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Biomedical subjects

J Xu

Publications and source records attributed to J Xu.

At least 91 records · Page 5Linked to original sources

Pharmacological profile of a novel, non-TZD PPARgamma agonist.

AIM: The purpose of this study was to characterize a novel, non-thiazolidinedione (TZD) peroxisome proliferator-activated receptor (PPAR)gamma agonist, RWJ-348260, via both in vitro and in vivo approaches. METHODS: The in vitro PPARgamma activities of RWJ-348260 were assessed in PPARgamma-GAL4 co-transfection assay, PPARgamma receptor binding assay, aP2 gene induction assay and preadipocyte differentiation assay. The in vivo efficacy of the compound was determined in rodent genetic diabetes models [ob/ob mouse, db/db mouse and Zucker diabetic fatty (ZDF) rat] following multiple days of oral administration. RESULTS: RWJ-348260 selectively activated PPARgammain vitro. In vivo, RWJ-348260 produced significant decreases in plasma glucose, HbA1c, insulin and triglyceride levels. RWJ-348260 also dose-dependently improved oral glucose tolerance. In db/db mice, the compound up-regulated PPARgamma target genes in white adipose tissues. RWJ-348260 produced a lower extent of hepatocyte lipid deposition and a smaller increase in liver weight compared to rosiglitazone in db/db mice. While RWJ-348260 effectively normalized hyperglycaemia and dyslipidaemia, it did not change haematocrit, transaminase, alkaline phosphatase, total bilirubin levels or liver weights in ZDF rats. CONCLUSIONS: RWJ-348260 is a potent PPARgamma agonist with efficacious antidiabetic activity in diabetic animal models. The compound has an improved side-effect profile compared to rosiglitazone.

Adipocytes↗

Amyloid-beta peptide enhances tumor necrosis factor-alpha-induced iNOS through neutral sphingomyelinase/ceramide pathway in oligodendrocytes.

Although accumulating evidence demonstrates that white matter degeneration contributes to pathology in Alzheimer's disease (AD), the underlying mechanisms are unknown. In order to study the roles of the amyloid-beta peptide in inducing oxidative stress damage in white matter of AD, we investigated the effects of amyloid-beta peptide 25-35 (Abeta) on proinflammatory cytokine tumor necrosis factor-alpha (TNF-alpha)-induced inducible nitric oxide synthase (iNOS) in cultured oligodendrocytes (OLGs). Although Abeta 25-35 by itself had little effect on iNOS mRNA, protein, and nitrite production, it enhanced TNF-alpha-induced iNOS expression and nitrite generation in OLGs. Abeta, TNF-alpha, or the combination of both, increased neutral sphingomyelinase (nSMase) activity, but not acidic sphingomyelinase (aSMase) activity, leading to ceramide accumulation. Cell permeable C2-ceramide enhanced TNF-alpha-induced iNOS expression and nitrite generation. Moreover, the specific nSMase inhibitor, 3-O-methyl-sphingomyelin (3-OMS), inhibited iNOS expression and nitrite production induced by TNF-alpha or by the combination of TNF-alpha and Abeta. Overexpression of a truncated mutant of nSMase with a dominant negative function inhibited iNOS mRNA production. 3-OMS also inhibited nuclear factor kappaB (NF-kappaB) binding activity induced by TNF-alpha or by the combination of TNF-alpha and Abeta. These results suggest that neutral sphingomyelinase/ceramide pathway is required but may not be sufficient for iNOS expression induced by TNF-alpha and the combination of TNF-alpha and Abeta.

Amyloid beta-Peptides↗

Serum antibody responses in children with rotavirus diarrhea can serve as proxy for protection.

