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Biomedical subjects

Fang Xia

Publications and source records attributed to Fang Xia.

At least 19 recordsLinked to original sources

[Preventive and therapeutic effects of qiongyugao on hepatocellular carcinoma via inhibition of the expression of HBxAg in hepatic carcinoma cells].

AIM: To investigate the effects of qiongyugao on the expression of hepatitis B x antigen (HBxAg) in BALB/c-nu mice into which human hepatic carcinoma cells were transplanted, and to analyze its specific mechanism in prophylaxis and treatment of hepatocellular carcinoma. METHODS: A nude mouse model with the transplantation of human hepatic carcinoma cells was established to observe the preventive and therapeutic effects of qiongyugao on the body weight and tumor weight of the mice. The expression of HBxAg in tumor and liver tissue wsa detected by immunohistochemical studies. RESULTS: Compared with model control group, prophylaxis and treatment with qiongyugao increased the body weight, depressed the tumor weight and inhibited HBxAg expression. The same efficacy was showed in both qiongyugao prophylaxis group and cyclophosphamide treatment group. CONCLUSION: Qiongyugao can slow down the growth of tumor and inhibit the expression of HBxAg, which may be an essential mechanism in prophylaxis and treatment of hepatocellular carcinoma.

Animals↗

Antiviral effect of Chinese medicine jiaweisinisan in hepatitis B virus transgenic mice.

AIM: To study the antiviral effect of Chinese medicine jiaweisinisan (JWSNS) on hepatitis B virus (HBV) infection in transgenic mice (TGM). METHODS: Twenty two 6-8 wk old HBV TGM in the third generation were divided into TGM control group and TGM treated group randomly. The normal control group included ten normal BC 57L/6 mice at the same age. The mice in treated group were administrated with JWSNS at the concentration of 4 g/mL and the dosage of 50 g/kg per d for 30 d, while the mice in TGM control group and normal control group were administrated with normal saline at the same dosage and the same time. Polymerase chain reaction (PCR) was used to assess the contents of HBV DNA in serum of HBV TGM before and after treatments, whereas blot hybridization was utilized to measure the contents of HBV DNA in the liver of both HBV TGM and normal BC 57L/6 mice. RESULTS: The levels of serum HBV DNA in TGM treated group were remarkably decreased after the treatment of JWSNS (7.662+/-0.78 vs 5.22+/-3.14, P < 0.05), while there was no obvious change after administration of normal saline in TGM control group (7.125+/-4.26 vs 8.932+/-5.12, P > 0.05). The OD values of HBV DNA in the livers of the mice in TGM treated group were significantly lower than those of TGM control group (0.274+/-0.096 vs 0.432+/-0.119, P < 0.01). CONCLUSION: JWSNS exerts suppressive effects on HBV DNA in the serum and liver of TGM.

Animals↗

Investigation of protein retention and selectivity in HIC systems using quantitative structure retention relationship models.

In the present work, the effect of stationary phase resin chemistry and protein physicochemical properties on protein binding affinity in hydrophobic interaction chromatography (HIC) was investigated using linear gradient chromatography and quantitative structure-retention relationship (QSRR) modeling. Linear gradient experiments were carried out for a set of model proteins on four different HIC resins having different backbone and ligand chemistry. The retention data exhibited significant differences in protein binding affinity, not only across the phenyl and butyl ligand chemistries, but also for the different backbone chemistries found in the Sepharose (cross-linked agarose) and the Toyopearl 650 M (polymethacrylate) series of resins. QSRR models based on a Support Vector Machine (SVM) approach were developed for the linear retention data using molecular descriptors based on protein crystal structure and primary sequence information as well as a set of new hydrophobicity descriptors based on the solvent accessible protein surface area. The results indicate that the QSRR models were successfully able to capture and selectivity predict the changes observed in these systems. Furthermore, the new descriptors resulted in physically interpretable models of protein retention and provided insights into the factors influencing protein affinity in these different HIC systems. The approach put forth in this study provides a framework for developing predictive tools and for gaining insight into protein selectivity in hydrophobic interaction chromatography.

Chromatography, Gel↗

Mitosis-independent survivin gene expression in vivo and regulation by p53.

