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Biomedical subjects

Xiao Xu

Publications and source records attributed to Xiao Xu.

At least 19 recordsLinked to original sources
PubMed2006

Impaired function and expression of P-glycoprotein in blood-brain barrier of streptozotocin-induced diabetic rats.

The aim was to investigate the effect of diabetes mellitus (DM) on P-glycoprotein (P-GP) function and expression in rat blood-brain barrier (BBB). P-GP function in BBB was assessed by measuring the brain-to-plasma concentration ratios (Kp values) of rhodamine 123 (Rho123) and vincristine (VCR), two well-known P-GP substrates, in control rats and 5-week streptozotocin (STZ)-induced diabetic rats. Evans blue (EB) dye was used as a BBB integrity indicator for examining the extravasation from the blood into the brain. P-GP expression in the brain cortex was evaluated with Western blot. The uptakes of Rho123 and VCR by cultured rat brain microvessel endothelial cells (rBMECs) incubated in diabetic and control rat serum for 72 h were also used to examine P-GP function, respectively. It was found that the Kp value of Rho123 (0.022+/-0.005 vs. 0.016+/-0.002 ml/g brain, p=0.033) and VCR (0.072+/-0.028 vs. 0.023+/-0.006 ml/g brain, p=0.006) in diabetic rats was significantly higher than that in control rats. The uptakes of Rho123 and VCR by cultured rBMECs incubated in the diabetic rat serum were higher than that in the control rat serum, respectively. No significant difference of the EB concentration in the brain cortex was found between the diabetic rats and control rats. Electron microscope examination of the brain cortex did not show a clear damage to the endothelial cells of microvessel in diabetic rats. In addition, the protein level of P-GP in the brains of the diabetic rats examined was significantly lower than that of control rats. These results suggested that the function and expression of P-GP might be impaired in the BBB of STZ-induced diabetic rats.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed2006

Label-free and real-time cell-based kinase assay for screening selective and potent receptor tyrosine kinase inhibitors using microelectronic sensor array.

Kinases are the 2nd largest group of therapeutic targets in the human genome. In this article, a label-free and real-time cell-based receptor tyrosine kinase (RTK) assay that addresses limitation of existing kinase assays and can be used for high-throughput screening and lead optimization studies was validated and characterized. Using impedance, growth factor-induced morphological changes were quantitatively assessed in real time and used as a measure of RTK activity. COS7 cells treated with epidermal growth factor (EGF) and insulin results in a rapid increase in cell impedance. Assessment of these growth factor-induced morphological changes and levels of receptor autophosphorylation using fluorescent microscopy and enzyme-linked immunosorbent assay, respectively, demonstrates that these changes correlate with changes in impedance. This assay was used to screen, identify, and characterize a potent EGF receptor inhibitor from a compound library. This report describes an assay that is simple in that it does not require intensive optimization or special reagents such as peptides, antibodies, or probes. More important, because the assay is cell based, the studies are done in a physiologically relevant environment, allowing for concurrent assessment of a compound's solubility, stability, membrane permeability, cytotoxicity, and off-target interaction effects.

Animals↗
PubMed2006

Synthesis and anti-tumor evaluation of new trisulfide derivatives.

New bis-aromatic and heterocyclic trisulfide derivatives 5, 7-10 were synthesized by optimizing lead dibenzyl trisulfide natural product (4) to evaluate their anti-tumor activities. Five compounds 5-7, 9, and 10 exhibited potent anti-tumor activities against eight different tumor cell lines with low cytotoxicity against HepG2. Initial SAR was discussed, and MOA of these anti-microtubule agents was suggested based on cell kinetic response patterns observed on RT-CES system.

Antineoplastic Agents↗
PubMed2006

Childbirth and pelvic floor dysfunction: an epidemiologic approach to the assessment of prevention opportunities at delivery.

