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1.
Front Genet ; 13: 935749, 2022.
Article in English | MEDLINE | ID: mdl-36186467

ABSTRACT

Immunotherapy is an individualized therapeutic strategy for nasopharyngeal carcinoma (NPC). However, few molecular targets are clinically satisfactory. This work aimed to integrate bulk and single-cell RNA sequencing data to identify novel biomarkers involved in NPC. We performed differentially expressed gene (DEG) analysis, Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and immune cell infiltration analysis prior to correlation analysis of the identified genes and immune cells and further assessed the prognostic effects of the biomarkers and immune cells in NPC. As a result, PKP1, a potential molecular biomarker associated with immune infiltration, and tumor-infiltrating lymphocyte-B cells (TIL-Bs) were identified as promising therapeutic targets for NPC. Importantly, immunohistochemistry (IHC) validated that PKP1 protein expression was mainly found in NPC cells rather than noncancerous cells. In addition, the tumor microenvironment (TME) of NPC was characterized by the infiltration of more dendritic cells (DCs) and γδT cells but fewer B cells. Our results suggest that the interaction of PKP1 and TIL-B cells is involved in NPC development. It is possible that TIL-B cells produce immunoglobulin G (IgG) to tumor antigens, such as PKP1, or viral antigens, including EBV and HPV, to execute antitumor ability through DC and T cells. In response, NPC cells express proteins such as PKP1 (absent in normal nasopharynx) to induce myeloid-derived suppressor cell (MDSC) expansion, which subsequently impairs the proliferation of B cells and results in B-cell death by generating iNOS and NOX2. In summary, our findings provide a potential therapeutic strategy for NPC by disrupting the interaction of PKP1 and TIL-Bs in the TME.

3.
Arch Virol ; 167(8): 1619-1636, 2022 Aug.
Article in English | MEDLINE | ID: mdl-35648293

ABSTRACT

Herpes simplex virus type 1 (HSV-1) is a common pathogen that infects 50-90% of the world's population and causes a variety of diseases, some of which can be life-threatening. Silver nanoparticles (AgNPs) have been shown to have broad-spectrum antiviral activity. In this study, we investigated the activity of AgNPs against HSV-1 and found that AgNPs effectively inhibited plaque formation and HSV-1 progeny production, reduced the genomic load, and interfered with HSV-1 mRNA expression and protein synthesis. Transmission electron microscopy showed that AgNPs interacted with HSV-1 and altered the shape of the viral particles. Furthermore, AgNPs affected the entry of HSV-1 into cells as well as their release and cell-to-cell spread. AgNPs were also found to downregulate the expression of pro-inflammatory cytokines upon HSV-1 infection. Combined treatment with AgNPs and acyclovir (ACV) confirmed that AgNPs significantly enhanced the inhibitory effect of ACV against HSV-1. Our findings may contribute to an understanding of the mechanism of the antiviral effect of AgNPs against HSV-1 and help to provide a theoretical basis for their clinical application.


Subject(s)
Herpes Simplex , Herpesvirus 1, Human , Metal Nanoparticles , Acyclovir/pharmacology , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Herpes Simplex/drug therapy , Herpesvirus 2, Human , Humans , Silver/pharmacology , Silver/therapeutic use
4.
Mater Horiz ; 8(2): 589-596, 2021 02 01.
Article in English | MEDLINE | ID: mdl-34821275

ABSTRACT

Severe corrosion of Mg and Mg alloys is a major issue hindering their wider application in transportation industry, medical implants and aqueous batteries. Previously, no Mg-based material has been found with a significantly lower corrosion rate than that of ultra-high-purity Mg, i.e. 0.25 mm y-1 in concentrated NaCl solution. In this work for the first time, highly corrosion-resistant Mg is found to be accomplishable by Ca micro-alloying, bringing "stainless Mg" closer. The designed Mg-Ca lean alloys possess incredibly low corrosion rates, less than 0.1 mm y-1 in 3.5 wt% NaCl solution, which are significantly lower than that of ultra-high-purity Mg and all Mg alloys reported thus far. The outstanding corrosion resistance is attributed to inhibition of cathodic water reduction kinetics, impurities stabilizing and a protective surface film induced by Ca micro-alloying. Combined with the environmental benignity and economic viability, Ca micro-alloying renders huge feasibility on developing advanced Mg-based materials for diverse applications.


