OBJECTIVE To investigate the protective effect of total saponins from stems and leaves of Panax ginseng (GSLS) on cisplatin (CDDP)-induced kidney damage in mice and its possible mechanism. METHODS Thirty-two male ICR mice were randomly divided into normal control group, CDDP group, and GSLS(150 and 300)+CDDP groups. GSLS was administered to mice by oral gavage once a day for 7 d. On the 7th day, a single injection of CDDP 20 mg·kg-1 was given 1 h after GSLS 150 and 300 mg·kg-1 before GSLS 150 and 300 mg·kg-1 continued to be given for 3 d. Blood urea nitrogen (BUN) and creatinine (CRE) , catalase (CAT) in renal tissue, reduced glutathione (GSH), tumor necrosis factorα(TNF-α) and interleukin 1β(IL-1β) of cisplatin induced mice were detected after 72 h. HE and PAS staining were used to observe the renal histopathological changes;While TUNEL and Hoechst33258 staining were employed to observe apoptosis in kidney tissues. RESULTS Compared with normal control group, CDDP group had a significant reduction in relative body mass (P<0.05), and the level of GSH and CAT in kidney tissues (P<0.05). The level of CRE, BUN, TNF-α, and IL-1βin serum and renal indexes significantly increased (P<0.05, P<0.01), especially BUN and CRE that respectively doubled and quadrupled. CDDP group developed glomerulus swelling, renal tubular expansion and epithelial cell necrosis. Trans?parent tube type of tube cavity appeared, the nucleus pycnosis disappeared, but renal interstitial edema and inflammatory cell infiltration appeared. There was a large amount of glycogen deposition and high expressions of TUNEL positive cells and Hoechst33258 positive cells. Compared with CDDP group, the levels of BUN and CRE in GSLS treatment group significantly decreased (P<0.05, P<0.01) in serum, glycogen deposition was reducted and apoptosis of renal tubular epithelial cells decreased in kidney tissues (P<0.05). The level of TNF-α, IL-1β(P<0.05) and the degree of renal tissue necrosis were significantly reduced (P<0.05) in CDDP+GSLS 300 group, but there was a significant increase in the level of CAT and GSH (P<0.05). CONCLUSION GSLS can protect against mouse kidney injury induced by cisplatin. The mechanism may be related to oxidation, reduced inflammation reaction and resistance to apoptosis.

To investigate the cytotoxicity of the homemade peptide cationic liposome CDO14 and its efficacy of RNA interference (RNAi). MTT method was used to determine the cytotoxicity of the liposome to a human lung cancer cell line Luc-A549 that can express luciferase stably. Luciferase siRNA (Luc-siRNA) was transfected into Luc-A549 cells by CDO14. Contents of luciferase in the transfected cells were detected by luminous instrument and contents of total protein in these cells were detected by BCA method. Nude mice were inoculated with Luc-A549 cells in axilla to establish xenograft tumor model. Complexes of Luc-siRNA and the cationic liposomes were injected into the modeling mice via tail vein. Contents of luciferase in the transfected mice were detected by the whole body imaging system. The cytotoxicity of the homemade cationic liposome was similar to that of commercial liposome DOTAP, and lower than that of Lipo2000. The siRNA transfection efficacy mediated by CDO14 was higher than that mediated by DOTAP. The homemade peptide cationic liposome CDO14 is expected to serve as delivery vector in gene therapy because of its low cytotoxicity and high transfection efficiency.
Animals ; Cations ; Cell Line, Tumor ; Fatty Acids, Monounsaturated ; Genetic Therapy ; Genetic Vectors ; Humans ; Liposomes ; Luciferases ; Lung Neoplasms ; Mice ; Mice, Nude ; Peptides ; Quaternary Ammonium Compounds ; RNA Interference ; RNA, Small Interfering ; Transfection