Female pelvic floor dysfunction is integral to the woman's role in the reproductive process, largely because of the unique anatomic features that facilitate vaginal birth and also because of the trauma that can occur during that event. Interventions such as primary elective cesarean delivery have been discussed for the primary prevention of pelvic floor dysfunction; however, existing data about potentially causal factors limit our ability to evaluate such strategies critically. Here we consider the conceptual principles of epidemiologic function and the availability of data that are necessary to make informed recommendations about prevention opportunities for pelvic floor dysfunction at delivery. Available epidemiologic data on pelvic floor dysfunction suggest that there may be substantial opportunities for the primary prevention of pelvic organ prolapse at delivery. Although definitive recommendations await further epidemiologic studies of the potential risk and benefits of obstetric practice change, it is hoped that this discussion will provide a novel, quantitative framework for the assessment of pelvic floor dysfunction prevention opportunities.

Cesarean Section↗
PubMed2006

Dynamic and label-free monitoring of natural killer cell cytotoxic activity using electronic cell sensor arrays.

A microelectronic sensor-based platform, the RT-CES (real time electronic sensing) system, is introduced for label free assessment of natural killer (NK) cell-mediated cytotoxic activity. The RT-CES system was used to dynamically and quantitatively monitor NK-mediated cytotoxic activity towards 8 different adherent target cell lines, including cancer cell lines commonly used in laboratories. The cytotoxic activity monitored by RT-CES system was compared with standard techniques such as MTT measurement and shows good correlation and sensitivity. To test the specificity of the assay, pharmacological agents that inhibit NK cell degranulation and cytotoxic activity were employed and were shown to selectively and dose-dependently inhibit NK-mediated cytotoxic activity toward target cells. In summary, the RT-CES system offers fully automated measurement of cytotoxic activity in real time, which enables large-scale screening of chemical compounds or genes responsible for the regulation of NK-mediated cytotoxic activity.

Animals↗
PubMed2006

Real-time monitoring of morphological changes in living cells by electronic cell sensor arrays: an approach to study G protein-coupled receptors.

G protein-coupled receptors (GPCRs) constitute important targets for drug discovery against a wide range of ailments including cancer, inflammatory, and cardiovascular diseases. Efforts are underway to screen selective modulators of GPCRs and also to deorphanize GPCRs with unidentified natural ligands. Most GPCR-based cellular screens depend on labeling or recombinant expression of receptor or reporter proteins, which may not capture the true physiology or pharmacology of the GPCRs. In this paper, we describe a noninvasive and label-free assay for GPCRs that can be used with both engineered and nonengineered cell lines. The assay is based on using cell-electrode impedance to measure minute changes in cellular morphology as a result of ligand-dependent GPCR activation. We have used this technology to assay the functional activation of GPCRs coupled to different signaling pathways and have compared it to standard assays. We have used pharmacological modulators of GPCR signaling pathways to demonstrate the specificity of impedance-based measurements. Our data indicate that cell-electrode impedance measurements offer a convenient, sensitive, and quantitative method for assessing GPCR function. Moreover, the noninvasive nature of the readout offers the added advantage of performing multiple treatments in the same well to study events such as desensitization and receptor cross-talk.

Animals↗
PubMed2006

Attenuation of acute phase shear stress by somatostatin improves small-for-size liver graft survival.

The major concern of living donor liver transplantation is small-for-size graft injury at the early phase after transplantation. Novel therapeutic strategies should be developed. To investigate the protective effect of somatostatin related to hemodynamic stress on small-for-size liver graft injury, we applied a treatment regimen of low-dose somatostatin in a rat orthotopic liver transplantation model using small-for-size grafts (median, 38.7%; range, 35-42%). Somatostatin was given at 5 minutes before total hepatectomy and immediately after reperfusion in the recipient (20 microg/kg). Graft survival, portal hemodynamics, intragraft gene expression and hepatic ultrastructural changes were compared between the rats with or without somatostatin treatment. Seven-day graft survival rates in the somatostatin treatment group were significantly improved compared to the control group (66.7% vs. 16.7%, P = 0.036). In the treatment group, portal pressure and hepatic surface blood flow were significantly decreased within the first 30 minutes after reperfusion, whereas in the control group, transient portal hypertension and excessive hepatic blood flow were observed. Intragraft expression (both messenger RNA and protein) of endothelin-1 was significantly downregulated accompanied with upregulation of heme oxygenase-1 and A20. Better preservation of liver function was found in the treatment group. Hepatic ultrastructure, especially the integrity of sinusoids, was well protected in the treatment group. In conclusion, low-dose somatostatin rescues small-for-size grafts from acute phase injury in liver transplantation by attenuation of acute-phase shear stress that resulted from transient portal hypertension.

