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2.  Prediction of synchronous colorectal cancers by computed tomography in subjects receiving an incomplete colonoscopy: A single-center study 
AIM: To assess the value of computed tomography (CT) for diagnosis of synchronous colorectal cancers (SCRCs) involving incomplete colonoscopy.
METHODS: A total of 2123 cases of colorectal cancer (CRC) were reviewed and divided into two groups according to whether a complete or incomplete colonoscopy was performed. CT results and final histological findings were compared to calculate the sensitivity and specificity associated with CT for detection of SCRCs following complete vs incomplete colonoscopy. Factors affecting the CT detection were also analyzed.
RESULTS: Three hundred and seventy-four CRC patients underwent incomplete colonoscopy and 1749 received complete colonoscopy. Fifty-six cases of SCRCs were identified by CT, and 36 were missed. In the incomplete colonoscopy group, the sensitivity and specificity of CT were 44.8% and 93.6%, respectively. The positive and negative predictive values were 23.6% and 95.0%, respectively. In contrast, the sensitivity and specificity of CT for the complete colonoscopy group were 68.3% and 97.0%, while the positive and negative predictive values were 22.2% and 98.7%, respectively. In both groups, the mean maximum dimension of the concurrent cancers identified in the CT-negative cases was shorter than in the CT-positive cases (incomplete group: P = 0.02; complete group: P < 0.01) Topographical proximity to synchronous cancers was identified as a risk factor for missed diagnosis (P = 0.03).
CONCLUSION: CT has limited sensitivity in detecting SCRCs in patients receiving incomplete colonoscopy. Patients with risk factors and negative CT results should be closely examined and monitored.
PMCID: PMC4323463
Synchronous colorectal cancer; Computed tomography; Colonoscopy
3.  Differential diagnosis of benign and malignant breast masses using diffusion-weighted magnetic resonance imaging 
Diffusion-weighted magnetic resonance imaging (DW-MRI) is different from conventional diagnostic methods and has the potential to delineate the microscopic anatomy of a target tissue or organ. The purpose of our study was to evaluate the value of DW-MRI in the diagnosis of benign and malignant breast masses, which would help the clinical surgeon to decide the scope and pattern of operation.
A total of 52 female patients with palpable solid breast masses received breast MRI scans using routine sequences, dynamic contrast-enhanced imaging, and diffusion-weighted echo-planar imaging at b values of 400, 600, and 800 s/mm2, respectively. Two regions of interest (ROIs) were plotted, with a smaller ROI for the highest signal and a larger ROI for the overall lesion. Apparent diffusion coefficient (ADC) values were calculated at three different b values for all detectable lesions and from two different ROIs. The sensitivity, specificity, positive predictive value, and positive likelihood ratio of DW-MRI were determined for comparison with histological results.
A total of 49 (49/52, 94.2%) lesions were detected using DW-MRI, including 20 benign lesions (two lesions detected in the same patient) and 29 malignant lesions. Benign lesion had a higher mean ADC value than their malignant counterparts, regardless of b value. According to the receiver operating characteristic (ROC) curve, the smaller-range ROI was more effective in differentiation between benign and malignant lesions. The area under the ROC curve was the largest at a b value of 800 s/mm2. With a threshold ADC value at 1.23 × 10−3 mm2/s, DW-MRI achieved a sensitivity of 82.8%, specificity of 90.0%, positive predictive value of 92.3%, and positive likelihood ratio of 8.3 for differentiating benign and malignant lesions.
DW-MRI is an accurate diagnostic tool for differentiation between benign and malignant breast lesions, with an optimal b value of 800 s/mm2. A smaller-range ROI focusing on the highest signal has a better differential value.
PMCID: PMC4328303
breast lesions; b value; differential diagnosis; diffusion-weighted imaging; magnetic resonance imaging
4.  Predictors of Percutaneous Catheter Drainage (PCD) after Abdominal Paracentesis Drainage (APD) in Patients with Moderately Severe or Severe Acute Pancreatitis along with Fluid Collections 
PLoS ONE  2015;10(2):e0115348.
Although we previously demonstrated abdominal paracentesis drainage (APD) preceding percutaneous catheter drainage (PCD) as the central step for treating patients with moderately severe (MSAP) or severe acute pancreatitis (SAP), the predictors leading to PCD after APD have not been studied.
Consecutive patients with MSAP or SAP were recruited between June 2011 and June 2013. As a step-up approach, all patients initially received medical management, later underwent ultrasound-guided APD before PCD, if necessary, followed by endoscopic necrosectomy through the path formed by PCD. APD primarily targeted fluid in the abdominal or pelvic cavities, whereas PCD aimed at (peri)pancreatic fluid.