We examined sera from 42 patients 1 to 30 months of age for rotavirus immunoglobulin M (IgM), IgA, IgG, and IgG subclasses and sought to determine if serum antibody could serve as a reliable marker for prediction of disease severity. Infants in the first few months of life usually had high maternal IgG titers and, when they were infected with rotavirus, had low IgM titers or no IgM in acute-phase sera and poor seroconversions 3 weeks later, suggesting that maternal antibodies had inhibited viral replication and antibody responses. All patients > or =6 months of age had IgM in acute-phase sera, indicating that IgM is a good marker for acute rotavirus infection. IgG was the best overall predictor of an infection, as the convalescent-phase sera of 81% of the patients had a fourfold rise in the IgG titer. IgA titers in convalescent-phase sera and conversion rates were higher among patients > or =12 months of age than among children younger than 12 months. IgG1 was the predominant subclass detected in the acute-phase sera of some children and in all 28 convalescent-phase serum samples examined. Patients with preexisting acute-phase IgG titers of > or =100 or > or =200 had diarrhea that was less severe or of a shorter duration. These results indicate that serum IgG is the most reliable marker for seroconversion and is a consistent proxy for protection against severe disease.

Antibodies, Viral↗

Tissue engineering scheming by artificial intelligence.

Tissue engineers are often confused when seeking the most effective, economical and secure scheme for tissue engineering. The aim of this study is to generate tissue engineering schemes with artificial intelligence instead of human intelligence. The experimental data of tissue engineered cartilage were integrated and standardized with a centralized database, and a scheme engine was developed using artificial intelligent methods (artificial neural networks and decision trees). The scheme engine was trained with existing cases in the database, and then was used to generate tissue engineering schemes for new experimental animals. Following the schemes generated by the artificial intelligent system, we cured 18 of the 20 experimental animals. In conclusion, artificial intelligence is a powerful method for decision making in the tissue engineering realm.

Algorithms↗

Survey of oral microbial diversity using PCR-based denaturing gradient gel electrophoresis.

Polymicrobial biofilms in the human oral cavity exhibit marked diversity. PCR-based denaturing gradient gel electrophoresis (PCR-DGGE) surveys microbial diversity by displaying PCR-generated 16S rDNA fragments that migrate at different distances, reflecting the differences in the base-pair (i.e., % G+C) composition of the fragment. This study examined DGGE-generated diversity profiles of cultivable bacteria from individuals with different caries status. Initially, we developed a set of PCR-DGGE running conditions appropriate to oral bacteria. Next, we assessed migration standards from known oral bacterial reference strains. To test the methods, we profiled 20 bacterial saliva samples cultivated from young adults. The study produced a battery of species-specific 16S rDNA amplicons that could be used as a migration distance standard necessary for computer-assisted profile analysis. From the clinical samples, we found a significantly greater diversity of oral microbes in caries-free individuals compared with caries-active individuals (P = 0.01). These findings suggest thtat a portion of oral microbiota of caries-active individuals may be absent, suppressed, or replaced.

Actinomyces↗

Impact of APOE in mild cognitive impairment.

OBJECTIVE: The authors aimed to use baseline data of an ongoing large, prospective study in subjects with mild cognitive impairment (MCI) to investigate the impact of APOE genotype on the symptom profile of the condition. METHODS: Cognitive assessments included the AD Assessment Scale cognitive subscale (ADAS-cog), the Mini-Mental State Examination (MMSE), and a cognitive battery for assessment of memory, attention, and executive function. Behavioral assessments included the Neuropsychiatric Inventory and Beck Depression Inventory. Activities of daily living were assessed by the AD Cooperative Study Activities of Daily Living (ADCS-ADL) scale. Hippocampal volumes were measured with MRI. RESULTS: A total of 494 of 1,018 study subjects provided APOE data. Approximately 40% of the subjects were APOE epsilon4 carriers. APOE epsilon4 carriers had lower MMSE (p = 0.01) and higher ADAS-cog (p < 0.0001) scores than noncarriers, indicating worse cognitive impairment. APOE epsilon4 carriers also had greater deficits on New York University delayed paragraph recall and Buschke free and cued selective reminding tests, and on the ADCS-ADL scale (p < 0.001). They also had smaller hippocampal volumes (p = 0.002). Behavioral scores were similar across the subgroups. CONCLUSION: MCI subjects carrying the APOE epsilon4 allele showed distinct cognitive and imaging profiles, which appeared to resemble those of early Alzheimer patients. APOE epsilon4 genotype was associated with greater impairments in memory and functional activities as well as hippocampal atrophy.

Activities of Daily Living↗

Formation and structure of a dense octahedral glass.