Animals↗
PubMed2006

Live cell quality control and utility of real-time cell electronic sensing for assay development.

In this paper we have explored the utility of the real-time cell electronic sensing (RTCES, ACEA Biosciences Inc., San Diego, CA) system for monitoring the quality of live cells in cell-based assays as well as for assay development. We have demonstrated that each cell type displays unique growth kinetic profiles that provide a quantitative account of cell behavior and can be used as a diagnostic tool for cellular quality control. The utility of the specific signature patterns was shown by demonstrating the significant differences in primary cell behavior depending on the supplier. In addition, the RT-CES system was able to differentiate cell behavior depending on the passage stage of the cells. The utility of the RT-CES system as an assay development tool was demonstrated in cytotoxicity assays. The RT-CES system not only provides information regarding the potency of cytotoxic compounds, but in addition relates potency to the rate of the response for each concentration of the compound tested, which is important for understanding the mechanism of compound action. Moreover, real-time display of cytotoxicity data by the RT-CES system allows for calculation of real-time 50% inhibitory concentration (IC50) values or determination of optimal IC(50) value. In summary, the RT-CES system provides high content and information-rich data that are beyond the scope of single-point assays.

Biological Assay↗
PubMed2006

Dynamic and label-free cell-based assays using the real-time cell electronic sensing system.

Cell-based assays have become an integral part of the preclinical drug development process. Recently, noninvasive label-free cell-based assay technologies have taken center stage, offering important and distinct advantages over and in addition to traditional label-based endpoint assays. Dynamic monitoring of live cells, the preclusion of label, and kinetics are some of the fundamental features of cell-based label-free technologies. In this article we will discuss the real-time cell electronic sensing (RT-CES, ACEA Biosciences Inc., San Diego, CA) system and some of its key applications for cell-based assays such as cell proliferation and cytotoxicity, functional assays for receptor-ligand analysis, cell adhesion and spreading assays, dynamic monitoring of endothelial barrier function, and dynamic monitoring of cell migration and invasion. Also, where appropriate we will briefly discuss other label-free technologies in an application-specific manner.

Biological Assay↗
PubMed2006

Sleep disturbances reported by refractory partial-onset epilepsy patients receiving polytherapy.

PURPOSE: Although sleep disturbances are common in epilepsy, few studies examined the prevalence and impact of sleep disturbance in epilepsy patients. This study investigates these in a cross-sectional survey. METHODS: We surveyed 201 adult partial-onset epilepsy patients taking stable regimens of two or more antiepileptic medications. Community-based U.S. neurologists recorded patient demographic and clinical information. Patients completed the Medical Outcomes Study (MOS) Sleep Scale, the Quality of Life in Epilepsy-10 instrument (QOLIE-10), and the EuroQol-5D (EQ-5D). We evaluated the associations of sleep with health-related quality of life and clinical and demographic characteristics by using correlation coefficients and analysis of variance. RESULTS: Mean (SD) age was 44.2 (12.5); 34% of patients had diagnosed sleep disturbances; 10% received prescription sleep medications. Patients with sleep disturbance reported poorer mean QOLIE-10 (55.2 vs. 63.7; p = 0.006) and EQ-5D (0.49 vs. 0.71; p < 0.001) scores relative to those without sleep disturbances. The mean (SD) MOS Sleep Problems Index score was 36.2 (20.8), worse than the general population mean of 26. Patients with physician-reported anxiety or depression had more sleep problems than did those without these comorbidities. Higher Sleep Problems Index scores were significantly (p < 0.001) correlated with poorer QOLIE-10 (r=-0.49) and EQ-5D (r=-0.56) scores. Patients experiencing a seizure within the past week reported higher MOS Sleep Problems Index scores than did those with a less-recent seizure (41.5 vs. 32.8; p = 0.003). CONCLUSIONS: Diagnosed and self-reported sleep disturbances in patients with partial-onset epilepsy are frequently overlooked, but are negatively associated with everyday functioning and well-being, and therefore contribute significantly to the burden of epilepsy.

