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Biomedical subjects

Li Chen

Publications and source records attributed to Li Chen.

At least 271 records · Page 15Linked to original sources
PubMed2003

[The reverse effect on drug-resistance against tyrosine kinase inhibitor STI571 in mdr1 and bcr-abl positive leukemic cells].

To explore the possibility of leukemia cell line of both bcr-abl and mdr-1 positive were cross-resistant to tyrosine kinase inhibitor STI571 and its reversal way, the inhibitory effect of STI571 on K562-n/VCR cells was detected with MTT method and reverse effects of CsA, TAM, IFN-alpha and CsA cominated with IFN-alpha were observed. The results showed that K562-n/VCR cell line expressing bcr-abl and mdr1 positive was resistant to STI571, and could be reversed by 5.18, 1.82 and 1.67-fold respectively, when treated with CsA, TAM, and IFN-alpha. It could be reversed by 34.87-fold with combination of half-dose CsA and IFN-alpha. In conclusion, amplification of mdr1 gene may contribute to drug-resistance of bcr-abl positive leukemic cells against STI571. The reversal agents, CsA, TAM and IFN-alpha show obviously reverse effects on drug-resistance. The combination of half-dose of both CsA and IFN-alpha display stronger effect than the full dose of either.

Antineoplastic Agents↗
PubMed2003

Clinical study on therapeutic effect of acupuncture on Behcet's disease.

Forty-six cases of Behcet's disease were randomly divided into two groups. The 26 cases in the treatment group were treated by acupuncture and the 20 cases in the control group with the drugs. The level of L-chain (kappa) of IgM and the level of the trace element Zn were determined before and after treatment in the treatment group. The results showed that the recurrence rate in the treatment group was significantly lower than that in the control group (P < 0.01), and the differences in the level of L-chain (kappa) of IgM and level of Zn in the treatment group before and after treatment were very significant (P < 0.01). These two indexes tended to become normal after treatment.

Acupuncture Therapy↗
PubMed2003

[Cloning and structural analysis of 5'-flanking sequence of human hepatic stimulator substance (hHSS) gene].

Human hepatic stimulator substance (hHSS) is a newly identified growth-promoting factor in liver. HSS is capable of stimulating the hepatic regeneration in hepaectomized rats and promoting the growth of hepatic tumor cells. To understand and elucidate the regulation of hHSS on hepatocyte growth at genetic level, the 4,890 bp of 5'-flanking region of hHSS gene have been isolated and sequenced. On basis of comparison of the 5'-flanking sequences with GenBank, hHSS gene was localized on human chromosome 16. Transcriptional start site was identified by reverse transcriptase-polymerase chain reaction (RT-PCR) and 5' rapid amplification of cDNA end (5'RACE). The initiation nucleotide was defined as 'C', which located at 254 bp upstream of the reported sequence of exon I.

5' Flanking Region↗
PubMed2002

Investigating the importance of proteasome-interaction for Rad23 function.

Rad23 contributes to diverse cellular functions that include DNA repair, stress response and growth control. An amino-terminal ubiquitin-like (UbL) domain in Rad23 interacts with catalytically active proteasomes and internal sequences bind multi-ubiquitinated proteins. Rad23 regulates the assembly of substrate-linked multi-ubiquitin chains, promotes efficient degradation of model substrates, and plays an overlapping role with the proteasome subunit, Rpn10. These and other results led to the hypothesis that Rad23 translocates proteolytic substrates to the proteasome to promote degradation. It was previously shown that the UbL domain in Rad23 could be functionally replaced by ubiquitin. However, monomeric ubiquitin does not bind the proteasome efficiently, and we therefore investigated whether proteasome interaction was required for all Rad23 functions. We report here that the ubiquitin moiety in Ub-rad23 is ubiquitinated in vivo and could provide an alternate mechanism for binding the proteasome. These results suggest that the localization of Rad23 to the proteasome, either by its UbL domain, or following ubiquitination of an amino-terminal ubiquitin moiety (Ub-rad23), is necessary for full activity.

Carrier Proteins↗
PubMed2002

Proteolysis of a nucleotide excision repair protein by the 26 S proteasome.

