OBJECTIVETo explore the possible association between activation of rat microsomal glutathione S-transferase 1 (mGST1) and chlorambucil toxicity on selected cancer cell lines.

METHODSHepatic microsomes were prepared from male Sprague-Dawley rats and washed to remove cytosolic contamination. mGST1 was purified and its activity was measured. PC-3, K562, HepG2 and P388D1 cell lines were exposed to chlorambucil (CHB) alone or to CHB with mGST1 at concentrations of 0 ~ 100 micromol/L for 8, 24, 48, 72 h. Cytotoxic effects of CHB were determined by cell growth inhibition (MTT assay), mitochondrial transmembrane potential (DeltaPsim), and fluorescence morphological examination (AO/EB staining).

RESULTSThe decreased cytotoxic effects of CHB on the cell lines altered by mGST1 were demonstrated in concentration- and time-dependant manners. The CHB-induced apoptosis on PC-3 and K562 cell lines altered by mGST1 was confirmed using DeltaPsim examination, JC-1 or AO/EB staining.

CONCLUSIONmGST1 can reduce the cytotoxic effects of CHB in selected cancer cell lines.

Animals ; Antineoplastic Agents, Alkylating ; metabolism ; pharmacology ; Apoptosis ; drug effects ; Cell Line, Tumor ; Cell Survival ; drug effects ; Chlorambucil ; metabolism ; pharmacology ; Dose-Response Relationship, Drug ; Glutathione Transferase ; isolation & purification ; metabolism ; Humans ; K562 Cells ; Microsomes, Liver ; enzymology ; Rats ; Rats, Sprague-Dawley

As one of the major sources of infection, viruses could infect all organisms including bacteria, plants, animals, and humans. Infectious diseases caused by viruses pose a great threat and damage to human health and economic activities all over the world. Adaptor-associated protein kinase 1 (AAK1) is a member of the Ark1/Prk1 family of serine/threonine kinases and a specific key kinase regulating the phosphorylation of AP-2 protein μ2 subunit T156. In the past, AAK1 has been regarded as a feasible biological target for the treatment of nerve pain. Recently, scientists have found that inhibiting AAK1 can regulate endocytosis and inhibit virus invasion into cells. Therefore, AAK1 could be the potential target of anti-virus therapy. This paper reviews the research progress of small molecule AAK1 inhibitors in the field of antiviral, analyzes the future research directions and challenges, and provides new ideas for the development of antiviral drugs targeting AAK1.

The biological properties of cultured mesenchymal stem cells (MSC) have been intensively investigated, while there is still a paucity of information about the definite in vivo sites that harbor these stem cells due to the lack of specific surface markers. Previous data have demonstrated that human and murine MSC can be isolated from the compact bones. To investigate if it is the case for other species, the femurs from Wistar rats, Beagles, C57 mice and New Zealand rabbits were collected, minced and digested with collagenase type I. The digested bone fragments were seeded into the medium for human bone marrow culture after removal of the suspended cells in the digestion. The results showed that the fibroblast-like cells were observed to migrate from the bone fragments after several days of culture, and they gradually formed an adherent confluent layer. The adherent cells could be passaged and expressed homogenously the mesenchymal cell marker vimentin. Differentiation assays showed that these cells had the capacity to differentiate into osteoblasts and adipocytes. In conclusion, the results here provide new information for the further investigations on the in vivo biological features of MSC in the context of the simplicity of the compact bone structure.
Animals ; Bone and Bones ; cytology ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Dogs ; Mesenchymal Stromal Cells ; cytology ; Mice ; Mice, Inbred C57BL ; Rabbits ; Rats ; Rats, Wistar

OBJECTIVETo investigate class I integron of Shigella flexneri, its prevalence in children, and its relation to bacterial resistance to antimicrobial agents.

METHODSTotally 51 strains of Shigella flexneri were isolated from fecal samples of children suffering from bacterial diarrhea seen between June 2004 and November 2004 at Children's Hospital of Fudan University. Polymerase chain reaction (PCR) was employed to amplify various integron markers, including intI1, gene cassette region and 3' conserved region of class I intrgron; susceptibility of Shigella flexneri strains to 7 antimicrobial agents was determined by K-B (Kriby-Bauer) method.