Adult↗
PubMed2006

Health effects of managed care among the near-elderly.

OBJECTIVE: The authors evaluate whether enrolling in a health maintenance organization (HMO) or preferred provider organization (PPO) affects the health of adults ages 55 to 64, relative to fee-for-service plans. METHODS: A nationwide random sample of 4,044 adults with employer-sponsored health insurance is drawn from the 1994 to 2000 waves of the Health and Retirement Study. Multinomial logit regressions are estimated for self-reported general health status, first using a sample of all near-elders, then using subsamples of near-elders with and without longstanding chronic health conditions. The possibility of selection bias into managed care plans is considered and explicitly addressed in model estimation. RESULTS: We find no ill effects of HMOs on health status, and older adults with a history of chronic health conditions actually fare better upon enrolling in these plans. DISCUSSION: More research is needed to understand the reasons for the observed beneficial effects of managed care.

Fee-for-Service Plans↗
PubMed2006

Current status and perspective of liver preservation solutions.

BACKGROUND: A safe and effective preservation solution is a precondition for liver transplantation, which is accepted as the radical treatment for patients with end-stage liver disease. The increasing use of marginal donors and non-heart beating donors as well as the establishment of a national organ allocation network call for better preservation. New preservation solutions like histidine-tryptophan-ketoglutarate (HTK) solution and Celsior solution have been introduced to liver preservation, and protective gene intervention and other modifications have also been investigated. In this article, we review recent advances in liver preservation solutions. DATA SOURCES: An English-language literature search was conducted using MEDLINE (1990-2005) on liver preservation solution, biliary complication, protective gene and other related subjects. RESULTS: Although the high viscosity of the University of Wisconsin (UW) solution proved harmful to the hepatic microcirculation, three solutions showed equivalent preservation effects. When the cold ischemia time was short, there were no significant differences among the three solutions in the incidence of biliary complications. So far, modifications of preservation solutions have achieved great success. Several types of protective genes like A20, Bcl-2, Bcl-X(L) and HO-1 were reported to have definite liver protective effects. The addition of other substrates like TNF-alpha antibody, tacrolimus (FK506) and fructose-1,6-bisphosphate (FBP) can also improve the preservation effect. However, addition of insulin to UW solution is harmful to the graft. CONCLUSIONS: In centers with highly-developed transplantation techniques, HTK and Celsior solutions are acceptable in liver preservation. Protective gene modification and addition of substrates like TNF-alpha antibody, FK506 and FBP are prominent approaches to improve liver preservation.

Adenosine↗
PubMed2006

[Study on the risk factors of repeated abortion among unmarried adolescents].

