Toll-like receptor 4(TLR4)is a member of the TLRs superfamily,mainly capable of identifying bacterial endotoxin,lipopolysaccharides and lipooligosaccharides of Gram-negative bacte?ria cell walls to prevent microbial invasion. Activation of TLR4 can induce production of proinflammato?ry cytokines and inflammatory chemokines and regulate natural immunity. However,dysregulation of TLR4 can lead to autoimmune diseases. This review summarized the biological structure of TLR4 and recognition mechanisms between TLR4 and its ligands,surveyed TLR4 ligands including lipid A ana?logues,natural products and synthetic small molecules,discussed the structure-activity relationship of TLR4 modulators and the ligand-receptor and protein-protein interactions in the complex,and outlined the prospect of future research and development of TLR4 ligands.

Thirteen novel oleanolic acid (OA) derivatives were designed and synthesized with modification at positions of C-3, C-12 and C-28 of OA. Their structures were confirmed by MS, 1H NMR and elemental analysis. Their in vitro cytotoxicities against various cancer cell lines (SGC7901, MCF-7 and A549) were evaluated by MTT assay. The results indicated that the tested derivatives were found to have stronger cell growth inhibitory activity than OA. Among them, compounds II2 and II3 showed more potent cytotoxicity on MCF-7 and A549 tumor cells than gefitinib (positive control). They are worthy to be studied further.

BACKGROUND: Prognosis is determined by degrees of outside force and time of spinal cord compression after spinal cord injury. The former factor cannot be changed, but the latter one can be changed through relieving spinal cord compression as early as possible to promote nervous function recovery.OBJECTIVE: To compare the effect of surgical intervention time on nervous function recovery within 72 hours and 10 to 14 days after cervical spinal cord injury.DESIGN: Randomized controlled and before-after controlled study.SETTING: Department of Spine Surgery of the Second Hospital affiliated to Harbin Medical University.PARTICIPANTS: A total of 32 patients with cervical spinal cord injury were selected from the Department of Spine Surgery of the Second Hospital affiliated to Harbin Medical University from April 1998 to August 2001.All patients were divided into two groups according to randomly alternative criteria. There were 16 cases including 10 males and 6 females in early surgical group (within 72 hours) and there were also 16 cases including 12males and 4 females in delayed surgical group (within 10-14 days).METHODS: Patients in early surgical group were undertaken operation at 72 hours after hospitalization, and patients in delayed surgical group were at 10-14 days after hospitalization. Frankel grade, sensory and motor scores were recorded according to criteria set by American Spinal Injury Association before operation and within 24 months after operation.MAIN OUTCOME MEASURES: ① Sensory and motor scores before and after operation; ② Frankel grade before and after operation.RESULTS: ① Improved level of sensory score (difference before and after operation) was higher in early surgical group than that in delayed surgical group (42.6±20.2, 19.2±19.1, P ＜ 0.01). ② Improved level of motor score (difference before and after operation) was higher in early surgical group than that in delayed surgical group (39.7±17.8, 17.3±18.6, P ＜ 0.01). ③Improved level of Frankel grade in early surgical group was superior to that in delayed surgical group (P ＜ 0.01).CONCLUSION: Nervous function recovery of patients with acute cervical spinal cord injury who were suffered from operation within 72 hours is superior to that of those within 10 to 14 days. Therefore, surgical intervention should be undertaken as early as possible in order to promote nervous function recovery after cervical spinal cord injury.

