AIM: We aimed to observe the expression of extracellular matrix (ECM) and cellular adhesion molecules (CAM) in cirrhotic liver tissues after hepatitis C virus (HCV) infection. METHODS: Twelve patients with post HCV in...AIM: We aimed to observe the expression of extracellular matrix (ECM) and cellular adhesion molecules (CAM) in cirrhotic liver tissues after hepatitis C virus (HCV) infection. METHODS: Twelve patients with post HCV inflammatory liver cirrhosis were selected to evaluate their liver function and other virological, pathological parameters. Then three specimens of cirrhotic patients whose health assessment results and laboratory data were similar and three normal liver specimens explanted from liver grafts prepared for liver transplantation were chosen for investigating gene expression of ECM and CAM using cDNA expression array. RESULTS: The cDNA array assay revealed 36.7% (36/96)of genes with changes, in which 26.3% (26/96) was up regulated and 10.1% (10/96) was down-regulated. Integrin (ITGA), collagen (COL), ADAMTS were identified as the characteristic changes of ECM and CAM gene expression levels. ITGA were demonstrated β1 and β2 sub-section changed in liver cirrhosis.CONCLUSION: ECM and CAM play an important role inthe progression of liver cirrhosis after HCV infection. The capital mechanism is related to the inflammatory cellsinfiltration, the activation and transformation of ECM producing cells and the imbalance between production and elimination of ECM.展开更多
Background Extracellular matrix (ECM) orchestrates cell behaviour including growth, death, apoptosis, adhesion, migration, and invasion by activating several signalling pathways Certain components of ECM, such as ...Background Extracellular matrix (ECM) orchestrates cell behaviour including growth, death, apoptosis, adhesion, migration, and invasion by activating several signalling pathways Certain components of ECM, such as integrins, may act as receptors or co-receptors of enterovirus ECM-activated gene expressions in myocardium of viral heart disease including myocarditis and partial cardiomyopathy remain elusive This study was to investigate the expression of ECM-activated genes in myocardium of mouse with viral myocarditis Methods BALB/c mice were infected with Coxsackie virus B 3 (CVB 3) to establish an animal model of myocarditis Uninfected mice were also prepared and served as controls Specific mRNA expression pattern in myocarditic mouse heart was analysed by an in-house cDNA microarray containing 8192 genes Overexpressed ECM genes were selected and subsequently confirmed by Northern blot analysis Results Nine ECM genes were isolated, from the array of 8192 genes, as overexpressed genes in hearts of myocarditic mice in comparison with controls Subsequent Northern blot analysis confirmed that four of the nine genes were highly expressed Expression of these four genes, Fin15, ILk, Lamr1 and ADAMTS-1, has not been reported previously to be induced by Coxsackie virus Conclusion CVB 3-induced myocarditis is associated with gene expression profiles of certain ECM components展开更多
A three-dimensional electrical-thermal coupling model based on the finite element method is applied to study thermal properties of implant-defined vertical cavity surface emitting laser （VCSEL） arrays. Several param...A three-dimensional electrical-thermal coupling model based on the finite element method is applied to study thermal properties of implant-defined vertical cavity surface emitting laser （VCSEL） arrays. Several parameters including inter-element spacing, scales, injected current density and substrate temperature are considered. The actual temperatures obtained through experiment are in excellent agreement with the calculated results, which proves the accuracy of the model. Due to the serious thermal problem, it is essential to design arrays of low self-heating. The analysis can provide a foundation for designing VCSEL arrays in the future.展开更多
Beam steering in implant defined coherently coupled vertical cavity surface emitting laser （VCSEL） arrays is simulated using the FDTD solution software. Angular deflection dependent on relative phase differences amo...Beam steering in implant defined coherently coupled vertical cavity surface emitting laser （VCSEL） arrays is simulated using the FDTD solution software. Angular deflection dependent on relative phase differences among elements, inter-element spacing, element size and emitted wavelength is analyzed detailedly and systematically. We design and fabricate 1×2 implant defined VCSEL arrays for optimum beam steering performance. Electroni- cally controlled beam steering with a maximum deflection angle of 1.6° is successfully achieved in the 1 × 2 VCSEL arrays. The percentage of the power in the central lobe is above 39% when steering. The results show that the steering is controllable. Compared with other beam steering methods, the fabrication process is simple and of low cost.展开更多
We analyzed the seismic waveforms from the December 26, 2004 Sumatra-Andaman earthquake recorded at broadband seismic stations in western Europe. Previous studies involving of the beam-forming technique and high frequ...We analyzed the seismic waveforms from the December 26, 2004 Sumatra-Andaman earthquake recorded at broadband seismic stations in western Europe. Previous studies involving of the beam-forming technique and high frequency analysis suggest that the earthquake ruptured with a duration of around 500 s. This very long duration makes P wave overlap with later arrivals such as PP wave, which follows P in about 200 s. Since P waves are crucial for modeling earthquake processes, we propose an iterative method to separate P and PP waveforms. The separated P waveform confirms a second large energy release around 300 s after the initial rupture. The iterative signal separation technique is particularly useful for mixed signals that are not independent and the number of recording stations far exceeds number of mixed signal sources.展开更多
The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on eluc...The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.展开更多
Synapses are essential units for the flow of information in the brain.Over the last 70 years,synapses have been widely studied in multiple animal models including worms,fruit flies,and rodents.In comparison,the study ...Synapses are essential units for the flow of information in the brain.Over the last 70 years,synapses have been widely studied in multiple animal models including worms,fruit flies,and rodents.In comparison,the study of human synapses has evolved significantly slower,mainly because of technical limitations.However,three novel methods allowing the analysis of molecular,morphological,and functional properties of human synapses may expand our knowledge of the human brain.Here,we briefly describe these methods,and evaluate how the information provided by each unique approach may contribute to the functional and anatomical analysis of the synaptic component of human brain circuitries.In particular,using tissue from cryopreserved human brains,synaptic plasticity can be studied in isolated synaptosomes by fluorescence analysis of single-synapse long-term potentiation（FASS-LTP）,and subpopulations of synapses can be thoroughly assessed in the ribbons of brain tissue by array tomography（AT）.Currently,it is also possible to quantify synaptic density in the living human brain by positron emission tomography（PET）,using a novel synaptic radio-ligand.Overall,data provided by FASS-LTP,AT,and PET may significantly contribute to the global understanding of synaptic structure and function in both healthy and diseased human brains,thus directly impacting translational research.展开更多
