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Biomedical subjects

Xin Hu

Publications and source records attributed to Xin Hu.

At least 37 records · Page 2Linked to original sources
PubMed2005

The application of inductively coupled plasma mass spectrometry in pharmaceutical and biomedical analysis.

With the development of life science, pharmaceutical and biomedical analysis becomes more and more important in medical science. Further studies will be hopefully established if it is possible to use inorganic elemental standards or small organic compounds in the quantitative determination of all kinds of drugs, nucleotides and sulfur or phosphorus containing peptides and proteins at appropriate concentration with an acceptable accuracy. Since 1980, inductively coupled plasma mass spectrometry (ICP-MS) has emerged as a new and powerful analytical technique which is suitable for element and isotope analysis. It offers extremely wide detection range of element and co-analysis of most elements in the periodic table. Also, it can be applied to perform qualitative, semiquantitative, and quantitative analysis and isotopic ratios through mass-to-electric charge ratio. With the help of ICP-MS, the struggle of searching for an excellent quantification technique in, e.g. drugs and proteomics has come appreciably close to an end. This review mainly focuses on the introduction of application of ICP-MS in pharmaceutical and biomedical analysis. Some problems in application and the handling strategies are simply presented at the end.

Biomedical Technology↗
PubMed2005

Interaction between Polyamines and the Mitogen-Activated Protein Kinase Pathway in the Regulation of Cell Cycle Variables in Breast Cancer Cells.

Inhibition of polyamine biosynthesis with alpha-difluoromethylornithine (DFMO) has been shown to inhibit proliferation of breast cancer cells although its mechanism of action has not been fully elucidated. To address this issue, we tested the effects of DFMO on cell cycle variables of MDA-MB-435 human breast cancer cells in culture. We also focused on the possible mediatory role of the mitogen-activated protein kinase (MAPK) pathway on the cell cycle effects of DFMO because this compound has been shown to activate MAPK signaling. We found that DFMO caused a p53-independent increase in p21 and its association with cyclin-dependent kinase (cdk)-2 and decreased cdk-2 protein as well as its phosphorylation on Thr160. In addition, DFMO markedly suppressed the expression of the full-length and low molecular weight forms of cyclin E. These effects of DFMO were reversible with exogenous putrescine, thus indicating that they are specifically mediated through polyamine depletion. Cdk-2 activity was drastically reduced in DFMO-treated breast cancer cells which exhibited a reduction in retinoblastoma (Rb) phosphorylation and protein. As a predictable consequence of these effects, DFMO caused a G1-S block. In addition, DFMO inhibited G2-M transition, most likely as a result of its induction of p21 expression. Inhibition of the MAPK pathway with PD98059 or U0126 blocked the DFMO-induced induction of p21 and the reduction of cdk-2 protein. PD98059 reversed the G2-M block induced by DFMO (probably as a result of suppression of p21) but not the G1-S arrest. MDA-MB-435 cells treated with PD98059 or U0126 in the presence and absence of DFMO exhibited a marked increase in the expression of p27 and its association with cdk-2, a decrease in phosphorylation of cdk-2 on Thr160, and a decrease in cyclin E expression. As predicted, PD98059 treatment reduced cdk-2 activity and Rb phosphorylation while reversing the decrease in Rb protein induced by DFMO. Neither DFMO nor PD98059, either alone or in combination, reduced cdk-4 activity despite a marked induction in p15 expression caused by DFMO. Our results indicate that activation of the MAPK pathway accounts for some of the effects of DFMO on cell cycle events of breast cancer cells. Inhibition of the MAPK pathway, however, does not reverse the cell cycle arrest induced by DFMO because of activation of alternative mechanisms leading to suppression of cdk-2 activity.

Breast Neoplasms↗
PubMed2005

Total concentrations and fractions of Cd, Cr, Pb, Cu, Ni and Zn in sewage sludge from municipal and industrial wastewater treatment plants.

