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1.  Effectiveness of immune therapy combined with chemotherapy on the immune function and recurrence rate of cervical cancer 
The aim of this study was to compare the immune function of patients with cervical cancer and the cancer recurrence rate in patients treated with biological immune therapy combined with chemotherapy or with chemotherapy only. A total of 79 postoperative patients with cervical cancer participated in the present study. They were randomly divided into a control group and an experimental group. Patients in the control group were treated with cisplatin chemotherapy. Patients in the experimental group were treated with dendritic cell-cytokine-induced killer (DC-CIK) cells combined with cisplatin chemotherapy. The CD3+, CD4+, CD8+, CD16+, CD56+ and CD4+CD25+ cell ratios in peripheral blood, and the expression levels of perforin, granzyme B (GraB) and CD107a of peripheral blood mononuclear cells (PBMCs) in all patients prior to and following treatment were observed. The changes of immune function and recurrence rate between these two groups prior to and following treatment were compared. Prior to treatment, the lymphocyte ratio had no significant difference between the two groups (P>0.05). Following treatment, the lymphocyte ratio in the experimental group was significantly higher than that in the control group (P<0.05). The positive expression levels of perforin, GraB and CD107a of PBMCs in the experimental group following treatment were significantly higher than those prior to treatment and those of the control group (P<0.05). The cumulative recurrence rate in the experimental group was significantly lower than that in the control group (P<0.05). In conclusion, in postoperative patients with cervical cancer, treatment with DC-CIK cells combined with cisplatin chemotherapy significantly improved the immune function, reduced the recurrence rate and prolonged the survival time of the patients.
PMCID: PMC4316956  PMID: 25667679
dendritic cell-cytokine-induced killer cell; cisplatin; cervical cancer; immune function; recurrence rate
2.  Lentiviral-Mediated Silencing of Farnesyl Pyrophosphate Synthase through RNA Interference in Mice 
BioMed Research International  2015;2015:914026.
Farnesyl pyrophosphate synthase (FPPS) plays a vital role in the mevalonate pathway and has been shown to be involved in hypertrophy and cardiovascular diseases. Lentivirus-mediated RNA interference (RNAi) to knock down a gene of interest has become a promising new tool for the establishment of transgenic animals. The interfering fragment, named pLVT202, was chosen from cardiomyocytes tested in vitro and was microinjected into the perivitelline space of zygotes from C57BL/6J mice via a lentivirus vehicle; 20 were identified as carrying copies of the transgene using the polymerase chain reaction (PCR). Real-time PCR and western blotting analysis showed that FPPS was downregulated in multiple tissues in the transgenic mice. The transgenic mouse model provides a novel means of studying the gene function of FPPS.
PMCID: PMC4320928
3.  Probing time-dependent mechanical behaviors of catch bonds based on two-state models 
Scientific Reports  2015;5:7868.
With lifetime counter-intuitively being prolonged under forces, catch bonds can play critical roles in various sub-cellular processes. By adopting different “catching” strategies within the framework of two-state models, we construct two types of catch bonds that have a similar force-lifetime profile upon a constant force-clamp load. However, when a single catch bond of either type is subjected to varied forces, we find that they can behave very differently in both force history dependence and bond strength. We further find that a cluster of catch bonds of either type generally becomes unstable when subjected to a periodically oscillating force, which is consistent with experimental results. These results provide important insights into versatile time-dependent mechanical behaviors of catch bonds. We suggest that it is necessary to further differentiate those bonds that are all phenomenologically referred to as “Catch bonds”.
PMCID: PMC4297987  PMID: 25598078
4.  Effects of transcutaneous electrical nerve stimulation on pain in patients with spinal cord injury: a randomized controlled trial 
[Purpose] To investigate the effects of transcutaneous electrical nerve stimulation (TENS) on pain in patients with spinal cord injury. [Subjects and Methods] Fifty-two spinal cord injury patients with central pain were randomly allocated into two groups TENS and control with 26 subjects per group. The patients in TENS and control groups were treated with TENS and sham TENS for 20 min (three times a week) for 12 consecutive weeks, respectively. The two group’s pain was assessed using visual analog scale (VAS) and the McGill Pain Questionnaire (including pain rating index-total, pain rating index-affective, pain rating index-sensory, present pain intensity, and number of words chosen) before and after the treatment. [Results] After the intervention, we found significant differences in VAS, pain rating index-total, pain rating index-affective, pain rating index-sensory, present pain intensity, and number of words chosen between the TENS group and the control group. [Conclusion] Our results suggest that TENS effectively decreases pain in patients with spinal cord injury.
