Male ; Humans ; Germ-Line Mutation ; Prostatic Neoplasms/genetics* ; BRCA2 Protein/genetics* ; Genetic Predisposition to Disease

Aim To investigate the effect of ginsenoside Rgl on PC 12 cell hypoxia-reoxygenation injury and its possible mechanism. Methods PC 12 cells were randomly divided into six groups. Except for the blank control group, all the other groups were hypoxia and hypoglycemia for 6 hours, and then reoxygenated and glycosylated for 24 hours to make OGD/R models. Each drug group was given corresponding drugs 2 hours before modeling pretreatment. DCFH-DA method was used to detect the ROS production in cells, Annexin V- FITC/PI double staining method was performed to detect cell apoptosis rate, ELISA method was used to detect LDH activity and IL-1 (3 content in cell supernatant, and Western blot was applied to detect the ex- pression of proteins of N0X2, p22phox, p47phox, NLRPl, ASC, Caspase-1, PSD95, Tau, p-Tau and observe the intervention effect of ginsenoside Rgl. Re sults Tempol, Apocynin and Rgl (5, 10 jjLmol • L"1) groups could significantly inhibit ROS production and apoptosis, reduce LDH release and IL-1 (3 content in cell supernatant; Apocynin and Rgl (5, 10 |xmol • L"1) groups could significantly down-regulate the expression of N0X2, p22phox and p47phox in cells. The Tempol, Apocynin and Rgl (5, 10 jxmol • L"1 ) groups could significantly decrease the protein expression of NLRP1, Caspase-1, ASC, IL-1 (3 and p-Tau, and markedly down-regulate the expression of PSD95 protein. Conclusion Rgl is likely to reduce the is- chemia-reperfusion injury of PC 12 cells by inhibiting the NOX2-NLRP1 pathway.

Objective To study the effect of ghost red blood cells (GRBCs) on white blood cell (WBC)-mediated adhesion of tumor cells (TCs) on endothelial cells (ECs) in shear flow. Methods GRBCs with hematocrit (Hct) of 20% were added in the parallel plate flow chamber to observe changes in the number of tethered WBCs on ECs, the collision between TCs and adhesive WBCs, and the number of firmly adhered TCs at different shear rates of 62.5, 100, 200 s-1, respectively. Results GRBCs could increase the number of adhered WBCs on ECs and the collision between TCs and adhesive WBCs, and finally enhance the adhesion of TCs on ECs, especially at high shear rate (200 s-1). However, the adhesion efficiency of TCs was not significantly influenced by GRBCs. Conclusions GRBCs in shear flow can promote TC adhesion on ECs, and the research finding will provide a theoretical basis for cancer therapy.

Objective To study the different effects from different concentration ratios of polymorphonuclear neutrophil (PMN) to tumor cell (TC) on the process of tumor cell adhesion to endothelial cell (EC) in shear flow. Methods PMNs and TCs with different concentration ratios (PMN-TC ratio) were added into the parallel plate flow chamber, and changes in the numbers of transient and accumulative adhered TCs on ECs at different shear rates (50 s-1，100 s-1，200 s-1) were analyzed. Results The transient and accumulative adhesion of TCs on ECs at PMN-TC ratio of 3︰1 significantly increased as compared to that at PMN-TC ratio of 1︰1, especially under high shear flow condition (100 s-1 and 200 s-1). Moreover, in the 5 minute-observation period, the effect of PMN-TC ratio on TC adhered to ECs occurred earlier when the shear rate increased. Conclusions The increase of PMN-TC concentration ratio can promote TC adhesion to ECs in shear flow, and the research findings provide significant references for studying TC metastasis in blood vessels and the target therapy of tumors.

