1.Effect of RNA interference targeting for cyclin D1 gene on growth,cell cycle and apoptosis of K562
Yi-Yuan WAN ; Xiao-Long CAO ; Wen-Qi JIANG ;
Chinese Journal of Primary Medicine and Pharmacy 2006;0(07):-
Objective cyclin D1 gene plays a significant role in regulating cell cycle progression.Suppression of cyclin D1 protcin expression can effect on cellular proliferation,distribution of cell cycle and apoptosis.This study was to determine whether this effect also existed in chronic leukemia ceil line K562 by inhibiting the expression of cyclin D1 protein through RNA interference in vetro.Methods Plasmid vectors expressing small hairpin RNA (shRNA) targeting at cyclin D1 gene were constructed and transfected into K562 cells by chitosan,cyclin D1 protein was examined by using Western blot analysis.Inhibition of cellular proliferation was evaluated hy soft agar colony formation assay.The cell cycle and apoptosis were determined by flow cytometry.Results Expression of cyclin D1 protein was markedly down-regulated and capability of colony formation was suppressed after transfection with pshRNA-419 and pshRNA-575 at 48h.Down-regulation of cyclin D1 protein could effect on distribution of cell cycle arrested at G_0/G_1 phase and markedly induce apoptosis of K562 cells.But there had no above biological effects ob- served after transfection with blank vector and control vector of m-pshRNA-790.Conclusion Down-regulation of cyclin D1 expression can inhibit growth of K562 cells,and effect on distribution of cell cycle arrested at G_0/G_1 phase.The primary results suggest that cyclin D1 gene might serve as an effective target for the treatment of leukemia.
3.Correlation factors for and clinical characteristics of urosepsis shock after endourology surgery
Yi LIU ; Wen NI ; Xiaolin WANG ; Yan MENG ; Xiaojian WAN ; Jinbao LI ; Keming ZHU ; Xiaoming DENG
Chinese Journal of Anesthesiology 2012;32(6):724-726
ObjectiveTo identify the correlation factors for urosepsis shock after endourology surgery and analyze its clinical characteristics.MethodsFifty-eight patients with urosepsis without shock and 15 patients with shock were studied.Factors which may be correlated with the development of sepsis were analyzed including age,sex,ASA physical status,history of urinary tract infection,preoperative leukocyturia,urine bacteria culture,prophylactic antimicrobial treatment,pyonephrosis,type of surgery,duration of operation,blood leukocyte count and concentration of creactive protein at the end of surgery,the time when the signs of infection (shivering,agitation,nausea or vomiting) first appeared.Changes in BP in patients with urosepsis shock,scores for multiple organ dysfunction syndrome as well as treatment and prognosis were also recorded.ResultsFemale sex and early emergence of signs of infection after surgery were correlated with urosepsis shock.Abrupt hypotension was usually the first manifestation of urosepsis shook.The lowest systolic BP was positively correlated with the time when diagnosis of shock was made and negatively correlated with the length of ICU stay and the highest multiple organ dysfunction syndrome scores but not correlated with shock correction time.All patients with urosepsis shock recovered completely when discharged from hospital.ConclusionFemale sex and patients with early emergence of signs of infection are prone to develop urosepsis shock after endourology operation.The prognosis of urosepsis shock is good if diagnosed and treated in time.