Today, the understanding of the sequence and structure of biologically relevant targets is growing rapidly and researchers from many disciplines, physics and computational science in particular, are making significant contributions to modern biology and drug discovery. However, it remains challenging to rationally design small molecular ligands with desired biological characteristics based on the structural information of the drug targets, which demands more accurate calculation of ligand binding free-energy. With the rapid advances in computer power and extensive efforts in algorithm development, physics-based computational chemistry approaches have played more important roles in structure-based drug design. Here we reviewed the newly developed computational chemistry methods in structure-based drug design as well as the elegant applications, including binding-site druggability assessment, large scale virtual screening of chemical database, and lead compound optimization. Importantly, here we address the current bottlenecks and propose practical solutions.
Computational Biology ; Drug Design ; Drug Discovery ; High-Throughput Screening Assays ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; Quantitative Structure-Activity Relationship

OBJECTIVETo categorize diffuse large B-cell lymphoma (DLBCL) into germinal center B cell-like (GCB) and non-germinal center B cell-like (non-GCB) subgroups by immunohistochemistry; and to investigate the underlying prognostic significance.

METHODSImmunohistochemical study for CD10, bcl-6 and MUM1 was performed on 133 cases of DLBCL. The cases were then categorized into GCB and non-GCB subgroups. The 5-year overall survival and 5-year progression-free survival rates were compared between the GCB and non-GCB groups, and among the cases with different immunohistochemical expression or with different IPI.

RESULTSAmongst the 133 case studied, CD10 was expressed in 33.1%, while bcl-6 was positive in 34.6% and MUM1 in 45.1%. CD10 expression had a favorable impact on 5-year overall survival (P=0.041) and 5-year progression-free survival (P=0.031). On the other hand, bcl-6 expression had a favor able impact on 5-year progression-free survival (P=0.044). Expression of MUM1 carried an adverse effect on 5-year overall survival (P=0.031) and 5-year progression-free survival (P=0.028). GCB immunophenotype was demonstrated in 40.6% of the cases, while 59.4% showed a non-GCB profile. GCB DLBCL had a significantly longer 5-year overall survival (P=0.004) and 5-year progression-free survival (P=0.003), as compared with the non-GCB group. When dividing the cases into two groups according to their IPI score (IPI=0 to 1 and IPI=2 to 5), it turned out that the 5-year overall and progression-free survival rates of the GCB group were significantly higher than those of the non-GCB group (P=0.019 and 0.014 respectively in cases with IPI of 0 to 1 and P=0.006 and 0.009 respectively in cases with IPI of 2 to 5). The non-GCB cases with a IPI of 2 to 5 had the poorest prognosis.

CONCLUSIONDLBCL subgrouping by immunohistochemistry and analysis of the subgrouping with IPI is feasible and useful in predicting clinical outcome.

Adolescent ; Adult ; Aged ; Aged, 80 and over ; B-Lymphocytes ; pathology ; Child ; Child, Preschool ; DNA-Binding Proteins ; metabolism ; Disease-Free Survival ; Female ; Follow-Up Studies ; Germinal Center ; pathology ; Humans ; Immunohistochemistry ; Interferon Regulatory Factors ; metabolism ; Kaplan-Meier Estimate ; Lymphoma, Large B-Cell, Diffuse ; classification ; immunology ; pathology ; Male ; Middle Aged ; Neprilysin ; metabolism ; Prognosis ; Proto-Oncogene Proteins c-bcl-6 ; Survival Rate ; Young Adult

OBJECTIVETo compare the clinical efficacy of 3 different treatment programs for oligospermia patients of Shen-essence deficiency syndrome (SEDS).

METHODSTotally 450 male patients were randomly assigned to 3 groups, i.e., the treatment group, the control group 1, and the control group 2, 150 in each group. Patients in the treatment group were treated by Bushen Yijing Decoction (BYD), tamoxifen tablet (TT), Licorzine Capsule (LC), and Vitamin E Soft Capsule (VESC). Those in the control group 1 were treated by BYD, LC, and VESC. Those in the control group 2 were treated by TT, LC, and VESC. All patients were treated for 3 months. Their pregnant rates were compared. Clinical efficacies of each Chinese medical symptom and sperm parameters [sperm density, grade a sperm motility rate, grade (a + b) sperm motility rate, grade (a + b + c) sperm motility rate, and normal sperm morphology rate] were compared before and after treatment.

