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1.  Parameterizing the Morse Potential for Coarse-Grained Modeling of Blood Plasma 
Journal of computational physics  2014;257(Pt A):726-736.
Multiscale simulations of fluids such as blood represent a major computational challenge of coupling the disparate spatiotemporal scales between molecular and macroscopic transport phenomena characterizing such complex fluids. In this paper, a coarse-grained (CG) particle model is developed for simulating blood flow by modifying the Morse potential, traditionally used in Molecular Dynamics for modeling vibrating structures. The modified Morse potential is parameterized with effective mass scales for reproducing blood viscous flow properties, including density, pressure, viscosity, compressibility and characteristic flow dynamics of human blood plasma fluid. The parameterization follows a standard inverse-problem approach in which the optimal micro parameters are systematically searched, by gradually decoupling loosely correlated parameter spaces, to match the macro physical quantities of viscous blood flow. The predictions of this particle based multiscale model compare favorably to classic viscous flow solutions such as Counter-Poiseuille and Couette flows. It demonstrates that such coarse grained particle model can be applied to replicate the dynamics of viscous blood flow, with the advantage of bridging the gap between macroscopic flow scales and the cellular scales characterizing blood flow that continuum based models fail to handle adequately.
PMCID: PMC4045626  PMID: 24910470
Morse potential; inverse problems; coarse-grained; blood plasma fluid
2.  Synergic interplay of the La motif, RRM1 and the interdomain linker of LARP6 in the recognition of collagen mRNA expands the RNA binding repertoire of the La module 
Nucleic Acids Research  2014;43(1):645-660.
The La-related proteins (LARPs) form a diverse group of RNA-binding proteins characterized by the possession of a composite RNA binding unit, the La module. The La module comprises two domains, the La motif (LaM) and the RRM1, which together recognize and bind to a wide array of RNA substrates. Structural information regarding the La module is at present restricted to the prototypic La protein, which acts as an RNA chaperone binding to 3′ UUUOH sequences of nascent RNA polymerase III transcripts. In contrast, LARP6 is implicated in the regulation of collagen synthesis and interacts with a specific stem-loop within the 5′ UTR of the collagen mRNA. Here, we present the structure of the LaM and RRM1 of human LARP6 uncovering in both cases considerable structural variation in comparison to the equivalent domains in La and revealing an unprecedented fold for the RRM1. A mutagenic study guided by the structures revealed that RNA recognition requires synergy between the LaM and RRM1 as well as the participation of the interdomain linker, probably in realizing tandem domain configurations and dynamics required for substrate selectivity. Our study highlights a considerable complexity and plasticity in the architecture of the La module within LARPs.
PMCID: PMC4288179  PMID: 25488812
3.  Rutin alleviates diabetic cardiomyopathy in a rat model of type 2 diabetes 
Diabetic cardiomyopathy (DCM), an independent coronary heart disease that develops in diabetic individuals, is characterized by changes in the myocardial structure and function. The aim of the present study was to investigate the protective effect of rutin on DCM in a streptozotocin-induced diabetic rat model. Rutin was orally administrated at a dose of 8 mg/kg body weight. Metabolic profiles, myocardial enzymes and oxidative stress were examined by biochemical tests. The expression levels of cellular proteins associated with apoptosis were measured by western blot analysis, while the levels of inflammatory factors were assessed by immunohistochemical analyses. Rats with DCM exhibited an abnormal metabolic profile, aberrant myocardial enzymes, elevation of oxidative stress markers, increased levels of inflammatory factors and enhanced apoptotic cell death. Notably, rutin was shown to protect and improve myocardial dysfunction, oxidative stress, apoptosis and inflammation in the hearts of the diabetic rats. In conclusion, these results indicated that rutin may have great therapeutic potential in the treatment of DCM, and possibly other cardiovascular disorders, by preventing oxidative stress, inflammation and cell death. However, further detailed studies are required to reveal the exact mechanisms underlying the protective effect of rutin.
PMCID: PMC4280949  PMID: 25574214
diabetic cardiomyopathy; rutin; diabetic rats; streptozocin; antioxidants
4.  let-7b/g silencing activates AKT signaling to promote gastric carcinogenesis 
Aberrant AKT activation contributes to gastric cancer cell survival and chemotherapy resistance, however its regulation is poorly understood. microRNAs have been established to be important regulators in gastric carcinogenesis. Here, we showed the functional role and putative target of let-7b and let-7g (let-7b/g) in gastric carcinogenesis.