4.Inhibitory effect of docetaxel on proliferation of human lens epithelial cells
Shao-ling, YI ; Bin, SHI ; Wan-wen, LI ; Li-jian, XU ; Chun-shun, ZHAO
Chinese Journal of Experimental Ophthalmology 2011;29(1):32-37
Background Some drugs with inhibitory effect on the proliferation of lens epithelial cells have a limiting application in clinic because of their adverse response.To screen the effective and less side-effect drug for supressing LECs growth is very inportant for the prevention and treatment of after cataract.Objective This study was to explore the effects of docetaxel on LECs growth and compare its role with epirubicin hydrochloride,pirarubicin hydrochloTide and rahitrexed.Methotis Immortalized human LECs line (SRA01/04) were cultured and passaged.Different concentrations of docetaxel,epirubicin hydrochloride,pirarubicin hydrochloride and rahitrexed were added into the medium respectively for 24.48 and 72 hours.The proliferation of LECs was detect by M1Yr.Flow cytometry analysis Was used to analyze the influence of different concentrations of docetaxel on cellular cycle at 48 hours after addition of docetaxel,and Annexin V-FITC/PI marking method was used to assesse the apoptosis of LECs under the action of docetaxel.Expression of bcl-2 protein in LECs Was evaluated by Westeru blot. Result The growth rate of LECs Wag 100%in 8-519 pmol/L doeetaxel groups with the normal cell shape.Majority of abnormal cells and low growth rate were found in 66 nmoVL docetaxel group at 48 and 72 hours.The IC50 of docetaxel was lowest in 48 and 72 hours in docetaxel group in comparison to epirubicin hydrochloride and pirarubicin hydrochloride. However,no evident inhibition on LECs growth in 23.22-523.56 μmol/L of raltitrexed.At 48 hours,the percentage of LECs in G2/M phase increased as the asccnte of concentration of docetaxel,showing a significant difference among 4 groups(F=2633.05,P<0.01).The percentage of early apoptotic cells increased to 22.4%(χ2=20.00,P<0.01) and 27.9%(χ2=42.68,P<0.01)from normal control 3.1% at 48 hours after LECs exposed to 8.3 nmol/L and 266 nmol/L docetaxe.The expression of bcl-2 protein in LECs was obviously weakened after addition of docetaxel,especially 8.3 nmol/L docetaxel group. Conclusion Docetaxel,epirubicin hydrochloride and pirarubicin hydrochloride can inhibit the proliferation of human LECs in vitro.But there is no supression on LECs growth inraltitrexed.Docetaxel is proved to have a strongly arrested effect on the proliferation of LECs in comparison with epirubicin hydrochloride and pirarubicin hydrochloride and play its role at concentration-and time-dependent manner.
5.Analysis of anti-infection drug usage in 11 hospitals of Shanghai during 2003-2005
Hai-Ying SUN ; Yan WEN ; Wan-Sheng CHEN ; Yi-Lei WANG ;
Academic Journal of Second Military Medical University 2000;0(08):-
Objective:To evaluate the current situation and trend of anti-infection drug usage in 11 hospitals of Shanghai during 2003-2005.Methods:Using the cost ranking approach,we analyzed the anti-infection drug usage in 11 major hospitals of Shanghai during 2003-2005.The drug species,consumption,cost,manufacturer,etc,were analyzed by Excel 2000 software. Results:It was found that the cost of anti-infection drugs in the 11 hospitals occupied 22.65% of the total drug expenditure during 2003-2005 and the expenditure decreased at an annual rate of 4.02%.We also found that 80% of the anti-infection drugs were antibiotics.The consumption of?-lactamase inhibitor valued 44.120 5,73.696 7 and 95.163 0 million Yuan in 2003,2004 and 2005,respectively(with a yearly growth of 46.86%),ranking the 3rd in 2003 and the 2nd in both 2004 and 2005.The consumption of cephalosporins ranked the first during 2003-2005.The top 20 anti-infection drugs occupied nearly 80% of the total consumption;the consumption of sulbactam sodium/cefoperazone raised from the 17th in 2003 to the 5th in 2004 and to the first in 2005.Conclusion:The consumption of anti-infection drugs has been restrained;cephalosporins are still the major drugs in clinical practice;and the consumption of sulbactam sodium/cefoperazone is on the rise year by year.
6.Effect of electroacupuncture on gastric motility, expressions of ghrelin and GHSR mRNA in gastric antrum tissue of diabetic gastroparesis rats
Yan PENG ; Yaping LIN ; Fenge HE ; Quanquan WAN ; Wen CHEN ; Qin LIU ; Shouxiang YI
Journal of Acupuncture and Tuina Science 2017;15(2):88-93
Objective: To explore the action mechanism of electroacupuncture (EA) in improving the gastric motility of rats with diabetic gastroparesis (DGP). Methods: Forty-eight healthy Sprague-Dawley (SD) rats were randomly assigned into four groups: a normal group (group A), a model group (group B), a group of EA at acupoints (group C), and a group of EA at non-acupoints (group D), 12 rats in each group. The animal model of DGP was established by intraperitoneal injection of streptozotocin (STZ) plus high glucose and fat diet. The blood glucose, urine glucose and gastric emptying rate (GER) were observed. The content of insulin (INS) in serum and ghrelin in gastric antrum tissue were detected by enzyme linked immunoassay (ELISA). The expression of growth hormone secretagogue receptor mRNA (GHSR mRNA) in gastric antrum tissue was detected by real-time fluorescent quantitative polymerase chain reaction (PCR). Results:Compared with group A, blood glucose and urine glucose increased significantly (P<0.01), GER, content of serum insulin, the content of ghrelin and expression of GHSR mRNA in gastric antrum tissue decreased significantly (P<0.05 orP<0.01) in group B. Compared with group B, blood glucose and urine glucose decreased significantly (P<0.05), GER, the content of insulin in serum, the content of ghrelin and expression of GHSR mRNA in gastric antrum tissue increased significantly (P<0.05 orP<0.01) in group C. Conclusion: EA at acupoints can down-regulate the content of blood and urine sugar, and promote gastric emptying, which is possibly related to the regulation of serum insulin, and the expressions of ghrelin and GHSR mRNA in gastric antrum.