OBJECTIVE:This study screened serum tumor biomarkers by surface enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) to establish a subset which could be used for the prediction of Qi de...OBJECTIVE:This study screened serum tumor biomarkers by surface enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) to establish a subset which could be used for the prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer;and as diagnostic model of Chinese medicine.METHODS:Serum samples from 63 lung cancer patients with Qi deficiency syndrome and phlegm and blood stasis,and 28 lung cancer patients with non-Qi deficiency syndrome and phlegm and blood stasis were analyzed using SELDI-TOF-MS with a PBS II-C protein chip reader.Protein profiles were generated using immobilized metal affinity capture(IMAC3) protein chips.Differentially-expressed proteins were screened.Protein peak clustering and classification analyses were performed using Biomarker Wizard and Biomarker Pattern software packages,respectively.RESULTS:A total of 268 effective protein peaks were detected in the 1,000-10,000 Da molecular range for the 15 serum proteins screened(P<0.05).The decision tree model was M 2284.97,with a sensitivity of 96.2% and a specificity of 66.7%.CONCLUSION:SELDI-TOF-MS techniques,combined with a decision tree model,can help identify serum proteomic biomarkers related to Qi deficiency syndrome and phlegm and blood stasis in lung cancer patients;and the predictive model can be used to discriminate between Chinese medicine diagnostic models of disease.展开更多
Background The prognostic relevance of World Health Organization （WHO） subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thym...Background The prognostic relevance of World Health Organization （WHO） subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thymomas will provide meaningful information for diagnosis and therapeutic management in type B thymoma. Methods Proteins extracted from twelve type B thymoma tissue specimens （six type B1 and six type B2） were analyzed by two-dimensional electrophoresis （2-DE） coupled with MALDI-TOF-MS. Differentially expressed proteins were then assayed in sixty-nine type B thymoma tissues （including B1, B2 and B3） by tissue array analysis with immunohistochemistry staining. The relationship of their expression with clinicopathological parameters, such as tumor stage or WHO classification, was estimated by Spearman＇s Rank Correlation Test. Results Sixteen differentially expressed proteins between type B1 and B2 thymoma tissues were identified. The differential levels of ezrin and glutathione S-transferase pi （GSTP1） were validated using immunohistochemistry staining. A statistically significant difference was observed in the positive rate of ezrin expression between type B1 thymoma and type B3 thymoma （Z= -2.963, P 〈0.01）. Ezrin showed a tendency to be expressed in higher classification tumors from type B1 to B3. A statistical analysis demonstrated that type B2 and B3 tumors had significantly higher positive expression of GSTP1 than the B1 group （type B2 vs. BI： Z= -2.582, P 〈0.01; type B3 vs. BI： Z= -4.012, P 〈0.001）. The results also showed a strong correlation between GSTP1 and WHO type staging of B1 to B3 tumors （Spearman＇s correlation coefficient： 0.633, P 〈0.001）. Statistical analysis showed that there was close correlation between GSTP1 and ezrin expression with the clinical stage （Spearman＇s correlation coefficients, ezrin： 0.481, P 〈0.05; GSTPI： 0.484, P 〈0.01）. Conclusions Differentially expressed proteins between type B1 and B2 thymoma tissues were analyzed by comparative proteomic analysis. The techniques of proteomic analysis and tissue array provide a potential tool for screening of key molecules in type B thymoma histological sub-classifications. The statistical analysis of ezrin and GSTP1 expression by immunohistochemistry, especially GSTP1, may be a useful approach for type B thymoma classification.展开更多
OBJECTIVE： To explore the nature of ＂Yin internal heat caused by Yin-deficiency＂ in terms of the theo- ry of Traditional Chinese Medicine, by studying en- ergy metabolism in rats with Yin-deficiency-heat syndrome a...OBJECTIVE： To explore the nature of ＂Yin internal heat caused by Yin-deficiency＂ in terms of the theo- ry of Traditional Chinese Medicine, by studying en- ergy metabolism in rats with Yin-deficiency-heat syndrome and analyzing the gene expression pro- file of their livers. METHODS： A Yin-deficiency-heat syndrome model was induced in rats using three Chinese medicinal herbs. Glycogen and triglycerides in blood plasma, and the enzyme activity of ATP in livers were mea- sured colorimetrically. Triiodothyronine （T3）, thyrox- ine （T4）, and thyroid stimulating hormone levels in blood plasma were also measured with enzyme linked immunosorbent assay. The gene expression profile of livers was detected with gene chip analy- sis. Differentially expressed genes were screened out and classified according to Gene Ontology. The accuracy of results were examined with reversetranscription-polymerase chain reaction RESULTS： Compared with the control group, body weight （P〈0.05） and hepatic glycogen （P〈0.05） were significantly lower in the Yin-deficiency-heat syndrome group. Moreover, toe temperature （P〈 0.01） and triglyceride （P〈0.05）, Na ＋-K＋-ATPase （P〈 0.01）, Mg2＋-ATPase （P〈0.01）, T3 （P〈0.05）, and 1-4 （P〈 0.01） levels were significantly higher. There were 99 differentially expressed genes in livers from the Y/n-deficiency-heat syndrome group. Genes were mainly related to sterol synthesis （Pc=0.0392）, de- fense response （Pc=0.0448）, and sterol metabolism （Pc=0.0533）. CONCLUSION： Abnormal expression genes in rats with Yin-deficiency-heat syndrome prompted the synthesis and metabolism of cholesterol, increased energy consumption, and reduced defense re- sponse. This gene expression might be the molecu- lar mechanism underlying ＂internal heat caused by Yin-deficiency＂ in the rats with Yin-deficiency-heat syndrome.展开更多
OBJECTIVE: To investigate changes in gene expression profiles in the hypothalamus related to the effects of acupuncture at the Renying(ST 9) acupoint in spontaneously hypertensive(SH) rats.METHODS: We randomly divided...OBJECTIVE: To investigate changes in gene expression profiles in the hypothalamus related to the effects of acupuncture at the Renying(ST 9) acupoint in spontaneously hypertensive(SH) rats.METHODS: We randomly divided 18 SH rats into Renying(ST 9) group and model control group, 9 body weight-matched Wistar-Kyoto rats were used as blank controls. Acupuncture was performed manually for 20-min daily over 28 d in the Renying(ST 9) group. Rat Gene 2.0 array technology was used for the determination of gene expression profiles and the screened key genes were verified by real-time quantitative polymerase chain reaction(RT-PCR) analyses.RESULTS: The different groups exhibited differential gene expression: compared with the blank control group, 48 genes were up-regulated and 91 genes were down-regulated in the model group;compared with the model group, 79 genes were up-regulated and 80 genes were down-regulated in Renying(ST 9) group. The RT-PCR results of the key genes including Chi3 l1, Ephx2, Klk1, 5-HT1 A and Cbs were consistent with that of gene chip analysis.CONCLUTION: Acupuncture at Renying(ST 9)could significantly lower the blood pressure of SH rats and affect their hypothalamic gene expression profile. Genes associated with the contraction of vascular smooth muscle and the regulation of inflammation, neurotransmitters may be involved in acupuncture's antihypertensive mechanism.展开更多