Heavy metals are one of the important factors that affect the final disposal of sewage sludge. In this paper, the metal mobility and bioavailability of heavy metals in sewage sludge were studied by using Community Bureau of Reference (BCR) sequential extraction procedure to get more information for the reasonable disposal of sludge. Sewage sludge was collected from five municipal wastewater treatment plants and three industrial wastewater treatment plants. The sludge was examined for and the total concentrations and different chemical fractions of Cd, Cr, Pb, Cu, Ni and Zn. The total metal concentrations of heavy metals in sludge varied greatly. The contents of Zn and Cu were the highest, followed by then Cr, Ni and Pb and the content of Cd was the least. There was no significant difference in total metal concentration between municipal and industrial wastewater treatment plants. Fractions extracted by the BCR sequential procedure were acid soluble/exchangeable, reducible and oxidizable fraction. Sludge pH was found to have profound effect on the chemical fractions of heavy metals. Acidic sludges (Xiamen and Jinlin Petrochemical Group Co., wastewater treatment plant) had higher proportion of the acid soluble/exchangeable fractions than in neutral sludge. In neutral sludges, Pb and Cr were principally distributed in between the oxidizable fraction and the residual fraction; Cu was in the oxidizable fraction; Cd mainly in the residual fraction in municipal wastewater treatment plants and had high percentage of acid soluble/exchangeable and reducible fractions in industrial wastewater treatment plants; Ni and Zn had higher percentage in the acid soluble/exchangeable and the oxidizable fraction.

Environmental Monitoring↗
PubMed2005

Molecular docking and 3D-QSAR studies of Yersinia protein tyrosine phosphatase YopH inhibitors.

Three-dimensional quantitative structure-activity relationship (QSAR) studies were conducted on two classes of recently explored compounds with known YopH inhibitory activities. Docking studies were employed to position the inhibitors into the YopH active site to determine the probable binding conformation. Good correlations between the predicated binding free energies and the inhibitory activities were found for two subsets of phosphate mimetics: alpha-ketocarboxylic acid and squaric acid (R2=0.70 and 0.68, respectively). The docking results also provided a reliable conformational alignment scheme for 3D-QSAR modeling. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were performed based on the docking conformations, giving q2 of 0.734 and 0.754 for CoMFA and CoMSIA models, respectively. The 3D-QSAR models were significantly improved after removal of an outlier (q2=0.829 for CoMFA and q2=0.837 for CoMSIA). The predictive ability of the models was validated using a set of compounds that were not included in the training set. Mapping the 3D-QSAR models to the active site of YopH provides new insight into the protein-inhibitor interactions for this enzyme. These results should be applicable to the prediction of the activities of new YopH inhibitors, as well as providing structural implications for designing potent and selective YopH inhibitors as antiplague agents.

Bacterial Outer Membrane Proteins↗
PubMed2005

Effects of polyamine synthesis inhibitors on primary tumor features and metastatic capacity of human breast cancer cells.

We have previously reported that inhibition of polyamine biosynthesis with alpha-difluoromethylornithine (DFMO) reduces pulmonary metastasis from MDA-MB-435 human breast cancer xenografts without affecting the volume of the primary tumors (Manni et al. Clin Exp Mets 20:321, 2003). In these experiments, we show that DFMO treatment (2% in drinking H(2)O) reduced the growth fraction of the primary tumors by 60%. However, this effect was counter-balanced by a similar reduction in non-apoptotic necrosis, thus accounting for the preservation of tumor volume in DFMO-treated mice. DFMO treatment caused a 4-fold increase in cytoplasmic staining for cleaved caspase-3 (as opposed to the nuclear staining observed in control tonsil tissue) in the absence of histologic evidence of apoptosis. DFMO treatment reduced the number of mice with pulmonary metastasis by approximately 80% and the number of metastasis per mouse by >90% in association with a reduction in invasiveness of the primary tumor in the surrounding dermis and muscle by approximately 30%. DFMO treatment increased ERK phosphorylation in the tumors, an effect that has been found by us in vitro to be causally linked to the anti-invasive effect of the drug (Manni et al. Clin Exp Metast 2004; 21: 461]. DFMO also increased tyrosine phosphorylation of STAT-3 and expression of STAT-1 and JNK proteins. Administration of SAM486A (1 mg/kg/i.p. daily), an inhibitor of S-adenosylmethionine decarboxylase, either individually or in combination with DFMO, was not found to exert any biological or biochemical effects, most likely as a result of its failure to suppress tissue polyamine levels under these experimental conditions.

Amidines↗
PubMed2005

[Study on fingerprint of unfinished product of Nauclea injection].

OBJECTIVE: To establish HPLC fingerprints of unfinished product of Nauclea injection. METHOD: A high performance liquid chromatography assay was developed with an Agilent-Extend C18 column, a gradient elution:water-5% acetonitrile (10 min), 5% acetonitrile-10% acetonitrile (10-60 min), 50% acetonitrile-water (60-70 min), a 0.7 mL x min(-1) flow rate, at detection wavelength, 245 nm within a 70 min total elution time. RESULT: The RSD of relative retention time and peak area of coexist peaks meet to method requirement during the investigation of precision, stability and repeatibity trials. All of the 10 batches of samples share a high similarity. CONCLUSION: This method can be used to control the quality of unfinished product of Nauclea injection.

