2007;59(2):227-232
Our previous study demonstrates that hypoxia promotes human bone marrow-derived mesenchymal stem cell (hMSC) proliferation. The aim of the present study was to investigate the gene profile involved in this process by using cDNA microarray. Cultured hMSCs were treated with hypoxia (3% O(2)) for 4 h, 12 h, 24 h, 36 h, 48 h and 72 h, respectively. Then these cells were collected to prepare total RNA. Hypoxia-induced gene expression profile was examined and analyzed by GenePix Pro 4.0 software. Some of cDNA microarray results were confirmed by RT-PCR. Microarray analysis identified that 282 genes expressed differentially, of which most were involved in metabolism. The number of differentially expressed genes at different hypoxia time points was different, and most genes were regulated after 24-hour hypoxia. Among the 282 differentially expressed genes, 4 hypoxia-inducible factor 1 (HIF-1) targeted genes and 10 genes that changed at 3 continuous time points were found. The results obtained indicated that 4 HIF-1 targeted genes, i.e., transforming growth factor beta3 (TGFbeta3), phospho-glycerate kinase 1 (PGK1), insulin-like growth factor binding protein 3 (IGFBP3) and BCL2/adenovirus E1B 19 kDa interacting protein 3 (BNIP3), displayed up-regulated pattern at 36 h under hypoxia. BNIP3 displayed a dynamically up-regulated pattern at 12, 36 and 72 h under hypoxia. However, TGFbeta3 and PGK1 were down-regulated at 72 h. In addition, the gene expressions of adenylate kinase 3-like 1 (HAC), neurofilament light polypeptide 68 kDa (NEFL), N-myc downstream regultated gene 1 (NDRG1), discoidin domain receptor family member 1 (DDR1), tribbles homolog 3 (TRIB3), nucleoprotein (AHNAK) and eukaryotic elongation factor selenocyteine-tRNA-specific (EESTS) were up-regulated. Moreover, the gene expressions of EESTS, NEFL were up-regulated at 5 different time points under hypoxia. Furthermore, it was found that the gene expressions of histone cluster 1 (HIS1) and transferring receptor (TFRC) were down-regulated. These results suggest that the proliferation of hMSCs induced by hypoxia is a complex process in which a number of genes may be involved.
Bone Marrow Cells
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cytology
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Cell Hypoxia
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Cell Proliferation
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Cells, Cultured
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Gene Expression Profiling
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Gene Expression Regulation
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Humans
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Mesenchymal Stromal Cells
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cytology
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metabolism
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Oligonucleotide Array Sequence Analysis
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Oxygen
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metabolism
;
Transcriptome
4.Expression of heparanase and nuclear factor kappa B in pancreatic adenocarcinoma.
Wu-Jun WU ; Cheng-En PAN ; Qing-Guang LIU ; Ke-Wei MENG ; Hai-Bo YU ; You-Li WANG ; Lin ZHAO
Journal of Southern Medical University 2007;27(8):1267-1270
OBJECTIVETo detect the expressions of heparanase and nuclear factor kappa B p65 (NF-kappaB p65) in pancreatic adenocarcinomas and analyze their relation to patients' prognosis and the regulatory mechanism of NF-kappaB on heparanase expression.
METHODSHeparanase and NF-kappaB p65 proteins in the tumor and adjacent tissues were detected by immunohistochemistry in 48 patients with pancreatic adenocarcinoma and analyzed for their clinicopathological significance.
RESULTSHeparanase and NF-kappaB p65 proteins were found in 30 (62.5%) and 22 (45.9%) tumor specimens, respectively, a rate significantly higher than that in the adjacent tissues. High heparanase expression was closely related to advanced TNM stage (P=0.031), lymph node metastasis (P=0.003) and decreased 3-year postoperative survival (20.0% vs 0%, P=0.001). NF-kappaB p65 expression was associated with lymph node metastasis (P=0.017) and distant metastasis (P=0.031), but had a higher positive rate in heparanase-positive cases than in heparanase-negative cases (P=0.018). Multivariate analysis showed that neither heparanase nor NF-kappaB p65 was the independent prognostic factors.