Subject(s)
Alloys , Magnesium , Corrosion , Materials Testing , Prostheses and Implants
5.
J Drug Target ; 29(3): 249-258, 2021 03.
Article in English | MEDLINE | ID: mdl-32969723

ABSTRACT

Pseudomonas aeruginosa is a gram-negative bacterium that exists in various ecosystems, causing severe infections in patients with AIDS or cystic fibrosis. P. aeruginosa can form biofilm on a variety of surfaces, whereby the bacteria produce defensive substances and enhance antibiotic-resistance, making themselves more adaptable to hostile environments. P. aeruginosa resistance represents one of the main causes of infection-related morbidity and mortality at a global level. Iron is required for the growth of P. aeruginosa biofilm. This review summarises how the iron metabolism contributes to develop biofilm, and more importantly, it may provide some references for the clinic to achieve novel anti-biofilm therapeutics by targeting iron activities.


Subject(s)
Biofilms/drug effects , Iron/metabolism , Pseudomonas aeruginosa/physiology , Acquired Immunodeficiency Syndrome/complications , Anti-Bacterial Agents/pharmacology , Cystic Fibrosis/complications , Drug Resistance, Bacterial , Humans , Pseudomonas Infections/drug therapy , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/drug effects , Pseudomonas aeruginosa/isolation & purification
6.
J Phys Chem Lett ; 11(20): 8790-8798, 2020 Oct 15.
Article in English | MEDLINE | ID: mdl-32985887

ABSTRACT

Magnesium primary cells are currently experiencing a renaissance following the suggestion of new strategies to boost their performance. The strategies suggested will maintain utilization efficiencies of 30-70%, which is considered to be relatively modest. In this work, the highest ever reported level of utilization efficiency of 82% is achieved for a Mg-based primary cell using a synergistic combination of electrolyte additives. It is demonstrated that the joint use of sodium nitrate and salicylate as electrolyte additives allows us to reach the aforementioned utilization efficiency of 5 mA/cm2 via offering an effective suppression of anode self-corrosion and uniform Mg dissolution under discharge conditions.

7.
J Proteome Res ; 19(8): 3109-3122, 2020 08 07.
Article in English | MEDLINE | ID: mdl-32567865

ABSTRACT

The decline of clinically effective antibiotics has made it necessary to develop more effective antimicrobial agents, especially for refractory biofilm-related infections. Silver nanoparticles (AgNPs) are a new type of antimicrobial agent that can eradicate biofilms and reduce bacterial resistance, but its anti-biofilm mechanism has not been elucidated. In this study, we investigated the molecular mechanism of AgNPs against multidrug-resistant Pseudomonas aeruginosa by means of anti-biofilm tests, scanning electron microscopy (SEM), and tandem mass tag (TMT)-labeled quantitative proteomics. The results of anti-biofilm tests demonstrated that AgNPs inhibited the formation of P. aeruginosa biofilm and disrupted its preformed biofilm. SEM showed that when exposed to AgNPs, the structure of the P. aeruginosa biofilm was destroyed, along with significant reduction of its biomass. TMT-labeled quantitative proteomic analysis revealed that AgNPs could defeat the P. aeruginosa biofilm in multiple ways by inhibiting its adhesion and motility, stimulating strong oxidative stress response, destroying iron homeostasis, blocking aerobic and anaerobic respiration, and affecting quorum sensing systems. Our findings offer a new insight into clarifying the mechanism of AgNPs against biofilms, thus providing a theoretical basis for its clinical application.


