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ABSTRACT: To investigate the effect of miR-122 on the expression of hepatitis B virus (HBV) proteins.
Anti-sense oligodeoxynucleotide (ASODN) of two different sequences against miR-122, anti-miR-122 and LNA-antimiR-122 (Locked nucleic acid), human miR -122 (hsa-miR-122), or the negative control anti-GFP were designed and synthesized, then transfected into HepG2.2.15 cells. After 24 h and 48 h, the levels of HBsAg and HBeAg in the supernatant were determined with a time-resolved immunofluorometric assay (TRFIA). HBV DNA in supernatant and miR-122 in cells were measured by quantitative real-time PCR.
After 48 h expressions of miR-122 in the LNA-antimiR-122 and anti-miR-122 groups were significantly suppressed and lower than those in the negative control (P<0.001), while the level of miR-122 in the hsa-miR-122 group was higher than that in the negative control (P<0.001). The expression of HBeAg and HBsAg in hsa-miR-122 group was lower than that in the negative control (P<0.01) 24 h and 48 h after transfection. The expression of HBeAg and HBsAg in the anti-miR-122 group and LNA-antimiR-122 group was significantly lower than that in negative control (P>0.001). The levels of viral DNA at both time-points in the various test groups were not significantly different from those of negative control group (P>0.05).
miR-122 may regulate HBV antigens and potentially affect the progress of pathogenesis, which might be the new targets for treatment of HBV infection.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 11/2011; 40(6):593-7.
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ABSTRACT: A 60-member 1,2,3-triazoles bearing biologically active sulfonamide moiety library was synthesized via azide-alkyne cycloaddition and examined for cytotoxic activity against human leukemia cell line HL-60. 25 of them were evaluated further in four additional cancer cell lines (HepG2, A549, PC3, SGC7901). Most of the 25 compounds showed moderate cytotoxic activities against the tested cell lines. Furthermore, the structure-activity relationships were discussed and a reliable 3D-QSAR model with good prediction (r²cv = 0.64, r² = 0.958) was generated on the basis of our synthesized 1,2,3-triazoles for their cytotoxic activities against the HL-60 cell line. The contour map of the CoMFA should aid in the design of new antitumor agents.
Molecular Diversity 07/2011; 15(4):927-46. · 3.15 Impact Factor
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ABSTRACT: New Chemical Entities (NCEs) development is a systematic long-term project that involves multiple disciplines. The translation research will help to build an advanced R&D system from the basic laboratory research, preclinical studies and clinical evaluation to clinical application of drug, for the purpose of shortening the R&D cycle and accelerate the launch of new drugs. In new drug R&D and its clinical application, drug disposition (absorption, distribution, metabolism, excretion, ADME) properties are important criteria for assessing drug-likeness of candidates. ADME evaluation of NCEs plays an important role in the translation research throughout innovative drug R&D process. Therefore, ADME evaluation at the early stage of drug design and development will be helpful to improve the success rate and reduce costs, and further access to safe, effective drugs.
Yao xue xue bao = Acta pharmaceutica Sinica 01/2011; 46(1):19-29.
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ABSTRACT: Three series of flavonoid derivatives were designed and synthesized. All synthesized compounds were evaluated for cytotoxic activities against five human cancer cell lines, including K562, PC-3, MCF-7, A549, and HO8910. Among the compounds tested, compound 9 d exhibited the most potent cytotoxic activity with IC(50) values of 2.76-6.98 μM. Further comparative molecular field analysis was performed to conduct a 3D quantitative structure-activity relationship study. The generated 3D-QSAR model could be used for further rational design of novel flavonoid analogs as highly potent cytotoxic agents.
Molecular Diversity 11/2010; 15(3):665-75. · 3.15 Impact Factor
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ABSTRACT: To investigate the effect of interleukin-18 (IL-18) on immune response induced by plasmid encoding hepatitis B virus middle protein antigen and to explore new strategies for prophylactic and therapeutic HBV DNA vaccines.
BALB/c mice were immunized with pCMV-M alone or co-immunized with pcDNA3-18 and pCMV-M and then their sera were collected for analysing anti-HBsAg antibody by ELISA; splenocytes were isolated for detecting specific CTL response and cytokine assay in vitro.
The anti-HBs antibody level of mice co-immunized with pcDNA3-18 and pCMV-M was slightly higher than that of mice immunized with pCMV-M alone, but there was not significantly different (P>0.05). Compared with mice injected with pCMV-M, the specific CTL cytotoxity activity of mice immunized with pcDNA3-18 and pCMV-M was significantly enhanced (P<0.05) and the level of IFN-Gamma in supernatant of splenocytes cul-tured with HBsAg in vitro was significantly elevated (P<0.05) while the level of IL-4 had no significant difference (P>0.05).
The plasmid encoding IL-18 together with HBV M gene DNA vaccines may enhance specific TH1 cells and CTL cellular immune response induced in mice, so that IL-18 is a promising immune adjuvant.
Journal of Zhejiang University SCIENCE 04/2004; 5(4):467-71.
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ABSTRACT: OBJECTIVE: To investigate the feasibility of HBV DNA vaccines. METHODS: HBV S gene was obtained by PCR and the PCR product was cloned into pcDNA3. The recombinant was screened by antibiotics, identified by digestion and confirmed by sequencing. The plasmid was then transfected into mammalian cell COS-7 for transient expression. Then the recombinant was injected into mice and the immune responses induced in mice were investigated. RESULTS: The sequence of HBV S gene was correct and HBsAg could be detected in cells transfected with pcDNA3-S. After immunization, the positive rate in mice immunized with pcDNA3-S and pCMV-S was 70%(7/10) and 80% (8/10). The mean levels of anti-HBs were (32.14+/-13.79)mIU/ml and (28.50+/-11.87)mIU/ml respectively. There was no statistically significant difference between them P 0.05 . The mean levels of anti HBs in the control group and blank groups were both less than 10 mIU/ml. In mice immunized with pcDNA3-S and pCMV-S the results were (35.40+/-4.85)% and (38.20+/-7.69)% when E/T was 20:1, or (23.95+/-3.98)% and (24.55+/-3.59)% when E/T was 10:1, again showing no difference statistically (P>0.05). The specific CTL cytotoxicity rate of control and blank groups was both less than 5%. CONCLUSION: A specific humoral and cellular immune response can be induced in mice by intramuscular injection of pcDNA3-S.
Zhejiang da xue xue bao. Yi xue ban = Journal of Zhejiang University. Medical sciences 08/2002; 31(6):440-443.