Of the 92 enrolled patients, 40 were managed with APD alone and 52 received PCD after APD (14 required necrosectomy after initial PCD). The overall mortality was 6.5%. Univariate analysis showed that among the 20 selected parameters, 13 factors significantly affected PCD intervention after APD. Multivariate analysis revealed that infected (peri)pancreatic collections (P = -0.001), maximum extent of necrosis of more than 30% of the pancreas (P = -0.024), size of the largest necrotic peri(pancreatic) collection (P = -0.007), and reduction of (peri)pancreatic fluid collections by <50% after APD (P = -0.008) were all independent predictors of PCD.
Infected (peri)pancreatic collections, a largest necrotic peri(pancreatic) collection of more than 100 ml, and reduction of (peri)pancreatic fluid collections by <50% after APD could effectively predict the need for PCD in the early course of the disease.
PMCID: PMC4319763  PMID: 25659143
5.  Transcriptome Analysis of Sexually Dimorphic Chinese White Wax Scale Insects Reveals Key Differences in Developmental Programs and Transcription Factor Expression 
Scientific Reports  2015;5:8141.
The Chinese white wax scale insect, Ericerus pela, represents one of the most dramatic examples of sexual dimorphism in any insect species. In this study, we showed that although E. pela males display complete metamorphosis similar to holometabolous insects, the species forms the sister group to Acyrthosiphon pisum and cluster with hemimetabolous insects. The gene expression profile and Gene Ontology (GO) analyses revealed that the two sexes engaged in distinct developmental programs. In particular, female development appeared to prioritize the expression of genes related to cellular, metabolic, and developmental processes and to anatomical structure formation in nymphs. By contrast, male nymphal development is characterized by the significant down-regulation of genes involved in chitin, the respiratory system, and neurons. The wing and appendage morphogenesis, anatomical and tissue structure morphogenesis programs activated after male nymphal development. Transcription factors (that convey juvenile hormone or ecdysone signals, and Hox genes) and DNA methyltransferase were also differentially expressed between females and males. These results may indicate the roles that these differentially expressed genes play in regulating sexual dimorphism through orchestrating complex genetic programs. This differential expression was particularly prominent for processes linked to female development and wing development in males.
PMCID: PMC4311254  PMID: 25634031
6.  Ultrastructural Exploration on the Histopathological Change in Phenacoccus fraxinus Infected with Lecanicillium lecanii 
PLoS ONE  2015;10(1):e0117428.
The histopathological changes of the second instar nymph of the mealybug Phenacoccus fraxinus infected with Lecanicillium lecanii strain 3.4505 were investigated using light, scanning and transmission electron microscopy. The results demonstrated that L. lecanii 3.4505 could infect P. fraxinus in a short period. At 24 h post-inoculation, the conidia of L. lecanii 3.4505 adhered to the indented gloves or intersegmental folds of the insect body surface. Subsequently, the germinated conidia produced germ-tubes, appressoria and extended hyphae, which tightly adhered to the cuticle. Penetration of cuticle could be achieved either by peg form appressoria or directly by hyphae. Also, the conidia and hyphae could secrete massive mucilages causing visible damage to the host cuticle. After 48 h, the body wall, tissues and organs, including cuticle, trachea, fat body, muscle, Malpighian tubules and nerve ganglion, were destroyed by ramification of hyphae as a result of infection. The endoplasmic reticulum hypertrophied and formed obvious fingerprint agglomerates, and the mitochondria swelled and deformed in the haemocytes. Finally, the mycelium fully occupied the entire haemocoel. The entire bodies were wrapped in a white mycelium, with the mycelium extending radically outward.
PMCID: PMC4309582  PMID: 25629309
7.  NADPH oxidase p47phox siRNA attenuates adventitial fibroblasts proliferation and migration in apoE(-/-) mouse 
Reactive oxide species (ROS) derived from NADPH oxidases is involved in atherosclerosis. However, as a key component of NADPH oxidase, how p47phox regulates NADPH oxidases activity, ROS production and adventitial fibroblasts (AFs) function remains unclear.
p47phox in aortic arteries of apoE(-/-) mice fed with hyperlipid diet was detected by immunohistochemistry. NADPH oxidase activity, superoxide anion (O2−) generation and p47phox expression were analyzed in primary AFs treated by diphenyleneiodonium (DPI). The proliferation and migration of AFs were also analyzed.
p47phox expression was low in the aortic adventitia but high in the site of intimal injury with continuous hyperlipidic diet. Compared to AFs from wild-type mice, AFs derived from apoE(-/-) mice exhibited elevated NADPH oxidase activity, O2− production and higher mRNA and protein levels of p47phox, correlated with increased capability of proliferation and migration. DPI inhibited NADPH oxidase activity and AFs proliferation and migration in a dose-dependent manner. In addition, siRNA mediated knockdown of p47phox attenuated the proliferation and migration of AFs derived from apoE(-/-) mice.
p47phox plays a critical role in the regulation of adventitial fibroblast proliferation and migration and may be a new therapeutic target for neointimal hyperplasia.
