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1.  Overexpression of Csk-binding protein decreases growth, invasion, and migration of esophageal carcinoma cells by controlling Src activation 
AIM: To investigate the mechanisms by which Csk-binding protein (CBP) inhibits tumor progression in esophageal carcinoma.
METHODS: A CBP overexpressing esophageal carcinoma cell line (TE-1) was established. The growth, invasion, and migration of CBP-TE-1 cells, as well as the expression of Src were then determined and compared with those in normal TE-1 cells.
RESULTS: The expression of Src was decreased by the overexpression of CBP in TE-1 cells. The growth, invasion, and migration of TE-1 cells were decreased by the overexpression of CBP.
CONCLUSION: This study indicates that CBP may decrease the metastasis of esophageal carcinoma by inhibiting the activation of Src. CBP may be a potential tumor suppressor and targeting the CBP gene may be an alternative strategy for the development of therapies for esophageal carcinoma.
PMCID: PMC4323457
Csk-binding protein; Esophageal carcinoma; Cell growth; Invasion; Migration
2.  Global Characterization of Differential Gene Expression Profiles in Mouse Vγ1+ and Vγ4+ γδ T Cells 
PLoS ONE  2014;9(11):e112964.
Peripheral γδ T cells in mice are classified into two major subpopulations, Vγ1+ and Vγ4+, based on the composition of T cell receptors. However, their intrinsic differences remain unclear. In this study, we analyzed gene expression profiles of the two subsets using Illumina HiSeq 2000 Sequencer. We identified 1995 transcripts related to the activation of Vγ1+ γδ T cells, and 2158 transcripts related to the activation of Vγ4+ γδ T cells. We identified 24 transcripts differentially expressed between the two subsets in resting condition, and 20 after PMA/Ionomycin treatment. We found that both cell types maintained phenotypes producing IFN-γ, TNF-α, TGF-β and IL-10. However, Vγ1+ γδ T cells produced more Th2 type cytokines, such as IL-4 and IL-5, while Vγ4+ γδ T cells preferentially produced IL-17. Our study provides a comprehensive gene expression profile of mouse peripheral Vγ1+ and Vγ4+ γδ T cells that describes the inherent differences between them.
PMCID: PMC4236085  PMID: 25405356
3.  Should antiplatelet therapy be interrupted in drug eluting stent recipients throughout the periendoscopic period? A very late stent thrombosis case report and review of the literature 
In-stent thrombosis after cessation of antiplatelet medications in patients with drug-eluting stents (DES) is a significant problem in medical practice, particularly in the perioperative period. We report a case of an 87-year-old man with a medical history of hypertension, coronary artery disease and chronic atrophic gastritis. Very late thrombosis of a sirolimus-eluting stent occurred 1207 days after implantation, seven months after discontinuation of clopidogrel, and the interruption of aspirin 13 days in preparation of an elective endoscopic gastrointestinal procedure presented with acute myocardial infarction. The patient was treated with thrombectomy and successfully revascularized with superimposition of two sirolimus-eluting stents. Medications administered in the catheterization laboratory included low molecular weight heparin and nitroglycerin. Flow was defined as grade 2 according to the thrombolysis in myocardial infarction scale. Electrocardiogram after the procedure revealed persistent, but decreased, ST-segment elevation in the anterolateral leads. The patient recovered and was discharged on aspirin and clopidogrel indefinitely. There was no cardiac event during the two year follow-up period. This case underlines the importance of maintaining the balance of thrombosis and bleeding during perioperation of non-cardiac procedure and the possible need for continuation of aspirin therapy during periendoscopic procedures among patients with low bleeding risks who received DES.
PMCID: PMC4178520  PMID: 25278977
Sirolimus-eluting stent; Thrombosis; Complication; Antiplatelet therapy
4.  Quick biochemical markers for assessment of quality control of intraoperative cell salvage: a prospective observational study 
Intraoperative Cell Salvage (ICS), hereby referred to ‘mechanical red cell salvage’, has been widely used in adult elective major surgeries to reduce requirement for homologous red blood cell transfusion and its associated complications. However, amount of free haemoglobin (fHb) from ICS has been shown related to incidence of renal failure. fHb is the most important indicator of quality control of cell salvaged blood, thus monitoring the fHb concentration is imperative to minimise renal injury. However, currently there has been lacking quick biochemical markers to monitor the levels of fHb during ICS. The aim of this study was to screen quick biochemical markers for evaluating the amount of fHb during use of intraoperative cell salvage.