The expression of let-7b/g in gastric cancer cell lines and primary tumors were evaluated by miRNA qRT-PCR. The putative target gene of let-7b/g was explored by TargetScan followed by further validation. Functional analyses including MTT proliferation, monolayer colony formation, cell invasion assays and in vivo study were performed in both ectopic expression and knockdown approaches.
let-7b/g was found down-regulated in gastric cancer and its downregulation was associated with poor survival and correlated with lymph node metastasis. let-7b/g inhibited AKT2 expression by directly binding to its 3’UTR, reduced p-AKT (S473) activation and suppressed expression of the downstream effector pS6. AKT2 mRNA expression showed negative correlation with the expression of let-7b/g in primary tumors. Short interfering RNA (siRNA) mediated knockdown of AKT2 phenocopied the tumor-suppressive effects of let-7b/g. Moreover, AKT2 re-expression partly abrogated the growth-inhibitory effect of let-7b/g.
In conclusion, our findings reveal decreased let-7b/g contributes to aberrant AKT activation in gastric tumorigenesis and provide a potential therapeutic strategy for gastric cancer.
Electronic supplementary material
The online version of this article (doi:10.1186/s12967-014-0281-3) contains supplementary material, which is available to authorized users.
PMCID: PMC4196013  PMID: 25288334
let-7b; let-7g; AKT2; Gastric cancer; Tumor suppressor
5.  Association between Dairy Intake and Gastric Cancer: A Meta-Analysis of Observational Studies 
PLoS ONE  2014;9(7):e101728.
Observational studies have given inconsistent findings on the relationship between intake of dairy products and gastric cancer. We therefore conducted a systematic review with a meta-analysis of observational studies to summarize available evidence on this point.
We searched the electronic literature databases of PubMed (Medline), EMBASE and the Chinese Biomedical Literature Database up until August 30, 2013. All studies were limited to the English language. Random-effects models were used to pool study results between dairy products consumption and the risk of gastric cancer. We also performed subgroup, publication bias and sensitivity analysis.
Eight prospective studies and 18 case-control studies were included in our analysis, with a total number of 7272 gastric cancer cases and 223,355 controls. Pooled relative risks of all studies showed no significant association between dairy intake and gastric cancer (odds ratio [OR]: 1.09, 95% confidence interval [CI]: 0.96–1.25). When study design was separately analyzed, population-based case-control studies showed a positive association between dairy intake and gastric cancer risk (OR: 1.36; 95% CI: 1.07–1.74), whereas no associations were shown by hospital-based case-control studies (OR: 0.86, 95% CI: 0.72–1.02) or cohort studies (OR = 1.01, 95% CI = 0.91–1.13).
The meta-analysis shows that no clear association apparently exists between consumption of dairy products and gastric cancer risk. Further well-designed cohort and intervention studies should be conducted to verify this lack of association.
PMCID: PMC4090187  PMID: 25006674
6.  Helicobacter pylori-induced STAT3 activation and signalling network in gastric cancer 
Oncoscience  2014;1(6):468-475.
Helicobacter pylori (H. pylori) is the most important gastric carcinogen. However, the mechanisms of H. pylori induced gastric carcinogenesis through STAT3 activation are largely unknown. We evaluated the effects of H. pylori infection on STAT3 activation and dissected the signalling network of STAT3 in H. pylori- infected gastric carcinogenesis.
The expression of phospho-STAT3 (pSTAT3) was evaluated by immunohistochemistry and western blot. Gene expression array and chromatin immunoprecipitation were used to dissect the STAT3 signalling network on H. pylori co-cultured AGS.
pSTAT3 was significantly higher in H. pylori -positive gastritis than in H. pylori -negative gastritis ( P = 0.003). In addition, 98% of H. pylori positive intestinal metaplasia specimens showed STAT3 activation, whereas pSTAT3 was significantly decreased in all 43 specimens one year after H. pylori eradication ( P < 0.001). Moreover, pSTAT3 was only detected in the H. pylori -infected gastric tissues of mice but not in control mice. We further identified 6 candidates ( BRUNOL4, FGFR1, SHOX2, JAK3, MAPK8, and PDPN ) were directly up-regulated by H. pylori induced STAT3 activation.