Objective:To study the role of 14-3-3εand Cdc25B in germinal vesicle (GV)-stage arrest of mouse oocytes,and to pay foundation for further study on the molecular mechanism of PKA/Cdc25B/14-3-3εpathway in GV-stage arrest of mouse oocytes.Methods:The eukaryotic expression vectors of pcDNA3.1-ZEO-HA-14-3-3ε, pcDNA3.1-MYC-Cdc25B-WT, pcDNA3.1-MYC-Cdc25B-S321A, and pcDNA3.1-MYC-Cdc25B-S321D were transcribed into mRNA invitro.The mouse GV-stage oocytes were collected after superovulation and divided into no injection group,TE buffer microinjection group,14-3-3εmRNA injection group,14-3-3εmRNAs + Cdc25B-WT mRNA injection group,and 14-3-3εmRNA + Cdc25B-S321A mRNA injection group,14-3-3εmRNA+Cdc25B-S321D mRNA injection group.The protein expression levels of HA-14-3-3εand MYC-Cdc25B and the phosphorylation status of Cdc2-pTyr15 were observed by Western blotting method.The morphological changes and germinal vesicle breakdown (GVDB)rates of mouse oocytes were observed under phase-contrast microscope. Results:None of the oocytes in no injection group, TE buffer microinjection group, 14-3-3εmRNA injection group,14-3-3εmRNA + Cdc25B-WT mRNAs injection group and 14-3-3εmRNA + Cdc25B-S321D mRNA were able to undergo GVBD until at least 20 h after injection (P>0.05 );the GVBD rates of oocytes in 14-3-3εmRNA+Cdc25B-S321A mRNA group at 1 h (5.00%±0.68%),2 h (62.00%±3.56%)and 3 h (100.00%± 0.00%)after injection were significantly higher than those in no injection group and TE buffer injection group (P<0.01);the oocytes in 14-3-3εmRNA+ Cdc25B-Ser321A mRNA group at 20 h (79.00%±2.80%)after injection progressed to MII (P<0.01).Conclusion:14-3-3εcan regulate the transition from GV to GVBD of mouse oocytes by means of phosphorylation and dephosphorylation of S321-Cdc25B.

Structure of natural product-ursolic acid was modified for increasing its antitumor activity. Ursolic acid was acylated, esterified, hydrolized or oxidized to obtain target pentacyclic triterpenoid compounds with different substitutes. Sixteen derivatives of ursolic acid were designed and synthesized including eleven new compounds. Anti-tumor activities of ursolic acid and these derivatives against HeLa, SKOV3 and BGC-823 cells in vitro were investigated by MTT assay. The results indicated that compounds 7a and 8a were found to have stronger cell growth inhibitory than ursolic acid on HeLa cells and SKOV3 cells separately, and are worth to be intensively studied further.

Objective:To observe the bone regeneration capacity of bone defects around BLB implants covered with or without membranes.Methods:Implants were installed into femoral bone of grown-up dogs.Near implants,3 mm horizontal width,5 mm vertical depth and 1,2,3,4 mm horizontal length(along the macroaxis of femoral bone) standard gradient bone defects were made.On one side,the incisions were directly sutured by lamination,and on the other side the incisions were sutured by lamination after using collagen membrane to cover on the defects.Three months after the operation the specimens were observed by stereomicroscopy.Results:In the groups with 1,2 and 3 mm defects,the defect areas had been filled completely with new bone which was mainly compact cortex.In the group with 4 mm defects,the defect areas were filled with new bone which was mainly trabecular bone.Bigger lacunes could be observed in the groups without membranes.Conclusion:If the defect is less than 3 mm,whether bioresorbable collagen membrane is used or not,osseointegration is well in the implant-bone interface.Improving bone regeneration should be done when the bone defect extension is bigger.

Catheter Ablation ; Cold Temperature ; Cysts ; congenital ; Humans ; Tongue ; pathology ; surgery

Objective To investigate the effect of curcumin (Cur)on AngⅡ-induced proliferation and oxidative stress of vascular smooth muscle cells (VSMCs).Methods Primary rat VSMCs were cultured and divided into control group,AngⅡ group,AngⅡ+Cur 5μmol/L group,AngⅡ+Cur 10μmol/L group,AngⅡ+Cur 20μmol/L group,and Cur 20μmol/L group.The proliferation of AngⅡ-induced VSMCs was measured by MTT assay.The mRNA and protein expressions of inducible nitric oxide synthase (iNOS)and p47phox were detected by real-time PCR and Western blot.Nitric oxide (NO)production was measured by Griess reaction.Production of intracellular reactive oxygen species (ROS)was measured by DCFH-DA staining,and the activities of superoxide dismutase (SOD)and glutathione peroxidase (Gpx)were detected by xanthine oxidase assay and visible spectrophotometer. small interfering RNA (siRNA)was used to silence the expression of p47phox to further explore the mechanism for Cur inhibiting the proliferation of AngⅡ-induced VSMCs and oxidative stress.Results VSMCs activities were not significantly affected by Cur at the concentration between 0 and 80μmol/L.Cur (5,10 and 20μmol/L)significantly inhibited AngⅡ-induced proliferation of VSMCs.Cur had an inhibitory effect on the overexpression of NO,iNOS, p47phox and ROS in VSMCs and upregulated the activities of SOD and Gpx in a concentration-dependent manner. AngⅡ-induced ROS production in VSMCs was significantly attenuated by pretreatment with p47phox specific siRNA.Conclusion Cur can inhibit the proliferation and oxidative stress of AngⅡ-induced VSMCs.