Chromatography, High Pressure Liquid↗
PubMed2005

[The effect of acetylcholine and atropine on proliferation and differentiation and mAchR1 expression of human SK-N-SH cells].

The SK-N-SH human neuroblastoma cells were treated with acetylcholine (Ach) and atropine (Atro), the proliferation activity of cells was detected by CCK-8 method and the cell cycle distribution was determined by flow cytometry. The changes of the mRNA and protein of mAchR1 and c-fos were analysed by fluorescence quantitative PCR, western blot and flow cytometry indirect-immunofluorescence. Results showed 1 mmol/L Ach could significantly stimulate the proliferation of SK-N-SH cells and 1 mmol/L Atro could prevent SK-N-SH cells from S phase growing into G2/M phase; 1 mmol/L Ach and 1 mmol/L Atro had feedback adjustment on the protein level of mAchR1, but had no significant effect on mRNA level of mAchR1. 1 mmol/L Ach increased the both levels of mRNA and protein of Fos obviously, this effect was reversed by Atro. All phenomena clue us cholinergic receptors joining the events of cell proliferation.

Acetylcholine↗
PubMed2005

[In vitro and in vivo pharmaceutical behaviors of lycopene microcapsules].

AIM: To evaluate in vitro release of lycopene microcapsules. Pharmacokinetic parameters of lycopene microcapsule and lycopene powder as reference were estimated after a single dose of oral administration to dogs. The relationship between in vitro dissolution and in vivo absorption was investigated. METHODS: The content of lycopene in the release medium was determined by UV spectroscopy method. Health hybrid male dogs were used as experiment subjects and lycopene powder used as standard to estimate the pharmacokinetics of lycopene microcapsules. HPLC method was used to assay the concentration of lycopene in dog plasma. Pharmacokinetics parameters were estimated by 3P87 program. The drug release percentage in stimulated intestinal fluid was compared with the absorption at a given time point. RESULTS: The release profiles of lycopene from microcapsule showed that the lycopene gelatin microcapsule exhibited enteric property. The pharmacokinetics parameters estimated after oral administration of lycopene powder and lycopene microcapsule in a single dose of 2.5 mg x kg(-1) body weight to dogs were 7.30 h, 15.06 h for T1/2alpha; 28.10 h, 46.76 h for T1/2beta; 22.32 h, 41.03 h for T(max); 1.67 microg x h x L(-1), 2.08 microg x h x L(-1) for AUC(0-infinity), respectively. The concentration-time curves could be fitted to a two-compartment model for both the lycopene powder and the lycopene microcapsule analyzed by 3P87 program. The relationship between in vitro dissolution and in vivo absorption was found to have good correlation (r = 0. 981 9) was found. CONCLUSION: It could be concluded that lycopene microcapsule was a sustained release dosage form. The result of release in vitro could be used to predict the absorption in vivo.

Administration, Oral↗
PubMed2004

Preparation of single rice chromosome for construction of a DNA library using a laser microbeam trap.

We report the development of a laser micromanipulation system and its application in the isolation of individual rice chromosomes directly from a metaphase cell. Microdissection and flow sorting are two major methods for the isolation of single chromosome. These methods are dependent on the techniques of chromosome spread and chromosome suspension, respectively. In the development of this system, we avoided using chromosome spread and cell suspension was used instead. The cell wall of metaphase rice cell was cut by optical scissors. The released single chromosome was captured by an optical trap and transported to an area without cell debris. The isolated single chromosome was then collected and specific library was constructed by linker adaptor PCR. The average insert size of the library was about 300 bp. Two hundred inserts of chromosome 4 library were sequenced, and 96.5% were aligned to the corresponding sequences of rice chromosome 4. These results suggest the possible application of this method for the preparation of other subcellular structures and for the cloning of single macromolecule through a laser microbeam trap.

Chromosomes, Plant↗
PubMed2004

Comprehensive vertical sample-based KNN/LSVM classification for gene expression analysis.

Classification analysis of microarray gene expression data has been widely used to uncover biological features and to distinguish closely related cell types that often appear in the diagnosis of cancer. However, the number of dimensions of gene expression data is often very high, e.g., in the hundreds or thousands. Accurate and efficient classification of such high-dimensional data remains a contemporary challenge. In this paper, we propose a comprehensive vertical sample-based KNN/LSVM classification approach with weights optimized by genetic algorithms for high-dimensional data. Experiments on common gene expression datasets demonstrated that our approach can achieve high accuracy and efficiency at the same time. The improvement of speed is mainly related to the vertical data representation, P-tree,Patents are pending on the P-tree technology. This work is partially supported by GSA Grant ACT#:K96130308. and its optimized logical algebra. The high accuracy is due to the combination of a KNN majority voting approach and a local support vector machine approach that makes optimal decisions at the local level. As a result, our approach could be a powerful tool for high-dimensional gene expression data analysis.