Subject(s)
Metal Nanoparticles , Pseudomonas aeruginosa , Anti-Bacterial Agents/pharmacology , Biofilms , Microbial Sensitivity Tests , Proteomics , Silver/pharmacology
8.
Int J Nanomedicine ; 14: 1469-1487, 2019.
Article in English | MEDLINE | ID: mdl-30880959

ABSTRACT

BACKGROUND: The threat of drug-resistant Pseudomonas aeruginosa requires great efforts to develop highly effective and safe bactericide. OBJECTIVE: This study aimed to investigate the antibacterial activity and mechanism of silver nanoparticles (AgNPs) against multidrug-resistant P. aeruginosa. METHODS: The antimicrobial effect of AgNPs on clinical isolates of resistant P. aeruginosa was assessed by minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC). In multidrug-resistant P. aeruginosa, the alterations of morphology and structure were observed by the transmission electron microscopy (TEM); the differentially expressed proteins were analyzed by quantitative proteomics; the production of reactive oxygen species (ROS) was assayed by H2DCF-DA staining; the activity of superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) was chemically measured and the apoptosis-like effect was determined by flow cytometry. RESULTS: Antimicrobial tests revealed that AgNPs had highly bactericidal effect on the drug-resistant or multidrug-resistant P. aeruginosa with the MIC range of 1.406-5.625 µg/mL and the MBC range of 2.813-5.625 µg/mL. TEM showed that AgNPs could enter the multidrug-resistant bacteria and impair their morphology and structure. The proteomics quantified that, in the AgNP-treated bacteria, the levels of SOD, CAT, and POD, such as alkyl hydroperoxide reductase and organic hydroperoxide resistance protein, were obviously high, as well as the significant upregulation of low oxygen regulatory oxidases, including cbb3-type cytochrome c oxidase subunit P2, N2, and O2. Further results confirmed the excessive production of ROS. The antioxidants, reduced glutathione and ascorbic acid, partially antagonized the antibacterial action of AgNPs. The apoptosis-like rate of AgNP-treated bacteria was remarkably higher than that of the untreated bacteria (P<0.01). CONCLUSION: This study proved that AgNPs could play antimicrobial roles on the multidrug-resistant P. aeruginosa in a concentration- and time-dependent manner. The main mechanism involves the disequilibrium of oxidation and antioxidation processes and the failure to eliminate the excessive ROS.


Subject(s)
Anti-Bacterial Agents/administration & dosage , Drug Resistance, Multiple, Bacterial/drug effects , Metal Nanoparticles/administration & dosage , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/drug effects , Silver/chemistry , Anti-Bacterial Agents/chemistry , Metal Nanoparticles/chemistry , Microbial Sensitivity Tests , Pseudomonas Infections/microbiology , Pseudomonas aeruginosa/growth & development
9.
Analyst ; 143(20): 5038-5045, 2018 Oct 08.
Article in English | MEDLINE | ID: mdl-30234206

ABSTRACT

The interaction between incident light and surface electrons in conductive nanoparticles produces localized plasmon oscillations with a resonant frequency that strongly depends on the composition, size, geometry, and dielectric environment. Hybrid heterostructure materials combining two or more materials in one structure represent a powerful way to achieve unique properties and multifunctionality compared to those of the individual nanoparticle components. Hybrid gold nanorods and gold nanoclusters (GNR/AuNCs) heterostructures prepared by intimate integration of GNRs with AuNCs exhibit both localized surface plasmon resonance (LSPR) property and peroxidase-like activity. It is found that the catalytic activity of the AuNC/GNR heterostructure could be remarkably enhanced by LSPR induced by photon-plasmon coupling in the visible to near-infrared (NIR) region. Meanwhile, the catalytic activity of enzyme-like AuNC/GNRs may be regulated by immunoreactions to realize specific recognition of a target analyte. Accordingly, a fast colorimetric assay within 5 min for the detection of prostate specific antigen (PSA) was developed based on a AuNC/GNRs heterostructure mask regulated by the target molecule under photon-plasmon coupling. The color intensity is inversely proportional to the PSA concentration, and quantitative analysis may be achieved in a range of 10 and 200 pg mL-1. This sensor was practically applied to detect PSA levels in prostate cancer serum samples and the determined values agreed well with those measured by the hospital using standard methods. This indicates that the AuNC/GNRs heterostructure-based assay has high accuracy for the analysis of practical samples. Moreover, the new method has the advantages of very fast determination and low sample volume requirements.