RESULTSForty-six strains of Shigella flexneri had intI gene with a positive rate of 90.2% (46/51); 24 strains of Shigella flexneri were positive for qacEDelta1-sul1, the positive rate was 47.1% (24/51); proportion of the isolates positive for all the three regions of class I integron was 43.1% (22/51); 46 strains of intI positive Shigella flexneri were all positive for ant (3'')-I. Among 46 strains of intI positive isolates, proportions of the isolates positive and negative for qacEDelta1-sul1 were 47.8% (22/46) and 52.2% (24/46), respectively. In the class I integron positive Shigella flexneri, the resistance rates of ampicillin (chi(2) = 10.13, P < 0.01) and chloramphenicol (chi(2) = 19.97, P < 0.01) were significantly higher than those in the class I integron-negative group.

CONCLUSIONSClass I integron was detected in 90.2% of Shigella flexneri in children; carriage of class I integron is related to antimicrobial resistance of Shigella flexneri.

Anti-Bacterial Agents ; pharmacology ; Child ; DNA, Bacterial ; genetics ; Diarrhea ; microbiology ; Drug Resistance, Bacterial ; genetics ; Dysentery, Bacillary ; drug therapy ; microbiology ; Feces ; microbiology ; Humans ; Integrons ; drug effects ; genetics ; Polymerase Chain Reaction ; Retrospective Studies ; Shigella flexneri ; drug effects ; genetics ; isolation & purification

OBJECTIVETo evaluate the antitumor activity of a novel class of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones in vitro, and to screen potential anticancer compounds for further study.

METHODSSeventeen compounds of 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g]quinazoline-7(6H)-ketones were synthesized with solid-phase method for biological evaluation of EGFR tyrosine kinase. MTT method was used to evaluate the cytotoxic activity in vitro against three human cancer cell lines (human lung carcinoma cell line A549, human leukemia cell lines K562 and human gastric carcinoma cell line SGC7901).

RESULTSCompound 7-13 and 7-14 showed potent antitumor activities against A549 cells, with IC(50) values of 8.10 and 8.12 mol/L, respectively. Eight compounds showed proliferative inhibition effect on K562 cells, especially 7-2, 7-13 and 7-17, with IC(50) values of 2.22,0.57 and 7.20 mol/L,respectively.And compound 7-13 and 7-3 showed potent antitumor activity against SGC7901 cells, with IC(50) values of 4.20 and 9.71 mol/L, respectively.

CONCLUSIONThe synthesized compounds 4, 8-Disubstituted-8, 9-dihydropyrazine[2, 3-g] quinazoline-7(6H)-ketones show inhibition effects on human cancer cell lines in vitro. Compound 7-13 has anticancer activity in all three cancer cell lines, which might be used as a potential antitumor drug for further study.

Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Humans ; K562 Cells ; Lung Neoplasms ; pathology ; Molecular Structure ; Pyrazines ; chemical synthesis ; chemistry ; pharmacology ; Quinazolines ; chemical synthesis ; chemistry ; pharmacology ; Receptor, Epidermal Growth Factor ; antagonists & inhibitors ; Stomach Neoplasms ; pathology ; Structure-Activity Relationship

OBJECTIVETo study the inhibition effect of celastrol on neovascularization.

METHODSThe effect of celastrol on the in vitro proliferation of endothelial cell of vessel (ECV) was examined by MTT assay. The effect of celastrol on endothelial cell migration, tube formation on Matrigel and Chick chorioallantoic membrane angiogenesis was also examined. Matrigel plug assay was used to evaluate the effect of celastrol on angiogenesis in vivo.

RESULTSThe proliferation of ECV was inhibited significantly by celastrol with IC(50) being 1.33 microg/ml. Celastrol inhibited endothelial cell migration and tube formation in a dose-dependent manner. Celastrol also inhibited angiogenesis both in Matrigel plug of mouse model and in chick chorioallantoic membranes.

CONCLUSIONCelastrol, which can inhibit angiogenesis, could be developed as an antiangiogenic drug.

Angiogenesis Inhibitors ; pharmacology ; Animals ; Endothelial Cells ; drug effects ; Mice ; Mice, Inbred BALB C ; Triterpenes ; pharmacology

Objective To explore the effect and indication of splenectomy in liver transplantation.Methods From January 2001 to April 2006,260 patients underwent piggyback orthotopic liver transplantation(PBOLT),and 28 patients had undergone combined PBOLT and splenectomy(splenectomy group).These patients were compared to 56 randomly selected non-splenectomy patients from the same transplant period,meaningly two controls were se- lected for every non-spleneetomy case.Two groups were analyzed with respect to rate of infection and survival rate, as well as biopsy-proven acute allograft rejection within 30 days after transplantation.Results Rate of infection in the splenectomy group was higher than that in the non-splenectomy patients(85.7% vs 55.4%,P

BACKGROUNDDelayed graft function (DGF) is common in kidney transplants from organ donation after cardiac death (DCD) donors. It is associated with various factors. Determination of center-specific risk factors may help to reduce the incidence of DGF and improve the transplantation results. The aim of this study is to define risk factors of DGF after renal transplantation.