In this investigation,the effect of friction stir welding(FSW)parameters such as tool pin profiles,rotational speed and welding speed on the mechanical properties of tensile strength,hardness and impact energy of magn...In this investigation,the effect of friction stir welding(FSW)parameters such as tool pin profiles,rotational speed and welding speed on the mechanical properties of tensile strength,hardness and impact energy of magnesium alloy AZ31 was studied.The experiments were carried out as per Taguchi parametric design concepts and an L9 orthogonal array was used to study the influence of various combinations of process parameters.Statistical optimization technique,ANOVA,was used to determine the optimum levels and to find the significance of each process parameter.The results indicate that rotational speed(RS)and transverse speed(TS)are the most significant factors,followed by tool pin profile(PF),in deciding the mechanical properties of friction stir welded magnesium alloy.In addition,mathematical models were developed to establish relationship between different process variables and mechanical properties.展开更多
The exceptional point(EP)is one of the typical properties of parity–time-symmetric systems,arising from modes coupling with identical resonant frequencies or propagation constants in optics.Here we show that in addit...The exceptional point(EP)is one of the typical properties of parity–time-symmetric systems,arising from modes coupling with identical resonant frequencies or propagation constants in optics.Here we show that in addition to two different modes coupling,a nonuniform distribution of gain and loss leads to an offset from the original propagation constants,including both real and imaginary parts,resulting in the absence of EP.These behaviors are examined by the general coupled-mode theory from the first principle of the Maxwell equations,which yields results that are more accurate than those from the classical coupled-mode theory.Numerical verification via the finite element method is provided.In the end,we present an approach to achieve lossless propagation in a geometrically symmetric waveguide array.展开更多
A simple microlens array is designed between VCSEL array and fiber array for integration of array module. We increase the optical coupling efficiency from -32.057 dBm to -0.9054 dBm by using our designed microlens array.
We propose and demonstrate a scheme to smooth and shape the on-target patterns in multimode fiber lasers, which includes expanding-collimating system and lens array （LA）. A smooth pattern with flat-top and sharp-edg...We propose and demonstrate a scheme to smooth and shape the on-target patterns in multimode fiber lasers, which includes expanding-collimating system and lens array （LA）. A smooth pattern with flat-top and sharp-edge profiles can be obtained with the irradiation nonuniformity decreasing significantly. We analyze the effects of the parameters such as defocus distance, the tilt angles, the number of the incident fiber lasers, and the diffraction-weakened LA on the uniformity irradiation of target by numerical simulations.展开更多
OBJECTIVE: To explore the relationship between genetic polymorphisms of the ethanol metabolizing enzymes and the occurrence of alcoholic liver disease (ALD). METHODS: Sixty-five healthy male controls and 165 alcoholis...OBJECTIVE: To explore the relationship between genetic polymorphisms of the ethanol metabolizing enzymes and the occurrence of alcoholic liver disease (ALD). METHODS: Sixty-five healthy male controls and 165 alcoholisms (including 122 ALD patients and 43 male alcohol abusers without liver complications defined as alcohol-dependent) were analyzed by polymerase chain reaction and hybridized with oligonucleotide microarray to detect the polymorphisms of the ethanol metabolizing enzymes genes. RESULTS: The frequencies of alcohol dehydrogenase gene 2 * 1 ( ADH2 * 1 ) allele were shown as 37.69%, 46.51% and 59.02% in control, alcohol-dependent and ALD groups respectively; while those of ADH2 * 2 allele were shown as 62.31 %, 53.49% and 40.98% respectively. No ADH2 * 3 was detected in any of the subjects. The frequency of ADH2 * 1 was significantly higher in alcoholisms (ALD group and alcohol-dependent group) than in healthy controls ( P展开更多
Objective： To investigate the effects of acupuncture on the number of associated phosphorylated proteins in brain tissues of middle cerebral artery occlusion （MCAO） rats, based on the protein microarray technique. ...Objective： To investigate the effects of acupuncture on the number of associated phosphorylated proteins in brain tissues of middle cerebral artery occlusion （MCAO） rats, based on the protein microarray technique. Methods： The MCAO model was prepared according to the modified occlusion method using occlusion lines. Forty healthy Sprague-Dawley （SD） rats were randomly divided into 4 groups using the lottery method： a sham operation group, a model group, a control point group and an acupoint group, with 10 rats in each group. Rats in the sham operation group and the model group only received binding without acupuncture. Rats in the acupoint group received acupuncture at Dazhui （GV 14）, Baihui （GV 20） and Shuigou （GV 25）; rats in the control point group received acupuncture at non-acupoint control points. The needle was twisted once for 1 min after insertion and another time in the middle of the 30 min needle retaining. Acupuncture was conducted once every 12 h for 6 consecutive times. At the end of the experiment, the neurological impairment score was collected, and cells of the ischemic brain tissues were extracted. The protein phosphorylation of the related signaling was detected using the 720 phosphorylated antibody microarray technique, and the differentially expressed proteins between groups were screened. Results： The neurological impairment scores after 72 h of treatment： compared with the sham operation group, the scores of the model group, the control point group and the acupoint group were significantly increased （P〈0.01）; compared with the model group, the scores of the acupoint group and the control point group were significantly decreased （P〈0.01,P〈0.05）; the score of the acupoint group was better than that of the control point group （P〈0.05）. The results of the protein microarray： compared with the sham operation group, 48 proteins showed up-regulated phosphorylation （≥1.5 times） in the model group and the down-regulated was 28; compared with the model group, 35 proteins showed up-regulated phosphorylation in the control point group, and the down-regulated was 24. There were 29 proteins showing up-regulated phosphorylation in the acupoint group and the down-regulated was 51. The numbers of proteins involved in the function and signal transduction pathways were also different. Conclusion： Acupuncture at Dazhui （GV 14）, Baihui （GV 20） and Shuigou （GV 25） can effectively repair brain injury. The ischemic injury of brain tissue may be caused by imbalance of a variety of proteins, and acupuncture can promote brain tissue repair by multi-functional and multi-channel regulation of the protein disorders.展开更多