We have performed in situ x-ray and neutron-diffraction measurements, and molecular dynamics simulations, of GeO2, an archetypal network-forming glass under pressure. Below 5 GPa, additional atoms encroaching on the first tetrahedral shell are seen to be a precursor of local coordination change. Between 6 and 10 GPa, we observe structures with a constant average coordination of approximately 5, indicating a new metastable, intermediate form of the glass. At 15 GPa, the structure of a fully octahedral glass has been measured. This structure is not retained upon decompression and, therefore, must be studied in situ.

Journal Article↗

Structure and order of a homologous series of bent-core molecules: a 13C NMR study.

A carbon-13 NMR study in a series of bent-core (banana-shaped) molecules is reported. In 1, 3- phenylene bis[4'-alkenyloxy biphenyl]-4-carboxylate derivatives the position of the chlorine substituent(s) connected to the central phenyl ring and/or the terminal chain length of the compounds were varied. By analyzing the observed chemical shift anisotropies, the order parameters S and bending angles in their nematic phase are compared. The biphenyl moiety on each arm of the molecular core is found to form a nonzero twist angle.

Journal Article↗

Taurine protected myocardial mitochondria injury induced by hyperhomocysteinemia in rats.

Taurine can protect against cardiovascular diseases, whereas elevated levels of plasma homocysteine are associated with atherosclerotic and thromboembolic cardiovascular diseases. To illustrate the effects of taurine on hyperhomocysteinemia, we observed the myocardial mitochondria dysfunction in the rats with hyperhomocysteinemia induced by diet methionine loading, and the therapeutic effect of taurine. A methionine diet increased plasma homocysteine concentration (133.51 +/- 27.91 micromol/L vs 12.31 +/- 2.58 micromol/L in control, P < 0.01), stimulated the production of reactive oxygen species (ROS) in the myocardial mitochondria, and inhibited the activities of mitochondrial Mn-superoxide dismutase and catalase. The 45Ca uptake and Ca2+-ATPase activity in the myocardial mitochondria were significantly lowered in rats with hyperhomocysteinemia. Taurine supplements effectively attenuated the hyperhomocysteinemia-induced ROS production and inhibition of Mn-superoxide dismutase and catalase activities in the myocardial mitochondria, and increased its 45Ca uptake and Ca2+-ATPase activity. Thus, taurine antagonizes the oxidative stress injury in the myocardial mitochondria induced by the hyperhomocysteinemia.

Animals↗

Monolithically integrated bacteriorhodopsin/semiconductor opto-electronic integrated circuit for a bio-photoreceiver.

The light-sensitive protein, bacteriorhodopsin (BR), is monolithically integrated with an InP-based amplifier circuit to realize a novel opto-electronic integrated circuit (OEIC) which performs as a high-speed photoreceiver. The circuit is realized by epitaxial growth of the field-effect transistors, currently used semiconductor device and circuit fabrication techniques, and selective area BR electro-deposition. The integrated photoreceiver has a responsivity of 175 V/W and linear photoresponse, with a dynamic range of 16 dB, with 594 nm photoexcitation. The dynamics of the photochemical cycle of BR has also been modeled and a proposed equivalent circuit simulates the measured BR photoresponse with good agreement.

Amplifiers, Electronic↗

Hereditary prostate cancer in African American families: linkage analysis using markers that map to five candidate susceptibility loci.

African American men have the highest incidence of prostate cancer in the world. Despite this statistic, linkage studies designed to localise prostate cancer susceptibility alleles have included primarily men of Caucasian descent. In this report, we performed a linkage analysis using 33 African American prostate cancer families from two independent research groups. In total, 126 individuals (including 89 men with prostate cancer) were genotyped using markers that map to five prostate cancer susceptibility loci, namely HPC1 at 1q24-25, PCAP at 1q42.2-43, CAPB at 1p36, HPC20 on chromosome 20, and HPCX at Xq27-28. Multipoint mode-of-inheritance-free linkage analyses were performed using the GENEHUNTER software. Some evidence of prostate cancer was detected to HPC1 using all families with a maximum NPL Z score of 1.12 near marker D1S413 (P=0.13). Increased evidence of linkage was observed in the 24 families with prostate cancer diagnosis prior to age 65 years and in the 20 families with male-to-male transmission. Some evidence of prostate cancer linkage was also detected at markers mapping to PCAP, HPC20, and HPCX. Continued collection and analysis of African American prostate cancer families will lead to an improved understanding of inherited susceptibility in this high-risk group.