PMCID: PMC4312606  PMID: 25628043
NADPH oxidase; p47phox; Adventitia fibroblasts; Atherosclerosis; ApoE(-/-)
8.  Defects in Silicene: Vacancy Clusters, Extended Line Defects, and Di-adatoms 
Scientific Reports  2015;5:7881.
Defects are almost inevitable during the fabrication process, and their existence strongly affects thermodynamic and (opto)electronic properties of two-dimensional materials. Very recent experiments have provided clear evidence for the presence of larger multi-vacancies in silicene, but their structure, stability, and formation mechanism remain largely unexplored. Here, we present a detailed theoretical study of silicene monolayer containing three types of defects: vacancy clusters, extended line defects (ELDs), and di-adatoms. First-principles calculations, along with ab initio molecular dynamics simulations, revealed the coalescence tendency of small defects and formation of highly stable vacancy clusters. The 5|8|5 ELD – the most favorable extended defect in both graphene and silicene sheets – is found to be easier to form in the latter case due to the mixed sp2/sp3 hybridization of silicon. In addition, hybrid functional calculations that contain part of the Hatree-Fock exchange energy demonstrated that the introduction of single and double silicon adatoms significantly enhances the stability of the system, and provides an effective approach on tuning the magnetic moment and band gap of silicene.
PMCID: PMC4306108  PMID: 25619941
9.  Association between brain metastasis from lung cancer and the serum level of myelin basic protein 
The aim of the present study was to determine the association between the expression of myelin basic protein in the serum and the metastasis of lung cancer to the brain. A total of 68 lung cancer patients, treated in the Department of Respiratory Medicine of the People’s Hospital of Rizhao (Rizhao, China), were divided into two groups, those with brain metastasis (32 cases) and those without brain metastasis (36 cases). The expression levels of myelin basic protein were measured for all the patients. The results indicated that the expression levels of myelin basic protein in the brain metastasis group were significantly higher when compared with those in the group without metastasis (P<0.05). However, there was no statistically significant correlation between the size of the brain metastasis and the expression levels of myelin basic protein (P>0.05). Furthermore, no statistically significant difference was found in the average level of myelin basic protein between the two subgroups of patients with brain tumor diameters of >1.5 cm and <1.5 cm (P>0.05). Therefore, the results demonstrated a statistically significant correlation between the expression of myelin basic protein in the serum and the metastasis of lung cancer to the brain. Myelin basic protein may thus prove useful in the early diagnosis of brain metastases in lung cancer patients.
PMCID: PMC4316904  PMID: 25667676
myelin basic protein; brain metastasis; lung cancer
10.  Dosimetric benefits of robust treatment planning for intensity modulated proton therapy for base-of-skull cancers 
Practical radiation oncology  2014;4(6):384-391.
The clinical advantage of intensity modulated proton therapy (IMPT) may be diminished by range and patient setup uncertainties. We evaluated the effectiveness of robust optimization that incorporates uncertainties into the treatment planning optimization algorithm for treatment of base of skull cancers.
Methods and materials
We compared 2 IMPT planning methods for 10 patients with base of skull chordomas and chondrosarcomas: (1) conventional optimization, in which uncertainties are dealt with by creating a planning target volume (PTV); and (2) robust optimization, in which uncertainties are dealt with by optimizing individual spot weights without a PTV. We calculated root-mean-square deviation doses (RMSDs) for every voxel to generate RMSD volume histograms (RVHs). The area under the RVH curve was used for relative comparison of the 2 methods’ plan robustness. Potential benefits of robust planning, in terms of target dose coverage and homogeneity and sparing of organs at risk (OARs) were evaluated using established clinical metrics. Then the plan evaluation metrics were averaged and compared with 2-sided paired t tests. The impact of tumor volume on the effectiveness of robust optimization was also analyzed.