H. pylori infection triggers the activation of STAT3 and de-regulates multitude of tumorigenic genes which may contribute to the initiation and progression of gastric cancer.
PMCID: PMC4284628  PMID: 25594045
Helicobacter pylori; STAT3; gastric carcinogenesis; molecular regulator
7.  Association between esophageal cancer risk and EPHX1 polymorphisms: A meta-analysis 
AIM: To summarize the relationship between p.Tyr113His and p.His139Arg polymorphisms in microsomal epoxide hydrolase (EPHX1) and risk for esophageal cancer (EC).
METHODS: The MEDLINE/PubMed and EMBASE databases were searched for studies of the association between EPHX1 polymorphisms and EC risk that were published from the database inception date to April 2013. A total of seven case-control studies, including seven on p.Tyr113His (cases, n = 1118; controls, n = 1823) and six on p.His139Arg (cases, n = 861; controls, n = 1571), were included in the meta-analysis. After data extraction by two investigators working independently, the meta-analyses were carried out with STATA 11.0 software. Pooled odds ratios and 95%CI were calculated using a fixed-effects model or a random-effects model, as appropriate.
RESULTS: The pooled EPHX1 p.Tyr113His polymorphism data showed no significant association with EC in any of the genetic models (OR = 1.00, 95%CI: 0.70-1.48 for Tyr/His vs Tyr/Tyr; OR = 1.10, 95%CI: 0.77-1.57 for His/His vs Tyr/Tyr; OR = 1.06, 95%CI: 0.75-1.49 for a dominant model; OR = 1.09, 95%CI: 0.89-1.34 for a recessive model). Similar results were obtained from the p.His139Arg polymorphism analysis (Arg/His vs His/His: OR = 1.02, 95%CI: 0.84-1.23; Arg/Arg vs His/His: OR = 0.96, 95%CI: 0.60-1.54; OR = 1.03, 95%CI: 0.78-1.37 for the dominant model; OR = 0.97, 95%CI: 0.61-1.56 for the recessive model). Subgroup analyses for ethnicity, subtype of EC, and source of controls (population-based or hospital-based) showed trends that were consistent with the pooled analysis (reported above), with no significant associations found.
CONCLUSION: This meta-analysis suggests that the p.Tyr113His and p.His139Arg polymorphisms in EPHX1 may not be associated with EC development.
PMCID: PMC4009551  PMID: 24803829
Esophageal cancer; Squamous cell carcinoma; Adenocarcinoma; EPHX1; Polymorphism; Meta-analysis
8.  Yin Yang 1 contributes to gastric carcinogenesis and its nuclear expression correlates with shorter survival in patients with early stage gastric adenocarcinoma 
Yin Yang 1 (YY1) is a transcription factor that regulates diverse biological processes and increasing recognized to have important roles in carcinogenesis. The function and clinical significance of YY1 in gastric adenocarcinoma (GAC) have not been elucidated.
In this study, the functional role of YY1 in gastric cancer was investigated by MTT proliferation assays, monolayer colony formation, cell cycle analysis, signaling pathway analysis, Western blot analysis and in vivo study through YY1 knockdown or overexpression. Immunohistochemical study with YY1 antibody was performed on tissue microarray consisting of 247 clinical GAC samples. The clinical correlation and prognosis significance were evaluated.
YY1 expression was up-regulated in gastric cancer cell lines and primary gastric cancers. Knocking down YY1 by siYY1 inhibited cell growth, inducing G1 phase accumulation and apoptosis. Ectopic YY1 expression enhanced cell proliferation in vitro and in vivo. Knocking down YY1 in gastric cancer cells suppressed proliferation by inhibiting Wnt/β-catenin pathway, whereas its overexpression exerted oncogenic property by activating Wnt/β-catenin pathway. In primary GAC samples, YY1 nuclear expression correlated with shorter survival and predicted poor prognosis in early stage GACs.
Our data demonstrated that YY1 contributes to gastric carcinogenesis in gastric cancer. In early stage GACs YY1 might serve as a poor prognostic marker and possibly as a potential therapeutic target.
PMCID: PMC3986816  PMID: 24674326
Yin Yang 1; Gastric adenocarcinoma; Prognostic marker; Oncogenic function
9.  Cadherin-17 induces tumorigenesis and lymphatic metastasis in gastric cancer through activation of NFκB signaling pathway 
Cancer Biology & Therapy  2013;14(3):262-270.