Survivin is an essential mitotic gene, and this has been speculated to reflect its primary function in development and cancer. Here, we generated a knock-in transgenic mouse (SVVp-GFP) in which a green fluorescent protein (GFP) reporter gene was placed under the control of the survivin promoter that regulates transcription at mitosis. The expression of endogenous survivin was widespread in mouse tissues during development and shortly after birth. In contrast, GFP reactivity was undetectable in transgenic mouse embryos, and was largely limited postnatally to mitotic cells in the testes. Double transgenic mice generated in the tumor-prone Min/+ background exhibited intestinal adenomas that strongly expressed endogenous survivin, but only isolated GFP-positive cells. Conversely, dysplastic adenomas (16%) stained intensely for GFP, and revealed focal reactivity for mutant, but not wild-type, p53. The expression of GFP was increased by approximately 10-fold in p53(-/-) as opposed to p53(+/+) HCT116 colorectal cancer cells, and reintroduction of p53 in p53(-/-) cells abolished GFP expression. Therefore, the mitotic transcription of the survivin gene is highly restricted in vivo, and unexpectedly negatively regulated by p53. Contrary to a commonly held view, the dominant function(s) of survivin in development and tumor ontogeny are largely cell cycle-independent.

Animals↗

Effect of pH changes on water release values in hydrophobic interaction chromatographic systems.

The effect on pH on protein binding in HIC systems was investigated. Isocratic experiments were carried out to determine the capacity factors of various proteins as a function of temperature, pH and salt type. This paper presents a framework based on the Maxwell linkage function for estimating the number of released water molecules during the adsorption/desorption process due to a change of buffer pH. This approach also enables one to predict the effect of pH change on the water released values upon binding at any temperature condition. The results indicate that the total number of released water molecules (delta nu) for a pH change increased more on aromatic surfaces (phenyl Sepharose) than on aliphatic resins (butyl Sepharose). The results also indicate that the total number of released water molecules (deltanu) for a pH change increased with salt concentration and when changing from chaotropic to kosmotropic salts. The (deltanu) values also increased as the buffer pH approached the protein's pI, and decreased away from its pI. This work helps to establish a framework for the investigation of pH effects on protein selectivity in HIC systems.

Buffers↗

[Effect of intestinal cytochrome P450 3A on phytochemical presystemic metabolism].

Phytochemicals, orally administered substances, are found to undergo presystemic metabolism mainly in the intestine. Although early researches confirmed the role of intestinal bacteria in phytochemical presystemic metabolism, along with the development of molecular biology in investigating intestinal metabolism, a breakthrough has been won in research into metabolizing enzymes and transporters in intestine, which demands more attention and further studies. Recently, Cytochrome P450 3A has been found to be the most effective enzyme in mediating both oxidative (PhaseI) and conjugative (PhaseII) metabolism in the intestine. The present review summarizes the current findings correlated with the effect of intestinal cytochrome P450 3A on phytochemical presystemic metabolism, which provides a good basis for further research on phytochemical pharmacokinetics.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Rational design of shepherdin, a novel anticancer agent.

Anticancer agents that selectively kill tumor cells and spare normal tissues are urgently needed. Here, we engineered a cell-permeable peptidomimetic, shepherdin, modeled on the binding interface between the molecular chaperone Hsp90 and the antiapoptotic and mitotic regulator, survivin. Shepherdin makes extensive contacts with the ATP pocket of Hsp90, destabilizes its client proteins, and induces massive death of tumor cells by apoptotic and nonapoptotic mechanisms. Conversely, shepherdin does not reduce the viability of normal cells, and does not affect colony formation of purified hematopoietic progenitors. Systemic administration of shepherdin in vivo is well tolerated, and inhibits human tumor growth in mice without toxicity. Shepherdin could provide a potent and selective anticancer agent in humans.

Adenosine Triphosphate↗

Estimating medication persistency using administrative claims data.

OBJECTIVES: To review the definitions and methods for measuring medication persistency, and to propose a uniform definition of and calculation for persistency using pharmacy claims data. STUDY DESIGN: Literature review. METHODS: A MEDLINE search (1966 to present) was performed to identify articles detailing a definition or method of persistency measurement based on automated pharmacy data. Articles were screened for relevance by title and abstract. References from identified articles were used to expand the search results. RESULTS: The concept behind medication persistency measurement is to capture the amount of time that an individual remains on chronic drug therapy. The methods to calculate medication persistency can be classified into 1 of 3 categories: (1) Persistency as a function of the medication possession ratio; (2) persistency as a function of medication availability at a fixed point in time; and (3) persistency as a function of the gaps between refills. CONCLUSIONS: The common goal of all persistency measures should be to reflect the continuity of medication usage and to capture the timeliness and the frequency of refilling. The measurement of persistency as a function of the gaps between refills provides the best assessment of refill compliance across a variety of medication and disease states and lends itself to the well-established measurements of survival analysis.

Drug Prescriptions↗

Evaluation of selectivity changes in HIC systems using a preferential interaction based analysis.