PMCID: PMC4305569  PMID: 25642029
Transcutaneous electrical nerve stimulation; Pain; Spinal cord injury
5.  Pancreas β cell regeneration and type 1 diabetes (Review) 
Diabetes mellitus, which may cause hyperglycemia and a number of complications, mostly results from a deficiency of β cell mass (type 1 diabetes) or a limitation of β cell function (type 2 diabetes). Currently, enhancing β cell regeneration and increasing cell proliferation have not only been described in experimental diabetes models, but have also been proven to improve outcomes for patients with diabetes. Therefore, understanding the mechanisms controlling the development and regeneration of β cells in the human pancreas may be helpful for the treatment of β cell-deficient disease. In this review, we first introduce the various cell types in the adult pancreas and thereby clarify their functions and origins. Then, the known mechanisms of β cell development and expansion in the normal human pancreas are described. The potential mechanisms of β cell regeneration, including β cell self-replication, neogenesis from non-β cell precursors and transdifferentiation from α cells, are discussed in the next part. Finally, the ability of the pancreas to regenerate mature β cells is explored in pathological conditions, including type 1 diabetes, chronic pancreatitis and persistent hyperinsulinemic hypoglycemia of infancy.
PMCID: PMC4316911  PMID: 25667609
diabetes mellitus; endocrine pancreas; β cell regeneration; type 1 diabetes
6.  Fezf2 expression identifies a multipotent progenitor for neocortical projection neurons, astrocytes and oligodendrocytes 
Neuron  2013;80(5):10.1016/j.neuron.2013.09.037.
Progenitor cells in the cerebral cortex sequentially generate distinct classes of projection neurons. Recent work suggests the cortex may contain intrinsically fate-restricted progenitors marked by expression of Cux2. However, the heterogeneity of the neocortical ventricular zone as well as the contribution of lineage-restricted progenitors to the overall cortical neurogenic program remains unclear. Here we utilize in vivo genetic fate mapping to demonstrate that Fezf2-expressing radial glial cells (RGCs) exist throughout cortical development and sequentially generate all major projection neuron subtypes and glia. Moreover, we show that the vast majority of CUX2+ cells in the VZ and SVZ are migrating interneurons derived from the subcortical telencephalon. Examination of the embryonic cortical progenitor population demonstrates that Cux2+ RGCs generate both deep- and upper-layer projection neurons. These results identify Fezf2+ radial glial cells as a multipotent neocortical progenitor and suggest that the existence, and molecular identity, of laminar-fate-restricted RGCs awaits further investigation.
PMCID: PMC3857588  PMID: 24314728
7.  Effect of Soluble Inducible Costimulator Level and Its Polymorphisms on Age-Related Macular Degeneration 
DNA and Cell Biology  2013;32(12):717-721.
Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly population. Evidence has shown that the human immune system may play critical roles in this disease. Inducible costimulator (ICOS) promotes T-cell activation, differentiation, and T:B-cell interactions. The aim of the study was to understand the effect of ICOS on the development of AMD from genetic polymorphism perspective and serum level perspective. Two ICOS polymorphisms, rs10183087A/C and rs10932037C/T, were tested in 223 AMD cases and 262 healthy controls. The serum level of soluble ICOS (sICOS) was compared among subjects with different genotypes, as well as between AMD patients and controls. Data showed that prevalence of rs10183087CC genotype was significantly increased in AMD than in controls (p=0.001). Function analysis revealed that subjects carrying rs10183087CC genotype had higher serum levels of sICOS than those with AA or AC genotypes (p<0.05). When we compared serum levels of sICOS between cases and controls, results showed that AMD patients had significantly increased sICOS levels than healthy donors (p<0.05). Also, wet type cases were observed to have higher sICOS levels than cases with dry type (p<0.05). These data suggested ICOS polymorphism could affect the susceptibility to AMD by elevating protein expression, and serum levels of sICOS may be closed correlated with the development and progression of this disease.
PMCID: PMC3864366  PMID: 24083358
8.  Structure of Bacterial Transcription Factor SpoIIID and Evidence for a Novel Mode of DNA Binding 
Journal of Bacteriology  2014;196(12):2131-2142.