Cadherin-17 (CDH17), as a structurally unique member of the cadherin superfamily, has been identified to predict a poor prognosis for gastric cancer (GC). Our previous study demonstrated the positive correlation between CDH17 and lymph node micrometastasis in GC. We sought to further identify the role of CDH17 in the tumorigenesis and lymphatic metastasis of GC. Hence, we inhibited the CDH17 expression in MKN-45 gastric cancer cells by using RNA interference. Consequently, the malignant potency of cancer cells was evaluated, and the change in NFκB signaling pathway was also probed. Tumor growth and lymphatic metastasis model were conducted in nude mice to confirm the hypothesis. Downregulation of CDH17 not only suppressed the proliferation, adherence and invasion potency of MKN-45 cells, but also induced cell cycle arrest. Meanwhile, the NFκB signaling pathway was inactivated as well, with the reductions of downstream proteins including VEGF-C and MMP-9. Moreover, silencing CDH17 inhibited tumor growth in vivo significantly, and there was no lymph node metastasis detected in the mice without CDH17 expression, as opposed to the positive nodes found in controls. CDH17 is a novel oncogene in gastric cancer cells, which is associated with lymphatic metastasis and proliferation strongly. The inactivation of NFκB signaling pathway might be involved in targeting CDH17 in GC. On the whole, CDH17 is proposed to serve as a biomarker and attractive therapeutic target in GC.
PMCID: PMC3595309  PMID: 23298905
NFκB signaling pathway; RNA interference; cadherin-17; gastric cancer; lymphatic metastasis
10.  Cloning, expression, purification, crystallization and preliminary X-ray diffraction studies of a major group 7 allergen, Der f 7, from the dust mite Dermatophagoides farinae  
The major group 7 allergen, Der f 7, from the dust mite Dermatophagoides farinae has been crystallized and diffracted X-rays to a resolution of 2.24 Å.
Der f 7 is a major group 7 allergen from the dust mite Dermatophagoides farinae that shows 86% sequence identity to the homologous allergen Der p 7 from D. pteronyssinus. Der f 7 was successfully overexpressed in an Escherichia coli expression system and purified to homogeneity using Ni–NTA affinity and size-exclusion column chromatography. SeMet-labelled Der f 7 was crystallized by the hanging-drop vapour-diffusion method using a reservoir solution consisting of 0.1 M bis-tris pH 7.4 and 28% polyethylene glycol monomethyl ether 2000 at 293 K. X-ray diffraction data were collected to 2.24 Å resolution using synchrotron radiation. The crystals belonged to the orthorhombic system, space group P212121, with unit-cell parameters a = 50.19, b = 58.67, c = 123.81 Å. Based on the estimated Matthews coefficient (2.16 Å3 Da−1), two molecules of Der f 7 could be present in the asymmetric unit of the crystal lattice.
PMCID: PMC3232152  PMID: 22139179
group 7 allergens; Der f 7; Dermatophagoides farinae
11.  Laparoscopic-endoscopic cooperative surgery for gastric submucosal tumors 
AIM: To assess the feasibility, safety, and advantages of minimally invasive laparoscopic-endoscopic cooperative surgery (LECS) for gastric submucosal tumors (SMT).
METHODS: We retrospectively analyzed 101 consecutive patients, who had undergone partial, proximal, or distal gastrectomy using LECS for gastric SMT at Peking Union Medical College Hospital from June 2006 to April 2013. All patients were followed up by visit or telephone. Clinical data, surgical approach, pathological features such as the size, location, and pathological type of each tumor; and follow-up results were analyzed. The feasibility, safety and effectiveness of LECS for gastric SMT were evaluated, especially for patients with tumors located near the cardia or pylorus.
RESULTS: The 101 patients included 43 (42.6%) men and 58 (57.4%) women, with mean age of 51.2 ± 13.1 years (range, 14-76 years). The most common symptom was belching. Almost all (n = 97) patients underwent surgery with preservation of the cardia and pylorus, with the other four patients undergoing proximal or distal gastrectomy. The mean distance from the lesion to the cardia or pylorus was 3.4 ± 1.3 cm, and the minimum distance from the tumor edge to the cardia was 1.5 cm. Tumor pathology included gastrointestinal stromal tumor in 78 patients, leiomyoma in 13, carcinoid tumors in three, ectopic pancreas in three, lipoma in two, glomus tumor in one, and inflammatory pseudotumor in one. Tumor size ranged from 1 to 8.2 cm, with 65 (64.4%) lesions < 2 cm, 32 (31.7%) > 2 cm, and four > 5 cm. Sixty-six lesions (65.3%) were located in the fundus, 21 (20.8%) in the body, 10 (9.9%) in the antrum, three (3.0%) in the cardia, and one (1.0%) in the pylorus. During a median follow-up of 28 mo (range, 1-69 mo), none of these patients experienced recurrence or metastasis. The three patients who underwent proximal gastrectomy experienced symptoms of regurgitation and belching.