Objective ：To study the differences of gene expression between earlier gestational skin and later gestational skin of rats with the aids of single primer amplification （SPA） and high-density oligonucleotide DNA arr...Objective ：To study the differences of gene expression between earlier gestational skin and later gestational skin of rats with the aids of single primer amplification （SPA） and high-density oligonucleotide DNA array to understand the molecular mechanism of scarless healing. Methods： Total RNAs were isolated from fetal rat skin of the scarless（E15） and scar-forming （ E18 ） periods of gestation （term = 21.5 days）. The RNAs from earlier gestational skin （ EGS ） and later gestational skin （ LGS ） were both reversely transcribed to cDNAs, then labeled with the incorporation of fluorescent dCTP for preparing the hybridization probes by SPA method. The mixed probes were then hybridized to the oligonucleotide DNA arrays which contained 5 705 probes representing 5 705 rat genes. After highly stringent washing, these DNA arrays were scanned for fluorescent signals to display the differentially expressed genes between the 2 groups of skin. Results. Among 5 705 rat genes, there were 53 genes （0.93%） with differentially expressed levels between EGS and LGS groups, 27 genes, including fibroblast growth factor 2 （ FGF2 ） and follistatin were up-regulated （0.47%） and 26 genes were down-regulated （0.46%） in fetal skin during scarless period versus scar-forming period. Higher expressions of FGF2 and follistatin in EGS than those in LGS were also revealed by RT-PCR method. Conclusions： High-density oligonucleotide DNA array provided a powerful tool for investigating differential gene expression in earlier and later gestational fetal skins. This technology validates that the mechanism of fetal scarless healing is very complicate and the change of many gene expressions is associated with fetal scarless healing.展开更多
Background The non-hemodynamic effects of angiotensin receptor blocker （ARB） in the delay of progression of chronic kidney disease （CKD） remain unclear. In this study, we investigated the influence of irbesartan o...Background The non-hemodynamic effects of angiotensin receptor blocker （ARB） in the delay of progression of chronic kidney disease （CKD） remain unclear. In this study, we investigated the influence of irbesartan on the urinary excretion of cytokines in patients with CKD. Methods In this randomized perspective clinical trial, different doses of irbesartan （150 mg/d and 300 mg/d） were given to two groups of patients in a cross-over design. Blood pressure （BP）, creatinine clearance （Ccr） and 24-hour proteinuria were examined. Urinary excretion of cytokines was determined by human inflammatory cytokine antibody array. A two-fold change in spot intensity was considered significant. Results Urinary excretion of cytokines （granulocyte colony stimulating factor （GCSF）, intercellular cell adhesion molecule-1 （ICAM-1）, interferon y （IFN-y）, interleukin 1β （IL-1β）, IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage inflammatory protein 1δ （MIP-Iδ） in group B （irbesartan 300 mg/d） was significantly decreased in comparison to group A （irbesartan 150 mg/d） after 8-week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold reduction in urinary cytokine levels （GCSF, GM-CSF, IFN-γ, IL-1α, IL-11, IL-12p40, MCP-2, MIP-1α）, while increasing the dosage to 300 mg/d further decreased the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1α by week 18. There was no significant difference in BP or Ccr between the two groups. However, 24-hour proteinuria was significantly reduced in both groups, and in group A the reduction was dose dependent.Conclusion Irbesartan offers additional renoprotection in a dose-dependent manner by reducing pro-inflammatory cvtokines excretion in the urine of CKD patients.展开更多
Background Neuroblastoma （NB） is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentrat...Background Neuroblastoma （NB） is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentration of cytochrome c （Cyt c） in the serum of the cancer patients.The aim of this research was to identify the source of the Cyt c in the serum when the tumor grows up by subcutaneous inoculation of human NB cells into nude mice.Methods We subcutaneously inoculated human NB cells （KP-N-NS） into nude mice and collected the sera of tumor-bearing mice （n=14） and control mice （n=25） 4 weeks later in order to screen for and identify differentially expressed proteins in the serum.Differentially expressed proteins in the serum were screened by surface-enhanced laser desorption/ionization-time-of-fiight （SELDI-TOF） mass spectrometry.Results The relative intensity of a protein having a mass-to-charge ratio （m/z） of 11 609 was 3338.37±3410.85 in the tumor group and 59.84±40.74 in the control group,indicating that the expression level of this protein in the tumor group was 55.8 times higher than that in the control group.Serum proteins were separated and purified by high-performance liquid chromatography （HPLC）.Liquid chromatography coupled with tandem mass spectrometry （LC-MS/MS） was performed to produce peptide mass fingerprints （PMFs）.Spectrum analysis and a database search revealed that the highly expressed protein （m/z=11605.4） from the serum of tumor-bearing mice was the mouse Cyt c.Conclusions Increased concentration of Cyt c in the serum of tumor-bearing nude mice might be partially attributed to the secretion of this protein by non-tumor cells.展开更多
文摘AIM: We aimed to observe the expression of extracellular matrix (ECM) and cellular adhesion molecules (CAM) in cirrhotic liver tissues after hepatitis C virus (HCV) infection. METHODS: Twelve patients with post HCV inflammatory liver cirrhosis were selected to evaluate their liver function and other virological, pathological parameters. Then three specimens of cirrhotic patients whose health assessment results and laboratory data were similar and three normal liver specimens explanted from liver grafts prepared for liver transplantation were chosen for investigating gene expression of ECM and CAM using cDNA expression array. RESULTS: The cDNA array assay revealed 36.7% (36/96)of genes with changes, in which 26.3% (26/96) was up regulated and 10.1% (10/96) was down-regulated. Integrin (ITGA), collagen (COL), ADAMTS were identified as the characteristic changes of ECM and CAM gene expression levels. ITGA were demonstrated β1 and β2 sub-section changed in liver cirrhosis.CONCLUSION: ECM and CAM play an important role inthe progression of liver cirrhosis after HCV infection. The capital mechanism is related to the inflammatory cellsinfiltration, the activation and transformation of ECM producing cells and the imbalance between production and elimination of ECM.