SpoIIID is evolutionarily conserved in endospore-forming bacteria, and it activates or represses many genes during sporulation of Bacillus subtilis. An SpoIIID monomer binds DNA with high affinity and moderate sequence specificity. In addition to a predicted helix-turn-helix motif, SpoIIID has a C-terminal basic region that contributes to DNA binding. The nuclear magnetic resonance (NMR) solution structure of SpoIIID in complex with DNA revealed that SpoIIID does indeed have a helix-turn-helix domain and that it has a novel C-terminal helical extension. Residues in both of these regions interact with DNA, based on the NMR data and on the effects on DNA binding in vitro of SpoIIID with single-alanine substitutions. These data, as well as sequence conservation in SpoIIID binding sites, were used for information-driven docking to model the SpoIIID-DNA complex. The modeling resulted in a single cluster of models in which the recognition helix of the helix-turn-helix domain interacts with the major groove of DNA, as expected. Interestingly, the C-terminal extension, which includes two helices connected by a kink, interacts with the adjacent minor groove of DNA in the models. This predicted novel mode of binding is proposed to explain how a monomer of SpoIIID achieves high-affinity DNA binding. Since SpoIIID is conserved only in endospore-forming bacteria, which include important pathogenic Bacilli and Clostridia, whose ability to sporulate contributes to their environmental persistence, the interaction of the C-terminal extension of SpoIIID with DNA is a potential target for development of sporulation inhibitors.
PMCID: PMC4054184  PMID: 24584501
9.  miR-29a promotes intestinal epithelial apoptosis in ulcerative colitis by down-regulating Mcl-1 
Objective: While it’s widely accepted that the etiology of ulcerative colitis (UC) involves both genetic and environmental factors, the pathogenesis of ulcerative colitis is still poorly understood. Intestinal epithelial apoptosis is one of the most common histopathological changes of UC and the expression of a number of apoptosis genes may contribute to the progression of UC. MicroRNAs have recently emerged as powerful regulators of diverse cellular processes and have been shown to be involved in many immune-mediated disorders such as psoriasis, rheumatoid arthritis, lupus, and asthma. A unique microRNA expression profile has been identified in UC, suggesting that, microRNAs play an important role in the pathogenesis of UC. We investigated the role of miR-29a in intestinal epithelial apoptosis in UC. Methods: The expression of miR-29a and Mcl-1, an anti-apoptotic BCL-2 family member, was evaluated in both UC patients and UC mice model induced by dextran sodium sulfate (DSS). The apoptosis rate of intestinal epithelial cells was also evaluated. Results: In UC patients and DSS-induced UC in mice, the expression of miR-29a and Mcl-1, were up-regulated and down-regulated, respectively. We identified a miR-29a binding site (7 nucleotides) on the 3’UTR of mcl-1 and mutation in this binding site on the 3’UTR of mcl-1 led to mis-match between miR-29a and mcl-1. Knockout of Mcl-1 caused apoptosis of the colonic epithelial HT29 cells. In addition, miR-29a regulated intestinal epithelial apoptosis by down-regulating the expression of Mcl-1. Conclusion: miR-29a is involved in the pathogenesis of UC by regulating intestinal epithelial apoptosis via Mcl-1.
PMCID: PMC4313986
MiR-29a; apoptosis; ulcerative colitis; Mcl-1
10.  Thermally assisted electric field control of magnetism in flexible multiferroic heterostructures 
Scientific Reports  2014;4:6925.
Thermal and electrical control of magnetic anisotropy were investigated in flexible Fe81Ga19 (FeGa)/Polyvinylidene fluoride (PVDF) multiferroic heterostructures. Due to the large anisotropic thermal deformation of PVDF (α1 = −13 × 10−6 K−1 and α2 = −145 × 10−6 K−1), the in-plane uniaxial magnetic anisotropy (UMA) of FeGa can be reoriented 90° by changing the temperature across 295 K where the films are magnetically isotropic. Thus, the magnetization of FeGa can be reversed by the thermal cycling between 280 and 320 K under a constant magnetic field lower than coercivity. Moreover, under the assistance of thermal deformation with slightly heating the samples to the critical temperature, the electric field of ± 267 kV cm−1 can well align the UMA along the two orthogonal directions. The new route of combining thermal and electrical control of magnetic properties realized in PVDF-based flexible multiferroic materials shows good prospects in application of flexible thermal spintronic devices and flexible microwave magnetic materials.
PMCID: PMC4220272  PMID: 25370605
11.  Notes on the genus Xenocerogria (Coleoptera, Tenebrionidae, Lagriini) from China 
ZooKeys  2014;93-108.