It is well established that salt enhances the interaction between solutes (e.g., proteins, displacers) and the weak hydrophobic ligands in hydrophobic interaction chromatography (HIC) and that various salts (e.g., kosmotropes, chaotropes, and neutral) have different effects on protein retention. In this article, the solute affinity in kosmotropic, chaotropic, and neutral mobile phases are compared and the selectivity of solutes in the presence of these salts is examined. Since solute binding in HIC systems is driven by the release of water molecules, the total number of released water molecules in the presence of various types of salts was calculated using the preferential interaction theory. Chromatographic retention times and selectivity reversals of both proteins and displacers were found to be consistent with the total number of released water molecules. Finally, the solute surface hydrophobicity was also found to have a significant effect on its retention in HIC systems.

Algorithms↗

An IAP-IAP complex inhibits apoptosis.

Regulators of apoptosis are thought to work in concert, but the molecular interactions of this process are not understood. Here, we show that in response to cell death stimulation, survivin, a member of the inhibitor of apoptosis (IAP) gene family, associates with another IAP protein, XIAP, via conserved baculovirus IAP repeats. Formation of a survivin-XIAP complex promotes increased XIAP stability against ubiquitination/proteasomal destruction and synergistic inhibition of apoptosis, which is abolished in XIAP(-/-) cells. Therefore, orchestration of an IAP-IAP complex regulates apoptosis.

Animals↗

NuRD complex component Mi-2beta binds to and represses RORgamma-mediated transcriptional activation.

RORgamma is a nuclear receptor that binds to DNA motifs as a monomer to constitutively activate target genes. RORgamma plays an important role in thymocyte development and lymph node organogenesis, while the regulation of RORgamma-mediated transcriptional activation is currently unclear. The purpose of this study was to identify other nuclear proteins that interact with RORgamma. A yeast two-hybrid screen with Y190 yeast cells under stringent conditions resulted in the identification of CHD4, also known as Mi-2beta, as a RORgamma-interacting protein. This interaction was confirmed by GST pull-down assays. This interaction occurred within the middle regulatory region (amino acids 719-1164) of Mi-2beta. Transfection of Gal4-RORgamma into HeLa cells resulted in constitutive transactivation of the MH100-tk-luc reporter. The addition of Mi-2beta resulted in a dramatic 50% decrease in Gal4-RORgamma-mediated transactivation. These data demonstrate that RORgamma forms a protein-protein interaction with the regulatory region of Mi-2beta, resulting in inhibition of RORgamma transcriptional activity. These results may provide evidence as to how RORgamma-mediated transactivation is regulated by other nuclear proteins.

Animals↗

Differences in preparative loadability between the charged and uncharged forms of ionizable compounds.

Ionizable compounds experience a drastic difference in preparative loadability as a function of pH. It can be shown that the preparative loadability of a compound in the ionic form is by a factor of 20 or more inferior to the loadability of the same compound in the unionized form. In this paper, we demonstrate the reason for this behavior, and show practical applications of the principle.

Adsorption↗

[Differential gene expression analysis of human leukemic cell line with different tumorigenic potentials in nude mice].

OBJECTIVE: To study the molecular mechanism of tumorigenicity in nude mice of human leukemia cell lines. METHODS: K562-n, is a human leukemic cell line with much higher tumorigenecity in nude mice compared with the parental K562 cell line by repeated in vitro and in vivo passages. Genes differentially expressed between K562 and K562-n cells were analyzed by using DNA microarray technique. RESULTS: Of 12 000 genes screened were differentially expressed significantly, among which 42 genes were up-regulated and 97 genes were down-regulated in K562-n cells. Eighty-five of the 139 genes have been registered in the GeneBank and 54 are unknown genes. The genes accessible from the GenBank include: 1. oncogenes and tumor-supressor genes, 2. genes related to transcription regulation, cell cycle and apoptosis, 3. genes related to cytoskeleton and cytokinetics, 4. genes related to metabolism and transport, 5. genes related to immune function. There were also some differentially expressed genes with mixed functions and some with unknown function differentially expressed. CONCLUSION: There are many genes differentially expressed between K562-n and K562 cells. The high tumorigenicity in nude mice of human leukemia cell line K562-n might be related to its specific gene expression profile.

Animals↗

Application of hydrophobic interaction displacement chromatography for an industrial protein purification.

Recently it has been established that low molecular weight displacers can be successfully employed for the purification of proteins in hydrophobic interaction chromatography (HIC) systems. This work investigates the utility of this technique for the purification of an industrial protein mixture. The study involved the separation of a mixture of three protein forms, that differed in the C-terminus, from their aggregate impurities while maintaining the same relative ratio of the three protein forms as in the feed. A batch high-throughput screening (HTS) technique was employed in concert with fluorescence spectroscopy for displacer screening in these HIC systems. This methodology was demonstrated to be an effective tool for identifying lead displacer candidates for a particular protein/stationary-phase system. In addition, these results indicate that surfactants can be employed at concentrations above their CMCs as effective displacers. Displacement of the recombinant proteins with PEG-3400 and the surfactant Big Chap was shown to increase the productivity as compared to the existing step-gradient elution process.

