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Biomedical subjects

Hao Chen

Publications and source records attributed to Hao Chen.

154 records · Page 9Linked to original sources
PubMed2002

In vivo pharmacokinetic features, toxicity profile, and chemosensitizing activity of alpha-cyano-beta-hydroxy-beta- methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13), a novel antileukemic agent targeting Bruton's tyrosine kinase.

The purpose of the present study was to examine the in vivo pharmacokinetics and activity of alpha-cyano-beta-hydroxy-beta-methyl-N-(2,5-dibromophenyl)propenamide (LFM-A13), a novel antileukemic agent targeting Bruton's tyrosine kinase (BTK). We have applied an analytical high-performance liquid chromatography method for the quantitative detection of LFM-A13 in plasma samples. Our findings indicate that LFM-A13 is quickly absorbed, with the time required to reach the maximum plasma drug concentration (t(max)) being 10-18 min after i.p. administration with nearly complete bioavailability. LFM-A13 had an elimination half-life of 17-32 min after i.p. administration at dose levels of 10-50 mg/kg. LFM-A13 exhibited a dose-dependent and significant increase in the values of normalized area under the curve and maximum concentration (C(max)) as well as a dose-dependent and significant decrease in clearance values, suggesting a saturable clearance mechanism. LFM-A13 was not toxic to mice when administered systemically at dose levels ranging from 10 to 80 mg/kg. Highly effective BTK-inhibitory and apoptosis-promoting plasma concentrations of LFM-A13 could be achieved in mice without toxicity. LFM-A13 exhibited a favorable pharmacokinetic behavior that was not adversely affected by the standard chemotherapy drugs vincristine, methylprednisolone, or L-asparaginase (when used as combination treatment, VPL) and significantly improved the chemotherapy response and survival outcome of mice challenged with BCL-1 leukemia cells. Whereas only 14% of mice treated with the standard triple-drug combination VPL became long-term survivors, 41% of mice treated with this combination plus LFM-A13 survived long-term. LFM-A13 prolonged the median survival time of VPL-treated mice from 37 to 58 days. Our results confirm and extend previous studies regarding the role of BTK chemotherapy resistance of B-lineage leukemic cells (S. Mahajan et al., J. Biol. Chem., 274: 9587-9599, 1999). BTK inhibitors such as LFM-A13 may be useful as a new class of chemosensitizing and apoptosis-promoting antileukemic agents for treatment of patients with chemotherapy-resistant B-lineage leukemias or lymphomas.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed2002

[Whether the impairment of grafted liver was induced by the inflammatory cells in cold and warm ischemia after transplantation].

OBJECTIVE: To investigate whether the impairment of grafted liver after transplantation was induced by the same inflammatory cells in cold and warm ischemia. METHODS: Male SD rats were divided into two groups randomly, 24 grafted livers in each group were stored for 120 or 240 min at 4 degrees Centigrade Ringer's solution. Also male SD rats were divided into three groups, in which 24 grafted livers in each group were experienced warm ischemia ranged from 90, 120 to 150 min from non-heart-beating donor. The recipients were killed after 1, 3, 6, and 24 hours of transplantation for sample collection. RESULTS: Along with the prolongation of cold and warm ischemia time, the serum ALT and AST levels were increased gradually after transplantation. Light microscopy showed some necroses in hepatocytes after 3 and 6 hours of transplantation in cold ischemia, and some neutrophilic infiltration in sinusoids. There were a large number of hepatocytes necroses after 3, 6 hours of transplantation in warm ischemia from non-heart-beating donor and a lot of lymphocytic infiltration in sinusoids. The findings in electron microscopy were as the same as those found in light microscopy, and the lymphocytes which infiltrated in sinusoids in warm ischemia were identified as T lymphocytes in electron microscopy. CONCLUSIONS: The impairment of grafted livers after transplantation seems to be induced by two different inflammatory cells in cold and warm ischemia, that is, neutrophils mediate the cold ischemia-reperfusion, and T lymphocytes mediate the warm ischemia-reperfusion from non-heart-beating donor.

Alanine Transaminase↗
PubMed2002

[Extraction and gas chromatographic analysis of residual trimethylamine(TMA) in the bakelite-type macromolecule complex material].

A method for the determination of residual TMA in the bakelite-type macromolecule complex material has been established. The whole process includes sample pretreatment, TMA extraction and GC analysis. After the samples have been pretreated, the TMA in them was extracted at (38 +/- 2) degrees C for 16 hours. Then the content of TMA in the liquid can be determined directly. From the experimental results we can conclude that the whole method is cheap, simple and accurate. It meets the requirement of microanalysis and can be used to determine real samples.