Relative to conventionally optimized plans, robustly optimized plans were less sensitive for both targets and OARs. In the nominal scenario, robust and conventional optimization resulted in similar D95% doses (D95% clinical target volume [CTV]: 63.3 and 64.8 Gy relative biologic effectiveness [RBE]), P <.01]) and D5%-D95% (D5%-D95% CTV: 8.0 and 7.1 Gy[RBE], [P < .01); irradiation of OARs was less with robust optimization (brainstem V60: 0.076 vs 0.26 cm3 [P <.01], left temporal lobe V70: 0.22 vs 0.41 cm3, [P = .068], right temporal lobe V70: 0.016 vs 0.11 cm3, [P = .096], left cochlea Dmean: 28.1 vs 30.1 Gy[RBE], [P = .023], right cochlea Dmean: 23.7 vs 25.2 Gy [RBE], [P = .059]). Results in the worst-case scenario were analogous.
Robust optimization is effective for creating clinically feasible IMPT plans for tumors of the base of skull.
PMCID: PMC4238033  PMID: 25407859
11.  Genome Sequence of an Extensively Drug-Resistant Strain of Klebsiella pneumoniae, Strain YN-1, with Carbapenem Resistance 
Genome Announcements  2015;3(1):e01279-14.
The emergence and spread of multidrug-resistant (MDR) Klebsiella pneumoniae has been regarded as one of the major challenges among health care-associated infections worldwide. Here, we report the draft genome sequence of an extensively drug-resistant (XDR) K. pneumoniae strain isolated in 2013 from Yunnan Province, China.
PMCID: PMC4290976  PMID: 25573939
12.  Enterocyte dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin expression in inflammatory bowel disease 
AIM: To investigate dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) expression in intestinal epithelial cells (IECs) in inflammatory bowel disease (IBD).
METHODS: The expression of DC-SIGN in IECs was examined by immunohistochemistry of intestinal mucosal biopsies from 32 patients with IBD and 10 controls. Disease activity indices and histopathology scores were used to assess the tissue lesions and pathologic damage. Animal studies utilized BALB/c mice with dextran sodium sulfate (DSS)-induced colitis treated with anti-P-selectin lectin-EGF domain monoclonal antibody (PsL-EGFmAb). Controls, untreated and treated mice were sacrificed after 7 d, followed by isolation of colon tissue and IECs. Colonic expression of DC-SIGN, CD80, CD86 and MHC II was examined by immunohistochemistry or flow cytometry. The capacity of mouse enterocytes or dendritic cells to activate T cells was determined by co-culture with naïve CD4+ T cells. Culture supernatant and intracellular levels of interleukin (IL)-4 and interferon (IFN)-γ were measured by enzyme-linked immunosorbent assay and flow cytometry, respectively. The ability of IECs to promote T cell proliferation was detected by flow cytometry staining with carboxyfluorescein diacetate succinimidyl ester.
RESULTS: Compared with controls, DC-SIGN expression was significantly increased in IECs from patients with Crohn’s disease (P < 0.01) or ulcerative colitis (P < 0.05). DC-SIGN expression was strongly correlated with disease severity in IBD (r = 0.48; P < 0.05). Similarly, in the DSS-induced colitis mouse model, IECs showed upregulated expression of DC-SIGN, CD80, CD86 and MHC, and DC-SIGN expression was positively correlated with disease activity (r = 0.62: P < 0.01). IECs from mouse colitis stimulated naïve T cells to generate IL-4 (P < 0.05). Otherwise, dendritic cells promoted a T-helper-1-skewing phenotype by stimulating IFN-γ secretion. However, DC-SIGN expression and T cell differentiation were suppressed following treatment of mice with DSS-induced colitis with PsL-EGFmAb. The proliferation cycles of CD4+ T cells from mice with DSS-induced colitis appeared as five cycles, which was more than in the control and treated groups. These results suggest that IECs can promote T cell proliferation.
CONCLUSION: IECs regulate tissue-associated immune compartments under the control of DC-SIGN in IBD.
PMCID: PMC4284334  PMID: 25574091
Dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin; Dendritic cells; Immune compartmentalization; Inflammatory bowel disease; Intestinal epithelial cells
13.  MS/MS-based networking and peptidogenomics guided genome mining revealed the stenothricin gene cluster in Streptomyces roseosporus 
The Journal of antibiotics  2013;67(1):99-104.
Most (75%) of the anti-infectives that save countless lives and enormously improve quality of life originate from microbes found in nature. Herein, we described a global visualization of the detectable molecules produced from a single microorganism, which we define as the ‘molecular network’ of that organism, followed by studies to characterize the cellular effects of antibacterial molecules. We demonstrate that Streptomyces roseosporus produces at least four non-ribosomal peptide synthetase-derived molecular families and their gene subnetworks (daptomycin, arylomycin, napsamycin and stenothricin) were identified with different modes of action. A number of previously unreported analogs involving truncation, glycosylation, hydrolysis and biosynthetic intermediates and/or shunt products were also captured and visualized by creation of a map through MS/MS networking. The diversity of antibacterial compounds produced by S. roseosporus highlights the importance of developing new approaches to characterize the molecular capacity of an organism in a more global manner. This allows one to more deeply interrogate the biosynthetic capacities of microorganisms with the goal to streamline the discovery pipeline for biotechnological applications in agriculture and medicine. This is a contribution to a special issue to honor Chris Walsh’s amazing career.
