[Show abstract][Hide abstract] ABSTRACT: Cerebral ischemia-reperfusion injury may simultaneously result in functional variation of multiple genes/pathways. However, most prior time-sequence studies on its pathomechanism only focused on a single gene or pathway. Our study aimed to systematically analyze the time-dependent variation in the expression of multiple pathways and networks within 24 h after cerebral ischemia-reperfusion injury.
By uploading 374 ischemia-related genes into the MetaCore software, the variation in the expression of multiple pathways and networks in 3 h, 12 h, and 24 h after cerebral ischemia-reperfusion injury had been analyzed. The conserved TNFR1-signaling pathway, among the top 10 pathways, was consistently enriched in 3 h, 12 h, and 24 h groups. Three overlapping pathways were found between 3 h and 12 h groups; 2 between 12 h and 24 h groups; and 1 between 3 h and 24 h groups. Five, 4, and 6 non-overlapping pathways were observed in 3 h, 12 h, and 24 h groups, respectively. Apart from pathways reported by earlier studies, we identified a novel pathway related to the time-dependent development of cerebral ischemia pathogenesis. The process of apoptosis stimulation by external signals, among the top 10 processes, was consistently enriched in 3 h, 12 h, and 24 h groups; 2, 1, and 2 processes overlapped between 3 h and 12 h groups, 12 h and 24 h groups, and 3 h and 24 h groups, respectively. Four, 5, and 5 non-overlapping processes were found in 3 h, 12 h and 24 h groups, respectively. The presence of apoptotic processes was observed in all the 3 groups; while anti-apoptotic processes only existed in 3 h and 12 h groups. Additionally, according to node degree, network comparison identified 1, 8,and 5 important genes or proteins (e.g. Pyk2, PKC, E2F1, and VEGF-A) in 3 h, 12 h, and 24 h groups, respectively. The Jaccard similarity index revealed a higher level of similarity between 12 h and 24 h groups than that between 3 h and 12 h groups.
Time-dependent treatment can be utilized to reduce apoptosis, which may activate anti-apoptotic pathways within 12 h after cerebral ischemia-reperfusion injury. Pathway and network analyses may help identify novel pathways and genes implicated in disease pathogenesis.
BMC Systems Biology 12/2015; 9(1):152. DOI:10.1186/s12918-015-0152-4 · 2.44 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Reverse transcriptase polymerase chain reaction assay (RT-PCR) has been proved to have high sensitivity and specificity to detect anaplastic lymphoma kinase (ALK) rearrangements. The aim of this study was to investigate the response to crizotinib in patients of advanced non-small-cell lung cancer (NSCLC) with ALK rearrangements detected by RT-PCR.
Only patients with advanced NSCLC who had their ALK rearrangement status detected by RT-PCR were included in this analysis. The utility of RT-PCR and fluorescence in situ hybridization assay (FISH) were compared in patients who were treated with crizotinib based on their positive ALK rearrangements.
1010 patients were included in this study. Among them, 104 patients were ALK RT-PCR positive and 53 of them received crizotinib treatment. Among 255 tumors simultaneously analyzed by FISH and RT-PCR, the latter successfully detected all the 25 tumors with arrangements, including two cases that were missed by FISH. The overall response rate (ORR) and median progression free survival (mPFS) of the 53 patients with ALK rearrangements who received crizotinib treatment were 60.4% (95%CI, 47.2-73.6) and 8.4 months (95% CI 6.75-10.05) respectively, which were similar to the 21 patients detected by FISH with ORR of 57.1% (95% CI 33.3-76.2) (p=0.799) and mPFS of 7.4 months (95% CI 4.43-10.38) (p=0.833) after crizotinib treatment. Interestingly, there were 2 patients responded to crizotinib had their ALK rearrangement detected by RT-PCR but not FISH.
RT-PCR should be considered as an alternative/supplemental approach to detect ALK fusion oncogene in NSCLC patients who might benefit from crizotinib treatment.