Algorithms↗
PubMed2004

A practical approach to docking of zinc metalloproteinase inhibitors.

Forty zinc-dependent metalloproteinase/ligand complexes with known crystal structures were re-docked using five docking/scoring approaches (DOCK, FlexX, DrugScore, GOLD, and AutoDock). Correct geometry of the coordination bonds between the ligand's zinc binding group (ZBG) and the catalytic zinc is important for docking accuracy and scoring reliability. More than 75% of docked poses with RMSD less than 2A were found to have appropriate ZBG binding, but for poor ZBG binding, about 95% of poses failed to dock correctly. Elimination of poses with inappropriate zinc binding resulted in better binding energy predictions that were further improved by dividing the ligands into subsets according to the ZBG (carboxylates, hydroxamates, and phosphorus containing groups). After a subset re-scoring using the regression functions obtained for individual subsets, DrugScore was able to explain 77% and the consensus scoring scheme X-CSCORE even 88% of variance in binding energies. The approach combining ZBG-based pose selection and subset re-scoring improved the hit rate in virtual screening for metalloproteinase inhibitors for all tested methods by 4-16%.

Algorithms↗
PubMed2004

Computational analysis of tyrosine phosphatase inhibitor selectivity for the virulence factors YopH and SptP.

Bacterial pathogens such as Yersinia and Salmonella represent an important medical concern, causing human diseases ranging from gastrointestinal disease to the plague. The development of novel treatments of these bacterial infections has gained high priority recently due to the emergence of antibiotic resistance in these pathogens and the threat of the use of microbial agents as biological weapons. YopH of Yersinia and SptP of Salmonella are virulence factors that belong to the family of protein tyrosine phosphatases (PTPs). A great challenge remains in the design of selective PTPs inhibitors due to their highly conserved active site. In this paper, we present a comparative docking study to probe the selective inhibition of YopH and SptP with PTP1B in order to better understand their binding interactions with the bacterial tyrosine phosphates. Characterized binding sites in PTP1B were compared with YopH and SptP. Molecular dynamics simulations were used to incorporate ligand-induced conformational changes in the binding sites. These results, together with those binding modes and binding affinities distinguished in individual PTPs, provide insight into the structure-based design of inhibitors for YopH and SptP.

Bacterial Outer Membrane Proteins↗
PubMed2004

Leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db) female mice do not develop oncogene-induced mammary tumors.

Being overweight is a risk factor for postmenopausal breast cancer and is associated with an increased incidence and shortened latency of spontaneous and chemically induced mammary tumors in rodents. However, leptin-deficient obese Lep(ob)Lep(ob) female mice have reduced incidences of spontaneous and oncogene-induced mammary tumors. Of interest, leptin enhances the proliferation of human breast cancer cell lines in which leptin receptors are expressed, which suggests that leptin signaling plays a role in tumor development. We evaluated oncogene-induced mammary tumor development in obese MMTV-TGF-alpha/Lepr(db)Lepr(db) mice that exhibit a defect in OB-Rb, which is considered to be the major signaling isoform of the leptin receptor. Lepr and MMTV-TGF-alpha mice were crossed, and the offspring were genotyped for oncogene expression and the determination of Lepr status. Lean MMTV-TGF-alpha/Lepr(+)Lepr(+) (homozygous) and MMTV-TGF-alpha/Lepr(+)Lepr(db) (heterozygous) mice and obese MMTV-TGF-alpha/Lepr(db)Lepr(db) mice were monitored until age 104 weeks. Body weights of MMTV-TGF-alpha/ Lepr(db)Lepr(db) mice were significantly heavier than those of the lean groups. No mammary tumors were detected in MMTV-TGF-alpha/Lepr(db)Lepr(db) mice, whereas the incidence of mammary tumors in MMTV-TGF-alpha/Lepr(+)Lepr(+) and MMTV-TGF-alpha/ Lepr(+)Lepr(db) mice was 69% and 82%, respectively. Examination of mammary tissue whole mounts indicated an absence of duct formation and branching for MMTV-TGF-alpha/Lepr(db)Lepr(db) mice. Both age at mammary tumor detection and tumor burden (tumors/mouse and tumor weights) were similar for the lean genotypes. Serum leptin levels of MMTV-TGF-alpha/Lepr(db)Lepr(db) mice were 12-20-fold higher than levels of lean mice. Thus, despite elevated serum leptin levels, leptin receptor-deficient MMTV-TGF-alpha/Lepr(db)Lepr(db) mice do not develop mammary tumors. This study provides additional evidence that leptin and its cognate receptor may be involved in mammary tumorigenesis.