The 26 S proteasome degrades a broad spectrum of proteins and interacts with several nucleotide excision repair (NER) proteins, including the complex of Rad4 and Rad23 that binds preferentially to UV-damaged DNA. The rate of NER is increased in yeast strains with mutations in genes encoding subunits of the 26 S proteasome, indicating that it could negatively regulate a repair process. The specific function of the 26 S proteasome in DNA repair is unclear. It might degrade DNA repair proteins after repair is completed or act as a molecular chaperone to promote the assembly or disassembly of the repair complex. In this study, we show that Rad4 is ubiquitylated and that Rad23 can control this process. We also find that ubiquitylated Rad4 is degraded by the 26 S proteasome. However, the interaction of Rad23 with Rad4 is not only to control degradation of Rad4, but also to assist in assembling the NER incision complex at UV-induced cyclobutane pyrimidine dimers. We speculate that, following the completion of DNA repair, specific repair proteins might be degraded by the proteasome to regulate repair.

DNA Ligases↗
PubMed2002

Effects of pH on survival, phosphorus concentration, adenylate energy charge and Na(+)-K(+) ATPase activities of Penaeus chinensis Osbeck juveniles.

Penaeus chinensis (Osbeck) juveniles were maintained for 14 days at pH 6.0, 7.0, 7.6, 8.0 and 8.5, respectively. The effects of pH on survival, phosphorus concentration, adenylate energy charge (AEC) and Na(+)-K(+) adenosine triphosphatase (ATPase) activities of prawns were investigated. The results showed that survival of P. chinensis was impaired at low and high pH levels. The total phosphate level and AEC in abdominal muscle increased with pH level in range of 6.0-7.6 reaching the maximum values at pH 7.6. Thereafter, the levels declined with increasing pH level in range of 7.6-8.5. The change of Na(+)-K(+) ATPase activity in gill of prawn was similar to that of total phosphorus content and AEC in muscle of prawn at different pH. The effect of pH on Na(+)-K(+) ATPase activity in the muscle was lower than on that in gill.

Animals↗
PubMed2002

N-Cycloalkanoyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.

A systematic structure-activity relationship investigation of the lead compound 1 resulted the identification of several N-[(substituted alkyl)cycloalkanoyl]-4-[((2,6-dichlorophenyl)carbonyl)amino]-L-phenylalanine derivatives as potent VCAM/VLA-4 antagonists. The data are consistent with a model of these compounds in which these alkanoylphenylalanines reside in a compact gauche (-) bioactive conformation.

Crystallography, X-Ray↗
PubMed2002

N-Aroyl-L-phenylalanine derivatives as VCAM/VLA-4 antagonists.

A series of N-benzoyl-4-[(2,6-dichlorobenzoyl)amino]-L-phenylalanine derivatives was prepared in order to optimize the substitution on the N-benzoyl moiety for VCAM/VLA-4 antagonist activity. Disubstitution in the 2- and 6-positions is favored and a range of small alkyl and halogen are tolerated. A model of the bioactive conformation of these compounds is proposed.

Heterocyclic Compounds↗
PubMed2002

Structure-activity relationship of linear peptide Bu-His-DPhe-Arg-Trp-Gly-NH(2) at the human melanocortin-1 and -4 receptors: arginine substitution.

A series of pentapeptides, based on Bu-His(6)-DPhe(7)-Arg(8)-Trp(9)-Gly(10)-NH(2) and modified at the Arg(8) position, was prepared and pharmacologically characterized. Peptides containing either cyanoguanidine or acylguanidine, two substantially less basic arginine surrogates, were found to retain the agonist activity of the parent peptide at both hMC1R and hMC4R. This study unequivocally shows that the positive charge of Arg(8) is not essential for efficient interactions of our pentapeptide with both hMC1R and hMC4R.

Amino Acid Substitution↗
PubMed2002

Two essential regions for tRNA recognition in Bacillus subtilis tryptophanyl-tRNA synthetase.

