Child ; Ectodermal Dysplasia ; diagnosis ; genetics ; Family Health ; Genes, Recessive ; genetics ; Humans ; Male ; Sex Factors

OBJECTIVETo explore the inhibition and molecular mechanism of icaritin (ICT) combined doxorubicin (DOX) on human osteosarcoma MG-63 cells in vitro.

METHODSThe control group, ICT groups (10, 20, 40, 80, and 160 µmol/L), DOX groups (1, 2, 4, 8, and 16 µg/mL), and combination groups (20 µmol/ L ICT +1 µg/mL DOX, 20 µmol/L ICT +2 µg/mL DOX, 20 µmol/L ICT +4 µg/mL DOX, 40 µmol/L ICT +1 µg/mL DOX, 40 µmol/L ICT +2 µg/mL DOX, 40 µmol/L ICT +4 µg/mL DOX, 80 µmol/L ICT +1 µg/mL DOX, 80 µmol/L ICT +2 µg/mL DOX, 80 µmol/L ICT +4 µg/mL DOX) were set up. Human osteosarcoma MG-63 cells were respectively cultured and their effects on morphological changes were observed using inverted phase contrast microscope after 24-and 48-h intervention. The cell proliferation inhibition rate of each group was de- termined using CCK-8, and IC50 calculated. The MG-63 apoptosis rate was detected using Annexin V-FITC/ PI double dye flow cytometry. Expression levels of bcl-2, caspase-3, and p21 were detected using RT-PCR.

RESULTSICT and DOX could obviously inhibit the proliferation of MG-63 cell. Along with ICT concentration increasing from 10 µmol/L to 160 µmol/L, the cell proliferation inhibition rate also increased gradually from 9.67% ± 3.62% to 89.18% ± 9.66%. The IC50 was 46.93 µmol/L and 3.87 µg/mL respectively. ICT and DOX could cause either early or late stage apoptosis, down-regulate Bcl-2 gene expression, and up-regulate gene expressions of Caspase-3 and p21 respectively (P < 0.05). Aforesaid changes were more obviously seen in combination groups than in lCT groups and DOX groups (P < 0.05).

CONCLUSIONCT combined DOX had additive or synergistic inhibition effect for the proliferation of osteosarcoma MG-63 cells, which might be related with regulating gene expressions of bcl-2, caspase-3, and p21.

Apoptosis ; Bone Neoplasms ; metabolism ; pathology ; Caspase 3 ; metabolism ; Cell Line, Tumor ; drug effects ; Cell Proliferation ; Cyclin-Dependent Kinase Inhibitor p21 ; metabolism ; Down-Regulation ; Doxorubicin ; pharmacology ; Drug Synergism ; Flavonoids ; pharmacology ; Humans ; Osteosarcoma ; metabolism ; pathology ; Proto-Oncogene Proteins c-bcl-2 ; metabolism

Objective:To determine whether ox-LDL (oxdized low-density lipoprotein) is highly deposited on the uremic vessel wall and its influence on the vascular remodeling. Methods: Segments of radial arteries were obtained from 21 uremic subjects during the operation of A-V fistula prior to hemodialysis. Segments of internal thoracic arteries of similar diameter were obtained from patients with benign chest tumors as control.The vascular lesions and ox-LDL, CD68,MCP-1, eNOS,ET-1, PCNA,FN on the vessel wall were determined by means of H-E stain and immunohistochemistry. Results： With H-E stain,atherosclerotic plaques were found in the radial arteries of 4 uremic patients. The middle layer of the arteries in uremic patients were obviously thickened, and the T/D　(thickness of the wall/external diameter) ratio was significantly higher than those in control group(P<0.01). ox-LDL,CD68,MCP-1, ET-1, PCNA,FN on the vessel wall in uremic patients were much higher than those in control group (P<0.01). Moreover, ox-LDL on the vessel wall was positively related to the expression of other above mentioned substances on the vessel wall (P<0.01). Whereas the expression of eNOS on the vessel wall was lower than control group (P<0.01),and was negatively related to ox-LDL on the vessel wall(P<0.01). Conclusion: ox-LDL is an important factor contributing to uremic vascular remodeling by increasing the migration,adhesion and infiltration of monocyte,the proliferation of vascular smooth muscle cell and dysfunction of endothelia.