Animals↗
PubMed2004

[Identification and analysis of a group of highly conserved trs-like genes in rice].

There are at least ten transcriptional trs-like genes in rice that have been confirmed by RT - PCR and sequencing, based on the annotation results of rice genome and homologous search. These ten genes correspond to six of the ten known subunits of TRAPP complex in yeast. Four pairs of them are duplicates while the other two are unique according to the known rice genomic sequences. All of the ten genes are constitutively expressed in rice tissues and share phylogenetic homology to some extent with other eukaryotic trs-like genes in their gene structures and protein sequences.

Genes, Plant↗
PubMed2004

Biological activity of the S-adenosylmethionine decarboxylase inhibitor SAM486A in human breast cancer cells in vitro and in vivo.

The antitumor activity of the S-adenosylmethionine decarboxylase (SAMDC) inhibitor SAM486A in human breast cancer cells was investigated. Our in vitro study focused on testing the effects of SAM486A on the proliferation, clonogenicity, invasiveness, cell signaling and PA levels of hormone-independent MDA-MB-435 human breast cancer cells. We also investigated the antitumor action, effects on polyamine pools and tolerability of SAM486A administered to nude mice carrying MDA-MB-435 xenografts. SAM486A suppressed anchorage-independent and -dependent growth and invasiveness of breast cancer cells and the inhibition of cell growth was associated with suppression of spermine synthesis. Combined administration of SAM486A and alpha-difluoromethylornithine (DFMO), a selective inhibitor of ornithine decarboxylase (ODC), exerted greater antiproliferative and anti-invasive effects and induced an overall greater suppression of cellular PA levels than the individual treatments. Both SAM486A and DFMO increased phosphorylation of STAT-1, -3, ERK1/2 and p38, thus indicating activation of both STAT signaling and the MAPK pathway. SAM486A (1 mg/kg) significantly suppressed the growth and spermine levels of established MDA-MB435 breast tumors in nude mice. SAM486A exerts a potent antitumor action in MDA-MB-435 breast cancer cells both in vitro and in vivo. Inhibition of cellular spermine is consistently observed with SAM486A treatment and may mediate its antitumor action. Combination treatment with DFMO may allow the use of lower and, hence, less toxic doses of each compound with preservation of optimal therapeutic effect. The role of activation of STAT signaling and the MAPK pathway in the antitumor action of SAM486A remains to be determined.

Adenosylmethionine Decarboxylase↗
PubMed2004

[Morphological analysis of acetabulum bony curved surface].

By using the reverse engineering (RE) technology, the mesh surface model of acetabulum was reconstructed by triangulation. Based on this kind of model, the local morphological analysis (LMA) and global morphological analysis (GMA) could be processed. The fitting minimal quadric surface method was applied to calculate the curvature of any point on the acetabulum bony surface, the local morphological character of its surface could be acquired, and its global surface character could be determined by GMA. The results showed that the acetabulum bony surface is elliptical surface, and its three eigenvalues (lambda1, lambda2, lambda3) relations on the three axes (x, y, z) are as follows: lambda1 is short than lambda2 and lambda3, lambda2 is close to lambda3.

Acetabulum↗
PubMed2004

[A study on new computer-aided modeling method of hip joint].

The main reason of invalidation of prosthetic hip joint is the prostheses flexibility and shift, dislocation and disjunction. Promoting the long time stability of the prostheses is the key of improving the long term hip joint replacement effect. Former research work was focused on the upper segment of femur, and assumed the acetabulum cup to be a spheric concave, and the external form of acetabulum prostheses was basically semi spheric. This paper presents a method of acquiring the point data on the surface of the hip bone using the reverse engineering technology. By analyzing the acetabulum surface fitting error we use rotating elliptical surface to fit the acetabulum surface, together with the optimal technique to build up the CAD model of acetabulum surface. We compare the fitting error between the sphere fitting and rotating elliptical surface fitting and get the result that the rotating elliptical surface fitting error is smaller than the sphere fitting error, and the rotating elliptical surface can describe the shape of the acetabulum better.

Acetabulum↗