Journal of thoracic oncology: official publication of the International Association for the Study of Lung Cancer 09/2015; DOI:10.1097/JTO.0000000000000668 · 5.28 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Our previous studies have showed that ursodeoxycholic acid (UA) and jasminoidin (JA) effectively reduce cerebral infarct volume in mice. In this study we explored the pure synergistic mechanism of these compounds in treatment of mouse cerebral ischemia, which was defined as synergistic actions specific for phenotype variations after excluding interference from ineffective compounds.
Mice with focal cerebral ischemia were treated with UA, JA or a combination JA and UA (JU). Concha margaritifera (CM) was taken as ineffective compound. Cerebral infarct volume of the mice was determined, and the hippocampi were taken for microarray analysis. Particular signaling pathways and biological functions were enriched based on differentially expressed genes, and corresponding networks were constructed through Ingenuity Pathway Analysis.
In phenotype analysis, UA, JA and JU significantly reduced the ischemic infarct volume with JU being superior to UA or JA alone, while CM was ineffective. As a result, 4 pathways enriched in CM were excluded. Core pathways in the phenotype-positive groups (UA or JA) were involved in neuronal homeostasis and neuropathology. JU-contributing pathways included all UA-contributing and the majority (71.7%) of JA-contributing pathways, and 10 new core pathways whose effects included inflammatory immunity, apoptosis and nervous system development. The functions of JU group included all functions of JA group, the majority (93.1%) of UA-contributing functions, and 3 new core functions, which focused on physiological system development and function.
The pure synergism between UA and JA underlies 10 new core pathways and 3 new core functions, which are involved in inflammation, immune responses, apoptosis and nervous system development.
[Show abstract][Hide abstract] ABSTRACT: To determine how the relative amino acid contents and metabolic pathways regulate the pharmacological phenotypes in rats with cerebral ischemia after treatment with varying doses of DanHong injection (DHI).
Adult male rats underwent middle cerebral artery occlusion (MCAO), and were injected with DHI (DH-1: 1 mL/kg; DH-2: 2.5 mL/kg; DH-3: 5 mL/kg, and DH-4: 10 mL/kg, iv) daily for 3 d. The neurological deficit score, body weights and infarct volume were assessed. Serum levels of 20 free amino acids were determined using HPLC, and the values were transformed through the quantitative analysis of the amino acids in the serum metabolic spectrum. Multivariate statistical analysis methods (PCA and PLS-DA) and web-based metabolomics tools (MetPa and MetaboAnalyst) were used to analyze the biological data sets for the amino acids.
Administration of DHI dose-dependently decreased cerebral infarct volume, and ameliorated neurological deficits. A total of 5, 6, 7 and 7 non-overlapping metabolites were identified in the DH-1, DH-2, DH-3, and DH-4 groups, respectively. Eight metabolites were shared between the DHI groups and the vehicle group. In addition, the serum levels of glutamic acid, aspartic acid and serine increased with increasing DHI dose. A total of 3, 2, 2 and 5 non-overlapping metabolic pathways were identified in the DH-1, DH-2, DH-3 and DH-4 groups, respectively, and glycine, serine, threonine and histidine metabolism were identified as overlapping pathways among the 4 dose groups.
Overlapping and non-overlapping amino acid metabolites and metabolic pathways are associated with the dose-dependent neuroprotective effect of DHI.
[Show abstract][Hide abstract] ABSTRACT: Nb doped TiO2 microspheres modified with WO3 (Nb-TiO2/WO3) was prepared by ultrasonic spray pyrolysis method combined with impregnation method. The microspheres were characterized with SEM, TEM, XRD, BET, photoluminescence and UV-vis absorption spectra. The Nb-doping was observed to extend the spectral absorption of TiO2 into visible spectrum, and the absorption onset was red-shifted for about 88 nm compared to pristine TiO2 microspheres. Nb-TiO2/WO3 microspheres do not display a red-shifted absorption edge compared with Nb doped TiO2 microspheres. Under solar irradiation, Nb-TiO2/WO3 microspheres showed higher photocatalytic activity for methylene blue degradation compared with that of pure TiO2 microspheres and Nb doped TiO2 microspheres, which could be ascribed to the extended light absorption range and the suppression of electron-hole pair recombination.
