[Show abstract][Hide abstract] ABSTRACT: For multicellular organisms, different tissues coordinate to integrate physiological functions, although this systematically and gradually declines in the aging process. Therefore, an association exists between tissue coordination and aging, and investigating the evolution of tissue coordination with age is of interest. In the past decade, both common and heterogeneous aging processes among tissues were extensively investigated. The results on spatial association of gene changes that determine lifespan appear complex and paradoxical. To reconcile observed commonality and heterogeneity of gene changes among tissues and to address evolution feature of tissue coordination with age, we introduced a new analytical strategy to systematically analyze genome-wide spatio-temporal gene expression profiles. We first applied the approach to natural aging process in three species (Rat, Mouse and Drosophila) and then to anti-aging process in Mouse. The results demonstrated that temporal gene expression alteration in different tissues experiences a progressive association evolution from spatial synchrony to asynchrony and stochasticity with age. This implies that tissue coordination gradually declines with age. Male mice showed earlier spatial asynchrony in gene expression than females, suggesting that male animals are more prone to aging than females. The confirmed anti-aging interventions (resveratrol and caloric restriction) enhanced tissue coordination, indicating their underlying anti-aging mechanism on multiple tissue levels. Further, functional analysis suggested asynchronous DNA/protein damage accumulation as well as asynchronous repair, modification and degradation of DNA/protein in tissues possibly contributes to asynchronous and stochastic changes of tissue microenvironment. This increased risk for a variety of age-related diseases such as neurodegeneration and cancer that eventually accelerate organismal aging and death. Our study suggests a novel molecular event occurring in aging process of multicellular species that may represent an intrinsic molecular mechanism of aging.
[Show abstract][Hide abstract] ABSTRACT: The predictive value of RRM1 to therapeutic efficacy of gemicitabine-containing chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) remains disputable. This meta-analysis is performed to systematically evaluate whether RRM1 expression is associated with the clinical outcome of gemcitabine-containing regimen in advanced NSCLC.
An electronic search was conducted using the databases Pubmed, Medline, EMBASE, Cochrane library and CNKI, from inception to May, 2011. A systemic review of the studies on the association between RRM1 expression in advanced NSCLC and clinical outcome of gemcitabine-containing regimen was performed. Pooled odds ratios (OR) for the response rate, weighted median survival and time to progression were calculated using the software Revman 5.0.
The search strategy identified 18 eligible studies (n=1243). Response rate to gemcitabine-containing regimen was significantly higher in patients with low/negative RRM1 (OR=0.31, 95% CI 0.21-0.45, P<0.00001). NSCLC patients with low/negative RRM1 who were treated with gemicitabine-containing regimen survived 3.94 months longer (95% CI 2.15-5.73, P<0.0001) and had longer time to progression for 2.64 months (95% CI 0.39-4.89, P=0.02) than those with high/positive RRM1.
Low/negative RRM1 expression in advanced NSCLC was associated with higher response rate to gemcitabine-containing regimen and better prognosis. Large phase III randomized trials are required to identify whether RRM1 detection is clinically valuable for predicting the prognosis and sensitivity to gemcitabine-containing regimen in advanced NSCLC.
No preview · Article · Aug 2011 · Lung cancer (Amsterdam, Netherlands)
[Show abstract][Hide abstract] ABSTRACT: Glucocorticoids play an important role in modulating allergic inflammation and immune response. However, little is known about the role of endogenous glucocorticoids in airway allergic disease.
To investigate the effects of endogenous glucocorticoids on regulating allergic inflammation and T(H)1/T(H)2 balance in an airway allergic murine model.
An ovalbumin-sensitized murine model was established by intraperitoneal injection sensitization and intranasal challenge with ovalbumin. Glucocorticoid release was inhibited by administration of metyrapone, and the peripheral glucocorticoid receptors were blocked by administration of RU486. The numbers of eosinophils in the lung, peripheral blood, and bone marrow were quantified. The changes in T(H)2/T(H)1 cells were investigated by flow cytometry, and their cytokines were tested by enzyme-linked immunosorbent assay, including interleukin 4, interleukin 5, and interferon gamma, in the supernatant of the spleen cell culture.
Inhibition of endogenous glucocorticoids caused more sneezing and further increased eosinophil counts in the peripheral blood and bone marrow of the sensitized mice. However, by inhibition of endogenous glucocorticoids, the interferon gamma levels were upregulated, the interleukin 4 and 5 levels were down-regulated, and the ratio of T(H)2/T(H)1 cells decreased significantly, indicating a shift to a T(H)1-predominant immune response in sensitized mice.
