OBJECTIVETo investigate the effect of Actinidia chinensis Planch polysaccharide (ACPS) on the growth and apoptosis of human gastric cancer SGC-7901 cells, and to explore the effect of SGC-7901 cells on p-p38 expression.

METHODSThe inhibition rates at different concentrations of ACPS on SGC-7901 cells at 24, 48, and 72 h were detected using CCK-8 method. Apoptosis ratios in SGC-7901 were determined by flow cytometry after 48-h treatment of different concentrations of ACPS. The expression of pro-caspase-9, PARP, and p-p38 in SGC-7901 cells after treated by different concentrations of ACPS was detected using Western blot. The expression of pro-caspase-9, PARP, and p-p38 was detected after SGC-7901 cells were pre-treated by p38 specific inhibitor.

RESULTSCompared with the control group, the optical density of SGC-7901 cells decreased after treated by 1, 2.5, 5, and 10 mg/mL ACPS (P < 0.05). Meanwhile, the longer the acting time, the lower the optic density (P < 0.01). IC50 was 7.43 mg/mL at 24 h; 3.88 mg/mL at 48 h, and 1.32 mg/mL at 72 h respectively. ACPS suppressed the protein expression of pro-caspase-9 (P < 0.01) and up-regulated the expression of PARP (89KD) (both P < 0.01). Further study showed that the protein expression of p-p38 was up-regulated in SGC-7901 cells treated by ACPS of different concentrations at 24 h (P < 0.05). The expression of phosphorylation p38 and the ACPS induced apoptosis of SGC-7901 cells could be inhibited after treated by specific inhibitor for 2 h.

CONCLUSIONSACPS could inhibit the growth of SGC-7901 cells and induce apoptosis. The underlying mechanism of inducing apoptosis was partially due to activating the p38MAPK path and further activating Caspase9 and PARP, finally leading to cell death.

Actinidia ; chemistry ; Apoptosis ; drug effects ; Caspase 9 ; metabolism ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; metabolism ; Polysaccharides ; pharmacology ; Stomach Neoplasms ; metabolism ; pathology ; p38 Mitogen-Activated Protein Kinases ; metabolism

Airway Obstruction ; complications ; etiology ; physiopathology ; Asphyxia ; etiology ; physiopathology ; Fibroma ; complications ; pathology ; Humans ; Infant, Newborn ; Oropharyngeal Neoplasms ; complications ; pathology ; Rare Diseases

Poly(ADP-ribose)polymerase-1 (PARP-1) plays a significant role in the DNA repair process by catalyzing the transfer of ADP-ribose from NAD+ to its receptors. It is a promising anticancer drug target and many PARP-1 inhibitors have been developed and used in the clinical trial. In this work, a series of 3-(2-oxo-2-substituted acetamido)benzamides have been synthesized and their inhibitory activities against PARP-1 were evaluated. Of all the tested compounds, six compounds displayed inhibitory activities with IC50 values ranging from 0.23 to 5.78 µmol.L-1 . The binding pose of compound 5a was predicted using molecular docking to facilitate further structural modification.
Antineoplastic Agents ; Benzamides ; chemistry ; DNA Repair ; Drug Design ; Humans ; Molecular Docking Simulation ; Poly(ADP-ribose) Polymerase Inhibitors ; chemical synthesis ; chemistry ; Poly(ADP-ribose) Polymerases

Poly(ADP-ribose) polymerase-1 (PARP-1) has emerged as a promising anticancer drug target due to its key role in the DNA repair process. It can polymerize ADP-ribose units on its substrate proteins which are involved in the regulation of DNA repair. In this work, a novel series of para-substituted 1-benzyl-quinazoline-2, 4 (1H, 3H)-diones was designed and synthesized, and the inhibitory activities against PARP-1 of compounds 7a-7e, 8a-8f, 9a-9c and 10a-10c were evaluated. Of all the tested compounds, nine compounds displayed inhibitory activities with IC50 values ranging from 4.6 to 39.2 micromol x L(-1). In order to predict the binding modes of the potent molecules, molecular docking was performed using CDOCKER algorithm, and that will facilitate to further develop more potent PARP-1 inhibitors with a quinazolinedione scaffold.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Drug Design ; Enzyme Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Molecular Docking Simulation ; Molecular Structure ; Poly (ADP-Ribose) Polymerase-1 ; Poly(ADP-ribose) Polymerases ; Quinazolinones ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