CONCLUSION: Laparoscopic-endoscopic cooperative surgery is feasible and safe for patients with gastric submucosal tumor. Endoscopic intraoperative localization and support can help preserve the cardia and pylorus during surgery.
PMCID: PMC3769911  PMID: 24039367
Laparoscopic-endoscopic cooperative surgery; Gastric submucosal tumor; Minimally invasive surgery; Laparoscopy; Endoscopy
12.  Antiferromagnetic FeSe monolayer on SrTiO3: The charge doping and electric field effects 
Scientific Reports  2013;3:2213.
By growing monolayer FeSe on SrTiO3(001) surface, researchers obtain the highest superconducting transition-temperature for iron-based superconductor. Here, we study the antiferromagnetic (AFM) checkerboard monolayer FeSe adsorbed on SrTiO3(001) surface. We show that the system has a considerable charge transfer from SrTiO3(001) substrate to FeSe monolayer, and so has a self-constructed electric field. The FeSe monolayer band structure near the Brillouin zone (BZ) center is sensitive to charge doping, and the spin-resolved energy bands at BZ corner are distorted to be flattened by the perpendicular electric field. It is revealed that the striking disappearance of the Fermi surface around the BZ center can be well explained by the AFM checkerboard phase with charge doping and electric field effects. We propose a tight-binding model Hamiltonian to take these key factors into account. We also show that this composite structure is an ideal electron-hole bilayer system, with electrons and holes respectively formed in FeSe monolayer and TiO2 surface layer.
PMCID: PMC3714653  PMID: 23863890
13.  Rational and Evolutionary Engineering Approaches Uncover a Small Set of Genetic Changes Efficient for Rapid Xylose Fermentation in Saccharomyces cerevisiae 
PLoS ONE  2013;8(2):e57048.
Economic bioconversion of plant cell wall hydrolysates into fuels and chemicals has been hampered mainly due to the inability of microorganisms to efficiently co-ferment pentose and hexose sugars, especially glucose and xylose, which are the most abundant sugars in cellulosic hydrolysates. Saccharomyces cerevisiae cannot metabolize xylose due to a lack of xylose-metabolizing enzymes. We developed a rapid and efficient xylose-fermenting S. cerevisiae through rational and inverse metabolic engineering strategies, comprising the optimization of a heterologous xylose-assimilating pathway and evolutionary engineering. Strong and balanced expression levels of the XYL1, XYL2, and XYL3 genes constituting the xylose-assimilating pathway increased ethanol yields and the xylose consumption rates from a mixture of glucose and xylose with little xylitol accumulation. The engineered strain, however, still exhibited a long lag time when metabolizing xylose above 10 g/l as a sole carbon source, defined here as xylose toxicity. Through serial-subcultures on xylose, we isolated evolved strains which exhibited a shorter lag time and improved xylose-fermenting capabilities than the parental strain. Genome sequencing of the evolved strains revealed that mutations in PHO13 causing loss of the Pho13p function are associated with the improved phenotypes of the evolved strains. Crude extracts of a PHO13-overexpressing strain showed a higher phosphatase activity on xylulose-5-phosphate (X-5-P), suggesting that the dephosphorylation of X-5-P by Pho13p might generate a futile cycle with xylulokinase overexpression. While xylose consumption rates by the evolved strains improved substantially as compared to the parental strain, xylose metabolism was interrupted by accumulated acetate. Deletion of ALD6 coding for acetaldehyde dehydrogenase not only prevented acetate accumulation, but also enabled complete and efficient fermentation of xylose as well as a mixture of glucose and xylose by the evolved strain. These findings provide direct guidance for developing industrial strains to produce cellulosic fuels and chemicals.