Our findings suggest that endogenous glucocorticoids play an important role in abating allergic inflammatory reaction and modulating the T(H)1/T(H)2 balance in an airway allergic murine model. Inhibition of endogenous glucocorticoids resulted in a shift to T(H)1 predominance, but that did not attenuate the severity of the allergic inflammatory reaction.
No preview · Article · Dec 2009 · Annals of allergy, asthma & immunology: official publication of the American College of Allergy, Asthma, & Immunology
[Show abstract][Hide abstract] ABSTRACT: A liquid chromatography coupled with mass spectrometry (LC/MS) based metabonomics approach was applied to characterize the aging of rats, and the anti-aging effect of total flavones of Epimedium (TFE), a traditional Chinese medicine, has also been investigated. Serum samples collected from 4, 10, 18 and 24 month-old rats and TFE-administered rats have been profiled by LC/MS. Thirty age-related endogenous metabolites were discovered by partial least squares (PLS) and Hotelling's T(2) control chart, among which 25 metabolites were structurally identified by MS(n) analysis and ten of them were further confirmed via authentic chemicals. All important age-related metabolites, such as unsaturated fatty acids, saturated fatty acids, nucleotides, carnosine, ergothioneine and amino acids, displayed age-related changes, and most of them were reset to a younger level after TFE administration. This study indicated that aging could be characterized by changes of lipid metabolisms and accumulation of free radicals. The anti-aging effects of TFE might due to the intervention on lipid metabolism and its property of anti-oxidation.
No preview · Article · Oct 2009 · Molecular BioSystems
[Show abstract][Hide abstract] ABSTRACT: A simple high performance liquid chromatographic method has been developed for the determination of nine flavonoids in Herba Epimedii, including quercetin-3-O-glucoside, epimedin A, hexandraside A, epimedin B, epimedin C, icariin, icariside I, icariside II, and icaritin. The chromatographic separation was performed on a Diamonsil C(18) column (5 microm, 250x4.6 mm) with gradient elution by acetonitrile-0.5% acetic buffer (adjusted to pH 5.00 with triethylamine). Methodological validation gave acceptable linearities (r(2) >0.9992) and recoveries (ranging from 98.9 to 102.4%). The limits of detection of these flavonoids ranged from 16.3 to 83.3 ng. The results indicated that the contents of flavonoids in Herba Epimedii varied significantly from habitat to habitat with contents ranging from 0.05 to 39.0 mg/g. Twenty five Herba Epimedii samples prepared from five different botanical materials were investigated by the established method, and the results showed the influence of the botanical material and the habitat on the quality of Herba Epimedii. The proposed method is simple, effective, and suitable for the evaluation of this traditional Chinese medicine.
No preview · Article · Dec 2007 · Journal of Separation Science
[Show abstract][Hide abstract] ABSTRACT: A rapid and sensitive method using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) was developed and validated for the simultaneous quantitative determination of icariin and its two major metabolites, icariside I and icariside II in rat plasma. The analytes were extracted by liquid-liquid extraction with ethyl acetate after internal standard (daidzein) spiked. The separation was performed by a ZORBAX SB-C(18) column (3.5 microm, 2.1 mm x 100 mm) and a C(18) guard column (5 microm, 4.0 mm x 2.0mm) with an isocratic mobile phase consisting of acetonitrile-water-formic acid (50:50:0.05, v/v/v) at a flow rate of 0.25 mL/min. The Agilent G6410A triple quadrupole LC-MS system was operated under the multiple reaction monitoring (MRM) mode using the electrospray ionization technique in positive mode. The nominal retention times for icariin, icariside I, icariside II and daidzein were 1.21, 1.88, 2.34 and 1.35 min, respectively. The lower limits of quantification (LLOQ) of icariin, icariside I and icariside II of the method were 1.0, 0.5 and 0.5 ng/mL, respectively. The method was linear for icariin and its metabolites with correlation coefficients >0.995 for all analytes. The intra-day and inter-day accuracy and precision of the assay were less than 12.5%. This method has been applied successfully to a pharmacokinetic study involving the intragastric administration of icariin to rats.
No preview · Article · Nov 2007 · Journal of Pharmaceutical and Biomedical Analysis