· AIM :To investigate the role of pericytes in growth of retinal microvascular endothelial cells with a co-culture system in order to understand some mechanism of angiogenesis in hypoxia induced retinal neovascular disorders.(RMECs) were isolated by a modified protocol using CD31 coated Dynabeads, and identified by immunocytochemical staining with anti-Factor Ⅷ and CD31 antibodies. Rat retinal pericytes were isolated and characterized by immunofluorescent staining with PDGFR-β; and desmin antibodies. Pericytes and RMECs were cultured in a contact co-culture system both under normoxia and hypoxia by Millicell chamber. RMECs proliferation was evaluated by MTT and cell cycle assay with flow cytometry. RT-PCR was used to detect the alteration of KDR/Flk-1 mRNA level in RMECs under normoxia or hypoxia in the co-culture system.harvested with the modified isolating method. The two cell types were identified by positive Factor Ⅷ, CD31 and PDGFR-β, desmin cytochemical staining respectively.RMECs proliferated significantly under hypoxia from 3 to 9d with a maximal rate on day 6 (24.9%, P ＜ 0.01) by MTT. In the co-culture system, the proliferation of RMECs was inhibited by pericytes. After 6d exposure to hypoxia,the fraction of S-phase RMECs number was greatly increased by 43.9% (P ＜ 0.01). In the co-culture system,RMECs proliferation was inhibited by pericytes through decreasing the fraction of S-phase cell number both under normoxia (3.6%, P＜0.05) and under hypoxia (15.1%,P＜0.01). KDR/Flk-1 mRNA level in single cultured RMECs was shown to increase approximately 1.3-fold when exposed to hypoxia. Compared with single cultured RMECs, co-culture with pericytes could decrease KDR/Flk-1 mRNA by 45.1% (P＜0.05) and 27.7% (P ＜ 0.05) under normoxia and hypoxia condition respectively.pericytes could inhibit proliferation of RMECs under both normoxia and hypoxia. The inhibition effects of pericytes maybe, at least in part, due to downregulation of KDR/Flk-1 of RMECs. These findings confirm that pericytes could be a potential inhibitor in the pathogenesis of retinal neovascularization.

OBJECTIVETo investigate the applications of percutaneous screw fixation for the treatment of pelvic fractures and its related surgical considerations.

METHODSFrom June 2010 to June 2012,19 patients with pelvic fractures were treated with percutaneous hollow screws. There were 13 males and 6 females, with an average age of 41 years (ranged from 22 to 58 years). Fractures were caused by traffic accidents in 11 cases, by falling down from high place in 8 cases. Based on the Tile classification, there were 15 cases of Tile C type and 4 case of Tile B type. The indexes such as screw inserting time, intraoperative blood loss, complications, functional recovery and reduction conditions were observed. Fixation methods included sacroiliac screws, cannulated screw fixation of the pubic ramus and cannulated screw fixation of the pubic symphysis separation.

RESULTSAnatomical reduction achieved in 7 cases, satisfactory reduction 11 cases, and unsatisfactory reduction 1 case. Union time of fracture union ranged from 8 to 12 weeks (mean 10 weeks). Wound infection,ununion of fracture and nerve injuries were not found. According to the Majeed standards, 12 patients obtained an excellent results, 6 good and 1 fair.

CONCLUSIONPercutaneous screw fixation for the treatment of pelvic fractures under fluoroscopy has several advantages such as less trauma, less blood loss, fewer rates of complications, reliable fixation and no blood transfusion, which can reconstruct the stability of the pelvic ring, but it needs adequate preoperative preparation and high requirements for the surgeon.

Adult ; Bone Screws ; Female ; Fracture Fixation, Internal ; Fractures, Bone ; diagnostic imaging ; surgery ; Humans ; Male ; Middle Aged ; Pelvic Bones ; diagnostic imaging ; injuries ; surgery ; Radiography ; Young Adult

