Background The development of retinopathy of prematurity(ROP) is associated with many regulatory cytokines related to neovascularization;however,the retinal expression and regulated mechanism of stromal cell-derived factor-1 (SDF-1) in mouse model of oxygen-induced retinopathy (OIR) remain uncertain.Objective This study was to investigate the expression of SDF-1 in retina of mouse model of OIR.Methods Forty 7-day-old C57BL/6J mice were divided into OIR group and control group.In OIR group,20 mice were exposed to 75% oxygen for 5 days and then to room air for 5 days.In control group,20 mice were raised in room air.The expression of SDF-1 in retina of mice was studied by immunochemistry and quantified by real time reverse transcriptase polymerase chain reaction (RT-PCR).Results The positive immunohistochemical staining for SDF-1 was found mainly locating at the ganglion cell layer in 12-day-old mice of OIR group;the stronger positive immunohistochemical staining for SDF-1 was noted mainly locating at the ganglion cell layer,vascular endothelial cells of inner retina,neovascular endothelial cells in 17-day-old mice of OIR group;the delicate positive immunohistochemical staining for SDF-1 was both found mainly locating at the inner retina and being around the retinal vascular in 12-day-old mice of control group and 17-day-old mice of control group.The expression of SDF-1 mRNA in 17-day-old mice of OIR group was higher than that of 12-day-old mice of OIR group (t=8.072,P＜0.05)and 17-day-old mice of control group(t=10.026,P＜0.05),respectively.The expression of SDF-1 mRNA in 12-day-old mice of OIR group was lower than that of 12-day-old mice of control group (t=4.336,P＜0.05).Conclusion SDF-1 might improve the onset of retinal neovascularization of OIR.

Objective To investigate the role of CTLA4-Ig and anti-CD40L monoclonal antibody in the acute rejection of pancreaticoduodenal transplantation model of rats.Methods Pancreaticoduo- denal transplantation model was established from the donor F344 rats to the Lewis recipients(diabetes models).The models were divided into 4 groups:groups A,B,C and D with 12 rats in each group. Two days after transplantation,recipients were injected intraperitoneally with saline,CTLA4-Ig(200?g),anti-CD40L monoclonal antibody(200?g),CTLA4-Ig(200?g)combined with anti-CD40L monoclonal antibody(200?g)respectively.On the day 1,4,7,10 after transplantation,the grafts were harvested for histopathological examination and RT-PCR to determine the levels of interleukin (IL)-2,interferon(IFN)-?,IL-4 and IL-10;The blood CD3~+,CD4~+and CD8~+ T cells were detected by flow cytometry.On the day 4 after transplantation,the CD4~+ CD25~+ T cells in the grafts were de- tected by flow cytometry.Results As compared with group A,the severity of the rejection of grafts in groups B,C and D were depressed;Down-regulation of IL-2 was observed in the groups B,C and D, and the levels in group D were lowest.Down-regulation of IFN-7 was detected in the groups B,C and D,but there was no significantly difference between groups D and B or groups D and C.Up-regulation of IL-4 was observed in the groups B and C,and the levels in group D were lower than in groups A,B and C.Up-regulation of IL-10 was observed in groups B and C,and there was significant difference between groups D and B or groups D and C.The CD3~+,CD4~+ and CD8~+ T cells in groups B,C and D were less,but more CID4~+ CD25~+ T ceils in transplanted pancreas were observed,more notably in group D than in group C.Conclusions Combined use of CTLA4-Ig and anti-CD40L monoclonal anti- body can remarkably diminish the severity of the rejection,which might be mediated by altering the balance in Th1/Th2 and increasing the number of CD4~+ CD25~+ regulatory T cells.Co-stimulation blockade with CTLA4-Ig and anti-CD40L monoclonal antibody induction seems to be an attractive strategy to control allograft rejection.

Objective To evaluate the clinical application of 2000 ArthroCare System in knee arthroscopic surgery. Methods 221 cases of knee problems were treated with 2000ArthroCare System. The disorders of the 221 cases diagnosed by the arthroscopy were as follows: 73 cases of osteoarthritis, 49 meniscus tear, 29 degenerative cartilage injury, 11 plica synovitis, 11 Kaschin Beck disease, 8 ACL, 5 osteochondritis dissecans, and 2 TKA brisement. The operative procedures, such as meniscectomy, meniscoplasty, fitting of cartilage and ligament, synovectomy, and release of lateral patellar retinaculum, were done with 2000ArthroCare System and arthroscopy. Results The Lysholm Knee scores were 43.92 preoperatively, 81.96 three months postoperatively, and 92.06 six months postoperatively. Conclusion Knee problems can be effectively released with 2000 ArthroCare system vaporization under arthroscopic guidance. The advantages of this procedure are very limited tissue damage, mild reaction, less blood loss, early rehabilitation, and fine functional recovery.