OBJECTIVE: To find out the rate of repeated induced abortion among unmarried abortion women and to study the relevant risk factors. METHODS: From July to September 2005, we used the method of hospital based descriptive epidemiological study to investigate 2295 abortion women below 25 years of age in Beijing, Shanghai and Zhengzhou. Case-control study was used as the method. We considered the women with history of repeated abortion as case group (736 women) and considered the women without history of repeated abortion as control group (1559 women). RESULTS: The mean age of respondents was 21.92 years with minimal age as 15 years. 17.2 % aborted women aged below 20 years with 32. 1% of them were ever having a history of previous induced abortion. Among 736 women with repeated abortion, 75.3 % of them had one time of induced abortion previously, 18.1% having two times, 4.2% having 3 times, 13 women having 4 times and 4 women having 5 times and one even with the maximum of having 8 times of previous abortion. In comparison with control group, the case group had higher rate among women whose first sex was below 18 years (16.2% vs. 9.4% , P<0.01). There were higher rates of women under following conditions: having exposed to sexual behavior for more than 3 years (33.6% vs. 6.6 % , P<0.01), having cohabited with male partner for over 1 year (64.6% vs. 23.9%, P <0.01), having regular sexual life (48.5 % vs. 37. 1%, P < 0.05), having multiple sexual partners (36.0% vs. 15.0%,P<0.01) having unwanted sex (6.0% vs. 3.9%, P<0.05), whose current pregnancy resulted from contraceptive failure (39.3% vs. 31.6%, P< 0.01), having a history of high-risk abortion (30.8% vs. 3.1%, P< 0.01) etc. In comparison with the control group, the case group showed higher rates of male partners not supporting this induced abortion, male partner not participating in decision-making on abortion and male partner not accompanying the female partners to seek for abortion service (rates of the three major factors in case group and in control group were 10.3% vs. 5.9%, P< 0.01, 30.3% vs. 24.0%, and 27.5% vs. 23.5%, P<0.01, respectively). CONCLUSION: The rate of repeated induced abortion among unmarried abortion women was relatively high. The risk factors for females would include: younger age of sex debut, longer duration from the beginning of first sex to the current abortion, cohabitation, regular sexual life, multiple sexual partners, unwanted sex, contraceptive failure and high risk induced abortion. Meanwhile, unmarried but repeated abortion was related to the differences of gender between males and females and male partner's concern on induced abortion.

Abortion, Induced↗
PubMed2005

[Clinical evaluation of emergency liver transplantation for patients with benign end-stage liver diseases].

OBJECTIVE: To evaluate the efficacy of emergency liver transplantation in treating patients with benign end-stage liver diseases and explore the possible prognostic factors. METHOD: The clinic data of 46 cases of recipients who underwent ELT were retrospectively analyzed. clinicopathological variables (including age, gender, etiology, serum creatinine, PT, INR, albumin, total bilirubin) were compared between the survival group (n = 32) and the dead group (n = 14). And the prognostic values of CTP and MELD score were analyzed. RESULTS: Higher serum creatinine level, MELD score and CTP score were found in the dead group, as compared to those in survival group. The survival rates among CTP or MELD categories showed significant difference. Three-and six months and one year survival rates of total recipients were 73.9% , 71.7% and 69.6% respectively. CONCLUSION: Emergency liver transplantation is an effective treatment to salvage patients in end-stage. Serum creatinine is the important prognostic factor to the posttransplant survival. MELD score system is more sensitive than CTP classification in predicting the prognosis.

Adult↗
PubMed2005

Dynamic monitoring of cell adhesion and spreading on microelectronic sensor arrays.

Cellular interaction with and adhesion on different biological surfaces is a dynamic and integrated process requiring the participation of specialized cell surface receptors, structural proteins, signaling proteins, and the cellular cytoskeleton. In this report, the authors describe a label-free and real-time method for measuring and monitoring cell adhesion on special microplates integrated with electronic cell sensor arrays. These plates were used in conjunction with the real-time cell electronic sensing (RT-CES) system to dynamically and quantitatively monitor the specific interaction of fibroblasts with extracellular matrix (ECM) proteins and compared with standard adhesion techniques. Cell adhesion on ECM-coated cell sensor arrays is dependent on the concentration of ECM proteins coated and is inhibited by agents that disrupt the interaction of ECM with cell surface receptors. Furthermore, the authors demonstrate that the integrity of the actin cytoskeleton is required for productive cell adhesion and spreading on ECM-coated microelectronic sensors. Confirming earlier results, it is shown that interfering with Src expression or activity, via siRNA or small molecule, results in the disruption of adhesion and spreading of Bx PC3 cells. The results indicate that the RT-CES system offers a convenient and quantitative means of assessing the kinetics of cell adhesion in a high-throughput manner.

Animals↗
PubMed2005

Biological impacts of "hot-spot" mutations of hepatitis B virus X proteins are genotype B and C differentiated.