CONCLUSIONHeparanase is overexpressed in pancreatic adenocarcinomas in association with decreased postoperative survival. NF-kappaB may up-regulate heparanase expression and promote heparanase-dependent tumor invasion and metastasis.
Adenocarcinoma ; diagnosis ; genetics ; Adult ; Aged ; Animals ; Female ; Gene Expression Regulation, Neoplastic ; Glucuronidase ; metabolism ; Humans ; Male ; Middle Aged ; Multivariate Analysis ; Pancreatic Neoplasms ; diagnosis ; genetics ; Prognosis ; Risk Factors ; Transcription Factor RelA ; metabolism
5.Electrophysiological study on rat conduit pulmonary artery smooth muscle cells under normoxia and acute hypoxia.
Ying HU ; Fei ZOU ; Chun-Qing CAI ; Hang-Yu WU ; Hai-Xia YUN ; Yun-Tian CHEN ; Guo-En JIN ; Ri-Li GE
Acta Physiologica Sinica 2006;58(5):477-482
The present study was designed to investigate the electrophysiological characteristics of rat conduit pulmonary artery smooth muscle cells (PASMCs) and the response to acute hypoxia. PASMCs of the 1st to 2nd order branches in the conduit pulmonary arteries were obtained by enzymatic isolation. The PASMCs were divided into acute hypoxia preconditioned group and normoxia group. Hypoxia solutions were achieved by bubbling with 5% CO2 plus 95% N2 for at least 30 min before cell perfusion. Potassium currents were compared between these two groups using whole-cell patch clamp technique. The total outward current of PASMCs was measured under normoxia condition when iBTX [specific blocking agent of large conductance Ca-activated K(+) (BK(Ca)) channel] and 4-AP [specific blocking agent of delayed rectifier K(+) (K(DR)) channel] were added consequently into bath solution. PASMCs were classified into three types according to their size, shape and electrophysiological characteristics. Type I cells are the smallest with spindle shape, smooth surface and discrete perinuclear bulge. Type II cells show the biggest size with banana-like appearance. Type III cells have the similar size with type I, and present intermediary shape between type I and type II. iBTX had little effect on the total outward current in type I cells, while 4-AP almost completely blocked it. Most of the total outward current in type II cells was inhibited by iBTX, and the remaining was sensitive to 4-AP. In type III cells, the total outward current was sensitive to both iBTX and 4-AP. Acute hypoxia reduced the current in all three types of cells: (1614.8+/-62.5) pA to (892.4+/-33.6) pA for type I cells (P<0.01); (438.3+/-42.8) pA to (277.5+/-44.7) pA for type II cells (P<0.01); (1 042.0+/-37.2) pA to (613.6+/-23.8) pA for type III (P<0.01), and raised the resting membrane potentials (E(m)) in all these three types of cells: (-41.6+/-1.6) mV to (-18.6+/-1.5) mV (P<0.01), (-42.3+/-3.8) mV to (-30.6+/-3.0) mV (P<0.01), (-43.3+/-1.6) mV to (-28.4+/-1.4) mV (P<0.01), for type I, II, III cells, respectively. These results suggest that acute hypoxia suppresses the potassium current and improves the E(m) in PASMCs. These effects may be involved in the modulation of constriction/relaxation of conduit artery under acute hypoxia. Different distribution of K(DR) and BK(Ca) channels in these three types of PASMCs might account for their different constriction/relaxation response to acute hypoxia.