Twenty patients undergoing elective cardiovascular surgery were enrolled. Blood was collected and processed using a Fresenius continuous auto-transfusion system device. The concentration of fHb, albumin (Alb), and calcium (Ca) in three washing modes were measured, and their clearance rates were calculated. The correlations among the clearances and concentrations of fHb, albumin, and calcium were analysed.
In three washing modes, concentrations of albumin and calcium are significantly associated with amount of fHb:fHb(g/L) = 0.111Alb(g/L) –0.108, R = 0.638, p = 0.000; fHb(g/L) = 1.721Ca(mmol/L) +0.091, R = 0.514, p = 0.000. Furthermore, the clearance rates of albumin and calcium significantly predict clearance of fHb, CRfHb = 0.310CRALB + 0.686, R = 0.753, p = 0.000, CRfHb = 0.073 CR Ca + 0.913, R = 0.497, p = 0.000.
In clinic practice, clearance rates of albumin, or calcium can be used to evaluate the quality of salvaged blood, fHb. Bed-side measurement of calcium could offer a more feasible means for clinicians to undertake a real-time assessment of fHb.
PMCID: PMC4046511  PMID: 24886505
Cell salvage; Clearance rate; Free haemoglobin; Albumin; Calcium
5.  The sequencing bias relaxed characteristics of Hi-C derived data and implications for chromatin 3D modeling 
Nucleic Acids Research  2013;41(19):e183.
The 3D chromatin structure modeling by chromatin interactions derived from Hi-C experiments is significantly challenged by the intrinsic sequencing biases in these experiments. Conventional modeling methods only focus on the bias among different chromatin regions within the same experiment but neglect the bias arising from different experimental sequencing depth. We now show that the regional interaction bias is tightly coupled with the sequencing depth, and we further identify a chromatin structure parameter as the inherent characteristics of Hi-C derived data for chromatin regions. Then we present an approach for chromatin structure prediction capable of relaxing both kinds of sequencing biases by using this identified parameter. This method is validated by intra and inter cell-line comparisons among various chromatin regions for four human cell-lines (K562, GM12878, IMR90 and H1hESC), which shows that the openness of chromatin region is well correlated with chromatin function. This method has been executed by an automatic pipeline (AutoChrom3D) and thus can be conveniently used.
PMCID: PMC3799458  PMID: 23965308
6.  Network calisthenics 
Cell Cycle  2011;10(18):3086-3094.
Stimulation of quiescent mammalian cells with mitogens induces an abrupt increase in E2F1–3 expression just prior to the onset of DNA synthesis, followed by a rapid decline as replication ceases. This temporal adaptation in E2F facilitates a transient pattern of gene expression that reflects the ordered nature of DNA replication. The challenge to understand how E2F dynamics coordinate molecular events required for high-fidelity DNA replication has great biological implications. Indeed, precocious, prolonged, elevated or reduced accumulation of E2F can generate replication stress that culminates in either arrest or death. Accordingly, temporal characteristics of E2F are regulated by several network modules that include feedforward and autoregulatory loops. In this review, we discuss how these network modules contribute to “shaping” E2F dynamics in the context of mammalian cell cycle entry.
PMCID: PMC3218619  PMID: 21900750
E2F; dynamics; feedback; feedforward; network; DNA replication
7.  In vitro drug release behavior from a novel thermosensitive composite hydrogel based on Pluronic f127 and poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) copolymer 
BMC Biotechnology  2009;9:8.
Most conventional methods for delivering chemotherapeutic agents fail to achieve therapeutic concentrations of drugs, despite reaching toxic systemic levels. Novel controlled drug delivery systems are designed to deliver drugs at predetermined rates for predefined periods at the target organ and overcome the shortcomings of conventional drug formulations therefore could diminish the side effects and improve the life quality of the patients. Thus, a suitable controlled drug delivery system is extremely important for chemotherapy.
A novel biodegradable thermosensitive composite hydrogel, based on poly(ethylene glycol)-poly(ε-caprolactone)-poly(ethylene glycol) (PEG-PCL-PEG, PECE) and Pluronic F127 copolymer, was successfully prepared in this work, which underwent thermosensitive sol-gel-sol transition. And it was flowing sol at ambient temperature but became non-flowing gel at body temperature. By varying the composition, sol-gel-sol transition and in vitro drug release behavior of the composite hydrogel could be adjusted. Cytotoxicity of the composite hydrogel was conducted by cell viability assay using human HEK293 cells. The 293 cell viability of composite hydrogel copolymers were yet higher than 71.4%, even when the input copolymers were 500 μg per well. Vitamin B12 (VB12), honokiol (HK), and bovine serum albumin (BSA) were used as model drugs to investigate the in vitro release behavior of hydrophilic small molecular drug, hydrophobic small molecular drug, and protein drug from the composite hydrogel respectively. All the above-mentioned drugs in this work could be released slowly from composite hydrogel in an extended period. Chemical composition of composite hydrogel, initial drug loading, and hydrogel concentration substantially affected the drug release behavior. The higher Pluronic F127 content, lower initial drug loading amount, or lower hydrogel concentration resulted in higher cumulative release rate.