PMCID: PMC3919142  PMID: 24149839
BioMAP; biosynthesis; cyclic peptides; cytological profiling; mass spectrometry; metabolic exchange
15.  Novel Patchouli Alcohol Ternary Solid Dispersion Pellets Prepared by Poloxamers 
The present study investigates the possibility of using poloxamers as solubility and dissolution rate enhancing agents of poorly water soluble bioactive constituent patchouli alcohol (PA) that can be used for the preparation of immediate release pellets formulation. Two commercially available grades poloxamer 188 (P 188) and poloxamer 407 (P 407) were selected, and solid dispersions (SDs) containing different weight ratio of PA and poloxamers, and the combination of P 188 and P 407 as dispersing carriers of ternary solid dispersions (tSDs) were prepared by a low temperature melting method and solidified rapidly by dropping into the 10-15 °C condensing agent atoleine. Both PA/P 188 and PA/P 407 binary solid dispersions (bSDs) could remarkably promote the dissolution rate of PA, increasing approximately 16 times in bSDs with poloxamers in comparison with pure PA within 180 min. P188 contributed to a faster dissolution rate than P 407, however, P 407 had a better solubility. It is interesting to note that the incorporation of P 188 in PA/P 407 bSD pellets could strongly enhance the dissolution rate of PA. DSC and FTIR were used to explore the characteristics of PA-SD pellets. The enhancement of dissolution from the SDs may be attributed partly to the reduction in particle size in PA crystalline due to the formation of eutectic system with poloxamers. Moreover, a simple, accurate in-vitro dissolution test method for volatility drug was established, and the process of PA-SD pellets preparation was simple, rapid, cost effective, uncomplicated and potentially scalable.
PMCID: PMC4277615  PMID: 25561908
Ternary solid dispersion pellets; Patchouli alcohol; Poloxamers; Eutectic mixtures; Closed in-vitro dissolution test method
16.  Quantitative Hepatitis B Core Antibody Level Is a New Predictor for Treatment Response In HBeAg-positive Chronic Hepatitis B Patients Receiving Peginterferon 
Theranostics  2015;5(3):218-226.
A recent study revealed that quantitative hepatitis B core antibody (qAnti-HBc) level could serve as a novel marker for predicting treatment response. In the present study, we further investigated the predictive value of qAnti-HBc level in HBeAg-positive patients undergoing PEG-IFN therapy. A total of 140 HBeAg-positive patients who underwent PEG-IFN therapy for 48 weeks and follow-up for 24 weeks were enrolled in this study. Serum samples were taken every 12 weeks post-treatment. The predictive value of the baseline qAnti-HBc level for treatment response was evaluated. Patients were further divided into 2 groups according to the baseline qAnti-HBc level, and the response rate was compared. Additionally, the kinetics of the virological and biochemical parameters were analyzed. Patients who achieved response had a significantly higher baseline qAnti-HBc level (serological response [SR], 4.52±0.36 vs. 4.19±0.58, p=0.001; virological response [VR], 4.53±0.35 vs. 4.22±0.57, p=0.005; combined response [CR], 4.50±0.36 vs. 4.22±0.58, p=0.009)). Baseline qAnti-HBc was the only parameter that was independently correlated with SR (p=0.008), VR (p=0.010) and CR(p=0.019). Patients with baseline qAnti-HBc levels ≥30,000 IU/mL had significantly higher response rates, more HBV DNA suppression, and better hepatitis control in PEG-IFN treatment. In conclusion, qAnti-HBc level may be a novel biomarker for predicting treatment response in HBeAg-positive patients receiving PEG-IFN therapy.
PMCID: PMC4279186  PMID: 25553110
quantitative anti-HBc;  chronic hepatitis B; PEG-IFN treatment; treatment response prediction; pretreatment biomarker.