PMCID: PMC3582614  PMID: 23468911
14.  Hepatitis B viral core protein disrupts human host gene expression by binding to promoter regions 
BMC Genomics  2012;13:563.
The core protein (HBc) of hepatitis B virus (HBV) has been implicated in the malignant transformation of chronically-infected hepatocytes and displays pleiotropic functions, including RNA- and DNA-binding activities. However, the mechanism by which HBc interacts with the human genome to exert effects on hepatocyte function remains unknown. This study investigated the distribution of HBc binding to promoters in the human genome and evaluated its effects on the related genes’ expression.
Whole-genome chromatin immunoprecipitation microarray (ChIP-on-chip) analysis was used to identify HBc-bound human gene promoters. Gene Ontology and pathway analyses were performed on related genes. The quantitative polymerase chain reaction assay was used to verify ChIP-on-chip results. Five novel genes were selected for luciferase reporter assay evaluation to assess the influence of HBc promoter binding. The HBc antibody immunoprecipitated approximately 3100 human gene promoters. Among these, 1993 are associated with known biological processes, and 2208 regulate genes with defined molecular functions. In total, 1286 of the related genes mediate primary metabolic processes, and 1398 encode proteins with binding activity. Sixty-four of the promoters regulate genes related to the mitogen-activated protein kinase (MAPK) pathways, and 41 regulate Wnt/beta-catenin pathway genes. The reporter gene assay indicated that HBc binding up-regulates proto-oncogene tyrosine-protein kinase (SRC), type 1 insulin-like growth factor receptor (IGF1R), and neurotrophic tyrosine kinase receptor 2 (NTRK2), and down-regulates v-Ha-ras Harvey rat sarcoma viral oncogene (HRAS).
HBc has the ability to bind a large number of human gene promoters, and can disrupt normal host gene expression. Manipulation of the transcriptional profile in HBV-infected hepatocytes may represent a key pathogenic mechanism of HBV infection.
PMCID: PMC3484065  PMID: 23088787
Hepatitis B virus; Hepatitis B core protein; Chromatin immunoprecipitation microarray; ChIP-on-chip; Gene expression; DNA-protein interaction
15.  Dapper Homolog 1 Is a Novel Tumor Suppressor in Gastric Cancer through Inhibiting the Nuclear Factor-κB Signaling Pathway 
Molecular Medicine  2012;18(1):1402-1411.
Dapper homolog 1 (DACT1) is a disheveled partner in the planar cell polarity pathway. By using genome-wide promoter methylation screening, dapper homolog 1 (DACT1) was found to be frequently methylated in gastric cancer. We aim to clarify its epigenetic inactivation, biological function and clinical implication in gastric cancer. We demonstrated that DACT1 was silenced in 7 of 10 gastric cancer cell lines and in primary gastric cancers. Transcriptional gene silence of DACT1 was mainly regulated by promoter hypermethylation. Ectopic expression of DACT1 in silenced gastric cancer cell lines (AGS, BGC823 and MGC803) by stable transfection suppressed colony formation (P < 0.001), induced cell apoptosis (P < 0.01) and retarded tumorigenesis in nude mice (P < 0.001). The tumor suppressive effect of DACT1 was further confirmed by loss of DACT1 function experiment. The proapoptotic and antiproliferative effect by DACT1 was associated with inhibition of nuclear factor (NF)-κB activation and its downstream factors, including B-cell CLL/lymphoma-2, Bcl-X, interleukin-8 and tumor necrosis factor-α. Moreover, promoter methylation of DACT1 was detected in 29.3% (60/205) of primary gastric tumors. DACT1 methylation was significantly associated with tumor metastasis (P < 0.05), invasion (P < 0.05) and advanced tumor stage (P < 0.0005). These findings provided insight into the role of DACT1 as a novel functional tumor suppressor in gastric cancer through inhibiting NF-κB signaling pathway. Promoter methylation of DACT1 is associated with tumor aggressiveness.
PMCID: PMC3533644  PMID: 23073659
16.  Motion artifacts associated with in vivo endoscopic OCT images of the esophagus 
Optics Express  2011;19(21):20722-20735.
3-D optical coherence tomography (OCT) has been extensively investigated as a potential screening and/or surveillance tool for Barrett’s esophagus (BE). Understanding and correcting motion artifact may improve image interpretation. In this work, the motion trace was analyzed to show the physiological origin (respiration and heart beat) of the artifacts. Results showed that increasing balloon pressure did not sufficiently suppress the physiological motion artifact. An automated registration algorithm was designed to correct such artifacts. The performance of the algorithm was evaluated in images of normal porcine esophagus and demonstrated in images of BE in human patients.