Objective:To determine whether ox-LDL (oxdized low-density lipoprotein) is highly deposited on the uremic vessel wall and its influence on the vascular remodeling. Methods: Segments of radial arteries were obtained from 21 uremic subjects during the operation of A-V fistula prior to hemodialysis. Segments of internal thoracic arteries of similar diameter were obtained from patients with benign chest tumors as control.The vascular lesions and ox-LDL, CD68,MCP-1, eNOS,ET-1, PCNA,FN on the vessel wall were determined by means of H-E stain and immunohistochemistry. Results： With H-E stain,atherosclerotic plaques were found in the radial arteries of 4 uremic patients. The middle layer of the arteries in uremic patients were obviously thickened, and the T/D　(thickness of the wall/external diameter) ratio was significantly higher than those in control group(P<0.01). ox-LDL,CD68,MCP-1, ET-1, PCNA,FN on the vessel wall in uremic patients were much higher than those in control group (P<0.01). Moreover, ox-LDL on the vessel wall was positively related to the expression of other above mentioned substances on the vessel wall (P<0.01). Whereas the expression of eNOS on the vessel wall was lower than control group (P<0.01),and was negatively related to ox-LDL on the vessel wall(P<0.01). Conclusion: ox-LDL is an important factor contributing to uremic vascular remodeling by increasing the migration,adhesion and infiltration of monocyte,the proliferation of vascular smooth muscle cell and dysfunction of endothelia.

Applications of network pharmacology are increasingly widespread and methods abound in the field of drug development and pharmacological research. In this study, we choose rosiglitazone compound as the object to predict the targets and to discuss the mechanism based on three kinds of prediction methods of network pharmacology. Comparison of the prediction result has identified that the three kinds of prediction methods had their own characteristics: targets and pathways predicted were not in accordance with each other. However, the calcium signaling pathway could be predicted in the three kinds of methods, which associated with diabetes and cognitive impairment caused by diabetes by bioinformatics analysis. The above conclusion indicates that the calcium signaling pathway is important in signal pathway regulation of rosiglitazone compound, which provides a clue to further explain the mechanism of the compound and also provides a reference for the selection and application of methods of network pharmacology in the actual research.
Calcium Signaling ; Cognitive Dysfunction ; Computational Biology ; Diabetes Mellitus ; Humans ; Pharmacology ; methods ; Thiazolidinediones ; pharmacology

Child ; Child, Preschool ; Erythema ; drug therapy ; etiology ; Fatal Outcome ; Female ; Fever ; drug therapy ; etiology ; Hematopoietic Stem Cell Transplantation ; adverse effects ; Humans ; Leukocyte Count ; Male ; Transplantation, Homologous

ObjectiveTo study the role and mechanism of resisitin in prophylactic and therapeutic treatments of rosiglitazone,a specific peroxisome proliferator-activated receptor-γ(PPARγ) ligand,in rats with severe acute pancreatitis (SAP) and pancreatitis-associated pulmonary injury.MethodsThe levels of amylase ( AMY ),Resistin,TNF-α,IL-1 β and C reactive protein (CRP) in blood plasma,lung myeloperoxidase ( MPO ) activity,pancreas/body weight ratio and lung wet/dry weight ratio were evaluated.Pancreatic and pulmonary pathology were observed.The expression of resistin in pancreas was detected byimmunohistochemistry.The gene expression of resistin mRNA was investigated by real-time PCR.ResultsBoth prophylactic and therapeutic treatments with rosiglitazone could obviously ameliorate the levels of AMY,resistin,TNF-αt,IL-1β and CRP ( all P ＜ 0.01 ).Compared with the control group,both prophylactic and therapeutic treatment groups were higher( all P ＜ 0.01 ).The prophylactic treatment group was not different from the therapeutic treatment group.Both prophylactic and therapeutic treatments with rosiglitazone could significantly reduce pancreas/body weight ratio,pancreatic pathology,MPO,pulmonary pathology ( all P ＜ 0.01 ).Compared with the SAP group,the expression of resistin mRNA in the prophylactic and therapeutic treatment groups were obviously decreased.ConclusionRosiglitazone could obviously ameliorate pancreatitis and pulmonary injury induced by L-arginine.