基金ThisworkwassupportedbytheNationalNatureScienceFoundationofChina (No 3 0 2 71665 )
文摘Background Extracellular matrix (ECM) orchestrates cell behaviour including growth, death, apoptosis, adhesion, migration, and invasion by activating several signalling pathways Certain components of ECM, such as integrins, may act as receptors or co-receptors of enterovirus ECM-activated gene expressions in myocardium of viral heart disease including myocarditis and partial cardiomyopathy remain elusive This study was to investigate the expression of ECM-activated genes in myocardium of mouse with viral myocarditis Methods BALB/c mice were infected with Coxsackie virus B 3 (CVB 3) to establish an animal model of myocarditis Uninfected mice were also prepared and served as controls Specific mRNA expression pattern in myocarditic mouse heart was analysed by an in-house cDNA microarray containing 8192 genes Overexpressed ECM genes were selected and subsequently confirmed by Northern blot analysis Results Nine ECM genes were isolated, from the array of 8192 genes, as overexpressed genes in hearts of myocarditic mice in comparison with controls Subsequent Northern blot analysis confirmed that four of the nine genes were highly expressed Expression of these four genes, Fin15, ILk, Lamr1 and ADAMTS-1, has not been reported previously to be induced by Coxsackie virus Conclusion CVB 3-induced myocarditis is associated with gene expression profiles of certain ECM components
基金Supported by the National Natural Science Foundation of China under Grant Nos 61376049,61076044,61107026,61204011and U1037602the Natural Science Foundation of Beijing under Grant Nos 4132006,4102003,and 4112006+1 种基金the Scientific Research Fund Project of Municipal Education Commission of Beijing under Grant No KM201210005004the Specialized Research Fund for the Doctoral Program of Higher Education under Grant No 20121103110018
文摘A three-dimensional electrical-thermal coupling model based on the finite element method is applied to study thermal properties of implant-defined vertical cavity surface emitting laser （VCSEL） arrays. Several parameters including inter-element spacing, scales, injected current density and substrate temperature are considered. The actual temperatures obtained through experiment are in excellent agreement with the calculated results, which proves the accuracy of the model. Due to the serious thermal problem, it is essential to design arrays of low self-heating. The analysis can provide a foundation for designing VCSEL arrays in the future.
基金Supported by the‘Supporting First Action’Joint Foundation for Outstanding Postdoctoral Program under Grant Nos Y7YBSH0001 and Y7BSH14001the National Natural Science Foundation of China under Grant No 61434006the National Key Basic Research Program of China under Grant No 2017YFB0102302
文摘Beam steering in implant defined coherently coupled vertical cavity surface emitting laser （VCSEL） arrays is simulated using the FDTD solution software. Angular deflection dependent on relative phase differences among elements, inter-element spacing, element size and emitted wavelength is analyzed detailedly and systematically. We design and fabricate 1×2 implant defined VCSEL arrays for optimum beam steering performance. Electroni- cally controlled beam steering with a maximum deflection angle of 1.6° is successfully achieved in the 1 × 2 VCSEL arrays. The percentage of the power in the central lobe is above 39% when steering. The results show that the steering is controllable. Compared with other beam steering methods, the fabrication process is simple and of low cost.
基金supported by CAS fund(KZCX2-YW-116-1)National Natural Science Foundation of China(40821160549 and 41074032)China Earthquake Administration fund(200808078)
文摘We analyzed the seismic waveforms from the December 26, 2004 Sumatra-Andaman earthquake recorded at broadband seismic stations in western Europe. Previous studies involving of the beam-forming technique and high frequency analysis suggest that the earthquake ruptured with a duration of around 500 s. This very long duration makes P wave overlap with later arrivals such as PP wave, which follows P in about 200 s. Since P waves are crucial for modeling earthquake processes, we propose an iterative method to separate P and PP waveforms. The separated P waveform confirms a second large energy release around 300 s after the initial rupture. The iterative signal separation technique is particularly useful for mixed signals that are not independent and the number of recording stations far exceeds number of mixed signal sources.
基金Part of studies cited in this review was in partsupported by Johns Hopkins Institutional ResearchGrant(Ye,SQ),a pilot project(Ye,SQ)in The Hop-kins DK Center for the Analysis of Gene Expres-sion(R24DK58757-01,NIDDK)and Dorothy WallisWagner Charitable Tru
文摘The wealth of DNA data generated by the human genome project coupling with recently invented high-throughput gene expression profiling techniques has dramatically sped up the process for biomedical researchers on elucidating the role of genes in human diseases. One powerful method to reveal insight into gene functions is the systematic analysis of gene expression. Two popular high-throughput gene expression technologies, microarray and Serial Analysis of Gene Expression (SAGE) are capable of producing large amounts of gene expression data with the potential of providing novel insights into fundamental disease processes, especially complex syndromes such as cardiovascular disease, whose etiologies are due to multiple genetic factors and their interplay with the environment. Microarray and SAGE have already been used to examine gene expression patterns of cell-culture, animal and human tissues models of cardiovascular diseases. In this review, we will first give a brief introduction of microarray and SAGE technologies and point out their limitations. We will then discuss the major discoveries and the new biological insightsthat have emerged from their applications to cardiovascular diseases. Finally we will touch upon potential challenges and future developments in this area.