Black or African American↗

Employment of 16 S rDNA gene sequencing techniques to identify culturable environmental eubacteria in a tertiary referral hospital.

Universal or 'broad-range' eubacterial polymerase chain reaction (PCR) was performed on 53 isolates from environmental water-associated sites in a haematology unit (N = 22) and the outer surfaces of cleaning lotion containers sited throughout a tertiary referral hospital (N = 31) 16 S rDNA PCR was performed using two sets of universal primers, including the novel reverse primer, XB4, to generate a composite amplicon of 1068 bp, which was sequenced to obtain each isolate's identity. Sequence analysis was able to identify 51 isolates. Most (75% from the haematology unit and 81% from cleaner containers) were Gram-positive. Nine different genera were identified from the haematology unit and 13 from the cleaning lotion containers. This study provides the first reports of Terrabacter spp. and Brachybacterium paraconglomeratum isolated from a hospital environment. As unusual and difficult-to-identify environmental organisms are unlikely to be clinically significant, and molecular identification is costly and labour-intensive, we recommend that molecular methods are only used as an adjunct to first-line phenotypic identification schemes where a definitive identification is required. Where molecular identification methods are justified, partial 16 S rDNA PCR and sequencing employing the novel universal primer XB4, is a valuable and reliable technique.

Actinomycetales↗

Electron microscopy investigation of gallium oxide micro/nanowire structures synthesized via vapor phase growth.

Large-scale micro/nanosized Ga(2)O(3) structures were synthesized via a simple vapor p9hase growth method. The morphology of the as-grown structures varied from aligned arrays of smooth nano/microscale wires to composite and complex microdendrites. We present evidence that the formation of the observed structure depends strongly on its position relative to the source materials (the concentration distribution) and on the growth temperature. A growth model is proposed, based on the vapor-solid (VS) mechanism, which can explain the observed morphologies.

Journal Article↗

Manipulation of in vitro toxicant sensors in an ultrasonic standing wave.

Multi-cellular spheroids are increasingly employed as in vitro sensors of toxicants and a single spheroid can be used as a test object. An ultrasonic standing wave trap (USWT) can hold small particles in a medium-flowing system. This study investigated the conditions for holding HepG2 spheroids in an USWT and its relevance to use in toxicity testing. It can take many hours to reach a detectable end point of cell damage in a standard cellular in vitro toxicant assay and the process might be accelerated through increased sample flow past the spheroid. A USWT was employed here to levitate and hold HepG2 spheroids stationary against a flow of 3 mm s(-1) when the acoustic pressure amplitude is 1.9 MPa. The ultrasonic drive frequency was 1.64 MHz. Acoustic microstreaming in the standing wave chamber generated 1 mm s(-1) flow past a levitated spheroid-scale (80 microm diameter) latex particle in the absence of sample through-flow. The conditions required to form aggregates of cells of a HepG2 cell line in a single half wavelength ultrasonic standing wave mini-chambers are also described here. It is argued that the manipulation capabilities demonstrated may have potential in increasing the efficiency of in vitro toxicant detection by spheroids. Preliminary, visual (unquantified) fluorescence microscopy observations of spheroids levitated in the standing wave in the presence of the toxicant DL-propranolol do suggest accelerated loss of viability compared with controls.

Biosensing Techniques↗

Gene transfer of interleukin-4 delays acute rejection of splenic allografts in rats.

Spleen transplantation is the treatment of choice for some diseases, such as hemophilia A. However, the risk and intensity of rejection after spleen transplantation is greater and more difficult to control than other types of transplant. In the present study, we demonstrated that perfusion of IL-4 expression plasmids into donor spleens pretransplantation led to overexpression of IL-4 and downregulation of IFN-gamma in situ, associated with delayed acute rejection of the allograft. Gene transfer of IL-4 may represent a potential therapeutic approach to induce tolerance to splenic allografts.

Animals↗