Three species of the genus Xenocerogria Merkl, 2007 have been recorded in China, Xenocerogria feai (Borchmann, 1911), Xenocerogria ignota (Borchmann, 1941) and Xenocerogria ruficollis (Borchmann, 1912). Xenocera xanthisma Chen, 2002 is proposed as a junior synonym of Xenocerogria ruficollis. Lectotype of Xenocerogria ignota is designated, and the species is transferred to the genus Lagria Fabricius, 1775. New Chinese province records of Xenocerogria ruficollis are provided.
PMCID: PMC4258622  PMID: 25493049
China; Lagriinae; lectotype designation; new synonym; redescription; Tenebrionidae; Xenocerogria
12.  Tuberculosis among Healthcare Workers in Southeastern China: A Retrospective Study of 7-Year Surveillance Data 
The baseline prevalence and characteristics of tuberculosis (TB) among general healthcare workers (HCWs) in southeastern China remains unknown. We conducted a retrospective study based on the TB surveillance data in Zhejiang Province from 2005 to 2011, which were extracted from the national Tuberculosis Information Management System (TIMS). We calculated and compared annual notification rates of different occupational groups and analyzed the epidemiological and clinical characteristics. The annual TB notification rates among general HCWs declined steadily from 2005 to 2011. On average, HCWs showed annual TB notification rates lower than the general population but higher than teachers. Recorded HCW TB patients averaged 35.5 years of age, with females outnumbering males (58.0% > 42.0%). The proportion of pulmonary tuberculosis (PTB) was higher among male than in the female patients (88.5% > 83.4%, P = 0.031). Our study suggested that general HCWs run a higher occupational risk than teachers although the two groups are socioeconomically comparable and that the priority should be given to the young female HCWs for TB prevention in healthcare institutions.
PMCID: PMC4245659  PMID: 25419877
tuberculosis (TB); healthcare workers (HCWs); surveillance
13.  Upregulated periostin promotes angiogenesis in keloids through activation of the ERK 1/2 and focal adhesion kinase pathways, as well as the upregulated expression of VEGF and angiopoietin-1 
Molecular Medicine Reports  2014;11(2):857-864.
Periostin, a secreted extracellular matrix protein, is highly expressed in wound healing and in various types of human cancer and is involved in angiogenesis. Keloids, considered dermal benign tumors, are granulomatous lesions characterized by capillary proliferation. However, the underlying regulatory mechanism of angiogenesis in keloids remains to be elucidated. The present study aimed to examine the effect of periostin on angiogenesis in keloids. The expression of periostin was upregulated and the vessel density was higher in human keloids compared with normal tissue, observed following staining with CD31 and CD105. Periostin demonstrated a markedly positive correlation with blood vessel density, which was assessed using CD31 staining (r=0.711; P<0.01) and a weak correlation was observed using CD105 staining (r=0.251; P<0.01). Conditioned medium from keloid fibroblasts (KFs) promoted the migration and tube formation of human umbilical vein endothelial cells (HUVECs) compared with normal fibroblasts and this effect may have been abrogated by the short hairpin RNA knockdown of periostin. Treatment with recombinant human periostin promoted the migration and tube formation of HUVECs by activating the extracellular signal-regulated kinase 1/2 and focal adhesion kinase signaling pathway. In addition, periostin increased the secretion of vascular endothelial growth factor and angiopoietin-1 in the KFs. In conclusion, these data suggested that upregulation in the level of periostin may promote angiogenesis directly and indirectly in keloids and may be a key factor in keloid development. Periostin may, therefore, be a promising therapeutic target in the treatment of keloids and other angioproliferative diseases.
PMCID: PMC4262479  PMID: 25369801
periostin; fibroblast; keloid; endothelial cells; angiogenesis
14.  Positive temperature coefficient of magnetic anisotropy in polyvinylidene fluoride (PVDF)-based magnetic composites 
Scientific Reports  2014;4:6615.
