Hepatic veno-occlusive disease (HVOD) is a serious complication of hematopoietic stem cell transplantation.The mortality rate of severe HVOD (sHVOD) approaches 100 ％.Defibrotide (DF) is a polydisperse mixture of single-stranded oligonucleotides with antithrombotic and fibrinolytic properties.Numerous clinical trials have demonstrated its effectiveness and safety in the prevention and treatment of HVOD.This review focuses on the possible mechanisms of action of DF and its use in the prevention and treatment of HVOD.

Adult ; Carcinoma, Hepatocellular ; secondary ; Humans ; Liver Neoplasms ; secondary ; Lymphoma, Non-Hodgkin ; pathology ; Male ; Spinal Neoplasms ; pathology

The morbidity of diabetes has been increasing rapidly in recent years. Delayed wound healing has become a common complication in diabetes, which seriously affects the orthobiosis of patients. Exploring and finding the molecular mechanisms of diabetic wound healing and the effective therapies to promote wound healing have important clinical significances. Stem cells transplant has become a research hotspot in accelerating diabetic wound healing. This article reviewed the present approaches concerning stem cells transplant in diabetic wound healing both at domestic and abroad, and looked forward the clinical therapy of stem cells on diabetic wound healing.
Diabetes Mellitus ; therapy ; Humans ; Stem Cell Transplantation ; Stem Cells ; Wound Healing

Identification and validation of a new target is one of the most important steps for new antituberculosis (TB) drug discovery. Researches have shown that Mycobacterium tuberculosis (Mtb) encodes 20 CYP450 enzymes which play important roles in the synthesis and metabolism of lipid, cholesterol utilization, and the electron transport of respiratory chain in Mtb. With the critical roles within the organism as well as the protein structures of six Mtb CYP450 enzymes being clarified, some of them have been highlighted as potential anti-tuberculosis targets. In this paper, the phylogenetic analysis, the structural features, and the enzymatic functions of Mtb CYPs, as well as the mechanism of interactions with selective inhibitors such as azole antifungal agents for the CYPs have been reviewed and summarized. The druggability of the CYPs has also been analyzed for their further utility as targets in high throughput screening and rational design of more selective inhibitors.
Antitubercular Agents ; chemistry ; pharmacology ; Azoles ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme Inhibitors ; chemistry ; pharmacology ; Cytochrome P-450 Enzyme System ; genetics ; metabolism ; Drug Delivery Systems ; methods ; Drug Discovery ; Humans ; Mycobacterium tuberculosis ; drug effects ; enzymology ; genetics ; Phylogeny ; Tuberculosis ; drug therapy ; microbiology

Objective To verify the dynamic changes of ANP during the diastolic heart failure and the protective effect of amlodipine. Methods Male SD rats underwent the abdominal aorta ligation. Four weeks after Surgery, 40 rats were divided into 4 groups: hypertension model group (group B), low-dose group (group C), mid-dose group (group D), high-dose group (group E). Another 10 healthy male SD rats were used as sham group (group A). During the experiment, different drugs were gavaged to different groups and the normal saline was used for control group. Results After 12 weeks, ANP levels increased in group B much more than in group A, while lower in group C(P < 0.05); LVSP and dp/dt max decreased in group B significantly than in group A, while higher in group C than in group B (P < 0.05); LVEDP and -dp/dt max had no statistically significant (P >0.05); HW/BW and LW/BW decreased in group B than in group A, while higher in group C than in group B (P < 0.05); The extent of myocardial necrosis and fibrosis in group C were much lower than in group B. But there was no Significant differences (P > 0.05). Conclusion ANP level gradually increased accompanying with the aggravation of heart failure, which is related with the dose of the drug within limits. Amlodipine can inhibit cardiomyocyte remodeling by interfering ANP secretion.

BACKGROUND:Endothelial progenitor cel s have been shown to play an important role in the pathogenesis of traumatic diseases in recent years. OBJECTIVE:To explore the effect of magnetic labeled endothelial progenitor cel transplantation on renal function of diabetic rats through a MRI imaging study.METHODS:Sixty Wistar rats were randomly divided into normal (no treatment), control and experimental groups. Intraperitoneal injection of 40 mg/kg streptozotocin was performed to make a rat model of type 1 diabetes in the control and experimental groups. Four weeks after modeling, rats in the experimental group were given intravenous injection of magnetic labeled endothelial progenitor cel s (0.15 mL, 1×109/L). Fasting blood glucose, serum insulin, serum creatinine, urea nitrogen and 24-hour urinary protein levels in rats were measured at 8 weeks after cel transplantation. MRI was used to trace transplanted cel s in vivo in comparison with renal biopsy findings, and rat body mass and kidney weight were measured to calculate kidney weight index. RESULTS AND CONCLUSION:After modeling, fasting blood glucose, serum creatinine, urea nitrogen and 24-hour urinary protein levels as wel as kidney weight index were increased significantly (P<0.05), while the insulin level decreased (P<0.05). Compared with the model group, the endothelial progenitor cel transplantation reversed these indices (P<0.05). Additional y, in the experimental group, there was slightly longer T1 and shorter T2 signals as wel as marked lesion edge, and the FLASH sequence became more remarkable compared with the T2-weighted RARE sequence. The other groups showed no significant low signal changes. Magnetic-labeled positive cel s in the experimental group showed by the MRI were consistent with the tissue biopsy results, while no positive cel s were found in the model and normal groups. To conclude, the magnetic labeled endothelial progenitor cel transplantation can improve renal dysfunction in diabetic rats to a certain extent.

