Biomedical subjects
Publications and source records attributed to Jin-Hui Wang.
Four novel cycloartanes, named sphaerophysone A (1), B (2), C (3) and D (4), were isolated from the ethanol extract of Sphaerophysa salsula (Pall.) DC. The structures were elucidated on the basis of spectral evidence, and the stereochemistry of compound 1 was defined by X-ray crystallographic analysis. Sphaerophysone B (2) may be an artifact formed in the isolation procedure.
Telomerase activity is a wide tumor marker. Human telomerase reverse transcriptase (hTERT), the catalytic subunit of the telomerase, is transcriptionally upregulated exclusively in about 90% of cancer cells. In this study, we constructed a novel adeno-associated virus (AAV) vector containing the human interferon-beta (hIFN-beta) gene under the control of hTERT promoter (AAV-hTERT-hIFN-beta) and investigated its antitumor effect against various human cancer cells in vitro. AAV-hTERT-hIFN-beta displayed cancer-specific hIFN-beta expression and cytotoxicity. The cytotoxic ratio was positively correlated with the time length of infection. AAV-hTERT-hIFN-beta-mediated apoptotic morphology was observed by transmission electron microscopy. Flow cytometry assay also revealed that the cytotoxicity of AAV-hTERT-hIFN-beta was mainly an apoptotic process. These data indicate that AAV in combination with hTERT-mediated therapeutic gene expression may open new possibilities for long-lasting and targeting gene therapy of varieties of cancers.
To provide necessary information for further understanding of molecular mechanism of hypoxia acclimatization, the differentially expressed genes of HepG2 cells exposed to normoxia, acute hypoxia-treated cells which were exposed to 1% oxygen for 48 h, and hypoxia-acclimatized HepG2 cells which were cultured for 6 circles of alternate low oxygen (1% oxygen for 24 h) and normal oxygen (21% oxygen for 24 h), were identified respectively by combining the suppression subtractive hybridization (SSH) and cDNA microarray. Thirty-seven genes were expressed differentially in cells exposed to 1% oxygen for 48 h compared with those in cells exposed to normoxia. The expression of all these 37 genes was down-regulated, including the genes participating in cell cycle, cell response to stimulus, and cell signal transduction, and cell cytoskeleton formation, the genes associated with transcription and cell metabolism, 4 expressed sequence tags (ESTs), and 12 genes of which the functions are not known. There is a novel gene sequence, which has not been found in existing databases. There were only 6 genes differentially expressed in the hypoxia-acclimatized cells compared with cells exposed to normoxia, including two mitochondrion genes, metalloprotease-1 gene, ferritin gene, thymosin beta-4 and TPT1 genes. The expressions of mitochondrion ND4, ferritin, thymosin beta-4 and TPT1 were up-regulated, while the expressions of mitochondrion ND1 gene and metalloproease-1 gene were down-regulated. Cell tolerance to hypoxia increased after the cells were hypoxia-acclimatized. The different gene expression patterns of the acute hypoxia-treated cells and the hypoxia-acclimatized cells may be related to the increased tolerance of the cells to hypoxia.
From the fruits of Celastrus orbiculatus Thunb., a new dihydroagarofuran sesquiterpene ester named 6alpha,13[beta-diacetoxy-1beta,8beta,9beta-tribenzoyloxy-beta-dihydroagarofuran (1) has been isolated, along with three known compounds: 1beta,6alpha,8beta-triacetoxy-9alpha-benzoyloxy-beta-agarofuran (2), 1beta,6alpha-diacetoxy-9alpha-benzoyloxy-beta-dihydroagarofuran (3) and beta-sitostrol (4). The structure of 1 was elucidated on the basis of spectroscopic methods.
Four phytoecdysteroids that have only 19 or 21 carbons, named 11alpha-hydroxyrubrosterone (1), dihydroxyrubrosterone (2), rubrosterone (3) and poststerone (4), were isolated from the whole plant of Cyanotis arachnoidea C.B. Clarke. Among them, 1 was a new compound. Their structures were elucidated by spectroscopic methods.
A new isocoumarin, 3-acetyl-3,4-dihydro-5,6-dimethoxy-1H-2-benzopyran-1-one, was isolated from the cortex of Phellodendron chinense schneid. The structure was determined on the basis of spectroscopic evidences.
Targeting to the tumor tissues can improve the therapeutic effect of gene transfer by preventing damage of healthy tissues and decreasing the risk of germ line transduction. Although targeting seems not important for intratumoral gene delivery, it becomes crucial when systemic gene transfer is performed. Targeted gene therapy of malignancies can be achieved through targeted gene delivery or targeted gene transcription. Recent advances in targeted delivery include the successful use of bifunctional crosslinkers to target adenoviral and retroviral vectors, inserting short targeting peptides and larger polypeptide-binding domains into the coat proteins of a number of different viral vectors, and replication-competent vectors which have been shown to be promise as anti-cancer agents. Some other non-viral therapeutic agents, including receptor-mediated DNA or liposome-DNA complex, and bacteria vehicles have also been developed. Some of these delivery systems are currently in clinical trials. For targeted and regulable gene transcription, tissue or tumor specific promoters and some manual regulatory systems are used to regulate therapeutic gene expression. Antisense oligonucleotides, some ribozyme and DNAzyme molecules are developed to inactivate genes that are essential to the development of many tumors.
