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Objective:To examine the expression of transmembrane emp24 domain-containing protein 4(TMED4) in liver tissue of patients with hepatocellular carcinoma, and to investigate the effects of TMED4 gene on the proliferation and migration of hepatocellular carcinoma cells and related molecular mechanisms. Methods:The expression of TMED4 at protein level in liver cancer tissue and paracancerous tissue of patients with hepatocellular carcinoma were detected by Western blotting and immunohistochemical stainning, and the correlation between its expression and clinicopathological features was analyzed. The effects of TMED4 overexpression or knockdown on proliferation, migration and healing ability of hepatocellular carcinoma cells in vitro and in vivo were determined by cell proliferation test, Transwell test, wound healing test and subcutaneous tumor formation in nude mice. The molecular mechanism of TMED4 in regulating the biological behavior of hepatocellular carcinoma cells was preliminarily explored by pathway analysis. Independent sample t test, Mann-Whitney U test and chi-square test were used for statistical analysis. Results:The results of Western blotting showed that the expression of TMED4 at protein level in hepatocellular carcinoma tissue was lower than that in paracancerous tissue(0.52±0.29 vs. 0.83±0.22), and the difference was statistically significant( t=2.54, P=0.022). The results of immunohistochemical examination indicated that the expression of TMED4 at protein level in liver cancer tissue was lower than that in paracancerous tissue(5.46±3.37 vs. 7.58±3.08), and the difference was statistically significant( t=3.49, P<0.001). The expression of TMED4 at protein level was significantly correlated with vascular invasion and Barcelona clinic liver cancer stage( χ2=6.83 and 4.20, P=0.009 and 0.040). The results of cell proliferation assay showed that the absorbance value of SMMC-7721 cells in TMED4 overexpression group was lower than that in control group(1.38±0.05 vs. 2.37±0.08), while the optical density value of HepG2 in TMED4 knockdown group was higher than that in control group(0.76±0.04 vs. 0.54±0.01), and the differences were statistically significant( t=18.23 and 8.85, both P<0.001). The results of Transwell test showed that the number of migrated SMMC-7721 cells in TMED4 overexpression group was less than that in control group(286.30±13.01 vs. 439.70±12.34), while the number of migrated HepG2 cells in TMED4 knockdown group was higher than that in control group(249.00±6.00 vs. 160.00±6.56), and the differences were statistically significant( t=14.81 and 17.34, both P<0.001). The wound healing test showed that the healing rate of SMMC-7721 cells in TMED4 overexpression group was lower than that in control group((0.21±0.01)% vs.(0.45±0.01)%), the healing rate of HepG2 cells in TMED4 knockdown group was higher than that in control group((0.46±0.01)% vs.(0.20±0.01)%), and the differences were statistically significant( t=200.10 and 30.46, both P<0.001). The results of subcutaneous tumor formation assay in nude mice showed that the growth rate of cells in TMED4 overexpression group was slower than that in control group. After cell inoculation for 6 weeks, the subcutaneous tumor volume of mice in TMED4 overexpression group was smaller than that in control group(27.36 mm 3(138.70 mm 3) vs. 1 741.62 mm 3(1 783.39 mm 3)), the tumor weight was lower than that in control group(0.06 g(0.14 g) vs. 1.46 g(1.09 g)), and the differences were statistically significant(both Z=-2.31, both P<0.001). The results of Western blotting showed that the expression of Snail at protein level in SMMC-7721 cells of the TMED4 overexpression group was lower than that of the control group(0.32±0.01 vs. 0.90±0.03), the protein level of Snail in HepG2 cells of TMED4 knockdown group was higher than that of control group(1.03±0.01 vs. 0.97±0.01), and the differences were statistically significant( t=28.49 and 12.31, both P<0.001). The results of real time fluorescent quantitative polymerase chain reaction showed that the expression of Snail at mRNA level in SMMC-7721 cells of TMED4 overexpression group was lower than that of control group(0.13±0.05 vs. 1.00±0.15), the expression of Snail at mRNA level in HepG2 cells of TMED4 knockdown group was higher than that of control group(1.25±0.32 vs. 0.21±0.14), and the differences were statistically significant( t=9.62 and 5.10, P<0.001 and P=0.007). Conclusion:TMED4 may affect the proliferation and migration of hepatocarcinoma cells by regulating the expression of Snail, and which is expected to become a potentially therapeutic target for hepatocellular carcinoma.
