Objective To assess the effects of 7,8-dihydroxyflavone (7,8-DHF) on the striatum (ST) in normal cynomolgus monkeys using 99Tcm-TRODAT-1 imaging.Methods A total of six healthy female cynomolgus monkeys were included in this study.Three of them were fed with normal food (control group),and the other three were given oral administration of 7,8-DHF in addition to normal food (experimental group).The SPECT/CT imaging was performed at different time after 99Tcm-TRODAT-1 injection.The ROI of ST was drawn on images of 3 consecutive transverse slices that could be visualized best.The cerebellum (CB) was taken as the background reference area.The radioactivity uptake ratios of ST/CB at 1,3,4 and 5 h were calculated respectively.Paired-t test was used to analyze the data.Results ST radioactive uptake ratios showed continuing increase on the delay images.ST/CB uptake ratios of the control group at 1,3,4 and 5 h were 1.43±0.04,1.82±0.06,2.04±0.12,2.42±0.23,respectively,and those of the experimental group were 1.35±0.08,2.40±0.09,2.74±0.13 and 3.25±0.15 respectively.There was no significant difference between the two groups at 1 h (t =2.57,P＞0.05),while ST/CB uptake ratios of the experimental group at 3,4 and 5 h were significantly higher (t values:2.77,2.87 and 2.92,all P＜0.05).Conclusion 99Tcm-TRODAT-1 SPECT/CT imaging can be used to assess the DAT activation effect by 7,8-DHF on ST of cynomolgus monkeys.

Background and purpose:Researches had indicated that about over 85%of malignant tumors highly express telomerase activity. So telomerase has become one of the important methods in the research field of tumor diagnosis and treatment. Nowadays, several reports about malignant tumor which over expresses hTERT targeting imaging with radionuclide labeled hTERT ASON had been published. In these reports, high quality of pictures can hardly be acquired because of poor anatomical and spacial resolution in nuclear imaging itself. Accordingly, in this study, we developed a method of detecting human telomerase in vivo with magnetic resonance imaging (MRI) and evaluate its feasibility. Methods:Firstly, Uniformly phosphorothioate-modified human telomerase reverse transcriptase antisense oligonucleotide (hTERT ASON) was labeled with Gd3+ through the bifunctional chelator 1, 4, 7, 10-tetraazacyclododecane-N, N’, N’’, N’’’-tetraacetic acid (DOTA) and iv vitro experiments were performed to characterize the antisense probes (for biodistribution and cellular uptake, 99mTc-DOTA-ASON was used in stead of Gd-DOTA-ASON). Then Gd-DOTA-ASON was injected intraperitoneally in pulmonary adenocarcinoma A375 nude mice tumor-bearing BALB/c for in vivo imaging using 7.0 T Micro MRI periodically, tumors and their surrounding tissues were defined as region of interest (ROI) to calculate the signal to noise ratio (SNR) of tumor to muscle using Gd-DTPA as control. Finally, immunohistochemical analysis of telomerase activity of each xenograft was operated 2 days after imaging. Results:The binding efficiency of Gd-DOTA-ASON reached was as high as 65%(63.2±2.4, n=6). And it can maintain 61%in fresh human serum and normal saline at 37℃over 24 h;A375 cells showed an uptake of 8.5%when incubated with 99mTc-DOTA-ASON;In comparing with DOTA-ASON and Gd-DTPA, cells transected with Gd-DOTA-ASON had higher SI when performed MRI with T1WI. The hTERT-expressing xenografts were obviously enhanced by Gd-DOTA-ASON at 0.5-6 h after injection and the SNR can reach 2.37, whereas obvious enhancement only could be found within 2 h after injection of Gd-DTPA. Both labeled and non-labeled antisense probes can suppress the activity of telomerase of A375 cells either in vitro or in vitro. Conclusion:Our research offers proof that Gd-DOTA-ASON can be used as tumor specific targeting MR probe for diagnosing malignant tumors with high expression of telomerase.

It was recently shown that several new synthetic 2-alkylsulfanyl-6-benzyl-3, 4-dihydropyrimidin-4(3H)-one (S-DABO) derivatives demonstrated anti-HIV-1 activity. Three of the derivatives namely RZK-4, RZK-5 and RZK-6 were used in this study to explore their inhibitory effects on a variety of HIV strains. These compounds at a concentration of 200 microg mL(-1) almost completely inhibited the activity of recombinant HIV-1 reverse transcriptase. All of the three compounds reduced replication of HIV-1 laboratory-derived strains, low-passage clinical isolated strain, and the drug resistant strain. In particular RZK-6 showed potent activity against the HIV-1 drug resistant strain. In general, the antiviral activities are similar in magnitude to nevirapine (NVP), which is a non-nucleoside reverse transcriptase inhibitor approved by FDA. The therapeutic indexes of these compounds were remarkable, ranging from 3704 to 38462 indicating extremely low cytotoxicity. These results suggest that the three S-DABO derivatives in this study have good potential for further development in anti-HIV-1 therapy. It may be particularly useful to target at the non-nucleoside reverse transcriptase inhibitors resistant HIV-1 strain.

Brain-derived neurotrophic factor (BDNF) exerts its survival-promoting effects on photoreceptors and retinal ganglion cells, however, delivery systems with little-to-no side effect are needed to sustain its controlled release and long-term efficacy. Our previous studies demonstrated that adipose-derived stem cells (ADSCs) are ideal delivery systems for gene therapy; moreover, ADSCs present unique properties like migration to damaged tissue sites, immunomodulation and anti-inflammation. Herein, we propose to employ ADSCs as the BDNF gene delivery vehicle. Different Analyses like flow cytometry, differentiation and cell proliferation assays etc demonstrated that BDNF were successfully transduced into ADSCs and the stemness of ADSCs was maintained even with the transduction. Real Time PCR and Western blot were used to measure mRNA and protein expressions of the BDNF-transduced ADSCs. The results demonstrated that the BDNF expression level of the lentiviral-BDNF transduced ADSCs is significantly increased and, moreover, enhanced the expression of other neurotrophic and downstream signaling factors. The data suggest that ADSCs are a reliable delivery vehicle for BDNF and could be used for the treatment of various diseases.