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Biomedical subjects

Xuejun Peng

Publications and source records attributed to Xuejun Peng.

7 recordsLinked to original sources

Multi-omic analyses of the same sample using metabolomics, lipidomics, proteomics, phosphoproteomics, and glycoproteomics.

Mass spectrometry (MS)-based multi-omics offers powerful tools to comprehensively characterize proteins, post-translational modifications, metabolites, and lipids. However, these measurements are typically performed using separate sample preparation workflows and modality-specific liquid chromatography mass spectrometry (LC-MS) platforms, limiting integration and constraining applications to small amounts of sample materials, especially scarce clinical specimens. Here, we describe a unified nano-LC-MS framework that enables metabolomic, lipidomic, proteomic, phosphoproteomic, and glycoproteomic analyses from the same starting material using a single nano-LC-MS platform, with only the chromatographic conditions, acquisition methods, and enrichment procedures tailored to each omics. This integrated strategy reduces workflow complexity and sample consumption while improves analytical continuity across molecular layers. By enabling deep multi-omics characterization from the same sample, this platform provides a practical foundation for comprehensive analysis of precious clinical samples.

Proteomics↗

Statistical implications of pooling RNA samples for microarray experiments.

BACKGROUND: Microarray technology has become a very important tool for studying gene expression profiles under various conditions. Biologists often pool RNA samples extracted from different subjects onto a single microarray chip to help defray the cost of microarray experiments as well as to correct for the technical difficulty in getting sufficient RNA from a single subject. However, the statistical, technical and financial implications of pooling have not been explicitly investigated. RESULTS: Modeling the resulting gene expression from sample pooling as a mixture of individual responses, we derived expressions for the experimental error and provided both upper and lower bounds for its value in terms of the variability among individuals and the number of RNA samples pooled. Using "virtual" pooling of data from real experiments and computer simulations, we investigated the statistical properties of RNA sample pooling. Our study reveals that pooling biological samples appropriately is statistically valid and efficient for microarray experiments. Furthermore, optimal pooling design(s) can be found to meet statistical requirements while minimizing total cost. CONCLUSIONS: Appropriate RNA pooling can provide equivalent power and improve efficiency and cost-effectiveness for microarray experiments with a modest increase in total number of subjects. Pooling schemes in terms of replicates of subjects and arrays can be compared before experiments are conducted.

Computational Biology↗

Antibodies to HSP70 and HSP90 in serum in non-small cell lung cancer patients.

Heat shock proteins (HSPs) are components of a physiologic stress response that are also over-expressed in various cancers including non-small cell lung cancer (NSCLC). During NSCLC serum-antibody screening of a NSCLC cDNA T7 phage library for immunogenic proteins we isolated HSP70 and HSP90 proteins. Isolation of these proteins suggested that corresponding antibodies could be elevated in NSCLC patient sera, a novel finding that could pilot their use as markers of NSCLC. We showed histochemically that patient sera were more reactive with each phage-expressed protein than normal sera. Antibody affinity for each phage-expressed protein was confirmed by limiting the dilution of individual sera assayed by Ab enzyme-linked immunosorbent assay (ELISA). Sera from 49 NSCLC patients assayed by Ab ELISA and normalized to 40 controls showed that HSP70 antibodies were significantly greater in patient sera than in normals (P=0.0002), while HSP90 antibodies were not significantly different (P=0.11). Analysis of the results with logistic regression and receiver operating characteristics (ROC) curves showed that HSP70 antibodies were modest markers of NSCLC (sensitivity 0.74 and specificity 0.73; area under the curve or AUC=0.731), while HSP90 antibodies appeared to be poor in both criteria with an AUC of 0.602. Further evaluation of HSP70 antibodies as potential markers of disease may be rational.

Antibodies↗

Age-related trends in gene expression in the chemosensory-nasal mucosae of senescence-accelerated mice.

We have utilized high-density GeneChip oligonucleotide arrays to investigate the use of the senescence-accelerated mouse (SAM) as a biogerontological resource to identify patterns of gene expression in the chemosensory-nasal mucosa. Gene profiling in chronologically young and old mice of the senescence-resistant (SAMR) and senescence-prone (SAMP) strains revealed 133 known genes that were modulated by a three-fold or greater change either in one strain or the other or in both strains during aging. We also identified known genes in our study which based on their encoded proteins were identified as aging-related genes in the aging neocortex and cerebellum of mice as reported by Lee et al. (2000) [Nat. Genet. 25 (2000) 294]. Changes in gene profiles for chemosensory-related genes including olfactory and vomeronasal receptors, sensory transduction-associated proteins, and odor and pheromone transport molecules in the young SAMR and SAMP were compared with age-matched C57BL/6J mice. An analysis of known gene expression profiles suggests that changes in the expression of immune factor genes and genes associated with cell cycle progression and cell death were particularly prominent in the old SAM strains. A preliminary cellular validation study supported the dysregulation of cell cycle-related genes in the old SAM strains. The results of our initial study indicated that the use of the SAM models of aging could provide substantive information leading to a more fundamental understanding of the aging process in the chemosensory-nasal mucosa at the genomic, molecular, and cellular levels.