Thirty healthy women and 101 patients with polycystic ovary syndrome (PCOS) were recruited. According to serum testosterone (T) level and homeostasis model assessment for insulin resistance (HOMA-IR) ,the correlation of T and body mass index (BMI) with insulin resistance was analyzed. The results showed that there were 39. 8％ normal,24. 5％ overweight,and 35.7％ obese among 101 PCOS patients. However,there were no significantly differences in BMI, fasting plasma glucose ( FPG ), triglyceride ( TG ), total cholesterol ( TC), low-density lipoprotein-cholesterol ( LDL-C), high-density lipoprotein-cholesterol ( HDL-C ), and HOMA-IR levels between PCOS patients with hyperandrogenemia ( T ≥ 0. 51 μg/L) and normal androgenemia ( T ＜ 0. 51 μg/L). BMI, FPG, TG, TC, and LDL-C levels were higher and HDL-C level was lower in patients with insulin resistance( HOMA-IR ≥ 2. 29 ) than in patients without insulin resistance ( HOMA-IR ＜ 2. 29, P＜0. 05 or P＜ 0. 01 ). Serum T levels were not significantly different between two groups. HOMA-IR was significantly correlated with BMI(P＜0. 01 ), not with serum T, suggesting that the gain of body weight is correlated with insulin resistance independent of serum T level.

cDNA for Insulin-like growth factor binding protein 3 was cloned and constructed a prokaryotic expression vector--pET-DsBA-IGFBP3. The construct was transformed into E. coli BL21 (DE3)plysS. The induced fusion protein (D-IGFBP3) was expressed successfully in soluble form. We obtained D-IGFBP3 the purify of which is over 95% after purification by His affinity chromatography. The product was identified by Western-blot. The cell assay showed that the obtained fusion protein can inhibit the growth of MCF-7 and bind with IGF-I in vitro.
Blotting, Western ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Chromatography, Affinity ; Dose-Response Relationship, Drug ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Escherichia coli ; genetics ; Gene Expression ; Humans ; Insulin-Like Growth Factor Binding Protein 3 ; genetics ; metabolism ; pharmacology ; Insulin-Like Growth Factor I ; metabolism ; Protein Binding ; Recombinant Proteins ; isolation & purification ; metabolism ; pharmacology ; Solubility

Diabetic peripheral neuropathy (DPN), one of the most common chronic complications of diabetes, is characterized by allodynia, hyperalgesia and spontaneous pain. Chinese epidemiological studies have shown that at least 25% diabetic patients suffered from painful DPN, which compromises patients' daily functioning and becomes a major health care problem. Although the pathogenesis of painful DPN is not fully understood and current treatment options are very limited, research in the field has advanced our understanding on the mechanism of painful DPN in the past Decade of Pain Research and Control. This review will mainly focus on evaluation of current diabetic animal models, possible molecular pathways and available therapies, with an emphasis on roles of purinergic receptor and its signaling transduction pathways. Common therapies address one or two DPN symptoms, while others offer wider symptom control, presumably by targeting pathophysiological mechanisms of DPN. Purinergic receptor signaling transduction pathways might become potential targets for treatment for painful DPN.
Animals ; Diabetes Mellitus ; physiopathology ; Diabetic Neuropathies ; physiopathology ; Humans ; Hyperalgesia ; physiopathology ; Pain ; physiopathology ; Receptors, Purinergic P2X ; physiology

OBJECTIVETo explore the protective mechanism of Nervilia fordii (NF) by observing the effect of its pretreatment on lung aquaporin 1 and 5 (AQP-1, AQP-5) expression in rats with endotoxin-induced acute lung injury (ALI).

METHODSTwenty-four SD rats were randomly divided into 3 groups, the normal group (A), the NF pre-intervention group (B) and the endotoxin model group (C). Rats in Group B and C were made into ALI by endotoxin (5 mg/kg) injection via sublingual vein, and NF pretreatment was applied to Group B. Animals were sacrificed at the 8 h after modeling, their lung were taken for observing the water permeability change by wet/dry weight ratio (W/D) measuring, pathological feature by HE staining, and the expression of AQP-1, AQP-5 was detected by immunohistochemistry and RT-PCR.

RESULTSThe W/D ratio of lung was higher in model rats than in normal rats, but as compared with Group C, it was significantly lower (P < 0.05) in Group B. The pulmonary edematous change was significantly mild and the AQP-1 and AQP-5 protein expressions were significantly higher in Group B than in Group C (P < 0.05).

CONCLUSIONNF pretreatment can promote lung AQP-1 and AQP-5 expression up-regulation, increase lung water clearance and transportation to improve the water balance and eliminate pulmonary edema, so as to effectively protect lung from acute injury.

Acute Lung Injury ; chemically induced ; drug therapy ; prevention & control ; Animals ; Aquaporin 1 ; metabolism ; Aquaporin 5 ; metabolism ; Drugs, Chinese Herbal ; therapeutic use ; Endotoxins ; Female ; Lung ; metabolism ; Male ; Phytotherapy ; Rats ; Rats, Sprague-Dawley ; Up-Regulation