Air Pollutants↗
PubMed2002

[Community constitute and phylogenetic analysis on soil uncultured microorganism].

Many evidences show bachteria that can be cultured in lab are only the minority of germs existing in nature. Most of bacteria, containing rich valuable gene resource, are unknown for they are uncultured. To research these uncultured bacteria, Directly extract crude DNA from farm soil, separate 16S rDNA mixture amplified by PCR from the crude DNA, sequence it and compare the sequences with the records of NCBI to classify the germs. The significant microbe community difference from respective soil, which have possibility in developing a new tool for researching soil bacteria diversity were finded.

Bacteria↗
PubMed2002

[Fingerprint analyses of fructus Forsythiae].

OBJECTIVE: To provide application basis of the Forsythia suspensa by studying the difference of HPLC-FP of F. suspensa fructification (medicinal materials). METHOD: Comparative work was done on F. suspensa produced in different areas, on different parts of Forsythia suspensa, and on the pseudo preducts with methods of HPLC-FP. RESULT: Different FP characteristics were shown respectively by different samples, which were from different producing areas, from different parts, and the pseudo products including the fructification of Syringa reticulata var. and F. viridissimac. CONCLUSION: The FP can be used to distinguish the F. suspensa coming from different producing areas and different sources.

Chromatography, High Pressure Liquid↗
PubMed2002

[The application of inductively coupled plasma atomic emission spectrometry/mass spectrometry in the trace elements and speciation analysis of traditional Chinese Medicine].

A review on the content and speciation analysis of trace element in traditional chinese medicine (TCM) by ICP-AES/MS was presented. The study is mainly focused on the following subjects: sample digestion techniques; determination and speciation analysis of trace elements. The development trend of this area in the near future is briefly introduced. 58 references are cited. The results show that the microwave digestion techniques is a idea pretreatment method of sample for tradition chinese medicine; ICP-AES/MS and all kinds of hyphenated techniques for atomic optical/mass spectrometry/chromatography are very useful for the determination and speciation analysis of trace elements in TCM.

Drug Contamination↗
PubMedDate not supplied

Virtual screening of novel noncovalent inhibitors for SARS-CoV 3C-like proteinase.

The SARS coronavirus 3C-like proteinase is considered as a potential drug design target for the treatment of severe acute respiratory syndrome (SARS). Owing to the lack of available drugs for the treatment of SARS, the discovery of inhibitors for SARS coronavirus 3C-like proteinase that can potentially be optimized as drugs appears to be highly desirable. We have built a "flexible" three-dimensional model for SARS 3C-like proteinase by homology modeling and multicanonical molecular dynamics method and used the model for virtual screening of chemical databases. After Dock procedures, strategies including pharmocophore model, consensus scoring, and "drug-like" filters were applied in order to accelerate the process and improve the success rate of virtual docking screening hit lists. Forty compounds were purchased and tested by HPLC and colorimetric assay against SARS 3C-like proteinase. Three of them including calmidazolium, a well-known antagonist of calmodulin, were found to inhibit the enzyme with an apparent K(i) from 61 to 178 microM. These active compounds and their binding modes provide useful information for understanding the binding sites and for further selective drug design against SARS and other coronavirus.

Binding Sites↗
PubMedDate not supplied

Improving the quality of 3D-QSAR by using flexible-ligand receptor models.

To address the problems associated with molecular conformations and alignments in the 3D-QSAR studies, we have developed the Flexible Ligand - Atomic Receptor Model (FLARM) 2.0 method. The FLARM 2.0 method has three unique features as compared to other pseudoreceptor model methods: (1) the training ligands are flexibly optimized inside the receptors to achieve minimal docking energies; (2) the receptor atoms are spatially moveable in the process of genetic evolving in order to avoid improper initial receptor shapes; and (3) void receptor sites are specially favored in order to obtain open receptor models that allow large gaps. Advantages of an open model include less noise information, a smaller risk of overfitting, and ease of locating the key interaction sites. The latter two features, inherited from the previous FLARM 1.0 method, can improve the predictive ability of the 3D-QSAR models, while the first feature is newly implemented to relieve the uncertainty caused by improper conformation and alignment. Three FLARM 2.0 case studies were performed, and the results show that FLARM 2.0 models are highly predictive and robust. FLARM 2.0 pseudoreceptor models can correspond well with the pharmacophore models and/or the binding sites of the real protein receptors.

Algorithms↗