17.  Codelivery of doxorubicin and curcumin with lipid nanoparticles results in improved efficacy of chemotherapy in liver cancer 
Liver cancer is a leading cause of cancer deaths worldwide. The combination therapy of cytotoxic and chemosensitizing agents loaded in nanoparticles has been highlighted as an effective treatment for different cancers. However, such studies in liver cancer remain very limited. In our study, we aim to develop a novel lipid nanoparticles loaded with doxorubicin (DOX) (an effective drug for liver cancer) and curcumin (Cur) (a chemosensitizer) simultaneously, and we examined the efficacy of chemotherapy in liver cancer. DOX and Cur codelivery lipid nanoparticles (DOX/Cur-NPs) were successfully prepared using a high-pressure microfluidics technique, showing a mean particle size of around 90 nm, a polydispersity index <0.3, and a zeta potential <−10 mV. The encapsulation efficacy was >90% for both DOX and Cur. The blank lipid nanoparticles were nontoxic, as determined by a cell cytotoxicity study in human normal liver cells L02 and liver cancer cells HepG2. In vitro DOX release studies revealed a sustained-release pattern until 48 hours in DOX/Cur-NPs. We found enhanced cytotoxicity and decreased inhibitory concentration (IC)50 in HepG2 cells and reduced cytotoxicity in L02 cells treated with DOX/Cur-NPs, suggesting the synergistic effects of DOX/Cur-NPs compared with free DOX and DOX nanoparticles (NPs). The optimal weight ratio of DOX and Cur was 1:1. Annexin-V-fluorescein isothiocyanate/propidium iodide double staining showed enhanced apoptosis in HepG2 cells treated with DOX/Cur-NPs compared with free DOX and DOX-NPs. An in vivo experiment showed the synergistic effect of DOX/Cur-NPs compared with DOX-NPs on liver tumor growth inhibition. Taken together, the simultaneous delivery of DOX and Cur by DOX/Cur-NPs might be a promising treatment for liver cancer.
PMCID: PMC4284012  PMID: 25565818
doxorubicin; curcumin; codelivery; liver cancer; cytotoxicity; tumor growth inhibition
18.  Genome Sequence of a Pandrug-Resistant Pseudomonas aeruginosa Strain, YN-1 
Genome Announcements  2014;2(6):e01280-14.
A highly rampant multidrug-resistant strain of Pseudomonas aeruginosa appeared in a hospital in Yunnan Province, China. Here, we report the genome sequence of the pandrug-resistant (PDR) P. aeruginosa strain recovered from a patient in 2013.
PMCID: PMC4276817  PMID: 25540339
19.  Directing Parthenogenetic Stem Cells Differentiate into Adipocytes for Engineering Injectable Adipose Tissue 
Stem Cells International  2014;2014:423635.
The selection of appropriate seed cells is crucial for adipose tissue engineering. Here, we reported the stepwise induction of parthenogenetic embryonic stem cells (pESCs) to differentiate into adipogenic cells and its application in engineering injectable adipose tissue with Pluronic F-127. pESCs had pluripotent differentiation capacity and could form teratomas that include the three primary germ layers. Cells that migrated from the embryoid bodies (EBs) were selectively separated and expanded to obtain embryonic mesenchymal stem cells (eMSCs). The eMSCs exhibited similar cell surface marker expression profiles with bone morrow mesenchymal stem cells (BMSCs) and had multipotent differentiation capacity. Under the induction of dexamethasone, indomethacin, and insulin, eMSCs could differentiate into adipogenic cells with increased expression of adipose-specific genes and oil droplet depositions within the cytoplasm. To evaluate their suitability as seed cells for adipose tissue engineering, the CM-Dil labelled adipogenic cells derived from eMSCs were seeded into Pluronic F-127 hydrogel and injected subcutaneously into nude mice. Four weeks after injection, glistering and semitransparent constructs formed in the subcutaneous site. Histological observations demonstrated that new adipose tissue was successfully fabricated in the specimen by the labelled cells. The results of the current study indicated that pESCs have great potential in the fabrication of injectable adipose tissue.
PMCID: PMC4284990  PMID: 25587287
20.  Cancer-associated fibroblasts in digestive tumors 
World Journal of Gastroenterology : WJG  2014;20(47):17804-17818.
The significant influence of tumor stroma on malignant cells has been extensively investigated in this era of targeted therapy. The tumor microenvironment, as a dynamic system, is orchestrated by various cells including tumor vascular composing cells, inflammatory cells and fibroblasts. As a major and important component in tumor stroma, increasing evidence has shown that spindle-shaped cancer-associated fibroblasts (CAFs) are a significant modifier of cancer evolution, and promote tumorigenesis, tumor invasion and metastasis by stimulating angiogenesis, malignant cell survival, epithelial-mesenchymal transition (EMT) and proliferation via direct cell-to-cell contact or secretion of soluble factors in most digestive solid tumors. CAFs are thought to be activated, characterized by the expression of α-smooth muscle actin, fibroblast activated protein, fibroblast specific protein, vimentin, fibronectin, etc. They are hypothesized to originate from normal or aged fibroblasts, bone marrow-derived mesenchymal cells, or vascular endothelial cells. EMT may also be an important process generating CAFs, and most probably, CAFs may originate from multiple cells. A close link exists between EMT, tumor stem cells, and chemo-resistance of tumor cells, which is largely orchestrated by CAFs. CAFs significantly induce immunosuppression, and may be a prognostic marker in various malignancies. Targeted therapy toward CAFs has displayed promising anticancer efficacy, which further reinforces the necessity to explore the relationship between CAFs and their hosts.