Objective To analysis and determine the possibility of the Citellus undulatus infected with Yersinia pestis surviving the winter in an experimental study, and to provide scientific experimental basis for the study on the mechanism of Yersinia pestis preservation. Method In 2006,09 to 2007,04 and 2007,09 to 2008,04 in Xinjiang Wusu-Gurtu natural foci of plague, under natural conditions, the over the winter process of Citellus undulatus carrying the plague bacteria was simulated, and 178 Citellus undulatus were infected with Yersinia pestis (1×107 Bacteria/mouse) using artificial injection method. One hundred seventy-eight Citellus undulatus infected with Yersinia pestis were kept into a construction of the black (1-5 ℃) basement (2 meters under the ground) in the plague focus. In doing so, these Citellus undulatuses almost simultaneously stepped into hibernation. After waking up from hibernation in following year in April, the survived mice carrying the plague bacteria were observed. Results Sixty-eight mice survived among the 178 infected with Yersinia pestis after 6 months of hibernation (through October to the following year in April), and the remaining 110 were all dead without pulling through the hibernation period. The survival rate was 38.2% (68/178). The organ culture of Yersinia pestis of the 110 dead mice(Citellus undnlatus) were tested, 67 were negative(-), 43 positive(+), with a positive rate of 39.1%(43/110). Among the rats with positive plague bacteria, the congestive pulmonary edema and the pathological changes of the hemorrhagic inflammation of the heart, liver, spleen, kidney and injection site could be seen clearly; the plague-free mice were not found to have any pathological changes. The survived 68 mice over the winter were autopsied and observed after being fed up for 20 days. No any pathological changes were found among these mice, and culturing of Yersinia pestis of the heart, liver, spleen, lungs and the tissue of injection site of these mice were all negative (-). Conclusions Citellus undulatus can carry Yersinia pestis during hibernation, but some fail to carry the bacteria through the entire process of hibernation persistently. Yersinia pestis was negative in the survived mice at the end of hibernation. The results showed that Citellus undulatus can not carry Yersinia pestis over the winter.

Objective To investigate the correlation between ankle-brachial index and ultrasonography in lower ex- tremities vascular in type 2 diabetic patients.Methods 218 type 2 diabetic patients were enrolled,and ankle-brachial index(ABI)measurements and uhrasonography in lower extremities vascular were performed in all patients.Lower extremi- ties vascular disease(LEVD)were divided into six species according to the uhrasonography results and scored in accord- ante with its serious degree,then investigate the correlation between ABI and uhrasonography results score.All patients were divided into deferent groups according to uhrasonography results and ABI range,and then compared their deference. Results The lower the ABI,the more serious of the LEVD showed by ultrasonography.ABI and ultrasonic inspection score was significantly negatively correlated(r=-0.65,P

In this study, the human umbilical vein endothelial cell model was used to study the regulating effect of lipophilic components in Salvia miltiorrhiza on angiogenesis, and explore its possible mechanism. The cell model was established to determine the effect of lipophilic components in S. miltiorrhiza on the proliferative activity and migration capacity of endothelial cells. Then the realtime fluorescence quantification PCR technology was applied to detect the changes in the gene expressions of angiogenesis-related cytokines VEGF-A, VEGF-C and MMP-9. The results showed that 5 mg x L(-1) lipophilic components in S. miltiorrhiza could inhibit the proliferation and migration of endothelial cells, and reduce the expression of VEGF-A and MMP-9 genes. It indicated that lipophilic components in S. miltiorrhiza may inhibit the proliferation and migration of endothelial cells by inhibiting the expression of VEGF-A and MMP-9 genes, so as to show the inhibitory effect on angiogenesis.
Angiogenesis Inhibitors ; chemistry ; pharmacology ; Cell Movement ; drug effects ; Cell Proliferation ; drug effects ; Drugs, Chinese Herbal ; chemistry ; pharmacology ; Human Umbilical Vein Endothelial Cells ; cytology ; drug effects ; metabolism ; Humans ; Matrix Metalloproteinase 9 ; genetics ; metabolism ; Salvia miltiorrhiza ; chemistry ; Vascular Endothelial Growth Factor A ; genetics ; metabolism