Objective To examine the induction effects of bone marrow mesenchymal stem cells(BMSCs) transfected with bone morphogenetic protein 7 (BMP7) gene differentiating into chondrocytes. Methods We observed the phenotype of cells which were stained with alcian blue and HE climbing to the six pore plate with invert microscope. The glycosaminoglycan (GAG) value in culture medium was detected in control group,BMP7 transfect and culture medium induced groups after 7,14 and 21 days using standard curve method. Standard curve was described using galacturonic-acid as reference substance. The content of collagen Ⅱ was detected by ELISA method. Results HE and Alcian blue staining showed that BMP7 gene transfection group and the group induced by fluid possess the characteristics of chondrocyte. BMP7 induced BMSCs differentiation to chondrocyte which secrete specific protein called collagen Ⅱ and GAG. Content of GAG were (17.1±3.4),(39.5±5.4),(40.8±6.1)mg/L in control group,BMP7 gene transfected group and induced group,collagen Ⅱ were (89.7±14.3),(152.8±14.5),(155.5± 19.3)μg/L in these three groups separately. Comparing with control group,GAG and collagen Ⅱ of BMP7 gene transfected group and culture medium induced group increased obviously(all P < 0.05),but there was no significant difference between BMP7 gene transfeeted group and culture medium induced group (P > 0.05). Conclusion This active protein induces BMSCs differentiating into chondrocyte,in a level similar to that of inducing medium.

This study was aimed to explore the factors impacting on effect of the recombinant human granulocyte colony-stimulating factor (rhG-CSF) in mobilizing and collecting peripheral blood stem/progenitor cells (PBSPC) from healthy donors, and to determine the optimal time for PBSPC harvest. A mobilization course in 431 healthy donors was retrospectively studied and the factors influencing the efficacy of mobilization were analyzed. The normal donors underwent leukapheresis for PBSPC collection in multicentres after mobilization with G-CSF administered. A variety of items analyzed included donor age, sex, weight, body mass index (BMI), daily G-CSF dose and schedule of G-CSF administration. The results showed that G-CSF was administered subcutaneously at median 5.7 microg/kg for mobilization for 3 - 5 days, The median number of peripheral blood mononuclear cells (PBMNC) count of per kg recipient weight was 9.57 x 10(8) and CD34(+) cells per kg recipient weight was 4.91 x 10(6) after a median of 1.7 leukapheresis. The side effects were mild and well tolerated. By univariate analysis, BMI, daily G-CSF dose and schedule of administration were significantly correlated with the yield of PBMNCs, CD34(+) cells. The best apheresis yields of PBMNCs and CD34(+) cells were achieved on day 5 after treatment with rhG-CSF. Because the narrow range and low dose of rhG-CSF administration, there were minor effects of rhG-CSF dose compared with schedule of administration. It is concluded that mobilization and leukapheresis are safe in healthy donors and that the low dose of rhG-CSF in 5-day administration are probably optimal for donor management.
Adult ; Female ; Granulocyte Colony-Stimulating Factor ; administration & dosage ; Hematopoietic Stem Cell Mobilization ; Humans ; Leukapheresis ; Male ; Middle Aged ; Peripheral Blood Stem Cell Transplantation ; methods ; Recombinant Proteins ; Tissue Donors ; Young Adult

The aim of this study is to evaluate anti-tumor activities and mechanism of a novel kinase inhibitor ZLJ213 which targeted Aurora A and vascular endothelial growth factor receptor (VEGFR) in vitro and in vivo against human colon cancer. Results showed that ZLJ213 inhibited cell proliferation and induced cell cycle arrest and apoptosis of HCT1 16 and SW48 cell lines. In HCT116-derived xenograft, ZLJ213 dosed at 100 mg · kg(-1) inhibited tumor growth by 73.24%. The IC50 of ZLJ213 on the expression of p-Aurora A was 0.258 µmol · L(-1) analyzed by ELISA. Under the concentration of 0.08 µmol · L(-1), ZLJ213 could inhibit the activities of Aurora A, Histone H3 and VEGFR of HCT116 and SW48 cell lines. Simultaneously, ZLJ213 induced activation of Caspase 3 and PARP cleavage. Above data suggested that ZLJ213 had the ability to inhibit cell proliferation and induce cell apoptosis both in vitro and in vivo in colon cancer, and down-regulate the expression of p-Aurora A and p-VEGFR. ZLJ213 might be a potential therapeutic agent against colon cancer.
Animals ; Apoptosis ; Aurora Kinase A ; antagonists & inhibitors ; Cell Cycle Checkpoints ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Colonic Neoplasms ; pathology ; Humans ; Protein Kinase Inhibitors ; pharmacology ; Receptors, Vascular Endothelial Growth Factor ; metabolism ; Xenograft Model Antitumor Assays