PMCID: PMC4273131  PMID: 25548479
Cancer-associated fibroblast; Tumor progression; Epithelial-mesenchymal transition; Tumor immunity; Targeted therapy
21.  Proinflammatory effects and molecular mechanisms of interleukin-17 in intestinal epithelial cell line HT-29 
World Journal of Gastroenterology : WJG  2014;20(47):17924-17931.
AIM: To evaluate the proinflammatory effects and molecular mechanisms of interleukin (IL)-17 in intestinal epithelial cell line HT-29.
METHODS: HT-29 cells were cultured with IL-17, tumor necrosis factor (TNF)-α, or the combination of both IL-17 and TNF-α. Real-time PCR and Western blot were used to measure the gene expression levels of neutrophil chemokines CXCL1, CXCL2, CXCL5, CXCL6, IL-8 and TH-17 cell chemokine CCL20, the phosphorylation levels of p38 and TNF-α, and the expression level of IL-8, after using the p38 inhibitor in HT-29 cells. The stable Act1 knockdown HT-29 cell line was established to further test the phosphorylation changes of p38, after using IL-17 and TNF-α.
RESULTS: After HT-29 cells were cultured with IL-17 and TNF-α, the expression levels of neutrophil chemokines (CXCL1, CXCL2, CXCL5, CXCL6, IL-8) and Th17 chemokine (CCL20) significantly improved (24.96 ± 2.53, 28.47 ± 2.87, 38.08 ± 2.72, 33.47 ± 2.41, 31.7 ± 2.38, 44.37 ± 2.73, respectively), and the differences were all statistically significant (P < 0.01). Western blot results showed that IL-17 obviously enhanced the phosphorylation level of p38, which was induced by TNF-α. Compared with the control group, the expression level of IL-8 significantly declined (9.47 ± 1.36 vs 3.06 ± 0.67, P < 0.01) when TH-29 cells were cultured with IL-17 and TNF-α. p38 inhibition assay showed that the p38 pathway played an essential role in the inflammatory response induced by IL-17. p38 phosphorylation levels could not be changed after using IL-17 and TNF-α in the stable Act1 knockdown HT-29 cell line.
CONCLUSION: IL-17 significantly promoted the gene expression levels of TNF-α-induced neutrophil chemokines and Th17 cell chemokine. It is obvious that IL-17 and TNF-α have synergistic effects on p38.
PMCID: PMC4273142  PMID: 25548490
IL-17; HT-29; TNF-α; Inflammatory bowel disease
22.  Construction and Analyses of Human Large-Scale Tissue Specific Networks 
PLoS ONE  2014;9(12):e115074.
Construction and analyses of tissue specific networks is crucial to unveil the function and organizational structure of biological systems. As a direct method to detect protein dynamics, human proteome-wide expression data provide an valuable resource to investigate the tissue specificity of proteins and interactions. By integrating protein expression data with large-scale interaction network, we constructed 30 tissue/cell specific networks in human and analyzed their properties and functions. Rather than the tissue specificity of proteins, we mainly focused on the tissue specificity of interactions to distill tissue specific networks. Through comparing our tissue specific networks with those inferred from gene expression data, we found our networks have larger scales and higher reliability. Furthermore, we investigated the similar extent of multiple tissue specific networks, which proved that tissues with similar functions tend to contain more common interactions. Finally, we found that the tissue specific networks differed from the static network in multiple topological properties. The proteins in tissue specific networks are interacting looser and the hubs play more important roles than those in the static network.