Subject(s)
Gold/chemistry , Nanotubes/chemistry , Prostate-Specific Antigen/blood , Benzidines/chemistry , Catalysis , Chromogenic Compounds/chemistry , Colorimetry/methods , Humans , Hydrogen Peroxide/chemistry , Male , Oxidation-Reduction , Surface Plasmon Resonance/methods
10.
ACS Appl Mater Interfaces ; 10(36): 30741-30751, 2018 Sep 12.
Article in English | MEDLINE | ID: mdl-30114361

ABSTRACT

Epoxy-based polymer was deposited as sealing agent on porous anodized coatings prepared by plasma electrolytic oxidation (PEO) to construct multilayered "soft-hard" coatings on Mg substrates. Different thicknesses and microstructures of the top epoxy layer were achieved by employing different dip-coating strategies. Atomic force microscopy, pull-off tests, and nanoindentation tests were conducted to study the surface roughness, the adhesion strength of the epoxy layer, and the mechanical properties of each component in the hybrid coating system. The micropores and other defects on the anodized layers were sealed by the epoxy polymer, which decreased the surface roughness. The dominant abrasive wear behavior of blank PEO coatings was significantly reduced by the epoxy layers, and the wear mechanism of the hybrid coatings was proposed considering both the microstructure of the hybrid coatings and the mechanical properties of the different components in the hybrid system.

11.
Exp Biol Med (Maywood) ; 242(12): 1227-1233, 2017 06.
Article in English | MEDLINE | ID: mdl-28343438

ABSTRACT

Human cytomegalovirus (HCMV) dormant infection can alter the expression of the hosts' microRNAs (miRNAs) and impact on the regulation of target genes. To investigate the differentially expressed miRNAs induced by HCMV in human glioma U251 cells, a comprehensive miRNA screen was performed. As a result, 19 up-regulated and 14 down-regulated miRNAs were determined. Of these, hsa-miR-27b (miR-27b) attracted our attention. MiR-27b levels in U251 cells increased 7.70-fold, 8.64-fold, and 4.78-fold, respectively, post 24 h, 48 h, and 72 h HCMV infection, compared to those in the mimic-infected cells, and this up-regulation was further confirmed by quantitative RT-PCR. The bioinformatic analyses show that miR-27b targets engrailed-2 (EN2) gene; however, the effect of miR-27b on EN2 is rarely encountered. In this study, we initially conducted dual luciferase assay to validate the target function of miR-27b on EN2. The results manifested that EN2 is a novel target of miR-27b, which could directly target the 3' untranslated region (3'-UTR) of the gene. We further found that the miR-27b transfected glioma U251 cells exhibited longer cell bodies with more synapses and multiple-angle shapes; moreover, Western blot detection revealed that the EN2 protein levels in these cells were significantly low. In conclusion, our study originally reports the up-regulation of miR-27b in HCMV-infected glioma cells. Our study also provides the first experimental evidence that miR-27b could affect glioma cells' growth, target EN2 and inhibit its expression in glioma cells. Our data indicate that miR-27b may be related to the development of neurological disorders with HCMV infection. The newly identified miR-27b/EN2 signal pathway may provide new insights into the glioma pathogenesis and a novel target for glioma therapy. Impact statement Our study is the first to demonstrate that the HCMV infection could alter the expression of cellular microRNAs of the host glioma cells, which may develop an understanding of the pathogenesis of the HCMV infection in the microRNA level. Recently, HCMV infection and engrailed-2 have been reported to be related to the autism spectrum disorder (ASD). In this study, we confirmed that engrailed-2 is the target of hsa-miR-27b. As far as we know, our findings of the hsa-miR-27b up-regulation in the HCMV-infected glioma cells, targeting engrailed-2 and inhibiting its expression have never been reported or documented. Our data indicate that miR-27b may be related to the development of neurological disorders with the HCMV infection. The newly identified miR-27b/EN2 signal pathway may provide new insights into the glioma pathogenesis and a novel target for glioma therapy.