7.Mechanisms of cordycepin on improving renal interstitial fibrosis via regulating eIF2α/TGF-β/Smad signaling pathway.
Liu-bao GU ; Rong-wen BIAN ; Yue TU ; Hao HU ; Yi-gang WAN ; Wei SUN
China Journal of Chinese Materia Medica 2014;39(21):4096-4101
OBJECTIVETo investigate the effects and mechanisms of cordycepin,an effective component of cordyceps militaris, on renal interstitial fibrosis (RIF) and its related eIF2α/TGF-β/Smad signaling pathway.
METHODFirstly, 15 C57BL/6 mice were randomly divided into 3 groups,the control group (Group A), the model group (Group B) and the cordycepin-treated group (Group C). After renal interstitial fibrotic model was successfully established by unilateral ureteral obstruction (UUO), the mice in Group C were intraperitoneally administrated with cordycepin(5 mg x kg(-1) d(-1)) and the ones in Group A and B were administrated with physiological saline for 5 days. At the end of the study, the obstructed kidneys were collected and detected for the pathological changes of RIF, and the mRNA expressions of collagen type I (Col I) and α-smooth muscle actin (α-SMA) in the kidney by Northern blot. Secondly, after renal tubular epithelial (NRK-52E) cells cultured in vitro were exposed to transforming growth factor (TGF) -β with or without cordycepin, the mRNA expressions of Col I and collagen type IV( Col IV) by Northern blot, and the protein expressions of eukaryotic initiation factor 2α (eIF2α), phosphorylated eIF2α ( p-eIF2α), Smad2/3 and phosphorylated Smad2/3 (p-Smad2/3) were tested by Western blot.
RESULTIn vivo, cordycepin alleviated RIF in model mice, including improving fibrotic pathological characteristics and mRNA expressions of Col I and α-SMA. In vitro, cordycepin induced the high expression of p-elF2α, and inhibited the expressions of p-Smad2/3, Col I and Col IV induced by TGF-β in NRK-52E cells.
CONCLUSIONCordycepin attenuates RIF in vivo and in vitro, probably by inducing the phosphorylation of eIF2α, suppressing the expression of p-Smad2/3, a key signaling molecule in TGF-β/Smad signaling pathway, and reducing the expressions of collagens and α-SMA in the kidney.
Actins ; analysis ; Animals ; Deoxyadenosines ; pharmacology ; Fibrosis ; Kidney ; drug effects ; pathology ; Male ; Mice ; Mice, Inbred C57BL ; Phosphorylation ; Protein-Serine-Threonine Kinases ; physiology ; Signal Transduction ; drug effects ; Smad Proteins ; physiology ; Transforming Growth Factor beta ; antagonists & inhibitors ; physiology
8.Research progress in drugs targeting tumor associated macrophage
Li-wen REN ; Yi-hui YANG ; Wan LI ; Yi-zhi ZHANG ; Hong YANG ; Sen ZHANG ; Fang XU ; Yue HAO ; Wan-xin CAO ; Guan-hua DU ; Jin-hua WANG
Acta Pharmaceutica Sinica 2023;58(12):3508-3518
Tumor brings great threat to human public health. In recent years, incidence rate and mortality of tumor were rapidly increased in the world. Anti-tumor therapies have undergone the development of cytotoxic therapy, targeted therapy, and immunotherapy. Among them, tumor immunotherapy is rapidly developed and becomes an important anti-tumor therapy in recent years, although it also brings some related side effects. Tumor microenvironment (TME) is composed of immune cells, vascular vessels, fibroblasts, the extracellular matrix, etc. TME significantly affects the efficacy of immunotherapy. Macrophages in the TME are named as tumor associated macrophages (TAMs). Recently, increasing studies have shown that TAMs play an important role in the regulation of tumor immunity, especially in tumor immune surveillance and immune escape. Currently, more and more anti-tumor immunotherapy strategies targeting TAMs are at the development stage. Based on the important role of TAMs in the TME and their potential as therapeutic targets in tumor immunotherapy, we first reviewed the subtypes and functions of TAMs, as well as the roles of TAMs in tumors. Furthermore, we summarized the research progress on anti-tumor strategies targeting TAMs and the current status of drug targeting TAMs. The current review will provide new ideas and novel insights for tumor immunotherapy.