The results showed that composite hydrogel prepared in this paper were biocompatible with low cell cytotoxicity, and the drugs in this work could be released slowly from composite hydrogel in an extended period, which suggested that the composite hydrogel might have great potential applications in biomedical fields.
PMCID: PMC2654890  PMID: 19210779
8.  Tuberculosis versus non-Hodgkin’s lymphomas involving small bowel mesentery: Evaluation with contrast-enhanced computed tomography 
AIM: To evaluate the specific computed tomography (CT) imaging criteria for differentiating tuberculosis involving the small bowel mesenteric lymph nodes from lymphomas.
METHODS: We retrospectively reviewed the anatomic distribution, CT enhancement patterns of lymphoma in 18 patients with mesenteric tuberculosis and 22 with untreated non-Hodgkin’s lymphomas (NHL) involving small bowel mesentery (SBM). Of the 18 patients with tuberculosis, 9 had purely mesenteric tuberculous lymphadenopathy (TL), and 9 had mesenteric TL accompanied with tuberculous mesenteritis (TLM).
RESULTS: CT showed that tuberculosis and NHL mainly affected lymph nodes in the body and root of SBM. Homogeneously enhanced lymph nodes in the body and root of SBM were found more often in the NHL (P < 0.05). Homogeneously mixed peripheral enhanced lymph nodes in the body of SBM were found more often in mesenteric TL and TLM (P < 0.05). Peripheral enhanced lymph nodes in the root of SBM were found more often in mesenteric TL and TLM (P < 0.01). “Sandwich sign” in the root of SBM was observed more often in NHL (P < 0.05).
CONCLUSION: Anatomic lymph node distribution, sandwich sign and specific enhancement patterns of lymphadenopathy in SBM on CT images can be used in differentiating between tuberculosis and untreated NHL involving SBM.
PMCID: PMC2721452  PMID: 18609719
Tuberculosis; Lymphoma; Mesentery; X-ray; Computed tomography
9.  Tuberculous abscess in hepatoduodenal ligament: Evaluation with contrast-enhanced computed tomography 
Two patients with tuberculous abscess in the hepatoduodenal ligament were studied. Both patients underwent contrast-enhanced computed tomography (CT) scan. The abscess showed a low density with an irregular thick wall in the hepatoduodenal ligament on CT images, the margin was poorly defined. Contrast-enhanced CT images showed the contrast-enhanced thick wall, homogeneous and peripheral-enhanced lymph nodes. Although features of the tuberculous abscess in the hepatoduodenal ligament could be conspicuously shown with contrast-enhanced CT, further experience is needed to evaluate the potential value of CT in detecting early tuberculous abscess in relation to other entities in the hepatoduodenal ligament.
PMCID: PMC2703863  PMID: 18407612
Tuberculosis; Abscess; Hepatoduodenal ligament; X-ray; Computed tomography; Lymph node
10.  Infection by Wolbachia bacteria and its influence on the reproduction of the stored-product psocid, Liposcelis tricolor 
Wolbachia are maternally inherited intracellular bacteria that infect a wide range of arthropods and nematodes and are associated with various reproductive abnormalities in their hosts. The infection by Wolbachia of the psocid, Liposcelis tricolor (Psocoptera: Liposcelididae), was investigated using long PCR amplification of the wsp gene that codes for a Wolbachia surface protein. The results showed that L. tricolor was positive for Wolbachia. Phylogenetic analysis showed that the Wolbachia found in L. tricolor was related to the B-group. Wolbachia infection in L. tricolor could be removed through antibiotic treatment. The results of crosses including ♀W+ x ♂ W+, ♀ W− x ♂W+, ♀ W+ x ♂ W−, and ♀W− x ♂ W−, suggested that the removal of Wolbachia resulted in lower egg production by L. tricolor. The mean embryonic mortality of offspring produced by L. tricolor without Wolbachia was significantly higher than that of control.