Objective To study the effect of the 18kDa translocator protein (TSPO) on U251cells of human glioma. Methods U251 cell line was cultured in vitro conventionally.The specific ligand ofTSPO,pk11195,was used in 5 experimental groups respectively with concentrations of 100,50,25,12.5 and 6.25 μmol/L,in comparison with a control group.MTr colorimetry and trypan blue staining were used to detect cell proliferation.Hoechst33342 staining and flow cytometry were applied to detect cell apoptosis. Western blotting and immumofluorescence method were used to detect the expression level of TSPO. DCFH-DA probe and GSH kit were used to respectively detect the level of reactive oxygen species (ROS) and GSH level in cells.Jc-1 staining was applied to detect the mitochondrial membrane potential.Luciferase enzyme was used to detect the quantity of ATP in cells. Results MTT showed the survival of U251 cells was significantly higher in the groups of 50 and 25 μmol/L pk11195than in the control group (P＜0.05). Trypan blue staining showed the cell death rate was significantlylower in the group of 50 μmol/L pk11195 than in the control group (P＜0.05).The apoptosis rate,TSPO expression,ROS and GSH levels decreased significantly in the groups of 6.25 and 50 μmol/L pk11195,compared with the control group; the apoptosis rate was significantly lower in the group of 50 μmol/Lpk11195 than in the group of 6.25 μmol/L pk11195 (P＜0.05).The cell membrane potential and ATP quantity were significantly higher in the groups of 6.25 and 50 μmol/L pk11195 than in the control group,and those in the group of 50 μmol/L pk11195 were significantly higher than in the group of 6.25 μmol/Lpk11195 (P＜0.05). Conclusion TSPO may promote apoptosis of U251 cells in human glioma and inhibit proliferation of glioma cells,functioning similarly as a cancer suppressor gene.

OBJECTIVETo identify the active material of anti-hepatic fibrosis from Amydae Carapax.

METHODSMembrane separation technology was adopted to screen active fraction in Amydae Carapax, and the active components were isolated from the active fraction using gel chromatography and high performance liquid chromatography. The purified active components in Amydae Carapax were further analyzed using 4700 series time-of-flight mass spectrometer.

RESULTSProteins and peptides of Amydae Carapax with molecular weight less than 6000 were proved to have biological activity. 8 components (Bj1-Bj8) were isolated from the active fraction. Bj4, Bj6 and Bj7 were screened as active components. Bj7 was further purified, resulting in 7 components (Bj701-Bj707). Bj704 and Bj707 showed significant biological activity. Mass spectrometry showed three molecular ion peaks with highest abundance, i.e. m/e 526, 542 and 572, i.e. m/e 526, 542 and 572, in Bj707 -A The amino acid sequences of above three peptide compounds were NDDY (Asn-Asp-Asp-Tyr), NPNPT (Asn-Pro-Asn-Pro-Thr), and HGRFG (His-Gly-Arg-Phe-Gly), respectively. And M572 was the most abandunt components.

CONCLUSIONThree active peptide compounds of anti-hepatic fibrosis of Amydae Carapax were identified.

Animals ; Cell Line ; Humans ; Liver Cirrhosis ; Medicine, Chinese Traditional ; Tissue Extracts ; isolation & purification ; pharmacology

Objective To study the characteristics of micro environmental flow and the process of macromolecular drug delivery in solid tumor. Method3D models simulating tumor hemodynamics and drug delivery were developed. Microcirculation and concentration distribution of two macromolecular drugs in tumor were simulated. ResultsThe model successfully reflected abnormal tumor hemodynamics, which results in impeded drug delivery and uneven concentration distribution of the drug. The results also shows that the drug with lower molecular weight is more easy to spread in tumor and excrete with interstitial fluid flow. In contrast, the drug with higher molecular weight tends to accumulate and maintain an effective concentration in tumor for a longer period. ConclusionsThe results derive from this model can reflect physiological conditions, providing a reliable numerical model for the investigation of tumor micro environment, drug delivery and strategy of therapy.