Materials Research Bulletin 03/2015; 63:105-111. DOI:10.1016/j.materresbull.2014.11.050 · 2.29 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: According to the principle of evidence-based medicine (EBM), Chinese medical literatures based descriptive statistical analysis of common Chinese medical syndrome types were performed. By data extraction, standardization, and frequency calculation of disease names and syndrome types from 286 literatures in line with the inclusion criteria, the frequencies of diseases and syndromes were obtained to analyze common syndrome types in clinical practice, to analyze the distribution features of disease related syndromes and syndrome related diseases, to analyze the distribution of basic Chinese medical syndrome types in clinical common diseases as a whole, thus providing reference for clinical and basic researches.
Zhongguo Zhong xi yi jie he za zhi Zhongguo Zhongxiyi jiehe zazhi = Chinese journal of integrated traditional and Western medicine / Zhongguo Zhong xi yi jie he xue hui, Zhongguo Zhong yi yan jiu yuan zhu ban 08/2014; 34(8):1013-6.
[Show abstract][Hide abstract] ABSTRACT: Di-(2-ethylhexyl) phthalate, as the most commonly used plasticizer, is considered to be related to the asthma prevalence. There are studies affirming that the DEHP has an adjuvant effect in the pathogenesis of allergy asthma. Oxidative stress is one possible pathway for DEHP-adjuvant effect. Thus, this study explored whether DEHP could induce adjuvant effect in mouse asthma model via oxidative stress pathway. Male BALB/c mice were randomly divided into six groups: (1) saline group, (2) DEHP group, (3) ovalbumin (OVA) group, (4) DEHP+OVA group, (5) OVA +vitamin E (Vit E) group, (6) DEHP+OVA+Vit E group. The exposure dose of DEHP was 30 mg/kg body weight (bw)/day. After 18 days of the exposure protocol. Reactive oxygen species (ROS), glutathione (GSH) and malonaldehyde (MDA) levels and biomarkers related to asthma model were measured. Collectively, these data indicated higher ROS and MDA levels and lower GSH contents in DEHP+OVA group than that in OVA group, while Vit E, an antioxidant, could restore ROS, MDA and GSH levels to control levels and attenuate the DEHP and/or OVA effects. Our observations suggested that there was a relationship between oxidative stress and the adjuvant effect induced by DEHP in this mouse asthma model.
Food and Chemical Toxicology 06/2014; 71. DOI:10.1016/j.fct.2014.06.012 · 2.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: TiO2-graphene porous microspheres were prepared by ultrasonic spray pyrolysis (USP) of aqueous suspension of graphene oxide containing TiO2 nanoparticles (Degussa P25). The composite microspheres were characterized with SEM, XPS, photoluminescence, Raman and UV-Vis absorption spectra. TiO2-graphene porous microspheres displayed higher photocatalytic activity for the degradation of methylene blue solution than pristine TiO2 microspheres under the irradiation of Xe lamp, and the highest activity was obtained at a weight percentage of graphene around 1%. The effect of graphene on photocatalytic activity of porous microsphere was discussed in terms of the enhanced charge separation by TiO2-graphene heterojunction, increased absorption of the visible light, as well as the possible hindrance of mass transportation in microspheres.
Journal of Alloys and Compounds 01/2014; 584:180-184. DOI:10.1016/j.jallcom.2013.08.203 · 3.00 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Waveband-dependent photochemical reduction properties of graphene oxide (GO) were investigated. The ratio of oxygenated carbon to graphitic carbon of the GO film was reduced to 39% and 28% by 400-800 nm and 350-800 nm irradiation, respectively from the initial value of 47%, while this ratio changed negligibly by 520-800 nm irradiation. This waveband-dependent photoreduction is closely related to the wide size distribution of sp2 carbon clusters with different band gaps within the GO sheet, which play the role of the photochemical reacting centers. In addition, the photochemical activity of GO was also demonstrated by photoreduction of Ag+ in water. Our research suggests the possibilities of tuning the microstructure of GO by careful selection of irradiation conditions and of preparing noble metal nanoparticles with a neat surface on GO sheets.