Chromatography↗

Modeling of adsorption in hydrophobic interaction chromatography systems using a preferential interaction quadratic isotherm.

A preferential interaction quadratic isotherm model for hydrophobic interaction chromatographic systems is presented in this paper. In this isotherm, the nonlinear effect of salt on the capacity factor is described using the preferential interaction model developed by Perkins et al. [J. Chromatogr. A, 766 (1997) 1]. This is then coupled with a quadratic nonlinear isotherm to describe nonlinear adsorption behavior at high solute concentrations. The resulting preferential interaction quadratic isotherm is examined for its ability to describe solute adsorption behavior under both linear and nonlinear conditions over a wide range of salt concentrations in HIC systems. The results indicate that this isotherm is well suited for predicting nonlinear adsorption behavior in HIC systems for both proteins and low-molecular mass HIC displacers.

Adsorption↗

Antioxidant therapy with Salvia miltiorrhiza decreases plasma endothelin-1 and thromboxane B2 after cardiopulmonary bypass in patients with congenital heart disease.

OBJECTIVE: The endothelium-derived vasoconstrictor endothelin-1 is increased after cardiopulmonary bypass in children with congenital heart defects. This study determines whether antioxidant therapy with Salvia miltiorrhiza injection, an herb extract containing phenolic compounds, prevents the postoperative increase of endothelin-1. The relationship between endothelin-1 and the endothelium-derived prostacyclin (prostaglandin I2) and thromboxane A2 postoperatively is also investigated. METHODS: Twenty children with congenital heart defects and pulmonary hypertension were randomly assigned to group A (placebo control, n=10) or B (200 mg/kg Salvia miltiorrhiza intravenously after anesthesia induction and at the time of rewarming, respectively; n =10) before cardiac surgery. Central venous blood samples were taken before operation (T(0)), 10 (T(1)) and 30 minutes (T(2)) after starting cardiopulmonary bypass, 10 (T(3)) and 30 minutes (T(4)) after aortic declamping, and 30 minutes (T(5)) and 24 hours (T(6)) after termination of cardiopulmonary bypass. Plasma lipid peroxidation product malondialdehyde, myocardial specific creatine kinase-MB activity, thromboxane B2, and 6-keto-prostaglandin F(1 alpha) (stable metabolites of thromboxane A2 and prostaglandin I2) were measured. RESULTS: Malondialdehyde increased significantly at T(1) in group A and remained significantly higher than in group B thereafter (P <.05). Malondialdehyde in group B did not significantly increase over time. At T(5), plasma creatine kinase-MB, thromboxane B2, and endothelin-1 in group B were lower than in group A (P <.05); malondialdehyde correlated significantly with creatine kinase-MB (r = 0.71, P =.0005). At T(6), endothelin-1 negatively correlated with the 6-keto-prostaglandin F(1 alpha)/thromboxane B2 ratio (r = -0.64, P =.0025). CONCLUSION: Antioxidant therapy reduces myocardial damage and attenuates postoperative vasoactive mediator imbalance.

Adolescent↗

Evaluation of a depression health management program to improve outcomes in first or recurrent episode depression.

OBJECTIVES: To evaluate the impact of telephone counseling and educational materials on medication adherence and persistency among members with newly diagnosed depression enrolled in a pharmacy benefit management-sponsored disease management program. STUDY DESIGN: Longitudinal cohort observation. METHODS: The study population comprised 505 members with a new or recurrent episode of depression who consented and enrolled in a depression disease management program. After written consent was obtained, program participants received up to 4 telephone-counseling calls and 5 educational mailings focused on the importance of medication compliance, barriers to medication compliance, quality of life, symptoms, and satisfaction with the program. A control group of 3744 members was selected from client companies that opted not to offer the depression program. Measures of medication adherence, persistency with prescription drug therapy, and patient refill timeliness were computed for both groups and compared. RESULTS: Patients enrolled in the depression disease management program were significantly more likely to adhere to their medication regimen during acute (89.0% vs 67.7%, P < .001) and continuation treatment phases (81.1% vs 57.6%, P < .001). In addition, members enrolled in the program were significantly more likely to continue their therapy after 7 months (77.8% vs 49.5%, P < .001) and refilled their prescriptions on a more timely basis (0 vs 18 days, P < .001). CONCLUSIONS: A pharmacy benefit management-sponsored health management depression program succeeded in encouraging patients with new or recurrent depression to stay on antidepressant medication and to reach treatment goals outlined by best practice guidelines.

Antidepressive Agents↗