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OBJECTIVE@#To investigate the expression profile of long non-coding RNAs (lncRNA) and identify potential lncRNA-related competing endogenous RNAs (ceRNA) in placenta accrete spectrum disorders (PAS).@*METHODS@#Five tissue specimens of placental implantation and 5 adjacent normal placental tissues were collected from cesarean section deliveries complicated by PAS in our hospital between December, 2017 and June, 2018. Human microarrays were used to identify the lncRNAs that were differentially expressed in PAS, and 5 of the identified lncRNAs were further validated using qRT-PCR. GO and KEGG pathway analyses were performed to indentify the most significant enrichment functions. A ceRNA network was constructed based on ENST00000511361 (RP5-875H18.4), NR_027457 (LINC00221) and NR_126415 (FOXP4-AS1) to pinpoint the potential lncRNAs-related ceRNA.@*RESULTS@#A total of 329 lncRNAs and 179 mRNAs were identified to have differential expression in PAS. The results of qRT-PCR were consistent with the human microarrays results. Transforming growth factor-β (TGF-β) signaling pathway was the most significantly enriched pathway. The constructed ceRNA network suggested that RP5-875H18.4--miRNA-218--SLIT2 had a potential ceRNA regulatory mechanism in PAS.@*CONCLUSIONS@#The differentially expressed lncRNAs are involved in the occurrence and progression of PAS possibly by regulating the TGF-β signaling pathway. The ceRNA network of RP5-875H18.4--miRNA-218--SLIT2 may play a role in the occurrence of PAS.
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Objective To observe the effects of hysteroscopic transcervical resection of endometrium combined with levonorgestrel-relea-sing intrauterine system in the treatment of adenomyosis. Methods Clinical data of 62 cases with adenomyosis from January 2009 to January 2011 were randomly divided into 2 groups with 31 cases each. The observation group was given hysteroscopic transcervical resection of endo-metrium ( TCRE) combined with levonorgestrel-releasing intrauterine system( LNG-IUS) ,the control group was given LNG-IUS. All patients were followed up in 0,1,3,6,12 months after treatmenting with LNG-IUS. The menstrual blood volume,score of VAS,volume of uterus, CA125 and the levels of serum reproductive hormone were analyzed before treatment and after treatment. Results After the therapy,the cur-ative effects of controlling menorrhea were improved and the the observation group was significantly better than the control group(P0. 05). Conclusion It is exact effect to treat adenomyosis by TCRE combined with LNG-IUS,which can prevent dripping bleeding induced by application of LNG-IUS effectively.
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Objective To study the effects of combined telmisartan and ramiprll on heart function and renin - angiotensin - aldoste-tone system and ventricle remodeling and brain natriuretie peptide in patients with chronic heart failure (CHF). Methods 100 patientswith chronic heart failure were randomly divided into three groups: telmisartan group (A group, treated with telmisartan 80mg once daily, n =33), ramipril group (B group treated with ramipril 5mg once daily, n =33) and telmisartan plus ramipril group (treated with telmis-artan 40mg plus ramipril 2.5mg once daily, n = 34). Left ventricular end - diastolic dimensions (LVEDD) and left ventricular ejection fraction (LVEF) were assessed, and plasma renin activity (Ren) , angiotensinIl (Angll), aldosterone (Aid) and brain natriuretic pep-tide (BNP) were measured before and after therphy. Results After 6 months of treatment, LVEDD and LVEF were improved in all groups(P < 0.01). All changs were significant in C group than those in A group or B group(P < 0.01). The concentration of Ren were in-creased in all groups(P <0.01). The concentration of Angll was increased in A group and decreased in B group(P <0.01)while there was no difference at pre or post treatment in C group (P > 0.01). The concentration of Ald and BNP was decreased in all groups (P < 0.01). Ald and BNP were decreased more significantly in C group than those in A group or B group. Conclusion Combination of low dose of telmisartan and ramipril therapy has more benificial clinical features than telmisartan or ramipril alone in patients with CHF.