[Show abstract][Hide abstract] ABSTRACT: Background and Purpose
With the increasing use of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) in patients with advanced non-small cell lung cancer (NSCLC), its acquired resistance has become a major clinical problem. Recent studies revealed that miR-21 was involved into the resistance of cytotoxic agents. The aim of this study was to investigate its role in the acquired resistance of NSCLC to EGFR-TKI.
EGFR-TKI-sensitive human lung adenocarcinoma cell line PC9 and the acquired resistant cell line, PC9R, were used. Lentiviral vectors were used to infect PC9 or PC9R to regulate the miR-21 expression. The expression of targeted proteins PTEN and PDCD4 was controlled by RNA interference. MicroRNA array, RT-PCR and TaqMan MicroRNA Assays were used to detect miR-21 expression. The MTT and Annexin V assays were used to determine proliferation and apoptosis. Western Blot and immunohistochemistry were used to analyze target protein expression (PTEN, PDCD4, Akt, p-Akt). We also constructed PC9R xenograft tumor model to observe the relationship between miR-21 and EGFR-TKI resistance in vivo and validated it in the clinical serum specimens of NSCLC patients treated with EGFR-TKI.
MiR-21 was overexpressed in the EGFR-TKI resistant cell line PC9R relative to PC9. The level of miR-21 was reversely correlated with the expression of PTEN and PDCD4 and positive correlated with PI3 K/Akt pathway. Inhibiting miR-21 with lentivirus vector induces apoptosis in PC9R cell line and inhibiting miR-21with ASO suppressed tumor growth in nude mice treated with EGFR-TKI. Furthermore, serum miR-21 expression in NSCLC patients treated with EGFR-TKI was significantly higher at the time of acquiring resistance than at baseline (p < 0.01).
miR-21 is involved in acquired resistance of EGFR-TKI in NSCLC, which is mediated by down-regulating PTEN and PDCD4 and activating PI3 K/Akt pathway.
[Show abstract][Hide abstract] ABSTRACT: Background. Baicalin (BA) exhibits ill understood neuroprotective, anti-inflammatory, and antioxidative effects in brain injury. Objective. To identify the differential network pathways associated with BA-related biological effects. Methods. MCAO-induced mice received BA 5 mg/Kg (BA group). Controls received vehicle only. Following ischaemia-reperfusion, ArrayTrack analysed the whole genome microarray of hippocampal genes, and MetaCore analysed differentially expressed genes. Results. Four reversing pathways were common to BA and controls, but only 6 were in the top 10 for BA. Three of the top 5 signalling pathways in controls were not observed in BA. BA treatment made absent 3 pathways of the top 5 signalling pathways from the top 5 in controls. There were 2 reversing pathways between controls and BA that showed altered gene expression. Controls had 6 networks associated with cerebral ischaemia. After BA treatment, 9 networks were associated with cerebral ischaemia. Enrichment analysis identified 10 significant biological processes in BA and controls. Of the 10 most significant molecular functions, 7 were common to BA and controls, and only 3 occurred in BA. BA and controls had 7 significant cellular components. Conclusions. This study showed that the clinical effectiveness of BA was based on the complementary effects of multiple pathways and networks.
Evidence-based Complementary and Alternative Medicine 11/2013; 2013:630723. DOI:10.1155/2013/630723 · 1.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The annexins are a multifamily of calcium-regulated phospholipid-binding proteins. To investigate the roles of annexins in fiber development, four genes encoding putative annexin proteins were isolated from cotton and designated AnnGh3, AnnGh4, AnnGh5 and AnnGh6. Quantitative RT-PCR results indicated that AnnGh3, AnnGh4 and AnnGh5 were preferentially expressed in fibers, while the transcripts of AnnGh6 were predominantly accumulated in roots. During fiber development, the transcripts of AnnGh3/4/5 genes were mainly accumulated in rapidly elongating fibers. With fiber cells further developed, their expression activity was dramatically declined to a relatively low level. In situ hybridization results indicated that AnnGh3 and AnnGh5 were expressed in initiating fiber cells (0-2 DPA). Additionally, their expression in fibers was also regulated by phytohormones and [Ca(2+) ]. Subcellular localization analysis discovered that AnnGh3 protein was localized in the cytoplasm. Overexpression of AnnGh3 in Arabidopsis resulted in a significant increase in trichome density and length on leaves of the transgenic plants, suggesting that AnnGh3 may be involved in fiber cell initiation and elongation of cotton.