基金supported by National Institutes of Health Grants R21-AG048506,P01-AG000538 and RO1-AG34667(to CWC)UC MEXUS-CONACYT Grant CN-16-170(to GAP and CWC)
文摘Synapses are essential units for the flow of information in the brain.Over the last 70 years,synapses have been widely studied in multiple animal models including worms,fruit flies,and rodents.In comparison,the study of human synapses has evolved significantly slower,mainly because of technical limitations.However,three novel methods allowing the analysis of molecular,morphological,and functional properties of human synapses may expand our knowledge of the human brain.Here,we briefly describe these methods,and evaluate how the information provided by each unique approach may contribute to the functional and anatomical analysis of the synaptic component of human brain circuitries.In particular,using tissue from cryopreserved human brains,synaptic plasticity can be studied in isolated synaptosomes by fluorescence analysis of single-synapse long-term potentiation（FASS-LTP）,and subpopulations of synapses can be thoroughly assessed in the ribbons of brain tissue by array tomography（AT）.Currently,it is also possible to quantify synaptic density in the living human brain by positron emission tomography（PET）,using a novel synaptic radio-ligand.Overall,data provided by FASS-LTP,AT,and PET may significantly contribute to the global understanding of synaptic structure and function in both healthy and diseased human brains,thus directly impacting translational research.
基金Supported by the National Natural Science Foundation of China(No.30572293)the "Eleventh Five" TCM Foundation for Major Clinical Research of PLA(No.2006051002)the Natural Science Foundation of Fujian Province,China(No. 2010J01197)
文摘OBJECTIVE:This study screened serum tumor biomarkers by surface enhanced laser desorption/ionization time-of-flight mass spectrometry(SELDI-TOF-MS) to establish a subset which could be used for the prediction of Qi deficiency syndrome and phlegm and blood stasis in patients with non-small cell lung cancer;and as diagnostic model of Chinese medicine.METHODS:Serum samples from 63 lung cancer patients with Qi deficiency syndrome and phlegm and blood stasis,and 28 lung cancer patients with non-Qi deficiency syndrome and phlegm and blood stasis were analyzed using SELDI-TOF-MS with a PBS II-C protein chip reader.Protein profiles were generated using immobilized metal affinity capture(IMAC3) protein chips.Differentially-expressed proteins were screened.Protein peak clustering and classification analyses were performed using Biomarker Wizard and Biomarker Pattern software packages,respectively.RESULTS:A total of 268 effective protein peaks were detected in the 1,000-10,000 Da molecular range for the 15 serum proteins screened(P<0.05).The decision tree model was M 2284.97,with a sensitivity of 96.2% and a specificity of 66.7%.CONCLUSION:SELDI-TOF-MS techniques,combined with a decision tree model,can help identify serum proteomic biomarkers related to Qi deficiency syndrome and phlegm and blood stasis in lung cancer patients;and the predictive model can be used to discriminate between Chinese medicine diagnostic models of disease.
基金This study was supported by grants from National Natural Science Foundation of China （No. 81001037）, Shanghai Municipal Natural Science Foundation （No. 10ZR1428100）.
文摘Background The prognostic relevance of World Health Organization （WHO） subtypes within type B thymomas is still controversial. Understanding of the molecular characteristics of the different histologic types of thymomas will provide meaningful information for diagnosis and therapeutic management in type B thymoma. Methods Proteins extracted from twelve type B thymoma tissue specimens （six type B1 and six type B2） were analyzed by two-dimensional electrophoresis （2-DE） coupled with MALDI-TOF-MS. Differentially expressed proteins were then assayed in sixty-nine type B thymoma tissues （including B1, B2 and B3） by tissue array analysis with immunohistochemistry staining. The relationship of their expression with clinicopathological parameters, such as tumor stage or WHO classification, was estimated by Spearman＇s Rank Correlation Test. Results Sixteen differentially expressed proteins between type B1 and B2 thymoma tissues were identified. The differential levels of ezrin and glutathione S-transferase pi （GSTP1） were validated using immunohistochemistry staining. A statistically significant difference was observed in the positive rate of ezrin expression between type B1 thymoma and type B3 thymoma （Z= -2.963, P 〈0.01）. Ezrin showed a tendency to be expressed in higher classification tumors from type B1 to B3. A statistical analysis demonstrated that type B2 and B3 tumors had significantly higher positive expression of GSTP1 than the B1 group （type B2 vs. BI： Z= -2.582, P 〈0.01; type B3 vs. BI： Z= -4.012, P 〈0.001）. The results also showed a strong correlation between GSTP1 and WHO type staging of B1 to B3 tumors （Spearman＇s correlation coefficient： 0.633, P 〈0.001）. Statistical analysis showed that there was close correlation between GSTP1 and ezrin expression with the clinical stage （Spearman＇s correlation coefficients, ezrin： 0.481, P 〈0.05; GSTPI： 0.484, P 〈0.01）. Conclusions Differentially expressed proteins between type B1 and B2 thymoma tissues were analyzed by comparative proteomic analysis. The techniques of proteomic analysis and tissue array provide a potential tool for screening of key molecules in type B thymoma histological sub-classifications. The statistical analysis of ezrin and GSTP1 expression by immunohistochemistry, especially GSTP1, may be a useful approach for type B thymoma classification.
基金Supported by the National Basic Research Program of China(973 Program,No.2007CB512601,2013CB531803)
文摘OBJECTIVE： To explore the nature of ＂Yin internal heat caused by Yin-deficiency＂ in terms of the theo- ry of Traditional Chinese Medicine, by studying en- ergy metabolism in rats with Yin-deficiency-heat syndrome and analyzing the gene expression pro- file of their livers. METHODS： A Yin-deficiency-heat syndrome model was induced in rats using three Chinese medicinal herbs. Glycogen and triglycerides in blood plasma, and the enzyme activity of ATP in livers were mea- sured colorimetrically. Triiodothyronine （T3）, thyrox- ine （T4）, and thyroid stimulating hormone levels in blood plasma were also measured with enzyme linked immunosorbent assay. The gene expression profile of livers was detected with gene chip analy- sis. Differentially expressed genes were screened out and classified according to Gene Ontology. The accuracy of results were examined with reversetranscription-polymerase chain reaction RESULTS： Compared with the control group, body weight （P〈0.05） and hepatic glycogen （P〈0.05） were significantly lower in the Yin-deficiency-heat syndrome group. Moreover, toe temperature （P〈 0.01） and triglyceride （P〈0.05）, Na ＋-K＋-ATPase （P〈 0.01）, Mg2＋-ATPase （P〈0.01）, T3 （P〈0.05）, and 1-4 （P〈 0.01） levels were significantly higher. There were 99 differentially expressed genes in livers from the Y/n-deficiency-heat syndrome group. Genes were mainly related to sterol synthesis （Pc=0.0392）, de- fense response （Pc=0.0448）, and sterol metabolism （Pc=0.0533）. CONCLUSION： Abnormal expression genes in rats with Yin-deficiency-heat syndrome prompted the synthesis and metabolism of cholesterol, increased energy consumption, and reduced defense re- sponse. This gene expression might be the molecu- lar mechanism underlying ＂internal heat caused by Yin-deficiency＂ in the rats with Yin-deficiency-heat syndrome.