PMCID: PMC3495872  PMID: 21997082
(110.4500) Optical coherence tomography; (170.2150) Endoscopic imaging; (100.3010) Image reconstruction techniques
17.  Crystal Structure of Der f 7, a Dust Mite Allergen from Dermatophagoides farinae 
PLoS ONE  2012;7(9):e44850.
Der f 7 is the group 7 allergen from the dust mite Dermatophagoides farinae, homologous to the major allergen Der p 7 from D. pteronyssinus. Monoclonal antibody that bind to residues Leu48 and Phe50 was found to inhibit IgE binding to residue Asp159, which is important for the cross-reactivity between Der f 7 and Der p 7.
Methodology/Principal Findings
Here, we report the crystal structure of Der f 7 that shows an elongated and curved molecule consisting of two anti-parallel β-sheets – one 4-stranded and the other 5-stranded – that wrap around a long C-terminal helix. The overall fold of Der f 7 is similar to Der p 7 but key difference was found in the β1–β2 loop region. In Der f 7, Leu48 and Phe50 are in close proximity to Asp159, explaining why monoclonal antibody binding to Leu48 and Phe50 can inhibit IgE binding to Asp159. Both Der f 7 and Der p 7 bind weakly to polymyxin B via a similar binding site that is formed by the N-terminal helix, the 4-stranded β-sheet and the C-terminal helix. The thermal stability of Der f 7 is significantly lower than that of Der p 7, and the stabilities of both allergens are highly depend on pH.
Der f 7 is homologous to Der p 7 in terms of the amino acid sequence and overall 3D structure but with significant differences in the region proximal to the IgE epitope and in thermal stability. The crystal structure of Der f 7 provides a basis for studying the function and allergenicity of this group of allergens.
PMCID: PMC3435378  PMID: 22970319
18.  Three-Dimensional Imaging of Ureter with Endoscopic Optical Coherence Tomography 
Urology  2011;77(5):1254-1258.
To verify the ability to identify the layered structures of ureteral wall and to image a segment of ureter in three dimensions with a high speed endoscopic optical coherence tomography (EOCT).
We imaged a porcine ureter ex vivo using a spectral domain EOCT with an specially designed circumferential scanning fiber catheter. The images were correlated with the histology to identify corresponding structures. Three-dimensional images and en face images at different depths from the luminal surface were reconstructed from the multiple cross-sectional images to visualize the layered structure of a segment of the ureter from different perspectives.
EOCT images can clearly reveal all layers of the ureteral wall as shown in the histological images. Especially, with the specially designed fiber catheter, the light beam was well centered during the rotation and pull back, which allowed constant acquisition of high fidelity images and unambiguous identification of the smooth muscle layers in all images. With high speed EOCT, a segment of ureter (20 mm) can be imaged in less than 90 seconds at a high resolution.
With its ability to visualize all layers of the ureteral wall, EOCT imaging offers the potential to stage urothelial cancers that have infiltrated the muscular wall (stage T2). This information will be complimentary to the diagnostic information obtained through ureteroscopic biopsy and CT urogram.
PMCID: PMC3087827  PMID: 21256548
Optical coherence tomography; Ureteral Cancer; Three dimensions; Endoscopic
19.  Stathmin1 Plays Oncogenic Role and Is a Target of MicroRNA-223 in Gastric Cancer 
PLoS ONE  2012;7(3):e33919.
Stathmin1 (STMN1) is a candidate oncoprotein and prognosis marker in several kinds of cancers. This study was aimed to analyze its expression and biological functions in gastric cancer. The expression of STMN1 was evaluated by qRT-PCR, western blot and immunohistochemistry. The biological function of STMN1 was determined by MTT proliferation assays, monolayer colony formation and cell invasion assays using small interference RNA technique in gastric cancer cell lines. We also explored the regulation of STMN1 expression by microRNA-223. STMN1 was upregulated in gastric cancer cell lines and primary gastric adenocarcinomas. STMN1-positive tumors were more likely to be found in old age group and associated with p53 nuclear expression. In diffuse type gastric adenocarcinomas, STMN1 expression was correlated with age (p = 0.043), T stage (p = 0.004) and lymph node metastasis (p = 0.046). Expression of STMN1 in diffuse type gastric adenocarcinoma was associated with poor disease specific survival by univariate analysis (p = 0.01). STMN1 knockdown in AGS and MKN7 cell lines suppressed proliferation (p<0.001), reduced monolayer colony formation (p<0.001), inhibited cell invasion and migration ability (p<0.001) and induced G1 phase arrest. siSTMN1 could also suppress cell growth in vivo (p<0. 01). We finally confirmed that STMN1 is a putative downstream target of miR-223 in gastric cancer. Our findings supported an oncogenic role of STMN1 in gastric cancer. STMN1 might serve as a prognostic marker and a potential therapeutic target for gastric cancer.
