Primary cilium and its role in tumorigenesis / 浙江大学学报·医学版

The primary cilium, a sensory organelle that protrudes from the surface of most eukaryotic cells, receives and transduces various critical signals that are essential for normal development and homeostasis. Structural or functional disruption of primary cilia causes a number of human diseases, including cancer. Primary cilia has cross talks with cell cycle and it may act as a cell cycle checkpoint to suppress cancer development. Moreover, primary cilia has cross-regulation with autophagy, which may affect tumor progression. We then discuss the association of the primary cilia with several oncogenic signaling pathways, including Shh, Wnt, Notch and platelet-derived growth factor receptor (PDGFR). Since these signaling pathways are often over-activated in many types of human cancers, primary cilia are likely to play a role in the tumorigenesis by modulating these pathways. Finally, we summarize current progress on the role of cilia during tumorigenesis and the challenges that the cilia-cancer field faces.

Hyperbaric oxygen improves the effectiveness of wet healing in the treatment of refractory skin ulcers / 中华物理医学与康复杂志

Objective:To explore the effect of combining hyperbaric oxygen inhalation with wet healing in the treatment of chronic refractory ulcers of the skin.Methods:Sixty male Sprague-Dawley rats were randomly formed into a general treatment group (group A), a wet healing group (group B), and a hyperbaric oxygen + wet healing group (group C), each of 20. Chronic and refractory skin ulcers were induced on all of the rats after one week of routine feeding and 6 hours of fasting. Six courses (once daily for 10 days/course)of the three treatments were then administered. After 2, 4 and 6 courses of treatment the wound healing rate and recovery were analyzed using histopathological methods.Results:After 2, 4 and 6 courses of treatment, the average wound healing rates of groups B and C were significantly higher than group A′s average, and that of group C was significantly better than that of group B. After 6 courses of treatment, group C′s average histopathology score was significantly higher than that of group B, and those of groups B and C were both significantly higher than group A′s average.Conclusion:Single wet healing is better than common treatment for chronic skin ulcers, but hyperbaric oxygen inhalation can further improve its effectiveness.

Neddylation inhibitor MLN4924 suppresses cilia formation by modulating AKT1

The primary cilium is a microtubule-based sensory organelle. The molecular mechanism that regulates ciliary dynamics remains elusive. Here, we report an unexpected finding that MLN4924, a small molecule inhibitor of NEDD8-activating enzyme (NAE), blocks primary ciliary formation by inhibiting synthesis/assembly and promoting disassembly. This is mainly mediated by MLN4924-induced phosphorylation of AKT1 at Ser473 under serum-starved, ciliary-promoting conditions. Indeed, pharmaceutical inhibition (by MK2206) or genetic depletion (via siRNA) of AKT1 rescues MLN4924 effect, indicating its causal role. Interestingly, pAKT1-Ser activity regulates both ciliary synthesis/assembly and disassembly in a MLN4924 dependent manner, whereas pAKT-Thr determines the ciliary length in MLN4924-independent but VHL-dependent manner. Finally, MLN4924 inhibits mouse hair regrowth, a process requires ciliogenesis. Collectively, our study demonstrates an unexpected role of a neddylation inhibitor in regulation of ciliogenesis via AKT1, and provides a proof-of-concept for potential utility of MLN4924 in the treatment of human diseases associated with abnormal ciliogenesis.

Introduction of a modified PICC blind puncture catheterization technique / 肠外与肠内营养

Objective:To investigate the application and feasibility of the night-vision puncture technique in performing peripherally inserted central catheter(PICC).Methods:Seventy patients were randomly divided into ultrasound guided puncture group or modified blind puncture group,35 cases in each group.The puncture success rate,the achievement ratio of catheterization,the puncture site,arm circumference,catheterization time and complications were recorded in two groups.Results:Two groups had no significant difference in the puncture success rate,the achievement ratio of catheterization,the puncture site,arm circumference,phlebitis incidence,subcutaneous congestion (bleeding) (P ＞ 0.05).The catheterization time in modified blind puncture group was shorter than the ultrasound guided puncture group (P ＜ 0.001).In modified blind puncture group,a negative correlation (correlation coefficient:-0.475,P =0.004)between arm circumference and the puncture success rate was found.Conclusion:The puncture success rate of the modified blind puncture technique in performing peripherally inserted central catheter (PICC) is high and close to the puncture success rate of the PICC under ultrasound.Additionally,the modified blind puncture technique does not increase the incidence of complications and delay the catheter time.

Effect of ethanol extracts from Polygonum multiflorum Thunb on expressions of signal pathway TLR4/TRIF/IRF-3 in LPS induced rats liver / 国际药学研究杂志

Objective To research the toxicity of ethanol extracts from Poylgonum multiflorum Thunb(PMT)induced by en?dotoxin of Gram-negative bacteria lipopolysaccharide(LPS)in rat liver,and then investigate the hepatotoxicity mechanisms of PMT on immune inflammatory signal pathway Toll-Like receptor 4(TLR4)-interferon regulated factor3(IRF-3). Methods SD rats were randomly assigned into normal control,LPS(4 mg/kg),acetaminophen APAP(625 mg/kg),PMT 6 g/kg(PMT-L),PMT 12 g/kg (PMT-H),LPS+APAP and LPS+PMT-L/-H groups. The 4 groups later were injected LPS 4 mg/kg by caudal vein,after 2 h,the corre?sponding drugs were administered once a day for 7 consecutive days,respectively. The changes of weight of rats were observed every day. The tissue morphology of liver tissue of rats on 2 h,14 h,5 d,8 d after administration were detected by hematoxylin-eosin stain? ing respectively. Real time quantitative PCR(RT-qPCR)method and Western blotting were used to detect the expression of TLR4, TRIF and IRF3 in the TLR4 signaling pathway in liver cells. Results Two hours after the rat tail vein injection of LPS,the liver tiny granulomas of rats could be observed in LPS-induced groups,and then,the liver injury of rats in LPS group was gradually recovered. Eight Days after LPS induction,the liver tissue structure of rats in LPS group was clear and complete,but in LPS+APAP group and LPS+PMT 6 or 12 g/kg groups,the focal necrosis of hepatocytes,with inflammatory cell infiltration could be observed. The results of RT-qPCR and Western blotting showed that in oral administration of PMT groups,the expression of TLR4,TRIF and IRF-3 mRNA and protein in the liver cells had no significant change compared with the normal control group. But in 4 groups induced with LPS,the expression of TLR4, TRIF and IRF-3 mRNA and protein in the liver cells were significantly higher than that of the normal control group and LPS group(P<0.05). Conclusion PMT can cause liver damage induced by LPS,the hepatotoxicity is related to the positive regulation of TLR4/IRF-3 signaling pathways,which is not related to the dosage of PMT. The results show that activating TLR4/IRF3 signaling pathway is one of the mechanisms of liver injury of PMT in rats induced by LPS.