Objective To investigate the effect of siRNA targeted against Bcl-xl on cell proliferation of rheumatoid arthritis (RA) and the effect on expres-ion of apoptosis relevant factors Bcl-xl,Bax,Caspase-3.Methods Human RA synovial cells were cultured and passed by tissue block collagenase digestion method.The siRNA plasmid targeting Bcl-xl gene was constructed by Bcl-xl cDNA sequence provided by gene banks,while single missense sequences were used as negative controls.LipofectamineTM 2000 was used to transfect synovial cells.The effect of Bcl-xl silencing on proliferation of synovial cells was evaluated by MTT at 24,48,72 hours after transfection.The expressions of Bcl-xl,Bax,Caspase-3 protein,synovial apoptosisrelated factors were determined by Western blotting after transfected at different time points.The average of multiple-sample average was analyzed by single-factor x2 test or LSD-t and Tamhane's T2 test was used for twotwo comparison.Results MTT result s showed that RNA interference that specifically silent Bcl-xl could obviously suppress the proliferation of sliding film cells,which was most eveident at 48 hours.This inhibition was gradually weakened with prolonged time,but when compared was the control group,differences was significant (P＜0.05).Western blotting results displayed that when compared to the control group,Bcl-xl protein expression obviously declined after transfection P＜0.01,which was the least at 48 h time point.Bax,Caspase3 protein expression were obviously increased when compared to the coutrol group.Conclusion The expression of Bcl-xl,a RA synovial cell anti-apoptotic factor,is significantly reduced by specific RNA interference silencing Bcl-xl,which may play an important role in inhibiting the excessive proliferation of synovial cells.

Objective To explore the diagnosis,treatment and prognosis of primary gastric malignant (lymphoma)(PGML).Methods The diagnosis and treatment data of 21 cases of PGML admitted in our(hospital) during 8 years was retrospectively analyzed.The diagnostic methods included barium meal(examination),gastroscopy,B type ultrasonography,and CT scan.All patients underwent operative treatment and most of the patients received adjuvant chemotherapy.Results Upper abdominal pain,digestive tract bleeding,emaciation and abdominal mass were common clinical manifestations of PGML.The resectabilty rate of PGML was 90.5% while the 5-year survival rate was 57.1%.Conclusions The key to a satisfactory prognosis was early diagnosis,radical curative operation and combined treatment.

ObjectiveTo investigate the effect of indomethacin on insulin resistance and metabolic response to surgical injury in patients with gastrointestinal tumor.MethodsFifty-eight cases with gastric cancer or colon cancer were divided into an indomethacin group (n =28) and a control group (n =30).All the operations were performed under general anesthesia.Patients in both groups were given parenteral nutrition 24 hours after operation for 5 ～ 7 days.The patients in the indomethacin group were treated with indomethacin suppository ( 100 mg/12 h).Fasting blood glucose (FBG),fasting serum insulin (FINS),creatinine (Cr),blood urine nitrogen (BUN),triglyceride (TG),free fatty acid (FFA) and C-reactive protein (CRP) of the two groups were detected on the day before operation,and 24,72,120 hours after operation.Insulin resistance index (HOMA-IR) was calculated by using the homeostasis model assessment (HOMA).The vital signs were observed in 72 hours after operation.ResultsThe vital signs in the indomethacin group were more steady.The levels of FBG,FINS,and InHOMA-IR of the control group 24 hours and 72 hours after operation were higher than before operation ( all P =0.000) and those of the indomethacin group ( all P ＜0.01 ).In both of the two groups,the levels of Cr,BUN,TG,and FFA were higher than those before operation,but declined over time.All the indexes in the indomethacin group 120 hours after operation decreased significantly compared with the levels 24 hours after operation ( all P =0.000 ),as well as with the levels in the control group 120 hours after operation ( all P ＜ 0.05 ).No significant difference was found in the level of CRP between the two groups and between before and after operation.ConclusionIndomethacin could reduce the postoperative stress hyperglycemia and insulin resistance in patients with gastrointestinal tumor.

Objective To reveal the role of PDK1 in vascular endothelial cells. Methods PDK1 was knocked out in endothelial cells by recombinase-mediated Cre to observe it′s effects on vascular endothelial cells. Results Abnormality of vascular development in rats could be found as a result of endothelial PDK1 deletion. Meanwhile, vascular leakage and bleeding phenotype were observed, and tissue analysis showed vascular endothelial cells abnormalities. Conclusions PDK1 plays an important role in the functioning and integrity of vascular endothelial cells, which made tentative explanation for PDK1-Akt signal path and laid basis for further research.