基金Supported by a Grant from the State Administration of Traditional Chinese Medicine Industry Subject:the Study and Application of Acupuncture in the Prevention and Treatment of Stroke of the Primary Hypertension(No.201507001-08)
文摘OBJECTIVE: To investigate changes in gene expression profiles in the hypothalamus related to the effects of acupuncture at the Renying(ST 9) acupoint in spontaneously hypertensive(SH) rats.METHODS: We randomly divided 18 SH rats into Renying(ST 9) group and model control group, 9 body weight-matched Wistar-Kyoto rats were used as blank controls. Acupuncture was performed manually for 20-min daily over 28 d in the Renying(ST 9) group. Rat Gene 2.0 array technology was used for the determination of gene expression profiles and the screened key genes were verified by real-time quantitative polymerase chain reaction(RT-PCR) analyses.RESULTS: The different groups exhibited differential gene expression: compared with the blank control group, 48 genes were up-regulated and 91 genes were down-regulated in the model group;compared with the model group, 79 genes were up-regulated and 80 genes were down-regulated in Renying(ST 9) group. The RT-PCR results of the key genes including Chi3 l1, Ephx2, Klk1, 5-HT1 A and Cbs were consistent with that of gene chip analysis.CONCLUTION: Acupuncture at Renying(ST 9)could significantly lower the blood pressure of SH rats and affect their hypothalamic gene expression profile. Genes associated with the contraction of vascular smooth muscle and the regulation of inflammation, neurotransmitters may be involved in acupuncture's antihypertensive mechanism.
文摘In this investigation,the effect of friction stir welding(FSW)parameters such as tool pin profiles,rotational speed and welding speed on the mechanical properties of tensile strength,hardness and impact energy of magnesium alloy AZ31 was studied.The experiments were carried out as per Taguchi parametric design concepts and an L9 orthogonal array was used to study the influence of various combinations of process parameters.Statistical optimization technique,ANOVA,was used to determine the optimum levels and to find the significance of each process parameter.The results indicate that rotational speed(RS)and transverse speed(TS)are the most significant factors,followed by tool pin profile(PF),in deciding the mechanical properties of friction stir welded magnesium alloy.In addition,mathematical models were developed to establish relationship between different process variables and mechanical properties.
基金National Natural Science Foundation of China(NSFC)(11274083,61405067)Guandong Natural Science Foundation(2015A030313748)Shenzhen Municipal Science and Technology Plan(JCYJ20150513151706573)
文摘The exceptional point(EP)is one of the typical properties of parity–time-symmetric systems,arising from modes coupling with identical resonant frequencies or propagation constants in optics.Here we show that in addition to two different modes coupling,a nonuniform distribution of gain and loss leads to an offset from the original propagation constants,including both real and imaginary parts,resulting in the absence of EP.These behaviors are examined by the general coupled-mode theory from the first principle of the Maxwell equations,which yields results that are more accurate than those from the classical coupled-mode theory.Numerical verification via the finite element method is provided.In the end,we present an approach to achieve lossless propagation in a geometrically symmetric waveguide array.
文摘A simple microlens array is designed between VCSEL array and fiber array for integration of array module. We increase the optical coupling efficiency from -32.057 dBm to -0.9054 dBm by using our designed microlens array.
基金supported by the National Natural Science Foundation of China under Grant No.11374285
文摘We propose and demonstrate a scheme to smooth and shape the on-target patterns in multimode fiber lasers, which includes expanding-collimating system and lens array （LA）. A smooth pattern with flat-top and sharp-edge profiles can be obtained with the irradiation nonuniformity decreasing significantly. We analyze the effects of the parameters such as defocus distance, the tilt angles, the number of the incident fiber lasers, and the diffraction-weakened LA on the uniformity irradiation of target by numerical simulations.
文摘OBJECTIVE: To explore the relationship between genetic polymorphisms of the ethanol metabolizing enzymes and the occurrence of alcoholic liver disease (ALD). METHODS: Sixty-five healthy male controls and 165 alcoholisms (including 122 ALD patients and 43 male alcohol abusers without liver complications defined as alcohol-dependent) were analyzed by polymerase chain reaction and hybridized with oligonucleotide microarray to detect the polymorphisms of the ethanol metabolizing enzymes genes. RESULTS: The frequencies of alcohol dehydrogenase gene 2 * 1 ( ADH2 * 1 ) allele were shown as 37.69%, 46.51% and 59.02% in control, alcohol-dependent and ALD groups respectively; while those of ADH2 * 2 allele were shown as 62.31 %, 53.49% and 40.98% respectively. No ADH2 * 3 was detected in any of the subjects. The frequency of ADH2 * 1 was significantly higher in alcoholisms (ALD group and alcohol-dependent group) than in healthy controls ( P
基金supported by National Natural Science Foundation of China No. 81303051, No. 30901901Province and Ministry Co-construction Key Laboratory for Internal Medicine of Traditional Chinese Medicine of the Education Ministry of China No. ZYNK201501+1 种基金Tuina Department of Yueyang Hostpital Affiliated to Hunan University of Chinese Medicine State Clinical Key SpecialtyTuina Key Discipline of State Administration of Traditional Chinese Medicine~~
文摘Objective： To investigate the effects of acupuncture on the number of associated phosphorylated proteins in brain tissues of middle cerebral artery occlusion （MCAO） rats, based on the protein microarray technique. Methods： The MCAO model was prepared according to the modified occlusion method using occlusion lines. Forty healthy Sprague-Dawley （SD） rats were randomly divided into 4 groups using the lottery method： a sham operation group, a model group, a control point group and an acupoint group, with 10 rats in each group. Rats in the sham operation group and the model group only received binding without acupuncture. Rats in the acupoint group received acupuncture at Dazhui （GV 14）, Baihui （GV 20） and Shuigou （GV 25）; rats in the control point group received acupuncture at non-acupoint control points. The needle was twisted once for 1 min after insertion and another time in the middle of the 30 min needle retaining. Acupuncture was conducted once every 12 h for 6 consecutive times. At the end of the experiment, the neurological impairment score was collected, and cells of the ischemic brain tissues were extracted. The protein phosphorylation of the related signaling was detected using the 720 phosphorylated antibody microarray technique, and the differentially expressed proteins between groups were screened. Results： The neurological impairment scores after 72 h of treatment： compared with the sham operation group, the scores of the model group, the control point group and the acupoint group were significantly increased （P〈0.01）; compared with the model group, the scores of the acupoint group and the control point group were significantly decreased （P〈0.01,P〈0.05）; the score of the acupoint group was better than that of the control point group （P〈0.05）. The results of the protein microarray： compared with the sham operation group, 48 proteins showed up-regulated phosphorylation （≥1.5 times） in the model group and the down-regulated was 28; compared with the model group, 35 proteins showed up-regulated phosphorylation in the control point group, and the down-regulated was 24. There were 29 proteins showing up-regulated phosphorylation in the acupoint group and the down-regulated was 51. The numbers of proteins involved in the function and signal transduction pathways were also different. Conclusion： Acupuncture at Dazhui （GV 14）, Baihui （GV 20） and Shuigou （GV 25） can effectively repair brain injury. The ischemic injury of brain tissue may be caused by imbalance of a variety of proteins, and acupuncture can promote brain tissue repair by multi-functional and multi-channel regulation of the protein disorders.