PMCID: PMC2990312  PMID: 19537991
endosymbionts; molecular detection; antibiotic treatment
11.  The "impact factor" revisited 
The number of scientific journals has become so large that individuals, institutions and institutional libraries cannot completely store their physical content. In order to prioritize the choice of quality information sources, librarians and scientists are in need of reliable decision aids. The "impact factor" (IF) is the most commonly used assessment aid for deciding which journals should receive a scholarly submission or attention from research readership. It is also an often misunderstood tool. This narrative review explains how the IF is calculated, how bias is introduced into the calculation, which questions the IF can or cannot answer, and how different professional groups can benefit from IF use.
PMCID: PMC1315333  PMID: 16324222
12.  Relevance similarity: an alternative means to monitor information retrieval systems 
Relevance assessment is a major problem in the evaluation of information retrieval systems. The work presented here introduces a new parameter, "Relevance Similarity", for the measurement of the variation of relevance assessment. In a situation where individual assessment can be compared with a gold standard, this parameter is used to study the effect of such variation on the performance of a medical information retrieval system. In such a setting, Relevance Similarity is the ratio of assessors who rank a given document same as the gold standard over the total number of assessors in the group.
The study was carried out on a collection of Critically Appraised Topics (CATs). Twelve volunteers were divided into two groups of people according to their domain knowledge. They assessed the relevance of retrieved topics obtained by querying a meta-search engine with ten keywords related to medical science. Their assessments were compared to the gold standard assessment, and Relevance Similarities were calculated as the ratio of positive concordance with the gold standard for each topic.
The similarity comparison among groups showed that a higher degree of agreements exists among evaluators with more subject knowledge. The performance of the retrieval system was not significantly different as a result of the variations in relevance assessment in this particular query set.
In assessment situations where evaluators can be compared to a gold standard, Relevance Similarity provides an alternative evaluation technique to the commonly used kappa scores, which may give paradoxically low scores in highly biased situations such as document repositories containing large quantities of relevant data.
PMCID: PMC1181804  PMID: 16029513
13.  Quantitative evaluation of recall and precision of CAT Crawler, a search engine specialized on retrieval of Critically Appraised Topics 
Critically Appraised Topics (CATs) are a useful tool that helps physicians to make clinical decisions as the healthcare moves towards the practice of Evidence-Based Medicine (EBM). The fast growing World Wide Web has provided a place for physicians to share their appraised topics online, but an increasing amount of time is needed to find a particular topic within such a rich repository.
A web-based application, namely the CAT Crawler, was developed by Singapore's Bioinformatics Institute to allow physicians to adequately access available appraised topics on the Internet. A meta-search engine, as the core component of the application, finds relevant topics following keyword input. The primary objective of the work presented here is to evaluate the quantity and quality of search results obtained from the meta-search engine of the CAT Crawler by comparing them with those obtained from two individual CAT search engines. From the CAT libraries at these two sites, all possible keywords were extracted using a keyword extractor. Of those common to both libraries, ten were randomly chosen for evaluation. All ten were submitted to the two search engines individually, and through the meta-search engine of the CAT Crawler. Search results were evaluated for relevance both by medical amateurs and professionals, and the respective recall and precision were calculated.
While achieving an identical recall, the meta-search engine showed a precision of 77.26% (±14.45) compared to the individual search engines' 52.65% (±12.0) (p < 0.001).
The results demonstrate the validity of the CAT Crawler meta-search engine approach. The improved precision due to inherent filters underlines the practical usefulness of this tool for clinicians.
PMCID: PMC539260  PMID: 15588311
14.  Division of labour between Myc and G1 cyclins in cell cycle commitment and pace control 
Nature Communications  2014;5:4750.
A body of evidence has shown that the control of E2F transcription factor activity is critical for determining cell cycle entry and cell proliferation. However, an understanding of the precise determinants of this control, including the role of other cell-cycle regulatory activities, has not been clearly defined. Here, recognizing that the contributions of individual regulatory components could be masked by heterogeneity in populations of cells, we model the potential roles of individual components together with the use of an integrated system to follow E2F dynamics at the single-cell level and in real time. These analyses reveal that crossing a threshold amplitude of E2F accumulation determines cell cycle commitment. Importantly, we find that Myc is critical in modulating the amplitude, whereas cyclin D/E activities have little effect on amplitude but do contribute to the modulation of duration of E2F activation, thereby affecting the pace of cell cycle progression.
The transcription factor E2F is critical for determining cell proliferation. By monitoring E2F activity in single cells throughout the cell cycle, Dong et al. provide evidence that Myc and G1 cyclin/CDKs regulate different aspects of E2F temporal dynamics, resulting in distinct phenotypic outputs.
PMCID: PMC4164785  PMID: 25175461

Results 1-14 (14)