Bacillus subtilis tryptophanyl-tRNA synthetase (TrpRS) is a homodimeric enzyme. A model for its ability to recognize tRNA(Trp) in B. subtilis was proposed by using computer modelling. This was based on the the fact that there is high homology among bacterial TrpRSs [Chen, Jiang, Jin and Wang (2001) Acta Biochim. Biophys. Sinica 33, 687-690], in which the enzyme dimer binds to two tRNA(Trp) molecules and each tRNA(Trp) is bound to two different domains across the surface of the dimer. In this work, three deletion mutants of TrpRS were constructed and their products were purified. After determining the kinetic parameters of the mutants in the two-step reaction, it was found that the relative activities of wild-type and mutant enzymes had changed little in the ATP-pyrophosphate exchange reaction. In contrast, the activities of three mutant proteins were much decreased in the tRNA(Trp) aminoacylation assay. Deletion of residues 108-122 and residues 234-238 caused 44% and 80% reductions in the activity, respectively. When both regions were deleted, the aminoacylation activity of the TrpRS mutant was too low to be determined using tRNA(Trp) at the limiting concentration. Gel-retardation assays showed that the acceptor minihelix and the anticodon microhelix were recognized by the domains of TrpRS spanning residues 108-122 and residues 234-238 respectively. In addition, the deletion of amino acids 234-238 affected the normal induced expression of TrpRS at 37 degrees C. In conclusion, residues 108-122 and 234-238 were found essential for tRNA(Trp) recognition.

Adenosine Triphosphate↗
PubMed2002

Only the large soluble form of preadipocyte factor-1 (Pref-1), but not the small soluble and membrane forms, inhibits adipocyte differentiation: role of alternative splicing.

We originally identified preadipocyte factor-1 (Pref-1) as an inhibitor of adipogenesis by the fact that constitutive expression of full-length Pref-1A inhibits differentiation of 3T3-L1 cells into adipocytes. Subsequently, we found that the membrane form of Pref-1 is proteolytically processed at two sites in the extracellular domain, resulting in the larger (50 kDa) and smaller (25 kDa) soluble forms. A specific form(s) of Pref-1, which is active in inhibiting adipocyte differentiation, has not been elucidated. Here, various artificial constructs and alternative-splicing variants of Pref-1 were stably transfected into 3T3-L1 cells, or conditioned media from COS cells transfected with the various forms were added into differentiating 3T3-L1 cells. Judging by Oil Red O staining for lipid accumulation and expression of adipocyte markers, we determined that, unlike the full-length Pref-1A and the constructed large soluble form, the artificial membrane form of Pref-1 lacking the processing site proximal to the membrane was not effective in inhibiting adipogenesis. Furthermore, conditioned media from COS cells transfected with the construct containing only the first three epidermal growth factor repeats, corresponding to the small soluble form, was not effective in inhibiting adipocyte differentiation. Of the four alternative-splicing products, Pref-1A and Pref-1B, which generate both large and small soluble forms, inhibited adipogenesis, whereas Pref-1C and Pref-1D, which lack the processing site proximal to the membrane and therefore generate only the smaller soluble form, did not show any effect. We conclude that only the large soluble form, and not the transmembrane or the small soluble form, of Pref-1 is biologically active and that alternative splicing therefore determines Pref-1 function in adipocyte differentiation.

3T3 Cells↗
PubMed2002

[Combination of mycophenolate mofetil with cyclosporine A and methotrexate for the prophylaxes of acute graft versus host disease in allogeneic peripheral stem cell transplantation].

OBJECTIVE: To evaluate the efficacy of combination of mycophenolate mofetil (MMF) with cyclosporine (CsA) and methotrexate (MTX) on prophylaxes of acute graft-versus-host disease (GVHD) in HLA-matched allogeneic peripheral blood stem cell transplantation (allo-PBSCT). METHODS: Thirty-nine patients with acute leukemia (n = 21) and chronic myeloid leukemia (n = 17) and severe aplastic anemia (n = 1) were treated with allo-PBSCT from HLA matched siblings (n = 36) or unrelated donors (n = 3). Twenty-six patients were in CsA + MTX group. CsA was given at a dosage of 2 mg.kg(-1).d(-1) by continuous intravenous injection for 24 h, since on day(-1) and injection of CsA was changed to oral administration of CsA around day 18. CsA was tapered by 10% per week after day + 90. MTX was given at the dosage of 15 mg at day + 1, and 10 mg at day + 3, + 6 and + 11, respectively. Thirteen patients were included in MMF + CsA + MTX group with the same dosage of CsA and MTX as above but omitted at day + 11. MMF of 2 g/day was added orally from day + 1 to day + 28 post transplantation. RESULTS: All patients in both groups were successfully engrafted. The days of recovery of neutrophils and platelets were not significantly different between two groups (P > 0.05). The incidence of acute GVHD in MMF + CsA + MTX group (7.6%) was significantly lower than that in CsA/MTX group (46.2%, P < 0.05). Incidence of grade II approximately IV GVHD in MMF group was 0 while that in control group was 23.0%. The incidence of severe mucositis was lower in MMF group (15.4%) than in the control group (30.8%) (P < 0.05). CONCLUSION: The regimen of MMF + CsA + MTX for prevention of acute GVHD in allo-PBSCT is more efficient than that of CsA + MTX, without adversely affecting the engraftment and relapse rate.