The magnetic anisotropy is decreased with increasing temperature in normal magnetic materials, which is harmful to the thermal stability of magnetic devices. Here, we report the realization of positive temperature coefficient of magnetic anisotropy in a novel composite combining β-phase polyvinylidene fluoride (PVDF) with magnetostrictive materials (magnetostrictive film/PVDF bilayer structure). We ascribe the enhanced magnetic anisotropy of the magnetic film at elevated temperature to the strain-induced anisotropy resulting from the anisotropic thermal expansion of the β-phase PVDF. The simulation based on modified Stoner-Wohlfarth model and the ferromagnetic resonance measurements confirms our results. The positive temperature coefficient of magnetic anisotropy is estimated to be 1.1 × 102 J m−3 K−1. Preparing the composite at low temperature can enlarge the temperature range where it shows the positive temperature coefficient of magnetic anisotropy. The present results may help to design magnetic devices with improved thermal stability and enhanced performance.
PMCID: PMC4196102  PMID: 25311047
15.  Design, Synthesis, and Anti-leukemic Activity of Stereochemically Defined Constrained Analogs of FTY720 (Gilenya) 
ACS medicinal chemistry letters  2013;4(10):10.1021/ml4002425.
FTY720 functions as an immunosuppressant due to its effect on sphingosine-1-phosphate receptors. At doses well above those needed for immunosuppression, FTY720 also has anti-neoplastic actions. Our published work suggests that at least some of FTY720’s anti-cancer activity is independent of its effects on S1P receptors and due instead to its ability to induce nutrient transporter down-regulation. Compounds that trigger nutrient transporter loss but lack FTY720’s S1P receptor-related, dose-limiting toxicity have the potential to be effective and selective anti-tumor agents. In this study, a series of enantiomerically pure and stereochemically diverse O-substituted benzyl ethers of pyrrolidines was generated and tested for the ability to kill human leukemia cells. The stereochemistry of the hydroxymethyl was found to be a key determinant of compound activity. Moreover, phosphorylation of this group was not required for anti-leukemic activity.
PMCID: PMC3834958  PMID: 24273632
FTY720; leukemia; pyrrolidine; arylmethyl ether
16.  Design, Synthesis, and Antileukemic Activity of Stereochemically Defined Constrained Analogues of FTY720 (Gilenya) 
ACS Medicinal Chemistry Letters  2013;4(10):969-973.
FTY720 functions as an immunosuppressant due to its effect on sphingosine-1-phosphate receptors. At doses well above those needed for immunosuppression, FTY720 also has antineoplastic actions. Our published work suggests that at least some of FTY720’s anticancer activity is independent of its effects on S1P receptors and due instead to its ability to induce nutrient transporter down-regulation. Compounds that trigger nutrient transporter loss but lack FTY720’s S1P receptor-related, dose-limiting toxicity have the potential to be effective and selective antitumor agents. In this study, a series of enantiomerically pure and stereochemically diverse O-substituted benzyl ethers of pyrrolidines was generated and tested for the ability to kill human leukemia cells. The stereochemistry of the hydroxymethyl was found to be a key determinant of compound activity. Moreover, phosphorylation of this group was not required for antileukemic activity.
PMCID: PMC3834958  PMID: 24273632
FTY720; leukemia; pyrrolidine; arylmethyl ether
17.  Elevated preoperative peripheral blood monocyte count predicts poor prognosis for hepatocellular carcinoma after curative resection 
BMC Cancer  2014;14(1):744.
Peripheral blood monocyte count is an easily assessable parameter of systemic inflammatory response. The aim of this study was to determine whether monocyte count was prognostic in hepatocellular carcinoma (HCC) following hepatic resection.
We retrospectively reviewed 351 patients with HCC treated with hepatic resection from 2006 to 2009. Preoperative absolute peripheral monocyte count, demographics, and clinical and pathological data were analyzed.
On univariate and multivariate analysis, elevated monocyte counts (≥545/mm3), tumor size ≥5 cm, non-capsulation, and multiple tumors were associated with poor disease-free survival (DFS) and overall survival (OS). The 1-, 3- and 5-year DFS rates were 58%, 41% and 35%, respectively, for patients with monocyte counts <545/mm3, and 36%, 23% and 21% for patients with monocyte counts ≥545/mm3. Correspondingly, the 1-, 3- and 5-year OS rates were 79%, 53% and 46% for monocyte counts <545/mm3, and 64%, 36% and 29% for monocyte counts ≥545/mm3. Subgroup analysis indicated that DFS after hepatic resection in hepatitis B virus (HBV)-infected patients was significantly better in those with a peripheral blood monocyte counts <545/mm3, but it did not differ between patients without HBV infection. In addition, DFS was significantly better for patients with a peripheral blood monocyte count <545/mm3, whether or not cirrhosis was present. Patients with elevated monocyte counts tended to have larger tumors.