4-Aminopyridine
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pharmacology
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Animals
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Calcium
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metabolism
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Cell Hypoxia
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Male
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Membrane Potentials
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drug effects
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Muscle, Smooth, Vascular
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cytology
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physiology
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Myocytes, Smooth Muscle
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physiology
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Peptides
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pharmacology
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Potassium Channels
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physiology
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Pulmonary Artery
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cytology
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physiology
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Rats
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Rats, Sprague-Dawley
6.Splenic hamartoma: case report and review of literature.
Hong-bo JIA ; Ying-ping LI ; De-en HAN ; Yao LIU ; Bin ZHANG ; De-quan WU ; Xi CHEN ; Ying JIANG ; Long-xian ZHENG ; Jin-rong DU ; Xue-hai JIANG
Chinese Medical Journal 2006;119(16):1403-1408
Adult
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Female
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Hamartoma
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complications
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diagnosis
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surgery
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Humans
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Kidney Calculi
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complications
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Spleen
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pathology
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surgery
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Splenectomy
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methods
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Splenic Diseases
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complications
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diagnosis
;
surgery
7.Effect of Paidu Baoshen Pill on renal fibrosis in 5/6 nephrectomized rats.
Shui-Hua WANG ; Bang-Ming CHEN ; Yong-Fang LIU ; Wei-Ping CHE ; Zhao-Dong WU ; Guo-Bing WANG ; Xiao-Qin XIA ; Hong-En HUANG ; Lin WEI ; Hai-Long ZHU ; Gan-Yan LIU
Chinese Journal of Integrated Traditional and Western Medicine 2015;35(1):81-87
OBJECTIVETo observe the anti-renal fibrosis effect of Paidu Baoshen Pill (PBP) on 5/6 nephrectomized rats and to explore its mechanism.
METHODSTotally 50 SD male healthy rats were randomly divided into the normal control group (n = 10), the sham-operation group (n = 10), and the nephrectomy model group (n = 30) according to the proportion of 1:1:3. Rats in the sham-operation group had their renal capsule isolated without nephrectomy. Rats in the nephrectomy model group had their kidneys 5/6 nephrectomized. Then 24 h urine was collected and 24 h urinary protein (24 h UP) detected. Serum blood urea nitrogen (BUN) and serum creatitine (SCr) were also tested. According to the SCr level 30 rats of the model group were further randomly divided into the model group, the PBP group, and the Niaoduqing Granule (NG) group, 10 in each group. Rats in the PBP group and the NG group were respectively administered with PBP (at the daily dose of 1.0 g/kg) and NG (at the daily dose of 3.33 g/kg) by gastrogavage (they were dissolved in distilled water). At the same time, 2 mL distilled water was administered by gastrogavage to rats in the normal control group, the sham-operation group, and the nephrectomy model group, once daily for 4 successive weeks. Mental conditions, activities, hair color, shape of stool, and the body weight were observed during administration. After 4 weeks, urine was collected to detect 24 h UP. Blood was sampled to detect SCr, BUN, transforming growth factor β1 (TGF-β1), type III procollagen (PC III), collagen type IV (Col IV), laminin (LN), and fibronectin (FN). After rats were killed, their left remnant renal tissues were collected for pathological examinations. The protein expression quantity of TGF-β1 and FN was detected by immunohistochemical method. mRNA expression levels of TGF-β1 and FN were detected using real time fluorescent quantitative PCR.
RESULTSThere was no statistical difference in the above indices between the normal control group and the sham-operation group (P > 0.05). Compared with the sham-operation group, rats' general condition was poorer in the model group, their body weight grew slower, and 24 h UP increased; serum levels of BUN, SCr, TGF-β1, PC III, Col IV, LN, and FN increased; the residual renal pathological lesion was serious; expression levels of TGF-β1, TGF-β1, mRNA, FN, and FN mRNA increased in the renal tissue (all P < 0.01). Compared with the model group, rats' general condition was better, their body weight grew faster, 24 h UP reduced (P < 0.05), blood levels of BUN and SCr decreased significantly (P < 0.01), serum levels of TGF-β1, PC III, CoL IV, LN, and FN decreased (P < 0.05, P < 0.01); the residual renal pathological lesion was attenuated in the PBP group and the NG group; expression levels of TGF-β1, TGF-β1, mRNA, FN, and FN mRNA decreased (P < 0.01). Compared with the NG group, blood levels of SCr and FN, and expression levels of FN and FN mRNA decreased more in the PBP group (P < 0.05).