[Show abstract][Hide abstract] ABSTRACT: Background
Recently, differences in tumor biology have been observed between Asian and Caucasian lung cancer patients, resulting in different sensitivities to targeted therapy. To date, all registered third-generation chemotherapeutic agents have been investigated mainly in Caucasians, but little is known whether this data can be transferred to an Asian population. The aim of this study was to provide evidence about the efficacy of chemotherapy in a Chinese population. Methods
Three thousand one hundred patients with advanced non-small-cell lung cancer NSCLC, treated between 2002 and 2009 with a platinum-based doublet first-line chemotherapy, including vinorelbine, gemcitabine, docetaxel or paclitaxel, were included for retrospective survival analysis. ResultsOverall survival (OS) was 12.1 months and progression free survival (PFS) was four months for all patients. No advantage in OS was seen for any of the four compounds. Gemcitabine was associated with a better PFS compared to the other three (P < 0.001). Docetaxel led to higher response rates, but this finding didn't reach statistical significance (P = 0,054). Chinese patients appear to have longer survival times compared to historical data in Caucasians. Conclusion
Our retrospective analysis suggests, that there is no difference in efficacy of third-generation chemotherapy between Asians and Caucasians.
Thoracic Cancer 05/2013; 4(2). DOI:10.1111/j.1759-7714.2012.00173.x · 0.90 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Trypanosoma brucei is a unicellular flagellated eukaryotic parasite that causes African trypanosomiasis in human and domestic animals with devastating health and economic consequences. Recent studies have revealed the important roles of the single flagellum of T. brucei in many aspects, especially that the flagellar motility is required for the viability of the bloodstream form T. brucei, suggesting that impairment of the flagellar function may provide a promising cure for African sleeping sickness. Knowing the flagellum proteome is crucial to study the molecular mechanism of the flagellar functions. Here we present a novel computational method for identifying flagellar proteins in T. brucei, called trypanosome flagellar protein predictor (TFPP). TFPP was developed based on a list of selected discriminating features derived from protein sequences, and could predict flagellar proteins with ∼92% specificity at a ∼84% sensitivity rate. Applied to the whole T. brucei proteome, TFPP reveals 811 more flagellar proteins with high confidence, suggesting that the flagellar proteome covers ∼10% of the whole proteome. Comparison of the expression profiles of the whole T. brucei proteome at three typical life cycle stages found that ∼45% of the flagellar proteins were significantly changed in expression levels between the three life cycle stages, indicating life cycle stage-specific regulation of flagellar functions in T. brucei. Overall, our study demonstrated that TFPP is highly effective in identifying flagellar proteins and could provide opportunities to study the trypanosome flagellar proteome systematically. Furthermore, the web server for TFPP can be freely accessed at http:/wukong.tongji.edu.cn/tfpp.
PLoS ONE 01/2013; 8(1):e54032. DOI:10.1371/journal.pone.0054032 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Intersectin-2L(ITSN-2L) is a long isoform of ITSN family, which is a multimodule scaffolding protein functioning in membrane-associated molecular trafficking and signal transduction pathways. ITSN-2L possesses a carboxy-terminal extension encoding a Dbl homology domain (DH), a pleckstrin homology domain (PH) and a C2 domain, suggesting that it could act as a guanine nucleotide exchange factor for Rho-like GTPases. But the role of C2 domain is obscure in this process. Here we report the crystal structure of human ITSN-2L C2 domain at 1.56 Å resolution. The sequence and structural alignment of ITSN-2L C2 domain with other members of C2 domain protein family indicate its vital cellular roles in membrane trafficking, the generation of lipid-second messengers and activation of GTPases. Moreover, our data show the possible roles of ITSN-2L C2 domain in regulating the activity of Cdc42.
Biochemical and Biophysical Research Communications 12/2012; 431(1). DOI:10.1016/j.bbrc.2012.12.087 · 2.30 Impact Factor