PMCID: PMC4267779  PMID: 25513809
23.  Polymorphisms in the gene encoding estrogen receptor alpha are associated with osteoarthritis in Han Chinese women 
Polymorphisms in the Xba I and Pvu II restriction enzyme recognition sites in the estrogen receptor-alpha gene (ESR1) have been associated with multiple diseases, including osteoarthritis. To determine whether such polymorphisms are associated with osteoarthritis in a Han Chinese population, 98 women with osteoarthritis and 196 healthy women were genotyped by PCR-RFLP of ESR1 with Xba I and Pvu II. Absence of a restriction polymorphism is indicated as an X or P allele; presence of the restriction polymorphism is indicated as an x or p allele. Clinical information was collected on each participant, including body weight, body mass index (BMI), knee radiograms, and bone mineral density (BMD). Body weight and BMI were higher for each Xba I genotype (all P < 0.05) in individuals with osteoarthritis compared to controls (p < 0.05). Femoral BMD was also significantly higher in the osteoarthritis group (p < 0.05). Additionally, the xx genotype for ESR1 was a significant risk factor for osteoarthritis (OR=1.98, 95% CI: 1.13~4.20, p=0.036). Thus, consistent with findings in other populations, the estrogen receptor genotype xx appears to be associated with susceptibility to osteoarthritis among Han Chinese women.
PMCID: PMC4307552  PMID: 25664105
Osteoarthritis; estrogen; estrogen receptor; Xba I; Pvu II
24.  Transplantation of placenta-derived mesenchymal stem cell-induced neural stem cells to treat spinal cord injury 
Neural Regeneration Research  2014;9(24):2197-2204.
Because of their strong proliferative capacity and multi-potency, placenta-derived mesenchymal stem cells have gained interest as a cell source in the field of nerve damage repair. In the present study, human placenta-derived mesenchymal stem cells were induced to differentiate into neural stem cells, which were then transplanted into the spinal cord after local spinal cord injury in rats. The motor functional recovery and pathological changes in the injured spinal cord were observed for 3 successive weeks. The results showed that human placenta-derived mesenchymal stem cells can differentiate into neuron-like cells and that induced neural stem cells contribute to the restoration of injured spinal cord without causing transplant rejection. Thus, these cells promote the recovery of motor and sensory functions in a rat model of spinal cord injury. Therefore, human placenta-derived mesenchymal stem cells may be useful as seed cells during the repair of spinal cord injury.
PMCID: PMC4316454  PMID: 25657742
nerve regeneration; stem cells; placenta-derived mesenchymal stem cells; spinal cord injury; neural stem cells; nerve-like cells; motor function; sensory function; neural regeneration
25.  Nanometer-long Ge-imogolite nanotubes cause sustained lung inflammation and fibrosis in rats 
Ge-imogolites are short aluminogermanate tubular nanomaterials with attractive prospected industrial applications. In view of their nano-scale dimensions and high aspect ratio, they should be examined for their potential to cause respiratory toxicity. Here, we evaluated the respiratory biopersistence and lung toxicity of 2 samples of nanometer-long Ge-imogolites.
Rats were intra-tracheally instilled with single wall (SW, 70 nm length) or double wall (DW, 62 nm length) Ge-imogolites (0.02-2 mg/rat), as well as with crocidolite and the hard metal particles WC-Co, as positive controls. The biopersistence of Ge-imogolites and their localization in the lung were assessed by ICP-MS, X-ray fluorescence, absorption spectroscopy and computed micro-tomography. Acute inflammation and genotoxicity (micronuclei in isolated type II pneumocytes) was assessed 3 d post-exposure; chronic inflammation and fibrosis after 2 m.
Cytotoxic and inflammatory responses were shown in bronchoalveolar lavage 3 d after instillation with Ge-imogolites. Sixty days after exposure, a persistent dose-dependent inflammation was still observed. Total lung collagen, reflected by hydroxyproline lung content, was increased after SW and DW Ge-imogolites. Histology revealed lung fibre reorganization and accumulation in granulomas with epithelioid cells and foamy macrophages and thickening of the alveolar walls. Overall, the inflammatory and fibrotic responses induced by SW and DW Ge-imogolites were more severe (on a mass dose basis) than those induced by crocidolite. A persistent fraction of Ge-imogolites (15% of initial dose) was mostly detected as intact structures in rat lungs 2 m after instillation and was localized in fibrotic alveolar areas. In vivo induction of micronuclei was significantly increased 3 d after SW and DW Ge-imogolite instillation at non-inflammatory doses, indicating the contribution of primary genotoxicity.
We showed that nm-long Ge-imogolites persist in the lung and promote genotoxicity, sustained inflammation and fibrosis, indicating that short high aspect ratio nanomaterials should not be considered as innocuous materials. Our data also suggest that Ge-imogolite structure and external surface determine their toxic activity.
Electronic supplementary material
The online version of this article (doi:10.1186/s12989-014-0067-z) contains supplementary material, which is available to authorized users.
PMCID: PMC4276264  PMID: 25497478
Lung; Inflammation; Fibrosis; Genotoxicity; Nanomaterial; Fibre; High aspect ratio; Biopersistence

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