Aging↗

Chiral separation of benzoporphyrin derivative mono- and diacids by laser induced fluorescence-capillary electrophoresis.

A method for the separation of benzoporphyrin derivative mono- and diacid (BPDMA, BPDDA) enantiomers by laser induced fluorescence-capillary electrophoresis (LIF-CE) has been developed. By using 300 mM borate buffer, pH 9.2, 25 mM sodium cholate and 10% acetronitrile as electrolyte, +10 kV electrokinetic sampling injection of 2 s and an applied +20 kV voltage across the ends of a 37 cm capillary (30 cm to the detector, 50 microm ID), all six BPD stereoisomers were baseline-separated within 20 min. Formation constants, free electrophoretic and complexation mobilities with borate and cholate were determined based on dynamic complexation capillary electrophoresis theory. The BPD enantiomers can be quantitatively determined in the range of 10(-2)-10(-5) mg mL(-1). The correlation coefficients (r2) of the least-squares linear regression analysis of the BPD enantiomers are in the range of 0.9914-0.9997. Their limits of detection are 2.18-3.5 x 10(-3) mg mL(-1). The relative standard deviations for the separation were 2.90-4.64% (n = 10). In comparison with high-performance liquid chromatography (HPLC), CE has better resolution and efficiency. This separation method was successfully applied to the BPD enantiomers obtained from a matrix of bovine serum and from liposomally formulated material as well as from studies with rat, dog and human microsomes.

Animals↗

Local tissue toxicity in response to extravascular extravasation of magnetic resonance contrast media.

RATIONALE AND OBJECTIVES: The relative toxicities of the gadolinium chelates currently available in the United States were compared when extravasated in soft tissue. The increasing use of these contrast agents in higher volumes and at faster injection rates, often with a power injector, was a principal motivation for this research. METHODS: Gadopentetate dimeglumine (Magnevist), gadoteridol (ProHance), gadodiamide (Omniscan), and gadoversetamide (Optimark) were evaluated at standard concentration and compared with a control (physiologic saline) and the conventional ionic radiographic contrast medium meglumine diatrizoate (Renografin 60). Each mouse received a subcutaneous injection in the hindlimb of 0.3 mL of contrast or saline. There were 6 experimental groups, with 15 animals in each group. The individual performing the injection was blinded to the identity of the contrast agent used in each mouse. After 48 hours, the mice were killed and tissue samples obtained for histopathology. A veterinary pathologist, also blinded to the agent injected, graded the degree of damage seen on microscopic examination. RESULTS: Of the four MR contrast agents, gadopentetate dimeglumine caused the greatest tissue damage, and gadoteridol and gadodiamide-the two lowest osmolar agents-the least. The difference was statistically significant in terms of both inflammation (P = 0.0008 for gadoteridol, and P = 0.006 for gadodiamide) and necrosis (P = 0.0067 for gadoteridol, and P = 0.031 for gadodiamide), when these agents were compared with gadopentetate dimeglumine. In regard to the control experiments, for all three variables (necrosis, edema, and inflammation), there was no statistically significant difference between the results with gadoteridol or gadodiamide and those with saline. In terms of both edema and inflammation, the effect of gadopentetate dimeglumine, although less, could not be differentiated with any statistical significance from that of meglumine diatrizoate. Gadoversetamide, which has an osmolality between the ionic agent (gadopentetate dimeglumine) and the other two nonionic agents, caused a reaction that could not be differentiated from that seen with gadopentetate dimeglumine for both necrosis and edema. Only in the scoring of inflammation was the effect less using gadoversetamide compared to gadopentetate dimeglumine with any statistical significance (P = 0.021). CONCLUSIONS: The risk of tissue damage due to extravasation is not widely appreciated for the gadolinium chelates. Care should be exercised during contrast injection, to avoid inadvertent extravasation and its deleterious consequences, in particular with the two higher osmolar agents (gadopentetate dimeglumine and gadoversetamide).

Animals↗

Geographic variation in breast-conserving surgery in Kentucky's Medicare population.

Breast cancer represents a significant disease burden in Kentucky, affecting some 2,900 newly diagnosed women each year. About 600 Kentucky women will die of breast cancer in 2001. Kentucky's age-adjusted death rate for breast cancer in 1995 was 24.2 per 100,000 women, ranking 30th in the United States. In Kentucky and nationally, it is known that breast cancer treatment and prognosis may be complicated by elderly women's age and comorbid illnesses. Not all differences in treatment and prognosis can be explained, however, by patient characteristics or illness severity. A large body of health services research has developed over the last thirty years that documents the relationship between the supply of health care resources (e.g., physicians, hospital beds) and variances in treatment. This line of research has particular significance in Kentucky, where the supply of resources varies greatly across the state. Because breast cancer treatment variations unrelated to breast cancer disease may affect prognosis and outcome, it is important that these treatment variations be understood. The purpose of this study was to determine the existence and extent to which Kentucky women over 65 with the same stage of breast cancer receive breast-conserving surgery in different geographic regions, and to link geographic differences to differences in population characteristics, and the availability of health care resources for cancer treatment.

Aged↗