Elevated preoperative monocyte count is an independent predictor of worse prognosis for patients with HCC after hepatic resection, especially for those with HBV infection. Postoperative adjuvant treatment might be considered for patients with elevated preoperative monocyte counts.
PMCID: PMC4192399  PMID: 25280428
Hepatocellular carcinoma; Monocyte; Hepatic resection; Prognosis
18.  99mTc-3P4-RGD2 Scintimammography in the Assessment of Breast Lesions: Comparative Study with 99mTc-MIBI 
PLoS ONE  2014;9(9):e108349.
To compare the potential application of 99mTc-3P-Arg-Gly-Asp (99mTc-3P4-RGD2) scintimammography (SMM) and 99mTc-methoxyisobutylisonitrile (99mTc-MIBI) SMM for the differentiation of malignant from benign breast lesions.
Thirty-six patients with breast masses on physical examination and/or suspicious mammography results that required fine needle aspiration cytology biopsy (FNAB) were included in the study. 99mTc-3P4-RGD2 and 99mTc-MIBI SMM were performed with single photon emission computed tomography (SPECT) at 60 min and 20 min respectively after intravenous injection of 738±86 MBq radiotracers on a separate day. Images were evaluated by the tumor to non-tumor localization ratios (T/NT). Receiver operating characteristic (ROC) curve analysis was performed on each radiotracer to calculate the cut-off values of quantitative indices and to compare the diagnostic performance for the ability to differentiate malignant from benign diseases.
The mean T/NT ratio of 99mTc-3P4-RGD2 in malignant lesions was significantly higher than that in benign lesions (3.54±1.51 vs. 1.83±0.98, p<0.001). The sensitivity, specificity, and accuracy of 99mTc-3P4-RGD2 SMM were 89.3%, 90.9% and 89.7%, respectively, with a T/NT cut-off value of 2.40. The mean T/NT ratio of 99mTc-MIBI in malignant lesions was also significantly higher than that in benign lesions (2.86±0.99 vs. 1.51±0.61, p<0.001). The sensitivity, specificity and accuracy of 99mTc-MIBI SMM were 87.5%, 72.7% and 82.1%, respectively, with a T/NT cut-off value of 1.45. According to the ROC analysis, the area under the curve for 99mTc-3P4-RGD2 SMM (area = 0.851) was higher than that for 99mTc-MIBI SMM (area = 0.781), but the statistical difference was not significant.
99mTc-3P4-RGD2 SMM does not provide any significant advantage over the established 99mTc-MIBI SMM for the detection of primary breast cancer. The T/NT ratio of 99mTc-3P4-RGD2 SMM was significantly higher than that of 99mTc-MIBI SMM. Both tracers could offer an alternative method for elucidating non-diagnostic mammograms.
PMCID: PMC4176966  PMID: 25250628
19.  Expressions of heparanase and upstream stimulatory factor in hepatocellular carcinoma 
The expression of heparanase (HPSE) was associated with postoperative metastatic recurrence in patients with hepatocellular carcinoma (HCC). The six E-box binding sites in the core promoter of the HPSE gene suggested that transcription factors of E-box such as upstream stimulatory factor (USF) might regulate the transcription of the HPSE gene. The aim of our study is to measure the levels of HPSE and USF expression and investigate the relationship between USF expression and clinicopathological parameters in patients with HCC.
HPSE, USF1 and USF2 expressions in human HCC cell lines (BEL-7402, HepG2 and HCCLM3) and 15 fresh human HCC tissue samples were measured by real-time reverse transcriptase-PCR and Western blot analysis. The normal liver cell line QSG7701 or fresh normal liver tissue samples obtained from 15 additional surgical patients with hepatic rupture was used as a control. The protein expressions were determined by immunohistochemistry in paraffin-embedded human HCC tissues and corresponding non-neoplastic tumor surrounding tissues (NTST) of 57 patients.
HPSE, USF1 and USF2 mRNA expressions were increased in HCC cell lines and HCC tissues compared with normal liver cell line and normal liver tissue. The protein expressions of HPSE, USF1 and USF2 in HCC cell lines and HCC tissues were also increased. Both USF1 and USF2 expressions were positively correlated with HPSE. USF1 and USF2 expressions were increased in patients with liver cirrhosis, worse tissue differentiation, advanced HCC stages and metastatic recurrence.
