1.The Molecular Mechanism of Glucocorticoid-Induced Insulin Resistance
Journal of Chinese Physician 2001;0(09):-
Objective To explore the effect of glucocorticoid on glucose transport activity and the expression of insulin signaling peptides in the primary cultured rat adipocytes .Methods Isolated rat adipocytes were cultured for 2h,8h,16h and 24h respectively at 5 mmol glucose with dexamethasone (Dex) 0 3?mol. Then the glucose uptake, cellular contents of insulin receptor substrate (IRS) 1/2, phosphatidylinositol 3-kinase 85 subunit (p85) and protein kinase B(PKB)were measured by Western blotting.Results These adipocytes treated with Dex have shown to impair the basal and insulin-induced glucose uptake with a maximum inhibition at 2h and 24h respectively; Dex down-regulated IRS1 protein expression in a time-dependent manner and up-regulated IRS2 content. The cellular p85 and PKB contents were also decreased by Dex. Conclusion Chronic exposure to glucocorticoid can inhibit glucose uptake and induce insulin resistance. The mechanism may be involved in affecting the expression of insulin signaling peptides.
2.Quality of Life and its Influencing Factors of 150 Aged Patients with Chronic Diseases
Journal of Chinese Physician 2001;0(04):-
Objective To understand current situation of live quality of old patients and to explore its influencing factors.Methods Age of all subjects more than 60 years who was aged in-patients with a chronic disease in geriatric ward,department of XiangYa Hospital. General physical examination were executed. Symptom Checklist 90(SCL-90) and Quality of Life (QOL) scales were measured.Results ⑴The problems of QOL and mentality were occurred in 78%,77 33% respectively of the patients. ⑵Multiple linear regression showed that financial condition, mentality, age and physical disease were major factors that affected the patients' quality of life . The linear equation was YQOL=36 967-0 734 X age+2 012 X financial-0 0352 X mentality-0 712 X diseases(P
3.Glucocorticoid Aggravates High Glucose-Induced Insulin Resistance
Journal of Chinese Physician 2001;0(06):-
Objective To explore the molecular mechanism of glucocorticoid and high glucose-induced insulin resistance(IR).Methods Isolated rat adipocytes were cultured for 24h at 5 or 25 mM glucose with or without dexamethasone (Dex) 0 3?M. Then the glucose uptake , the phosphorylation of tyrosine of insulin receptor substrate (IRS)1/2 and expression of IRS 1/2 and protein kinase B(PKB) protein were measured by western blot analysis with molecular dynamics. Results These adipocytes treated with 25 mM glucose have shown to impair glucose uptake, IRS1 phosphorylation and the protein expression; Combined treatment with Dex enhanced high glucose-induced the suppression, and inhibited IRS1 tyrosine phosphorylation; High glucose increased IRS2 protein expression, Dex abolished partly its the effect. Conclusions High glucose can induce IR, Dex can aggravate the effect induced with high glucose. The mechanism may be involved in affecting the phosphorylation and expression of insulin signaling proteins.
4.Comparative Study of the Effects and the Safety of Different Dose of Simvastatin on Aged Patients With Hyperlipidemia
Journal of Chinese Physician 2001;0(08):-
Objective To investigate the effects and the safety of different dose of simvastatin on aged patients with hyperlipidemia.Method The 70 patients were divided into two groups at random. 40 in group A was given orally simvastatin 20 mg/d, and 30 patients in group B was given orally simvastatin 40 mg/d,respectively; The levels serum total cholesterol(TCH), low-density lipoprotein cholesterol(LDL-C), high-density lipoprotein cholesterol(HDL-C) and triglyceride(TG) were measured following the 4th week, the 8th week and the 12th week . And the changes of the functions of the patients'liver and kidney, the serum glucose level and the activities of myocardial enzymes in the two groups before and after the simbastatin treatment were also observed. Results In the 4th , 8th and 12th week at the treatment with simvastatin 20mg/d, the patients' TCH levels were decreased by 32 1%,32 1%,36 0% respectively;the TG levels were decreased by 35 1%,49 6%,52 9% respectively;the LDL levels were decreased by 39 3%,37 3%,35 2% respectively;and the HDL-C levels were increased by 2 0%,0 8%,8 3%, respectively. While in the 4th, 8th and 12th week at the treatment of simvastatin 40mg/d,the patients' TCH levels were decreased by 41 8%,48 0%,51 0%, TG levels were decreased by 18 4%,32 3%,38 4%, the LDL levels were decreased by 42 4%,47 5%,50 8%, and the HDL-C levels were increased by 1 0%,2 0%,13 0% respectively. There were no obviously changes of the results of the tests of the liver function,the kidney function,the blood glucose level and the myocardial enzymes before and after both treatment groups in the different dose of the simvastain. Conclusion The effects and the safety of the treatments of simvastatin on aged patients with hyperlipidemia were similar at the dose of 20mg/d and the dose of 40mg/d.