Une new flavonoids named as notabilisin K (1), together with four known compounds, morusin (2), mulberrofuran A (3), neocyclomorusin (4) and mornigrol F (5) are separated from 95% ethanol extracts of the twigs of Morus notabilis. Compounds 2-5 are separated from this plant for the first time. Notabilisin I, notabilisin J exhibits certain effect against cells of HCT-116, HepG2 and A2780 with IC50 values ranging from 1.47 μmol x L(-1) to 5.46 μmol x L(-1). Morusin exhibits strong effect against five kinds of human cancer cells (BGC823, A2780, HCT-116, HepG2 and NCI-H1650) with IC50 values ranging from 0.74 μmol x L(-1) to 1.58 μmol x L(-1).
Antineoplastic Agents, Phytogenic ; chemistry ; Benzofurans ; chemistry ; Flavonoids ; chemistry ; Hep G2 Cells ; Humans ; Inhibitory Concentration 50 ; Morus ; chemistry ; Plant Extracts ; chemistry ; Terpenes ; chemistry

Hypoxia is a general characteristic of most solid malignancies and intimately related to cancer progression. Homeostatic response to hypoxia is primarily mediated by hypoxia inducible factor-1alpha (HIF-1alpha) that elicits transcriptional activity through recruitment P300 coactivator. Targeting the interaction of HIF- alpha and P300 would thus constitute a novel approach for cancer treatment by suppressing tumor angiogenesis and metastasis. Here, a screening assay was developed for inhibitors targeting the interaction between HIF-1alpha and P300. The nucleotide sequence of human HIF-1alpha and P300 were cloned into pBIND and pACT vectors, named pBIND-HIF1alpha and pACT-P300. The interaction of HIF-1alpha and P300 was identified in HEK293 cell using mammalian two-hybrid system. And compound chetomin decreased their interaction in this mammalian two-hybrid system. We further verified HIF-1 inhibition effect of chetomin in U251-HRE cells. Therefore, we established a screening assay combined HIF-1alpha and P300 mammalian two-hybrid system and U251-HRE reporter assay for HIF-1 selective inhibitors.
Cell Hypoxia ; Disulfides ; pharmacology ; Drug Screening Assays, Antitumor ; E1A-Associated p300 Protein ; antagonists & inhibitors ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit ; antagonists & inhibitors ; Indole Alkaloids ; pharmacology ; Two-Hybrid System Techniques

A series of novel sorafenib analogues were designed and synthesized. The cytotoxic activities of these compounds were tested in four tumor cell lines. Some of the compounds showed potent antiproliferative activity against the tested cell lines with IC50 = 4-20 micromol x L(-1). Some compounds demonstrated competitive antiproliferative activities to sorafenib against tested cancer cell lines. Among them, compound 7c demonstrated significant inhibitory activities on ACHN, HCT116 and MDA-MB-231 cell lines with IC50 values of 9.01, 4.97, 6.61 micromol x L(-1), respectively.
Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Niacinamide ; analogs & derivatives ; chemical synthesis ; chemistry ; pharmacology ; Phenylurea Compounds ; chemical synthesis ; chemistry ; pharmacology ; Structure-Activity Relationship

Objective To study the mutability of ultra sodium pyrosulfite intake on ultrastructure changes and spermatogonium mice testis.Methods Forty male Kunming mice were used.Experimental group had been exposed to ultra sodium pyrosulfite by fed for 10 days,and sodium pyrosulfite′s contaminated dose were 1% and 1‰.Mice were killed at 11~(th) day,and ultrastructure changes were observed under transmission electron microscopy(TEM) and the tests of sister chromosome exchanges(SCE) were made.Mmutation of ultra sodium pyrosulfite on spermatogonium of mice testis was judged.Results Compared with control group,there was a significant increase of SCE ratio in spermatogonium of testis in experimental groups(P