RESULTSAt 3 months after treatment 61 patients were pregnant in the treatment group, 36 patients were pregnant in the control group 1, and 30 patients were pregnant in the control group 2. The differences in the sperm density, grade a sperm motility rate, and grade (a + b) sperm motility rate, and grade (a + b + c) sperm motility rate between before and after treatment were significantly higher in the treatment group than in the control group 1 and the control group 2 (P < 0.01). The difference in the normal sperm morphology rate between before and after treatment was obviously higher in the treatment group and the control group 1 than in the control group 2 (P < 0.01). Better results were obtained in the treatment group and the control group 1 in improving the sexual apathy, soreness and weakness of waist and knees, impotence, premature ejaculation, seminal emission, dizziness, tinnitus, forgetfulness, alopecia, when compared with the control group 2 (P < 0.01, P < 0.05). There was no statistical difference in the total effective rate of improving Chinese medical symptoms between the treatment group and the control group 1 (P > 0.05).

CONCLUSIONBYD combined with TT, LC, and VESC could significantly improve sperm qualities and clinical Chinese medical symptoms of oligospermia patients of SEDS.

Adult ; Drugs, Chinese Herbal ; therapeutic use ; Humans ; Male ; Medicine, Chinese Traditional ; methods ; Oligospermia ; diagnosis ; therapy ; Phytotherapy ; methods ; Young Adult

This study was aimed to investigate the function defect of partial homing receptor on cord blood hematopoietic stem cells (CBHSC) and explore efficacy and feasibility of intervention in vitro. The expression and activity of active groups in P, E-selectin ligands on CD34+ cells from cord blood, bone marrow and peripheral blood were detected by flow cytometry; meanwhile the expression of active groups in selectin ligands on CD34+ cells treated by fucosyl transferase in vitro was determined by flow cytometry. The results indicated that the expression levels of CD26 on the surface of stem/progenitor cells (CD34+) from cord blood, bone marrow and peripheral blood were (7.62+/-0.63)%, (6.35+/-0.89)% and (6.18+/-0.91)% (p>0.05) respectively. And the activities of CD26 of the three sources of stem cells were 67.15 U/1000 cells (1 U=1 pmol/min), 26.85 U/1000 cells and 20.95 U/1000 cells respectively, in which the activity of CD26 on surface of CD34+ from cord blood was significantly higher than that from other both sources (p<0.01). The expression levels of P-selectin ligand on the stem/progenitor cells three kinds were (83.46+/-6.33)%, (15.65+/-0.89)% and (80.17+/-6.85)%, and the expression levels of E-selectin ligand on stem/progenitor cells of three kinds were (25.31+/-1.03)%, (26.34+/-0.89)% and (29.79+/-1.78)% respectively. The expression of E-selectin ligand on the surface of cord blood stem/progenitor cell CD34+ increased from (25.31+/-1.03)% to (63.23+/-1.08)% after glycosylation engineering. It is concluded that there is no significant difference of the expression of CD26 between the three sources of stem/progenitor cells, but the activity of CD26 in cord blood was obviously higher than that in bone marrow and peripheral blood. The expression of P-selectin ligand on bone marrow stem/progenitor cell was lower than that on stem cells of cord blood and peripheral blood. Glycosylation engineering can promote and elevate the expression of E-selectin ligand on the surface of CD34+ cells from cord blood.
Antigens, CD34 ; metabolism ; Bone Marrow Cells ; cytology ; metabolism ; Cells, Cultured ; Dipeptidyl Peptidase 4 ; metabolism ; Fetal Blood ; cytology ; Hematopoietic Stem Cells ; cytology ; metabolism ; Humans ; Receptors, Fibroblast Growth Factor ; metabolism ; Sialoglycoproteins ; metabolism ; Stem Cells ; cytology ; metabolism