基金This work was supported in part by National Basic Science and Development Program (973 Program, 2005CB52203 )National Natural Science Foundation of China ( 30230370,30400172)
文摘Objective ：To study the differences of gene expression between earlier gestational skin and later gestational skin of rats with the aids of single primer amplification （SPA） and high-density oligonucleotide DNA array to understand the molecular mechanism of scarless healing. Methods： Total RNAs were isolated from fetal rat skin of the scarless（E15） and scar-forming （ E18 ） periods of gestation （term = 21.5 days）. The RNAs from earlier gestational skin （ EGS ） and later gestational skin （ LGS ） were both reversely transcribed to cDNAs, then labeled with the incorporation of fluorescent dCTP for preparing the hybridization probes by SPA method. The mixed probes were then hybridized to the oligonucleotide DNA arrays which contained 5 705 probes representing 5 705 rat genes. After highly stringent washing, these DNA arrays were scanned for fluorescent signals to display the differentially expressed genes between the 2 groups of skin. Results. Among 5 705 rat genes, there were 53 genes （0.93%） with differentially expressed levels between EGS and LGS groups, 27 genes, including fibroblast growth factor 2 （ FGF2 ） and follistatin were up-regulated （0.47%） and 26 genes were down-regulated （0.46%） in fetal skin during scarless period versus scar-forming period. Higher expressions of FGF2 and follistatin in EGS than those in LGS were also revealed by RT-PCR method. Conclusions： High-density oligonucleotide DNA array provided a powerful tool for investigating differential gene expression in earlier and later gestational fetal skins. This technology validates that the mechanism of fetal scarless healing is very complicate and the change of many gene expressions is associated with fetal scarless healing.
文摘Background The non-hemodynamic effects of angiotensin receptor blocker （ARB） in the delay of progression of chronic kidney disease （CKD） remain unclear. In this study, we investigated the influence of irbesartan on the urinary excretion of cytokines in patients with CKD. Methods In this randomized perspective clinical trial, different doses of irbesartan （150 mg/d and 300 mg/d） were given to two groups of patients in a cross-over design. Blood pressure （BP）, creatinine clearance （Ccr） and 24-hour proteinuria were examined. Urinary excretion of cytokines was determined by human inflammatory cytokine antibody array. A two-fold change in spot intensity was considered significant. Results Urinary excretion of cytokines （granulocyte colony stimulating factor （GCSF）, intercellular cell adhesion molecule-1 （ICAM-1）, interferon y （IFN-y）, interleukin 1β （IL-1β）, IL-2, IL-6, IL-8, IL-11, IL-15 and macrophage inflammatory protein 1δ （MIP-Iδ） in group B （irbesartan 300 mg/d） was significantly decreased in comparison to group A （irbesartan 150 mg/d） after 8-week treatment. In group A, 8 weeks of treatment induced a two- to nine-fold reduction in urinary cytokine levels （GCSF, GM-CSF, IFN-γ, IL-1α, IL-11, IL-12p40, MCP-2, MIP-1α）, while increasing the dosage to 300 mg/d further decreased the excretion of GCSF, GM-CSF, IL-12p40, MCP-2 and MIP-1α by week 18. There was no significant difference in BP or Ccr between the two groups. However, 24-hour proteinuria was significantly reduced in both groups, and in group A the reduction was dose dependent.Conclusion Irbesartan offers additional renoprotection in a dose-dependent manner by reducing pro-inflammatory cvtokines excretion in the urine of CKD patients.
文摘Background Neuroblastoma （NB） is one of the most common malignant solid tumors of childhood.It is still not clear whether the apoptosis of tumor cells or the non-tumor cells contributes to the increase of concentration of cytochrome c （Cyt c） in the serum of the cancer patients.The aim of this research was to identify the source of the Cyt c in the serum when the tumor grows up by subcutaneous inoculation of human NB cells into nude mice.Methods We subcutaneously inoculated human NB cells （KP-N-NS） into nude mice and collected the sera of tumor-bearing mice （n=14） and control mice （n=25） 4 weeks later in order to screen for and identify differentially expressed proteins in the serum.Differentially expressed proteins in the serum were screened by surface-enhanced laser desorption/ionization-time-of-fiight （SELDI-TOF） mass spectrometry.Results The relative intensity of a protein having a mass-to-charge ratio （m/z） of 11 609 was 3338.37±3410.85 in the tumor group and 59.84±40.74 in the control group,indicating that the expression level of this protein in the tumor group was 55.8 times higher than that in the control group.Serum proteins were separated and purified by high-performance liquid chromatography （HPLC）.Liquid chromatography coupled with tandem mass spectrometry （LC-MS/MS） was performed to produce peptide mass fingerprints （PMFs）.Spectrum analysis and a database search revealed that the highly expressed protein （m/z=11605.4） from the serum of tumor-bearing mice was the mouse Cyt c.Conclusions Increased concentration of Cyt c in the serum of tumor-bearing nude mice might be partially attributed to the secretion of this protein by non-tumor cells.