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Objective To set up the proteomic protein profiling of adenomyotic tissue and normal uterine muscle and identify the abnormally expressed proteins in adenomyotic tissue. Methods Samples of adenomyotic tissue (adenomyosis group) and age-matched healthy uterine muscle (control group) were collected from totally 10 patients undergoing transabdominal hysterectomy for adenomyosis and cervical diseases at Peking Union Medical College Hospital from January 2007 to October 2007. The proteomics profiling of adenomyotic tissue and normal uterine tissue were established using two dimensional gel electrophoresis (2-DE) and gel staining method. The differently expressed protein spots were detected by gel comparison using image analysis software and identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS). Results In Coomassie blue stained gels there were on average (512 ± 36) spots and compared with the reference gel the matching rate was 83.7%. In silver stained gels there were (762 +54) spots and compared with the reference gel the matching rate was 81.1%.Compared with normal uterine muscle, there were 15 protein spots disregulated in adenomyotic tissue.Among them 10 protein spots were successfully identified by mass spectrometry. The functions of these disregulated proteins included cell skeleton, oxidation, apoptosis and immune reaction. Conclusions Comparative proteomics analysis is a useful approach for the study of adenomyosis. Compared with normal uterine muscle there are abnormalities in cell skeleton, oxidation, apoptosis and immune reaction. These life processes may participate in pathophysiology of adenomyosis.
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Objective To study the effects of combined telmisartan and ramipril on heart function and renin-angiotensin-aldosterone system and ventricle remodeling and brain natriuretic peptide in patients with chronic heart failure(CHF).Methods 100 patients with chronic heart failure were randomly divided into three groups: telmisartan group(A group,treated with telmisartan 80mg once daily,n=33),ramipril group(B group treated with ramipril 5mg once daily,n=33) and telmisartan plus ramipril group(treated with telmisartan 40mg plus ramipril 2.5mg once daily,n=34).Left ventricular end-diastolic dimensions(LVEDD) and left ventricular ejection fraction(LVEF) were assessed,and plasma renin activity(Ren),angiotensinII(AngII),aldosterone(Ald) and brain natriuretic peptide(BNP) were measured before and after therphy.Results After 6 months of treatment,LVEDD and LVEF were improved in all groups(P0.01).The concentration of Ald and BNP was decreased in all groups(P
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AIM To explore the roles of vascular endothelial growth factor (VEGF) in hypoxia pulmonary hypertension and effects of suramin. METHODS Thirty SD rats were randomly divided into normal control group (N), hypoxia hypercapnia group(F), hypoxia hypercapnia +suramin group (S). The levels of VEGF in serum and in lung tissue were measured by ELISA, the ultrastructure of pulmonary arterioles was observed by electron microscopy, the expression of VEGF was observed by immunohistochemistry, the expression of VEGFmRNA was observed by in situ hybirdization. RESULTS ①Mean pulmonary arterial pressure(mPAP), weight ratio of RV to LV+S, the leves of VEGF in serum and in lung tissue of group F were significantly higher than that of group N and group S (P
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AIM: To study the effect of hypoxia and hypercapnia on nitric oxide (NO) in plasma and superoxide dismutase (SOD), catalase (CAT), soluble guanylate cyclase (sGC), cyclic guanosine monophospholate (cGMP) in lung tissue in rats, and to explore the effect of NO- and H_2O_2-sGC pathway on the development of the pulmonary hypertension. METHODS: The model of hypoxic and hypercapnic 1, 2, 4-week group (HH 1 week, HH 2 weeks, HH 4 weeks) and control group was set up. NO content in plasma, CAT and SOD in rat lung were determined by spectrophotometry. The sGC activity in lung tissue was detected by enzyme kinetic analysis. cGMP content in lung tissue was examined with ~ 125 I-radioimmunoassay. RESULTS: The mean pulmonary artery pressure (mPAP) showed significantly higher in HH 1 week, HH 2 weeks and HH 4 weeks groups compared with control group (all P