CONCLUSIONSPBP had the effect of anti-renal fibro- sis in 5/6 nephrectomized rats. Down-regulating expression levels of TGF-β1, and FN from gene transcription and protein translation levels might be one of its mechanisms.
Animals ; Blood Urea Nitrogen ; Collagen Type IV ; Drugs, Chinese Herbal ; therapeutic use ; Fibronectins ; Kidney ; Kidney Diseases ; drug therapy ; Laminin ; Male ; Nephrectomy ; Rats ; Transforming Growth Factor beta1
8.Therapeutic effects of curcumin treatment on hepatic fibrosis.
Jian-chang SHU ; Guo-rong YE ; Xia LÜ ; Li FANG ; Hai-en WU ; Xiao-juan CHEN
Chinese Journal of Hepatology 2007;15(10):753-757
OBJECTIVETo investigate the therapeutic effects and mechanisms of curcumin treatment on hepatic fibrosis.
METHODSA model of hepatic fibrosis was established using carbon tetrachloride intraperitoneal injections in rats. Curcumin was administered to one group of the model rats (curcumin group) and the other rats were used as controls (control group). Serum levels of ALT, AST, HA, LN, PCIII, and NO were measured, and Hyp, MDA, and SOD in liver tissues were measured. Liver tissue slides were stained with HE and Masson staining to study the pathological changes in the livers. Grades of hepatic fibrosis were evaluated according to a semiquantitative scoring system.
RESULTSIn the curcumin group, serum levels of ALT, AST, NO, HA, LN, PCIII, MDA, and Hyp, were (218.50+/-48.89) U/L, (376.60+/-79.13) U/L, (47.96+/-6.53) micromol/L, (289.96+/-60.43) mg/L, (107.35+/-27.24) mg/L, (148.95+/-28.63) microg/L, (236.10+/-30.54) nmol/g, (478.40+/-75.74) microg/g and all were lower than those of the control group (693.75+/-117.57) U/L, (892.50+/-105.69) U/L, (70.95+/-10.23) micromol/L, (468.22+/-93.45) mg/L, (346.44+/-75.08) mg/L, (279.82+/-54.00) microg/L, (402.25+/-39.16) nmol/g, and (752.50+/-77.62) microg/g. The differences were significant. In the curcumin group, the level of SOD (90.39+/-21.23) in the liver tissues was significantly higher than that of the control group (46.52+/-20.01). The hepatic fibrosis scores in the curcumin group were significantly lower than those of the control group. These effects were dose-dependent.
CONCLUSIONSCurcumin reduces rat hepatic fibrosis. Anti-peroxidation and regulation of collagen metabolism in liver tissues may be involved in the therapeutic effectiveness of curcumin on hepatic fibrosis.
Animals ; Curcumin ; therapeutic use ; Drugs, Chinese Herbal ; metabolism ; therapeutic use ; Lipid Peroxidation ; Liver Cirrhosis, Experimental ; drug therapy ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley
9.Association of suicidal ideation with family environment and psychological resilience in adolescents.
En-Zhao CONG ; Yan WU ; Yi-Yun CAI ; Hai-Ying CHEN ; Yi-Feng XU
Chinese Journal of Contemporary Pediatrics 2019;21(5):479-484
OBJECTIVE:
To study the association of suicidal ideation with family environment and psychological resilience in adolescents.