AIM: To investigate the biological impacts of "hot-spot" mutations on genotype B and C HBV X proteins (HBx). METHODS: Five types of "hot-spot" mutations of genotype B or C HBV X genes, which sequentially lead to the amino acid substitutions of HBx as I127T, F132Y, K130M+V131I, I127T+K130M+V131I, or K130M+V131I+F132Y, respectively, were generated by means of site-directed mutagenesis. To evaluate the anti-proliferative effects, HBx or related mutants' expression vectors were transfected separately to the Chang cells by lipofectamine, and the cells were cultured in hygromycin selective medium for 14 d, drug-resistant colonies were fixed with cold methanol, stained with Giemsa dyes and scored (increase of the colonies indicated the reduction of the anti-proliferation activity, and vice versa). Different types of HBx expression vectors were co-transfected separately with the reporter plasmid pCMVbeta to Chang cells, which were lysed 48 h post-transfection and the intra-cellular beta-galactosidase activities were monitored (increase of the beta-galactosidase activities indicated the reduction of the transactivation activity, and vice versa). All data obtained were calculated by paired-samples t-test. RESULTS: As compared to standard genotype B HBx, mutants of I127T and I127T+K130M+V131I showed higher transactivation and anti-proliferative activities, while the mutants of F132Y, K130M+V131I, and K130M+V131I+F132Y showed lower activities. As compared to standard genotype C HBx, I127T mutant showed higher transactivation activity, while the other four types of mutants showed no differences. With regard to anti-proliferative activity, compared to standard genotype C HBx, F132Y and K130M+ V131I mutants showed lower activities, and K130M+V131I +F132Y mutant, on the other hand, showed higher activity, while the mutants of I127T and I127T+K130M+V131I showed no differences. CONCLUSION: "Hot-spot" mutations affect the anti-proliferation and transactivation activities of genotype B and/or C HBx, and the biological impacts of most "hot-spot" mutations on HBx are genotype B and C differentiated.

Amino Acid Sequence↗
PubMed2005

[Biliary complications following early hepatic arterial insufficiency in liver transplantation].

OBJECTIVE: To explore the clinical feature and treatment efficiency of patients with early hepatic arterial insufficiency (HAI) and biliary complications (BC) following liver transplantation (LT). METHODS: The clinical data of 240 patients receiving LT from February 1999 to February 2004 were analyzed retrospectively. End-to-end choledococholocostomy was applied to 236 patients as the major biliary reconstructive method. Hemodynamic monitoring of the hepatic artery was performed to discover HAT, including hepatic arterial thrombosis (HAT) or hepatic arterial stenosis (HAS) in the first 3 months after transplantation. RESULTS: In HAI Group, 7 cases of stricture of biliary tract and 4 cases of biliary leakage occurred; and 6 cases underwent endoscopic and/or intervention treatment, 4 cases underwent repair of anastomotic stoma and biliary drainage, 1 case underwent medication. Eight patients died and 3 were cured. A total of 32 patients (13.3%) developed biliary complications (BCs), Eleven of the 32 patients with BCs, biliary stricture in 8 cases and biliary leakage in 3 cases, had early HAI (HAI Group) with an incidence of 4.6% for BC with background of HAI (11/236). Another 21 patients with BCs (21/236, 8.7%) did not showed background of HAI (non-HAI Group). Preoperative serum total bilirubin levels were 373.3 +/- 93.9 micromol/L in HAI Group and 110.8 +/- 45.0 micromol/L in non-HAI Group (P = 0.008). Three cases with HAT underwent emergency thrombectomy then the hepatic arterial flow turned to normal. Two cases with HAS received short-term anticoagulant therapy. Recipients with BC underwent radiological and/or endoscopic interventional treatment (n = 6), surgical repair of leak site and biliary drainage (n = 4), and ordinary medication (n = 1). The 1 and 3-year survival rates of HAI Group were 54.6% and 16.4% respectively; both significantly lower than those of non-HAI Group (66.3% and 61.2%, both P = 0.042). CONCLUSION: The recipients with BC following early HAI are associated with poor outcome. The monitoring protocol of hepatic hemodynamics by color dopplar ultrasonography should be enhanced, which contributes to urgent revascularization or recovery of hepatic hemodynamics. Interventional therapies should be immediately applied and transferred to surgical treatment or even retransplantation when necessary for patients with BC following early HAI.

Arterial Occlusive Diseases↗