5.Effects of Lorsartan, Fosinopril on myocardial fibrosis, angiotensin Ⅱ and cardiac remolding in hypertensive rats
Bixiu HE ; Guolong YU ; Xiaoqiu LIANG
Journal of Central South University(Medical Sciences) 2001;26(2):118-120
Objective: To investigate effects of lorsartan, fosinopril on myocardial fibrosis, angiotensin Ⅱ and cardiac remolding in the spontaneously hypertensive rats (SHR). Methods: 16-week-old SHRs were divided randomly into 3 groups: SHR-L (treated with lorsartan), SHR-F (treated with fosinopril) and SHR-C (untreated), each group consisting of 10 rats. After 8 weeks' and 16 weeks' therapeutic period, collagen volume fraction (CVF), perivascular circuferential area (PVCA), plasma and myocardium angiotensin Ⅱ concentrations were examined by pathological examination with computed processing and radioimmunoassay respectively. Results: (1) Compared with SHR-C after 8 weeks' and 16 weeks' therapeutic period, the systolic blood pressure (SBP) was decreased similarly in both treatment groups. Heart and left ventricular weights, heart weight and eft ventricular mass indexes were lower significantly in both treatment groups than in SHR-C. Left ventricular mass index was reduced to a lower extent in SHR-F group than in SHR-L group after 16 weeks. (2) Compared with SHR-C, CVF, PVCA after 8 weeks and 16 weeks were reduced significantly in SHR-F and SHR-L. Meanwhile, CVF after 16 weeks in SHR-F than in SHR-L. (3) Compared with SHR-C after both therapeutic periods, plasma and myocardium angiotensin Ⅱ concentrations were increased Significantly in SHR-L, but plasma angiotensin Ⅱ concentrations were not altered significantly in SHR-F. However, myocardium angiotensin Ⅱ concentrations were reduced significantly in SHR-F after 8 weeks and 16 weeks in SHR-F. Conclusion: Lorsartan, fosinopril inhibit myocardial fibrosis and reverse heart hypertrophy. Fosinopril may be more effective in these above effects than Lorsartan. The mechanism of the both drug's cardioprotective effects was related to inhibition of myocardium rennin-angiotension-aldsteron system.
6.Clinical Observation of Efficacy of Rosiglitazone Combined with Insulin in Treatment of Elderly Type 2 Diabetes Mellitus
Huixia LIU ; Aiping QIN ; Bixiu HE
Journal of Chinese Physician 2000;0(11):-
Objective To study the clinical efficacy and safety of Rosiglitazone (RSG) combined with insulin in treatment of elderly type 2 diabetes mellitus (type 2 DM) that had poor response to insulin treatment. Methods 68 cases of elderly type 2 DM patients with poor response to insulin treatment were randomly divided into experimental group and control group.The control group was treated with proper dose of insulin,and the experimental group were administered RSG 4mg/day plus insulin for 20 weeks. 4 weeks and 20 weeks after treatment FBC, PBC, HbA1C, UAER of 24 hrs, daily changes of insulin dosage and side-effect of the medicine were observed. Results In the experimental group the levels of FBG and PBG decreased in 4 weeks(P
7.Influence of MMP-9 antiseme oligonudeotide on proliferation and apoptosis of human lung adenocarcinom A549 cells
Bixiu HE ; Chengping HU ; Dongbo ZHOU ; Xuebing LI
Journal of Chinese Physician 2008;10(8):1013-1017
Objective To approach the effects of MMP-9 antisensc oligonucleotide(ASODN)on human lung adcnocarcinoma(A549) cell apoptosis and proliferation capability.Methods MTT.was used to analyze the effect that MMP-9 transfection on A549 cell growth.Flow cytometry was used to analyze the ratio of cell proliferation and apoptosis.RT-PCR WaS used to detect the expression of MMP-9mRNA and Western blot was used to detect the changes of MMP-9 protein.Results In some degree,MMP-9 ASODN that inhibited the survival rate of the A549 cell presented concentration and time dependence manner.The best dependence concentration of ASODN was 600nmol/L for 24 hour.After trasnfection of MMP-9ASODN to A549 cell.the perceive of A549 apoptosis cell was significandy higher than that in control group(P<0.01).When the antisense oligonucleotides concentration is 600nmol/L and the action time is 48 hours,the relative expression level of MMP-9mRNA and MMP-9 protein are obviously less than that in control group(P<0.01).Conclusion MMP-9ASODN may down regulate the expression of MMP-9mRNA and MMP-9 protein,effectively inhibit the proliferation of A549 cell and promote the apoptosis of A549 cell.