Subject(s)
Brain Neoplasms/virology , Cytomegalovirus Infections/complications , Gene Expression Regulation, Neoplastic/physiology , Glioma/virology , Homeodomain Proteins/biosynthesis , MicroRNAs/biosynthesis , Nerve Tissue Proteins/biosynthesis , Brain Neoplasms/genetics , Cell Line, Tumor , Glioma/genetics , Homeodomain Proteins/genetics , Humans , MicroRNAs/genetics , Nerve Tissue Proteins/genetics , Up-Regulation
12.
Anal Chem ; 88(2): 1412-8, 2016 Jan 19.
Article in English | MEDLINE | ID: mdl-26651518

ABSTRACT

It is broadly interesting but remains a big challenge to explore nanomaterials-based methods to enable naked-eye observation and determination of ultratrace biomarkers and drugs. In this study, we developed a straightforward and extendable plasmonic nanosensor to enable visually quantitative determination of ultratrace target molecules through combining the use of enzyme-mimetic gold nanoclusters (AuNCs). Starting from sandwiched antibody-antigen (i.e., an analyte)-antibody structure, we conjugated AuNCs on the outer layer antibody to catalyze the decomposition of hydrogen peroxide used to reduce HAuCl4 into gold nanopartilces (AuNPs) for naked eye readout. This strategy is in theory applicable to all immunoreactions available and the protocol proposed to attach AuNCs onto an antibody is suitable to all proteins. The applicability of this type of nanosensor was validated by the determination of various ultratrace analytes such as protein avidin, breast cancer antigen, thyroid hormone, and even methamphetamine (MA), giving a naked-eye-readout limit of detection (LOD), down to 1.0 × 10(-20) M protein avidin, 7.52 × 10(-14) U/mL breast cancer antigen 15-3, 2.0 × 10(-15) mg/mL 3,5,3'-L-triiodothyronine and 2.3 × 10(-18) mg/mL MA. This strategy is thus considered an ultrasensitive way to fabricate plasmonic nanosensors, having wide and invaluable application potential in clinical, biological, and environmental studies, and in food quality control.


Subject(s)
Biosensing Techniques , Breast Neoplasms/chemistry , Gold/chemistry , Metal Nanoparticles/chemistry , Nanotechnology , Antigen-Antibody Complex/chemistry , Antigens, Neoplasm/analysis , Avidin/analysis , Female , Humans , Methamphetamine/analysis , Thyroid Hormones/analysis
13.
J Med Virol ; 87(3): 516-21, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25604457

ABSTRACT

Existing data on the genotype distribution of human papillomavirus (HPV) are limited in Hunan province, central south China. To evaluate the prevalence of HPV infection and its genotype among women with invasive cervical cancer in Hunan, a total of 1,336 patients were included in this study between July 2012 and June 2013. Eighteen high-risk and eight low-risk genotypes of HPV were detected by Luminex xMAP technology. The results show that HPV prevalence in invasive cervical cancer in Hunan was 75.7%. A single HPV infection was found in 82.3% of the HPV-positive samples, and 91.8% of the cases had high-risk HPV infection. The most common HPV type was HPV 16 (50.6%), followed by HPV 58 (12.4%), HPV 52 (10.9%), HPV 18 (7.3%), HPV 33 (5.5%), HPV 59 (4.2%), HPV 39 (4.0%), HPV 61 (3.4%), HPV 31 (3.3%), and HPV 56 (3.2%). A single infection with HPV 16 was detected in 42.5% of the samples, which was significantly more frequent than any other HPV type in this population. Dual-infection with HPV 16 and HPV 52 were relatively common. The available vaccines for HPV 16 and 18 are therefore expected to have a substantial impact on reducing the burden of cervical cancer in China, even though HPV 18 showed a lower frequency. In addition to HPV 16 and 18, other HPV types including 58, 52, and 33, should be targeted in the next generation HPV vaccines.