METHODS:
Cluster sampling was used to perform an investigation among 3 230 junior and senior high school students in Xinxiang of Henan Province, China December 2014. A general social information questionnaire, 11-Item Kutcher Adolescent Depression Scale(KADS-11), Family Environment Scale-Chinese Version (FES-CV) and Connor-Davidson Resilience Scale (CD-RISC; Chinese version ) were used for evaluation. A multivariate logistic regression analysis and a case-control study were used to investigate the association of suicidal ideation with family environment and psychological resilience in adolescents.
RESULTS:
A total of 2 960 usable questionnaires were received. Among the 2 960 adolescents, 247 (8.50%) had suicidal ideation (98 boys and 149 girls). The multivariate logistic regression analysis showed that after adjustment for age and sex, single-parent/remarried family was associated with an increased risk of suicidal ideation (OR=2.655). Suicidal ideation in boys was negatively correlated with family cohesion (OR=0.750, P<0.001) and organization (OR=0.855, P=0.036) and was positively correlated with family conflict (OR=1.159, P=0.017). Suicidal ideation in girls were negatively correlated with family cohesion (OR=0.771, P<0.001), emotional expression (OR=0.815, P=0.001) and intellectual-cultural orientation (OR=0.915, P=0.037). The adolescents with suicidal ideation had a significantly lower total score of psychological resilience than those without suicidal ideation (P<0.05). Compared with those without suicidal ideation, the adolescents with suicidal ideation had significantly lower scores on 4 factors of the CD-RISC (ability, tolerance of negative emotions, acceptance of changes and control) (P<0.05).
CONCLUSIONS
Family cohesion is a protective factor against suicidal ideation in adolescents. Family organization in boys and family emotional expression in girls are associated with a decreased risk of suicidal ideation. Enhanced psychological resilience may help to reduce the incidence of suicide ideation in adolescents.
Adolescent
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Case-Control Studies
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China
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Female
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Humans
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Male
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Resilience, Psychological
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Risk Factors
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Students
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Suicidal Ideation
10.Unicompartmental knee arthroplasty used for advanced spontaneous osteonecrosis of the knee
hui En FENG ; jun Xiu MAI ; ming Yong HUANG ; wu Zhen CAO ; yao Kang CHEN ; tao Hai SU
Chinese Journal of Tissue Engineering Research 2017;21(35):5577-5582
BACKGROUND: Unicompartment knee replacement is more popular for small trauma, rapid recovery, low less complications and almost normal knee mechanics, and has been used to repair unicompartmental knee diseases. At abroad, unicompartmental knee arthroplasty for advanced spontaneous osteonecrosis of knee (SONK) has obtained satisfactory outcomes, but its long-term efficacy and safety are not known in China. OBJECTIVE: To explore the short-term effectiveness of unicompartmental knee arthroplasty for advanced SONK. METHODS: Clinical data of 12 SONK patients (12 knees) admitted between January and August 2015 were analyzed retrospectively. Unicompartmental knee arthroplasty was operated by the same surgical team using the 3rdgeneration of Oxford?Unicompartmental Knee. The Visual Analogue Scale, femorotibial angle, range of motion of the knee and Hospital for Special Surgery scores were used to evaluate the curative efficacy at 3, 6, 12, and 18 months postoperatively. RESULTS AND CONCLUSION: (1) All patients were followed up for 12-18 months. The incision in all patients achieved primary union, and no infection, lower limb venous thrombosis or fracture occurred. (2) At the end of follow-up, the Visual Analogue Scale scores were significantly reduced from preoperative (6.67±0.78) to (1.75±0.97); the Hospital for Special Surgery scores were significantly increased from preoperative (63.92±7.27) to (91.67±2.87); the femorotibial angle changed from preoperative (178.28±3.38)° to (176.82±2.37)°(All P < 0.05). But the range of motion of the knee joint did not differ significantly before and after surgery. (3) That is to say, unicompartmental knee arthroplasty obtains satisfactory short-term efficacy in the treatment of advanced SONK.