Increased USF in HCC is associated with HPSE expression. USF might be an important factor in regulating HPSE expression and act as a novel marker of metastatic recurrence of HCC patients.
PMCID: PMC4237794  PMID: 25149140
Heparanase; Upstream stimulatory factor; Hepatocellular carcinoma; Recurrence
20.  Quantitative Estimation of Renal Function with Dynamic Contrast-Enhanced MRI Using a Modified Two-Compartment Model 
PLoS ONE  2014;9(8):e105087.
To establish a simple two-compartment model for glomerular filtration rate (GFR) and renal plasma flow (RPF) estimations by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI).
Materials and Methods
A total of eight New Zealand white rabbits were included in DCE-MRI. The two-compartment model was modified with the impulse residue function in this study. First, the reliability of GFR measurement of the proposed model was compared with other published models in Monte Carlo simulation at different noise levels. Then, functional parameters were estimated in six healthy rabbits to test the feasibility of the new model. Moreover, in order to investigate its validity of GFR estimation, two rabbits underwent acute ischemia surgical procedure in unilateral kidney before DCE-MRI, and pixel-wise measurements were implemented to detect the cortical GFR alterations between normal and abnormal kidneys.
The lowest variability of GFR and RPF measurements were found in the proposed model in the comparison. Mean GFR was 3.03±1.1 ml/min and mean RPF was 2.64±0.5 ml/g/min in normal animals, which were in good agreement with the published values. Moreover, large GFR decline was found in dysfunction kidneys comparing to the contralateral control group.
Results in our study demonstrate that measurement of renal kinetic parameters based on the proposed model is feasible and it has the ability to discriminate GFR changes in healthy and diseased kidneys.
PMCID: PMC4139329  PMID: 25141138
21.  Pinocembrin, a major flavonoid in propolis, improves the biological functions of EPCs derived from rat bone marrow through the PI3K-eNOS-NO signaling pathway 
Cytotechnology  2012;65(4):541-551.
The number and quality of endothelial progenitor cells (EPCs) are damaged to varying degrees in patients at risk for developing atherosclerosis. The improvement of the quantity and functions of EPCs can enhance repair of injured endothelial monolayer resulting in inhibiting atherosclerosis. The purpose of this study was to investigate the effect of pinocembrin (PIN), a major flavonoid in propolis on the differentiation and biological functions of EPCs and the potential mechanisms of these effects. Flow cytometry analysis revealed that PIN treatment increased the number of CD34+, CD133+, FLK-1+, CD133+/FLK-1+ and CD34+/FLK-1+ mononuclear cells (MNCs) in the peripheral blood of apoE−/− mice compared to untreated control mice. In vitro PIN treatment significantly increased the number of CD34+, CD133+, FLK-1+ and CD133+/FLK-1+ MNCs derived from SD bone marrow compared to untreated controls by 42.1, 84.6, 165.9 and 23.1 %, respectively. Additionally, PIN can improve biological functions of EPCs, such as proliferation, migration, adhesion, and in vitro tube formation and NO release. All of these improvements were inhibited by LY294002, while L-NAME only inhibited the PIN-induced increase in EPC proliferation and adhesion. We conclude that PIN can both promote the differentiation of EPCs in vitro and ex vivo and improve the biological functions of EPCs. The PI3K-eNOS-NO signaling pathway may be involved in the PIN-induced increase in the proliferation and adhesion of EPCs.
PMCID: PMC3720980  PMID: 23179089
Pinocembrin; Endothelial progenitor cells; Mononuclear cells; CD133; FLK-1
22.  Activating Transcription Factor 4 Promotes Esophageal Squamous Cell Carcinoma Invasion and Metastasis in Mice and Is Associated with Poor Prognosis in Human Patients 
PLoS ONE  2014;9(7):e103882.
Activating transcription factor 4 (ATF4) is a stress response gene that is involved in homeostasis and cellular protection. However, its expression and function in esophageal squamous cell carcinoma (ESCC) remains unknown. In this study, we aimed to determine the clinicopathologic significance of ATF4 in ESCC and its potential role in ESCC invasion and metastasis.
Methodology/Principal Findings
We demonstrated that ATF4 overexpression is correlated with multiple malignant characteristics and indicates poor prognosis in ESCC patients. ATF4 expression was an independent factor that affected the overall survival of patients with ESCC after surgical resection. ATF4 promoted cell invasion and metastasis by promoting matrix metalloproteinase (MMP)-2 and MMP-7 expression, while its silencing significantly attenuated these activities both in vitro and in vivo.