Subject(s)
Cervix Uteri/virology , Papillomaviridae/classification , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Uterine Cervical Neoplasms/virology , Adult , Aged , China/epidemiology , Coinfection/epidemiology , Coinfection/virology , Female , Genotype , Humans , Middle Aged , Papillomaviridae/genetics , Papillomavirus Infections/complications , Papillomavirus Infections/virology , Prevalence , Young Adult
14.
Analyst ; 139(6): 1498-503, 2014 Mar 21.
Article in English | MEDLINE | ID: mdl-24466568

ABSTRACT

Ultra-sensitive colorimetric determination of H2O2 is accomplished based on the intrinsic peroxidase-like activity of Au nanoclusters (AuNCs) stabilized by glutathione (GSH). The color change of 3,3,5,5-tetramethylbenzidine (TMB) catalyzed by AuNCs offers an indirect method to measure glucose. This sensing platform makes use of a dual optical signal change, including the color change in an aqueous solution under visible light illumination and an ultra-sensitive fluorescent assay arising from efficient fluorescence resonance energy transfer (FRET) between the AuNCs and oxidized TMB. The detection limits of H2O2 and glucose are 4.9 × 10(-13) M and 1.0 × 10(-11) M, respectively. In addition, enhanced fluorescence is observed from the AuNCs due to the use of ethanol which produces clear changes in the quantum yield and lifetime of the AuNCs. The quantum yield of AuNCs is enhanced from ∼12.5% as an isolated fluorophore to 38.9% in an AuNCs-ethanol complex. The enhanced fluorescence lowers the detection limits of H2O2 and glucose by 2 orders of magnitude compared to those attained from the original AuNCs.


Subject(s)
Blood Glucose/analysis , Fluorescence Resonance Energy Transfer/methods , Gold/chemistry , Hydrogen Peroxide/analysis , Nanostructures/chemistry , Benzidines/chemistry , Chromogenic Compounds/chemistry , Colorimetry/methods , Glutathione/chemistry , Humans , Limit of Detection , Nanostructures/ultrastructure
15.
Anal Chem ; 85(19): 9142-7, 2013 Oct 01.
Article in English | MEDLINE | ID: mdl-24024584

ABSTRACT

Accurate determination of copper in complex biological media such as cells is quite difficult, and an analytical strategy based on copper-modulated formation of core-shell gold nanorods is described. Selective and label-free sensing can be achieved by measuring the change in the localized surface plasmon resonance absorption. The technique can determine trace amounts of copper in human serum, urine, and red blood cells without or with minimal sample pretreatment. The Cu detection limits are 20.67 µM in human serum, 0.193 µM in human urine, and 3.09 × 10(-16) g in a single cell. The advantages of the technique are the high selectivity, simple or no sample pretreatment, and label free. Boasting a practical detection limit down to 2 fM, only 10(3) red blood cells are needed to conduct the analysis and the technique may be extended to the detection of trace amounts of copper in a single cell.


Subject(s)
Copper/analysis , Gold/chemistry , Nanotubes/chemistry , Humans , Surface Plasmon Resonance
16.
Parasitol Res ; 112(4): 1701-8, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23403993

ABSTRACT

Schistosomiasis is a worldwide parasitic disease. Currently, chemotherapy is the main effective method to treat schistosomiasis; however, it does not prevent reinfection. No effective vaccine is currently available to prevent schistosomiasis. Sj-F1 (GenBank accession number AY261995) is a novel gene that was discovered through screening adult Schistosoma japonicum worm cDNA library with female S. japonicum antigen-immunized sera. Streptococcus gordonii, a normal inhabitant of the human oral cavity, has been a prime candidate in recent investigations toward developing a live oral vaccine vector. One of the approaches for the surface expression of heterologous antigens in S. gordonii is to surface-localize them with the M6 protein from Streptococcus pyogenes. Here, we develop a recombinant S. gordonii strain that expresses the M6-Sj-F1 fusion protein on the bacterial surface. Intranasal immunization in mice with such M6-Sj-F1-expressing S. gordonii bacteria induced strong serum IgG, serum IgA, and saliva IgA against Sj-F1. The results of protective immunity against a challenge with cercariae of S. japonicum showed statistically significant protection following this treatment, with a worm reduction rate of 21.45% and an egg reduction rate of 34.77%. Our data indicate that the described M6-Sj-F1-expressing S. gordonii is highly immunogenic and can partially protect mice from challenge infection with S. japonicum. Intranasal immunization with recombinant S. gordonii may be an alternative to developing a novel S. japonicum vaccine in a safe, effective, and feasible way.


