Complement factor B knockdown by short hairpin RNA inhibits laser-induced choroidal neovascularization in rats

AIM:To evaluate whether recombinant complement factor B(CFB)short hairpin RNA(sh RNA)reduces laserinduced choroidal neovascularization(CNV)in rats.METHODS:Laser-induced rat CNV model was established,and then the animals underwent fundus fluorescence angiography(FFA)and hematoxylin and eosin(HE)staining.On day 3 and 7 after photocoagulation,the expression of CFB and membrane attack complex(MAC)was detected by immunhischemistry.A recombinant CFBsh RNA plasmid was constructed.CFB and scrambled sh RNA plasmids were intravenous injected into rats via the tail vein on the day of laser treatment,respectively.On day 7,the incidence of CNV was determined by FFA,and the expression of CFB and vascular endothelial growth factor(VEGF)in retinal pigment epithelium(RPE)/choroidal tissues was detected by immunhischemistry,Western blot and/or semi-quantitative reverse transcription-polymerase chain reaction(RT-PCR)in CFB and scrambled sh RNA groups.The possible adverse effects of CFB-sh RNA injection were assessed by transmission electron microscopy and electroretinography.RESULTS:FFA and HE results indicated that a laserinduced rat CNV model was successfully established on day 7 after photocoagulation.The expression of CFB and MAC was extremely weak in normal retina and choroid,and increased on day 3 after photocoagulation.However,it started to reduce on day 7.CFB sh RNA plasmid was successfully constructed and induced CFB knockdown in the retinal and choroidal tissues.FFA showed CFB knockdown significantly inhibited incidence of CNV in rats.Moreover,CFB knockdown significantly inhibited the expression of VEGF in RPE/choroidal tissues.CFB sh RNA caused no obvious side effects in eyes.CONCLUSION:CFB knockdown significantly inhibits the formation and development of CNV in vivo through reducing the expression of VEGF,which is a potential therapy target.The alternative pathway of complement activation plays an important role in CNV formation.

Graph Designs for all Graphs with Six Vertices and Eight Edges

Graph designs for all graphs with six vertices and eight edges are discussed. The existence of these graph designs are completely solved except in two possible cases of order 32.

Structural effects and competition mechanisms targeting the interactions between p53 and MDM2 for cancer therapy

Approximately half of all human cancers show normal TP53 gene expression but aberrant overexpres- sion of MDM2 and/or MDMX. This fact suggests a promising cancer therapeutic strategy in targeting the interactions between p53 and MDM2/MDMX. To help realize the goal of developing effective in- hibitors to disrupt the p53-MDM2/MDMX interaction, we systematically investigated the structural and interaction characteristics of p53 with inhibitors of its interactions with MDM2 and MDMX from an atomistic perspective using stochastic molecular dynamics simulations. We found that some spe- cific a helices in the structures of MDM2 and MDMX play key roles in their binding to inhibitors, and that the hydrogen bond formed by the Trp23 residue of p53 with its counterpart in MDM2 or MDMX determines the dynamic competition processes of the disruption of the MDM2-p53 interaction and replacement of p53 from the MDM2-p53 complex in vivo. The results reported in this paper are expected to provide basic information for designing functional inhibitors and realizing new strategies of cancer gene therapy.

Incorporation of polyoxometalate-based acid–base pair into a sulfonated MIL-101 for achieving proton-conduction materials with high proton conductivity and high stability

Currently,it is of great significance to develop new proton-conduction materials with high proton conductivity,high stability,and good conducting durability to meet the demands of fuel cell and sensors.Herein,we prepared two composites DETA-HPW@MIL-101-SO_(3)H 1 and TETA-HPW@MIL-101-SO3H 2(DETA=diethylenetriamine,HPW=H_(3)PW_(12))_(4)0·xH_(2)O,MIL=Material Institut Lavoisier,TETA=triethylenetetramine)by encapsulating polyoxometalate(POM)and organic amine into a sulfonated MIL-101 through a step-by-step dipping method.Delightedly,1 and 2 have high proton conductivities of 6.4×10^(−2) and 2.9×10^(−2) S·cm^(−1) at 65℃ and 95%relative humidity(RH),respectively,which can be attributed to the fast proton transfer among acid–base pairs formed between HPW and organic amine as well between sulfonic acid and organic amine.Moreover,the time-dependent test in proton conductivity displays that their proton-conduction properties have good stability and durability,which benefit from that the electrostatic interactions among acid–base pairs and the limitation of opening size of MIL-101-SO3H make HPW and organic amine stably exist in the cages of MIL-101-SO_(3)H.The remarkable proton-conduction properties(high proton conductivity and high stability)of the two composites make them become promising proton-conduction materials.