8.Phase Ⅰ / Ⅱ clinical trial of docetaxel, cisplatin, and fluorouracil induction chemotherapy followed by intensity-modulated radiotherapy and concomitant chemotherapy in locally advanced nasopharyngeal carcinoma
Qun ZHANG ; Fang HE ; Dehua KANG ; Zhenyu WANG ; Bixiu WEN ; Wei LUO
Chinese Journal of Radiation Oncology 2013;(2):129-132
Objective To investigate the maximum-tolerated dose (MTD) of cisplatin in docetaxel,cisplatin,and fluorouracil (TPF) induction chemotherapy followed by intensity-modulated radiotherapy (IMRT) and concomitant chemotherapy as well as the safety and short-term efficacy of TPF induction chemotherapy in the treatment of locally advanced nasopharyngeal carcinoma (NPC).Methods Thirtythree patients with locally advanced NPC were enrolled in this trial.The MTD of cisplatin was determined by dose escalation study,and the short-term efficacy and toxicities were evaluated.Results When the doses of docetaxel and fluorouracil were 60 mg/m2 d1 and 550 mg/m2 d1-5,respectively,the MTD of cisplatin was 65 mg/m2 d1.In this regimen (repeated every 3 weeks),grade 3-4 toxicities included neutropenia (67%),febrile neutropenia (9%),diarrhea (21%),and oral mucositis (6%).Except those who experienced dose-limited toxicity,other patients completed the whole treatment schedule.After TPF induction chemotherapy,the overall response rate was 97%,and the complete response rate was 21%.Conclusions In the endemic areas of NPC,induction chemotherapy with docetaxel (60 mg/m2 d1),cisplatin (65 mg/m2 d1),and fluorouracil (550 mg/m2 d1-5),which is repeated every 3 weeks,is proved safe and effective for Asian patients with locally advanced NPC.
9.Effects of matrix metalloproteinase-9 antisense oligonucleotide on the apoptosis and metastasis of the human lung adenocarcinoma cell.
Bixiu HE ; Chengping HU ; Shuo LIANG ; Xuebing LI
Chinese Journal of Lung Cancer 2007;10(5):351-355
BACKGROUNDMatrix metalloproteinase-9 (MMP-9) is one of significant extracellular matrix catabolic enzymes, which is known to relate to the initiation, progression and growth of the tumor. The aim of this study is to investigate the effects of MMP-9 antisense oligonucleotide (ASODN) on the apoptosis and metastasis of human lung adenocarcinoma A549 cell.
METHODSMTT was used to analyze the effect of MMP-9 ASODN transfection on A549 cell growth. Flow cytometry was used to analyze the cell cycle and apoptosis. MTT chromometry and scratch migration were used to observe the capability of adhesion and immigration of the A549 cell.
RESULTSMMP-9 ASODN inhibited the survival rate of the A549 cell and the action was concentration-and time-dependent. The peak concentration of MMP-9 ASODN was 600 nmol/L at 48 hours after transfection. After transfection of MMP-9 ASODN to A549 cell, the percentage of A549 apoptosis cell was significantly higher than that of control group (P < 0.01), but the adhesion and migration cut down predominantly (P < 0.01).
CONCLUSIONSMMP-9 ASODN can depress the adhesion and migration and inhibit proliferation of adenocarcinoma A549 cell effectively, and can promote apoptosis of the A549 cell.
10.Construction of RBM5 vector, establishment of stably transfected A549 cell line and preliminary research on the function of RBM5 gene.
Jian XIAO ; Nian LI ; Xiaowei XING ; Bixiu HE
Journal of Central South University(Medical Sciences) 2014;39(10):994-1000
OBJECTIVE:
To establish a stable A549 cell line transfected by RNA binding motif 5 (RBM5) expression vector, and to investigate the effect of RBM5 gene on proliferation of A549 cell line and the expression of DEAH box polypeptide 15 (DHX15).
METHODS:
The eukaryotic expression vector pcDNA3.1 (+)/RBM5 was constructed by a twostep PCR technique. Then, the recombinant plasmid pcDNA3.1 (+)/RBM5 was verified by DNA sequencing and transfected into the lung adenocarcinoma cell A549. The positive cells with overexpression of RBM5 gene were identified by Western blotting. Flow cytometry was used to analyze the cell cycles of the positive A549 cells [pcDNA3.1 (+)/RBM5-A549] and the negative controls [pcDNA3 .1 (+)- A549]. Finally, RT-PCR was used to detect the expression of DHX15, a splicing-related factor, in the positively transfected A549 cells and the negative controls.
RESULTS:
A pcDNA3.1 (+)/RBM5 eukaryotic expression vector has been constructed successfully, and the A549 cell line that stably transfected with RBM5 gene has been established. Compared with negative control cells, the percentage of G1 phase cells in the positive cells was increased, while the percentage of S phase was decreased (both P<0.01), and the expression of DHX15 is upregulated (P<0.01).
CONCLUSION
RBM5 gene can inhibit the cell cycle and upregulate the expression of DHX15 in A549 cells.
Cell Cycle
;
Cell Cycle Proteins
;
genetics
;
Cell Line, Tumor
;
Cell Proliferation
;
DNA-Binding Proteins
;
genetics
;
Genetic Vectors
;
Humans
;
RNA Helicases
;
metabolism
;
RNA-Binding Proteins
;
genetics
;
Transfection
;
Tumor Suppressor Proteins
;
genetics