Acute Disease↗
PubMed2002

Mutational analysis of the enterocin favorskii biosynthetic rearrangement.

[reaction: see text] A mutational analysis of the enterocin biosynthesis genes revealed that the putative oxygenase and the methyltransferase gene products EncM and EncK, respectively, jointly catalyze a biosynthetic Favorskii-like rearrangement. Inactivation of either gene terminated enterocin production and caused the accumulation of four nonrearranged, nonmethylated polyketides. The structure elucidation of the new wailupemycins E-G is reported.

Bridged-Ring Compounds↗
PubMed2002

[Increased resistance against oxidant-induced injury in the rat vascular smooth muscle cells transfected with human heme oxygenase-1 gene].

The heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme metabolism, has been recently defined as a novel stress-stimulated protein, since the intracellular expression of HO-1 in response to various stimuli as oxidation, ischemia and endotoxin injury has been proved to be able to protect the cells from damage. In this study, a retroviral vector containing human HO-1 gene was constructed and transfected to rat vascular smooth muscle cells (VSMCs). Using Southern and Northern blot analyses, the integration and mRNA expression of HO-1 gene in the transfected cells were confirmed. The profound protein expression of HO-1 as well as HO enzyme activity in the transfected cells increased by 1.8-fold and 2.0-fold respectively as compared with the non-transfected cells. It was found that the HO-1 transfected-VSMCs presented dominant resistance to toxicity produced by exposure to H2O2, as a significant protective effect of HO-1 marked by cell survival and LDH leakage was observed when 200, 400 and 600 micromol/L of H2O2 were used. The protection of HO-1 rapidly declined after the transfected-VSMCs were pretreated 24 h with an HO-1 specific inhibitor (ZnPP-IX). The results of this investigation suggest that the functional expression of HO-1 gene within VSMCs raises an alternative ability to protect the vascular cells against active oxygen injury.

Animals↗
PubMed2002

[Prokaryotic expression and purification of human hepatic stimulator substance].

To explore the possibility of prokaryotic expression of human hepatic stimulator substance (hHSS), hHSS gene was inserted in the downstream of glutathion S-transferase (GST) in a pET-42a expression vector and recombinant GST-hHSS fusion protein was expressed under IPTG induction in BL-21(DE3) cells. The recombinant HSS was purified with His.Tag affinity chromatography, and its bioactivity was analyzed. The results showed that GST-hHSS fusion protein was expressed both as a soluble or a inclusive body in bacterial cytosol. The soluble GST-hHSS expression reached up to 30% of the whole soluble protein of bacteria as determined by densitometry. The cleavage of GST-hHSS fusion protein with Factor Xa produced two fragments of the protein, which sized 33 and 15 kD, respectively. The molecular weight of recombinant HSS protein was identical to theoretical deduction based on the DNA sequences. The protein homology of 15 kD hHSS could be efficiently eluted out after Factor Xa cleavage. It is further indicated that the recombinant hHSS is able to proliferate hepatoma cells of BEL-7402 in the preliminary experiments.

Cell Division↗
PubMed2002

N-acyl-L-phenylalanine derivatives as potent VLA-4 antagonists that mimic a cyclic peptide conformation.

A series of N-benzylpyroglutamyl-L-phenylalanine derivatives bearing carbamoyl substituents in the 3- or 4-positions was prepared and assayed for inhibition of the interaction between VCAM and VLA-4. Potent inhibition was observed in a number of analogues with substitution in the 4-position favored over the 3-position. A crystal structure of the key intermediate 25 indicates that it accesses a low energy conformation which closely matches key pharmacophores of a structurally characterized cyclic peptide.

Cell Line↗