Objective In order to provide a more realistic microvasculature model for the study on tumor hemodynamics and drug delivery, a simulated tumor microvascular network was developed by the technique of numerical simulation and post processing. Method We constructed a tumor microvascular model with host arteriole venule system, in which the variation in vascular branching and dimensions was taken into account. A sensitivity analysis was made for the parameters of the model to evaluate the adjustability of simulated results. The connectivity of the vascular network was tested to ensure the integrity of the network. The vascular network was smoothed afterwards to reduce flow resistance resulting from numerical networks. Results The simulated results are consistent with the characteristics of real tumor microvasculature, which show intact circulation, local adjustability, high network connectivity and smooth degree. Conclusions This study provid a numerical microvasculature model for the research on tumor hemodynamics, drug delivery and vascular targeted therapy.

BACKGROUNDThe pelvis often needs to be reconstructed after bone tumor resection. A major challenge here for the orthopedic surgeons is to choose a method that gives the best performance which depends upon its biomechanical properties. In this study, a 3-dimensional finite element analysis (FEA) was used to analyze the biomechanical properties of reconstructed pelvis using fibula transplant fixed by four commonly used rod-screw systems.

METHODSA total pelvic finite-element model including the lumbar-sacral spine and proximal femur was constructed based on the geometry of CT image from a healthy volunteer. Three-dimensional finite element models of different implants including fibula, rod and screw were simulated using ways of solid modeling. Then various reconstructed finite element models were assembled with different finite element implant model and type I resected pelvic finite element model. The load of 500 N was imposed vertically onto the superior surface of L3 vertebral body, and the pelvis was fixed in bilateral leg standing positions. FEA was performed to account for the stress distribution on the bones and implants. The pelvis displacement of the different rod-screw fixation methods and the maximum equivalent stress (max EQV) on all nodes and element were figured out to evaluate the advantages and disadvantages of different reconstructive methods.

RESULTSStress concentration in the fibula transplant was extremely high in the reconstructed pelvis, but could be substantially decreased by internal fixation, which partially transferred the stress from the fibula to the rod-screw systems. High stress concentration was also found in the implants, especially in the connection sites between screw and rod. Among the four methods of fixation, a double rod system with L5-S1 pedicle and ilium screws (L5-S1 HR) produced the best performance: least stress concentrations and least total displacement.

CONCLUSIONAccording to the stability and stress concentration, the method of L5-S1 HR fixation combined with fibula transplantation is better than other fixation methods in pelvic reconstruction after type I resection.

Adult ; Biomechanical Phenomena ; Bone Neoplasms ; surgery ; Bone Screws ; Femur Neck ; surgery ; Fibula ; transplantation ; Finite Element Analysis ; Humans ; Male ; Pelvic Bones ; surgery ; Reconstructive Surgical Procedures ; methods

OBJECTIVETo analyze the pelvic stability after type I resection of iliac tumor.

METHODSSix adult cadaveric specimens were tested. The iliac subtotal resection models were established according to Ennecking's type I resection. Markers were affixed to the key region of the pelves. Axial loading from the proximal lumbar was applied by MTS load cell in the gradient of 0-500 N in the double feet standing state. Images in front view were obtained using CCD camera. Based on Image J software, displacements of the first sacral vertebrae (S1) of the resected pelves and the intact pelves were calculated using digital marker tracing method with center-of-mass algorithm.

RESULTSSerious instabilities were found in the resected pelves. S1 rotational movements around the normal side femoral head of the resected pelvis were found. The average vertical displacement of S1 of the resected pelvis was (7 +/- 3) mm under vertical load of 500 newtons, which were 8.3 times compared to the intact pelvis. The average angle of S1 rotation around the normal side femoral head of the resected pelvis was (4.0 +/- 1.8) degrees, which were 12.5 times compared to the intact pelvis.

CONCLUSIONSBiomechanical model of type I resection of iliac tumor are established. Essential pelvic reconstruction must be introduced because of the serious instability of the bone defection after tumor resection.

Adult ; Aged ; Biomechanical Phenomena ; Bone Neoplasms ; physiopathology ; surgery ; Female ; Humans ; Ilium ; injuries ; Male ; Middle Aged ; Models, Biological ; Pelvis ; physiopathology ; Range of Motion, Articular