Subject(s)
Antigens, Helminth/immunology , Drug Carriers , Schistosoma japonicum/immunology , Schistosomiasis japonica/prevention & control , Streptococcus gordonii/genetics , Vaccines, Synthetic/immunology , Administration, Oral , Animals , Antibodies, Helminth/analysis , Antibodies, Helminth/blood , Antigens, Bacterial/genetics , Antigens, Bacterial/immunology , Antigens, Helminth/genetics , Bacterial Outer Membrane Proteins/genetics , Bacterial Outer Membrane Proteins/immunology , Carrier Proteins/genetics , Carrier Proteins/immunology , Cell Surface Display Techniques , Disease Models, Animal , Female , Immunoglobulin A/analysis , Immunoglobulin A/blood , Immunoglobulin G/blood , Mice , Parasite Load , Recombinant Fusion Proteins/genetics , Recombinant Fusion Proteins/immunology , Saliva/immunology , Schistosoma japonicum/genetics , Schistosomiasis japonica/immunology , Vaccines, Attenuated/administration & dosage , Vaccines, Attenuated/genetics , Vaccines, Attenuated/immunology , Vaccines, Synthetic/administration & dosage , Vaccines, Synthetic/genetics
17.
Clin Transl Sci ; 5(5): 379-85, 2012 Oct.
Article in English | MEDLINE | ID: mdl-23067349

ABSTRACT

BACKGROUND: Chronic kidney disease (CKD) is the end point of a number of renal and systemic diseases. The metabolomics with a highly multiplexed and efficient manner is a challenging goal in nephrology. METHODS: A (1) H-NMR based metabolomics approach was applied to establish a human CKD serum metabolic profile. Serum samples were obtained from CKD patients with four stages (N= 80) and healthy controls (N= 28). The data acquired by CMPG spectrum were further processed by pattern recognition (PR) analysis. Principal components analysis (PCA) and partial least-squares-discriminant analysis (PLS-DA) was capable of clustering the disease groups and establishing disease-specific metabolites profile. RESULTS: The classification models could grade CKD patients with considerably high value of Q(2) and R(2) . The significant endogenous metabolites that contributed to distinguish CKD in different stages included the products of glycolysis (glucose, lactate), amino acids (valine, alanine, glutamate, glycine), organic osmolytes (betaine, myo-inositol, taurine, glycerophosphcholine), and so on. Based on these metabolites, the model for diagnosing patients with CKD achieved the sensitivity and specificity of 100%. CONCLUSION: The study illustrated that serum metabolic profile was altered in response to renal dysfunction and the progression of CKD. The identified metabolic biomarkers may provide useful information for the diagnosis of CKD, especially in early stages.


Subject(s)
Magnetic Resonance Spectroscopy , Metabolome , Metabolomics/methods , Renal Insufficiency, Chronic/blood , Adult , Case-Control Studies , Discriminant Analysis , Female , Humans , Least-Squares Analysis , Male , Middle Aged , Pattern Recognition, Automated , Pilot Projects , Principal Component Analysis , Protons , Reproducibility of Results
18.
Rheumatol Int ; 32(3): 585-93, 2012 Mar.
Article in English | MEDLINE | ID: mdl-21120503