Neovascularization is a prerequisite for progressive growth of most tumors and their metastases. Therefore, inhibition of angiogenesis could be one of the most promising strategies that might lead to the development of novel anticancer therapy. New blood vessels forming in tumors can be avoided by interfering the process of angiogenesis through suppressing the proangiogenic signal or augmenting the antiangiogenic factors. Concentrated efforts in this area have lead to the discovery of many proangiogenic factors as well as their inhibitors, and antiangiogenic factors. For the established tumor vasculature, tumor vasculature-targeted delivery of antiangiogenic substances and endothelial cell vaccines has been explored. Although some antiangiogenic drugs are currently in clinical development, for future reason, more efficient therapeutic methods, including antiangiogenic gene therapy strategy, targeted drug delivery system, and the combination of antiangiogenic agents with immunotherapy, chemotherapy or radiotherapy are being explored. With the development of tumor model assessment system, clinical use of the above antiangiogenic tumor therapy methods could be achieved.
AIM: To express a novel Gln98-deleted human interleukin-13 in E.coli. METHODS: Total RNA was isolated from Jurkat cells costimulated with PHA and ConA. A 358 bp-specific DNA fragment encoding hIL-13 was amplified by semi-nested RT-PCR. DNA sequencing showed that the target DNA was a Gln98-deleted novel splicing of hIL-13. This hIL-13 cDNA and plasmid pBV220 were ligated at BamH I and EcoR I sites to construct the expression vector. After transforming E.coli strain DH5alpha, the expression of the novel splicing hIL-13 gene was induced by shifting culture temperature from 30 degrees Celsius to 42 degrees Celsius. The expression product was then purified by chromatography on Sepharcryl-200 gel column, and the bioactivity was detected by MTT colorimetry on the growth of TF-1 cell line. RESULTS: The novel rhIL-13 was expressed in the form of inclusion bodies. After purification and renaturation, the specific activity of the novel rhIL-13 was 1.6x10(6) IU/mg. CONCLUSION: The novel rhIL-13 with biological activity has been obtained, which lays the foundation for treating cancer and septicemia by the cytokine in future.
The antinociceptive effect of interleukin-2 gene on rat carrageenan-induced pain was explored using different delivery methods. Intrathecal (i.t.) or plantar s.c. delivery of plasmid harbouring the interleukin-2 gene produced a marked antinociceptive effect, which was maintained up to 6 days; the administration of recombinant human interleukin-2 only had a transitory effect. The antinociceptive effect lasted longer and was more potent when the interleukin-2 gene was administered i.t. than when delivered s.c. The effect of the interleukin-2 gene was related to its protein expression, was dose dependent, and could be potentiated by liposome. The results suggest that the interleukin-2 gene has a good prospect for clinical use.
Heat shock protein 70 (HSP70), an antiapoptotic chaperon protein, is highly expressed in human breast tumors and renders them resistant to such therapy as hyperthermia. In the present study, we inhibited the expression of HSP70 by blocking the heat shock transcription factor 1 (HSF1) function with its dominant-negative mutant (mHSF1) in Bcap37 cells, a thermotolerant breast cancer cell line. Here we report that retrovirus-mediated transfer of mHSF1 led to massive cell death of Bcap37 after hyperthermia. mHSF1 sensitized Bcap37 cells to hyperthermia by promoting apoptosis induced by heat shock. We also examined the efficacy of mHSF1 gene therapy in the nude mouse. mHSF1 transfection led to diminution of tumor growth with hyperthermia therapy. Thus, disrupting HSF1 in combination with hyperthermia may open new possibilities for treatment of cancers that have acquired resistance to heat treatment.
From Cyanotis arachnoidea C.B. Clarke, a new phytosterone named cyanosterone A (1), along with three known compounds--beta-ecdysone (2), ajugasterone C (3) and beta-sitosterol (4) were isolated. The structure of the new compound was determined as 3beta,14alpha,20R,22R-tetrahydroxy-5alpha-cholest-7-en-6-one on the basis of physicochemical properties and spectral analysis.
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Three new flavonol glycosides, kaempferol-3-O-(6-trans-caffeoyl)-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside (1), kaempferol-3-O-(6-trans-caffeoyl)-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside-7-O-beta-D-glucopyranoside (2), and kaempferol-3-O-(6-trans-p-coumaroyl)-beta-D-glucopyranosyl-(1 --> 2)-beta-D-glucopyranoside-7-O-beta-D-glucopyranoside (3), were isolated from the aerial part of Camptosorus sibiricus. Their structures were elucidated by spectroscopic methods, including 2D NMR spectral techniques.