We report that ATF4 is a potential biomarker for ESCC prognosis and that its dysregulation may play a key role in the regulation of invasion and metastasis in ESCC cells. The targeting of ATF4 may provide a new strategy for blocking ESCC metastasis.
PMCID: PMC4117569  PMID: 25078779
23.  Enhanced photocatalytic hydrogen evolution by combining water soluble graphene with cobalt salts 
There is tremendous effort put in the pursuit for cheap and efficient catalysts for photocatalytic hydrogen evolution systems. Herein, we report an active catalyst that uses the earth-abundant element cobalt and water-dispersible sulfonated graphene. The photocatalytic hydrogen evolution activity of the catalyst was tested by using triethanolamine (TEOA) as electron donor and eosin Y (EY) as the photosensitizer under LED irradiation at 525 nm. Hydrogen was produced constantly even after 20 h, and the turnover number (TON) reached 148 (H2/Co) in 4 h with respect to the initial concentration of the added cobalt salts was shown to be 5.6 times larger than that without graphene.
PMCID: PMC4142871  PMID: 25161850
cobalt salts; earth-abundant catalyst; photocatalysis; photocatalytic hydrogen evolution; water-dispersible sulfonated-graphene
24.  Integrated System of Structural Health Monitoring and Intelligent Management for a Cable-Stayed Bridge 
The Scientific World Journal  2014;2014:689471.
It is essential to construct structural health monitoring systems for large important bridges. Zhijiang Bridge is a cable-stayed bridge that was built recently over the Hangzhou Qiantang River (the largest river in Zhejiang Province). The length of Zhijiang Bridge is 478 m, which comprises an arched twin-tower space and a twin-cable plane structure. As an example, the present study describes the integrated system of structural health monitoring and intelligent management for Zhijiang Bridge, which comprises an information acquisition system, data management system, evaluation and decision-making system, and application service system. The monitoring components include the working environment of the bridge and various factors that affect bridge safety, such as the stress and strain of the main bridge structure, vibration, cable force, temperature, and wind speed. In addition, the integrated system includes a forecasting and decision-making module for real-time online evaluation, which provides warnings and makes decisions based on the monitoring information. From this, the monitoring information, evaluation results, maintenance decisions, and warning information can be input simultaneously into the bridge monitoring center and traffic emergency center to share the monitoring data, thereby facilitating evaluations and decision making using the system.
PMCID: PMC4129177  PMID: 25140342
25.  Predicting Local Dengue Transmission in Guangzhou, China, through the Influence of Imported Cases, Mosquito Density and Climate Variability 
PLoS ONE  2014;9(7):e102755.
Each year there are approximately 390 million dengue infections worldwide. Weather variables have a significant impact on the transmission of Dengue Fever (DF), a mosquito borne viral disease. DF in mainland China is characterized as an imported disease. Hence it is necessary to explore the roles of imported cases, mosquito density and climate variability in dengue transmission in China. The study was to identify the relationship between dengue occurrence and possible risk factors and to develop a predicting model for dengue’s control and prevention purpose.
Methodology and Principal Findings
Three traditional suburbs and one district with an international airport in Guangzhou city were selected as the study areas. Autocorrelation and cross-correlation analysis were used to perform univariate analysis to identify possible risk factors, with relevant lagged effects, associated with local dengue cases. Principal component analysis (PCA) was applied to extract principal components and PCA score was used to represent the original variables to reduce multi-collinearity. Combining the univariate analysis and prior knowledge, time-series Poisson regression analysis was conducted to quantify the relationship between weather variables, Breteau Index, imported DF cases and the local dengue transmission in Guangzhou, China. The goodness-of-fit of the constructed model was determined by pseudo-R2, Akaike information criterion (AIC) and residual test. There were a total of 707 notified local DF cases from March 2006 to December 2012, with a seasonal distribution from August to November. There were a total of 65 notified imported DF cases from 20 countries, with forty-six cases (70.8%) imported from Southeast Asia. The model showed that local DF cases were positively associated with mosquito density, imported cases, temperature, precipitation, vapour pressure and minimum relative humidity, whilst being negatively associated with air pressure, with different time lags.
Imported DF cases and mosquito density play a critical role in local DF transmission, together with weather variables. The establishment of an early warning system, using existing surveillance datasets will help to control and prevent dengue in Guangzhou, China.
PMCID: PMC4097061  PMID: 25019967

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