9.Application of hydrogen proton magnetic resonance spectroscopy in diagnosis of peripheral tumor cell infiltration of gliomas
Yi-ling, FAN ; Yong, WANG ; Jie-qing, WAN ; Zheng-wen, ZHOU ; Ji-yao, JIANG ; Jia-lin, SHENG ; Fei-ping, LI
Journal of Shanghai Jiaotong University(Medical Science) 2009;29(7):854-857
Objective To explore the application of hydrogen proton magnetic resonance spectroscopy (1H-MRS) in the diagnosis of peripheral tumor cell infiltration of gliomas. Methods Forty patients with glioma were examined by 1H-MRS preoperation, and were divided into low grade glioma group (n=20) and high grade glioma group (n=20) according to postoperative pathological diagnosis. Tumor resection with peripheral tissues marked previously was carried out under the guidance of neuronavigator system. All the pathological sections were divided into positive group and negative group according to the presence or absence of tumor cells, and the differences in pathological findings of peripheral regions (region 1, 2 and 3) and 1H-MRS values were analyzed in these two groups. Results No infiltration was found in the peripheral regions of low grade glioma group except for one case in peripheral region 1, while infiltration was found in all peripheral regions of high grade glioma group. There was no significant difference in 1H-MRS values between positive group (n=24) and negative group (n=36) in patients with high grade glioma (P>0.05). Conclusion 1H-MRS enjoys some advantages over routine radiological examinations in the diagnosis of peripheral tumor cell infiltration of gliomas. Total removal can be expected when combined with neuronavigator system, while there is room for improvement for relevant techniques.
10.Experimental study of interventional infusion thermochemotherapy in rabbit liver VX2 tumor
Yi-Yong LIU ; Zi-Ming WAN ; Wei CHAO ; Hong-Xin ZHANG ; Wen-Xian LI ; Xiang-Yang QIN ;
Journal of Interventional Radiology 2006;0(12):-
Objective Effectiveness of two kinds of thermochemotherapy infusion from intraarterial approach were studied in the grafted liver VX2 tumors of rabbit.Methods VX2 tumor model was established in 30 Newzland rabbit's livers.Percutaneous transfemoral hepatic arterial catheterization with fixation of the cathether tip inside the feeding vessel was carried out under DSA guidance.All 30 rabbits were divided into three groups(n=10 in each group),normal temperature 100 ml saline+Adriamycin(ADM)infusion(group 1),60℃100 ml saline+ADM continuous perfusion(group 2)and 60℃100 ml saline+ADM intermittent perfusion(group 3).After the perfusion,the lasting time periods of 43-45℃for tumor tissue of group 2 and 3 together with the concentrations of ADM within tumor's tissue were measured.Results Concentrations of ADM were shown as(12.013?2.237)?g/ml,(17.622?1.368)?g/ml,and(11.519?1.225)?g/ml for group 2, group 3 and group 1 respectively.60℃intermittent perfusion vs 60℃continuous perfusion showed P<0.05, 60℃continuous pefusion vs normal temperature perfusion also showed P>0.05. 43-45℃period lasting time (min)for 60℃continuous pefusion vs 60℃intermittent pefusion were(4.1?2.7)min and(11.3?3.3)min respectively,the latter was three times more than the former.There were no differences shown betwen the temperature,respiration and heart rate of group 2 and group 3.Conclusion Intermittent intraarterial perfusion thermochemotherapy is a more effective interventional management among all thermochemotherapies.