PMCID: PMC3314670  PMID: 22470493
20.  Endoscopically guided spectral-domain OCT with double-balloon catheters 
Optics Express  2010;18(16):17364-17372.
Fourier-domain optical coherence tomography (OCT) and balloon-based catheters have furthered the potential of OCT as a real-time surveillance tool for Barrett’s esophagus (BE). However, a balloon catheter, which expands the esophagus and centers the catheter, applies direct pressure on the esophagus. This may affect the tissue appearance and the ability to detect dysplasia in BE. To study this effect, we propose a double-balloon catheter to allow imaging with and without balloon-tissue contact. A system design based on a spectral-domain OCT platform is reported and validated by acquisition of high quality, volumetric images of swine esophagus in vivo.
PMCID: PMC3408909  PMID: 20721123
(110.4500) Optical Coherence Tomography; (170.2150) Endoscopic imaging
21.  Effect of ω-3 Fatty Acid on Gastrointestinal Motility after Abdominal Operation in Rats 
Mediators of Inflammation  2011;2011:152137.
Objective. To investigate whether ω-3 fatty acid could stimulate gastrointestinal motility after abdominal operation. Method. Wistar rats were randomly divided into 3 group (normal saline group, intralipid group, and ω-3 fatty acid group, n = 18/group) after partial caecectomy and gastrostomosis, each group was divided into 3 groups (POD1, POD3, and POD6, n = 6/group). Serum gastrin (GAS), motilin (MTL), interleukin-1 (IL-1), interleukin-6 (IL-6), tissue necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2), gastric emptying rate, and small bowel propulsion rate were measured. Results. On POD 3, gastric emptying rate and small bowel propulsion rate in ω-3 fatty acid group were higher than those in normal saline group and intralipid group. Serum GAS and MTL levels in ω-3 fatty acid group were higher than those in normal saline group, but serum IL-1, IL-6, TNF-α, and COX-2 levels were lower than those in normal saline group and intralipid group. Conclusion. ω-3 fatty acid could accelerate the recovery of gastrointestinal mobility after abdominal operation in rats, mainly by relieving postoperative inflammation.
PMCID: PMC3086275  PMID: 21547255
22.  Hexaaqua­cobalt(II) tetra­aqua­bis(2-amino­pyrazine-κN 4)cobalt(II) disulfate dihydrate 
The reaction of cobalt(II) sulfate and 2-amino­pyrazine affords the title salt, [Co(H2O)6][Co(C4H5N3)2(H2O)4](SO4)2·2H2O. The metal atoms in the tetra­aqua-coordinated and hexa­aqua-coordinated complex cations lie on centers of inversion in slightly distorted octa­hedral geometries. The cations, anions and solvent water mol­ecules are linked by O—H⋯O, O—H⋯N and N—H⋯O hydrogen bonds into a three-dimensional network.
PMCID: PMC2971832  PMID: 21578554
23.  Tetra­kis(2-amino­pyrazine-κN 4)dichlorido­cobalt(II) 
The CoII atom in the title complex, [CoCl2(C4H5N3)4], exists in an all-trans Cl2N4Co octa­hedral geometry. The CoII atom lies on a special position of 2 site symmetry. Adjacent mol­ecules are linked by N—H⋯N and N—H⋯Cl hydrogen bonds into a three-dimensional network.
PMCID: PMC2972178  PMID: 21578553
24.  Outbreaks of Hemotrophic Mycoplasma Infections in China 
Emerging Infectious Diseases  2009;15(7):1139-1140.
PMCID: PMC2744233  PMID: 19624945
Hemotrophic mycoplasmas; hemoplasmas; China; bacteria; letter

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