ABSTRACT

To identify and quantify protein profiles from peripheral blood mononuclear cells (PBMC) of systemic lupus erythematosus (SLE) patients with isobaric Tagging for Relative and Absolute protein Quantification (iTRAQ)-based proteomic technology and to find differentially expressed proteins in SLE. PBMC were collected from patients of six stable SLE, six active SLE, six rheumatoid arthritis (RA), and six healthy donors. After protein extraction and concentration, the pooled protein content was labeled with iTRAQ reagents and then subjected to multiple chromatographic fractionation and tandem mass spectrometry. ProteinPilot™ 3.0 software and a database of IPI (International Protein Index) human 3.62 were used for database searching and statistical analysis. A total of 452 proteins were identified. Of these, 67 unique proteins were observed twofold or more alteration in levels across groups. The proteins determined support existing knowledge and uncover novel biomarker candidates. These results indicate that iTRAQ-based technology can serve as a useful aid for identification and quantification proteins from PBMC.


Subject(s)
Leukocytes, Mononuclear/chemistry , Lupus Erythematosus, Systemic/blood , Proteins/chemistry , Proteomics/methods , Adult , Biomarkers/analysis , Biomarkers/metabolism , Chromatography, High Pressure Liquid , Female , Humans , Leukocytes, Mononuclear/pathology , Lupus Erythematosus, Systemic/pathology , Male , Middle Aged , Proteins/analysis , Proteome , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Staining and Labeling , Tandem Mass Spectrometry , Young Adult
19.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 28(3): 538-42, 2011 Jun.
Article in Chinese | MEDLINE | ID: mdl-21774219

ABSTRACT

This paper is aimed to establish and optimize proteomic research platform using isobaric tags for relative and absolute quantitation (iTRAQ) so as to facilitate further proteomic research of human peripheral blood mononuclear cells (hPBMC). We collected hPBMC, after protein extraction and trypsin digestion, we labeled the samples with iTRAQ reagents and then subjected to mass spectrometry. In triplicates, thirty precursors were randomly selected and detected; as a result, 26, 28 and 29 peptides were respectively tagged with ITRAQ reporter ions. The labeling efficiencies ranged between 86.7%-96.7%, with no significant difference among the groups (P>0.05). The coefficient of variance for the relative ratios of peptides from different proteins was ranged from 7.6% to 25.5% and there were no significant differences across the groups (P>0.05). The coefficient of variance for the relative ratios of different peptides from the same protein was varied from 9.3% to 19.1% and the differences across groups were not significant (P>0.05). The labeling of iTRAQ combined with tandem mass spectrometry in PBMC was successful with favourable reproducibility and accuracy, which could lay a foundation for further proteomic study of hPBMC in autoimmune disorders.


Subject(s)
Leukocytes, Mononuclear/chemistry , Proteins/chemistry , Proteomics/methods , Staining and Labeling , Tandem Mass Spectrometry/methods , Humans , Proteins/analysis , Proteome
20.
Ann Saudi Med ; 30(6): 489-92, 2010.
Article in English | MEDLINE | ID: mdl-20864786

ABSTRACT

Isodicentric chromosome 18 [idic(18)] is rare structural aberration. We report on a prenatal case described by conventional and molecular cytogenetic analyses. The sonography at 24 weeks of gestation revealed multiple fetal anomalies; radial aplasia and ventricular septal defect were significant features. Routine karyotyping showed a derivative chromosome replacing one normal chromosome 18. The parental karyotypes were normal, indicating that the derivative chromosome was de novo. Array comparative genomic hybridization (array-CGH) revealed 18p11.21→qter duplication and 18p11.21→pter deletion for genomic DNA of the fetus. The breakpoint was located at 18p11.21 (between 12104527 bp and 12145199 bp from the telomere of 18p). Thus, the derivative chromosome was ascertained as idic(18)(qter→p11.21::p11.21→qter). Fluorescent in situ hybridization (FISH) confirmed that the derivative chromosome was idic(18). Our report describes a rare isodicentric chromosome 18 and demonstrates that array-CGH is a useful complementary tool to cytogenetic analysis for reliable identifying derivative chromosome.


Subject(s)
Abnormalities, Multiple/diagnostic imaging , Abnormalities, Multiple/genetics , Chromosomes, Human, Pair 18/genetics , Ultrasonography, Prenatal , Adult , Female , Humans , Karyotyping , Pregnancy
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