The paper is aimed to investigate the effect of cyclosporine A (CyA) on the pharmacokinetics of ginkgolide B (GB) in rats, and to look for the mechanism of the changes in pharmacokinetic behaviors of GB. GB concentration in plasma, brain homogenate and urine samples of rats was determined by LC-MS. Effects of CyA on plasma levels, brain distributions as well as urinary excretions after intravenous administration of GB were evaluated. CyA co administrated intravenously at 10 mg kg(-1) or 20 mg kg(-1) significantly increased AUC(0-360 min) (P < 0.01) and decreased total CL of GB in rats. While co administrated CYP3A inhibitor itraconazole (ICZ) has no appreciable effect on the pharmacokinetic behavior of GB. CyA increased the brain uptake of GB in a dose-dependent manner. The brain distribution of GB was significantly increased at 5 min by different doses of CyA (P < 0.001), while at 20 and 60 min only high dose of CyA could significantly increase the levels of GB in the brain (P < 0.01 and P < 0.001). Different P-gp inhibitors CyA or verapamil (VER) or digoxin (DGX) decreased the urinary GB excretion, the urinary excretion of GB in 0-8 h were about 34.8% (P < 0.001), 59.4% (P < 0.001) and 79.7% (P < 0.05) of the control, separately. No appreciable effect of ICZ was observed on urinary excretion of GB. Coadministration of P-gp inhibitors CyA could significantly increase the plasma level, accelerate the brain distribution and decrease the urinary excretion of GB.
Animals ; Cyclosporine ; pharmacology ; Ginkgolides ; pharmacokinetics ; Herb-Drug Interactions ; Lactones ; pharmacokinetics ; Male ; Rats ; Rats, Sprague-Dawley ; Tissue Distribution

This study was purposed to evaluate the sensitivity and specificity of G/(1, 3-β-D glucan)/GM (galactomannan) combined detection for early diagnosis of invasive fungal disease (IFD), determine the GM positive cut-off value, and investigate the change of diagnostic level before and after G/GM test and the relation of GM value with therapeutic effect. The ELISA with double antibody sandwich was used to detect the serum levels of G and G/M. The results showed that according to determined GM positive cut-off value, the sensitivity, specificity, positive and negative predictive value of G/GM combined detection were 100%, 65.7%, 67.6% and 100%, respectively. The case number of the clinical diagnosis of IFD increased from 1 to 24 cases, the diagnosis of 12 non-infective patients was changed as suspected IFD with the help of G/GM combined detection; the GM cut-off value decreased in patients whose GM cut-off value was higher before therapy and antifungal therapy was effective, while the GM cut-off value increased in patients no-responded to therapy. It is concluded that G/GM combined detection can increased the sensitivity of the diagnosis and reduce false negative rate in the early diagnosis of IFD. The dynamically monitoring G/GM cut-off value can be used as evaluation indicator of therapeutic efficacy.
Adolescent ; Adult ; Aged ; Antigens, Fungal ; analysis ; Child ; Child, Preschool ; Early Diagnosis ; Female ; Hematologic Neoplasms ; complications ; microbiology ; Hematopoietic Stem Cell Transplantation ; Humans ; Male ; Middle Aged ; Mycoses ; diagnosis ; etiology ; immunology ; Sensitivity and Specificity ; Young Adult

Purpose: Gastric cancer (GC) has high morbidity and mortality and is a serious threat to public health. The flavonoid compound vitexin is known to exhibit anti-tumor activity. In this study, we explored the therapeutic potential of vitexin in GC and its underlying mechanism. Materials and Methods: The viability, migration, and invasion of GC cells were determined using MTT, scratch wound healing, and transwell assays, respectively. Target molecule expression was determined by western blotting. Tumor growth and liver metastasis were evaluated in vivo using nude mice. Protein expression in the tumor tissues was examined by immunohistochemistry. Results: Vitexin inhibited GC cell viability, migration, invasion, and epithelial-mesenchymal transition (EMT) in a dose-dependent manner. Vitexin treatment led to the inactivation of phosphatidylinositol-3-kinase (PI3K)/AKT/hypoxia-inducible factor-1α (HIF-1α) pathway by repressing HMGB1 expression. Vitexin-mediated inhibition in proliferation, migration, invasion and EMT of GC cells were counteracted by hyper-activation of PI3K/AKT/HIF-1α pathway or HMGB1 overexpression. Finally, vitexin inhibited the xenograft tumor growth and liver metastasis in vivo by suppressing HMGB1 expression. Conclusions Vitexin inhibited the malignant progression of GC in vitro and in vivo by suppressing HMGB1-mediated activation of PI3K/Akt/HIF-1α signaling pathway. Thus, vitexin may serve as a promising therapeutic agent for the treatment of GC.