METHODSFrom March 2010 to June 2012, 56 cases of recipients who received DCD kidneys were selected. The subjects were divided into two groups: immediate graft function (IGF) and DGF groups. Transplantation factors of donors and recipients as well as early post-transplant results of recipients were compared between the two groups.

RESULTSOn univariate analysis, preoperative dialysis time of recipients (P < 0.001), type of dialysis (P = 0.039), human leucocyte antigen (HLA) mismatch sites (P < 0.001), the cause of brain death (P = 0.027), body mass index (BMI) of donors (P < 0.001), preoperative infection (P = 0.002), preoperative serum creatinine of donors (P < 0.001), norepinephrine used in donors (P < 0.001), cardiopulmonary resuscitation (CPR) of donors (P < 0.001), warm ischemia time (WIT) (P < 0.001) and cold ischemia time (CIT) (P < 0.001) showed significant differences. Recipients who experienced DGF had a longer hospital stay, and higher level of postoperative serum creatinine.

CONCLUSIONMultiple risk factors are associated with DGF, which had deleterious effects on the early post-transplant period.

Adolescent ; Adult ; Aged ; Case-Control Studies ; Death ; Delayed Graft Function ; etiology ; Female ; Humans ; Kidney Transplantation ; adverse effects ; Male ; Middle Aged ; Retrospective Studies ; Risk Factors ; Tissue Donors

BACKGROUND AND OBJECTIVEPatients with clinical stage I seminoma accounts for 70%-80% of patients with this disease. This study was to analyze the relationship between different therapeutic methods and the prognosis of this disease.

METHODSThe data of all patients with clinical Stage I seminoma treated by multi-disciplinary approach from 1999 to 2008 in Sun Yat-sen University Cancer Center were analyzed. The patients were divided into 3 groups based on the treatment they received after orchiectomy: 30 patients treated with chemotherapy, 8 with radiotherapy, and 20 under surveillance. The prognosis of different treatment groups was evaluated.

RESULTSAmong the 58 patients with stage I seminoma, 57 were followed up successfully. The median follow-up time was 50 months (range, 8-115 months). No relapse or metastasis was seen in the chemotherapy group. One patient relapsed in the radiotherapy group. Four patients had metastasis of retroperitoneal lymph node in the surveillance group. The disease-free survival was higher in the chemotherapy group than that in the surveillance group (P=0.005). There was no significant difference in the relapse-free survival between the surveillance group and the radiotherapy group (P=0.364).

CONCLUSIONSChemotherapy is a safe and effective treatment for patients with Stage-1 seminoma after radical orchidectomy.

Adolescent ; Adult ; Antineoplastic Combined Chemotherapy Protocols ; therapeutic use ; Bleomycin ; therapeutic use ; Cisplatin ; therapeutic use ; Combined Modality Therapy ; Disease-Free Survival ; Etoposide ; therapeutic use ; Follow-Up Studies ; Humans ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Orchiectomy ; methods ; Retrospective Studies ; Seminoma ; drug therapy ; pathology ; radiotherapy ; surgery ; Testicular Neoplasms ; drug therapy ; pathology ; radiotherapy ; surgery ; Treatment Outcome ; Young Adult

OBJECTIVETo study the clinical significance of piggy-back liver transplantation in treating acute liver failure (ALF).

METHODSFifteen ALF patients (13 caused by HBV and 2 with acute Wilson disease) had piggy-back liver transplantations (PBLT) in our hospital from Sept 1999 to Feb 2006. The outcomes of these patients were retrospectively analyzed.

RESULTSOne year survival rate of the 15 patients was 87% (13/15). Excellent outcome was achieved in the 2 acute Wilson disease cases: their corneal Kayser-Fleischer rings disappeared and serum ceruloplasmin levels returned to normal. Among the 15 cases, one died of severe pulmonary infection and another died of multiple organ system failure on the 6th and 11th postoperative days. HBsAg positivity was observed in 13 cases before liver transplantation. Eleven patients survived and later received anti-HBV treatment recommended by the American Association for the Study of Liver Diseases. Their HBsAg became negative.

CONCLUSIONLiver transplantation is an effective therapy for ALF and can improve survival rate significantly.

Adolescent ; Adult ; Aged ; Female ; Humans ; Liver Failure, Acute ; mortality ; surgery ; Liver Transplantation ; methods ; mortality ; Male ; Middle Aged ; Retrospective Studies ; Survival Rate ; Young Adult