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1.  The Effect of Chinese Traditional Exercise-Baduanjin on Physical and Psychological Well-Being of College Students: A Randomized Controlled Trial 
PLoS ONE  2015;10(7):e0130544.
The physical and mental health of college students tends to continuously decline around the world, therefore, it is important to improve their health during college period. Baduanjin, a traditional Chinese exercise which combines movements with breath and mind, may be one of the selectable effective exercises. However, the effect of Baduanjin exercise on college students has not been established. In this study, we systematically assessed the effectiveness and safety of Baduanjin exercise on physical and mental health of college students by a rigorous randomized, parallel-controlled design.
A total of 222 college students from Fujian University of Traditional Chinese Medicine were recruited and randomly allocated at an equal ratio into control or Baduanjin training. Participants in control group were informed to maintain their original activity habit, and those in Baduanjin exercise group received a 12-week Baduanjin exercise training with a frequency of 1 hour per day and 5 days per week on the basis of their original activity habit. The physical and psychological outcomes, including lumbar muscle strength, lower limb proprioception function, physical fitness, as well as self-reported symptom intensity, stress, self-esteem, mood, quality of life, quality of sleep, and adverse events, were evaluated at baseline, 13 weeks (at the end of 12-week intervention), and 25 weeks (after the 12-week follow-up period). Intention-to-treat analysis was performed for the above outcomes.
Compared with controls, significant improvements in Baduanjin exercise group at the end of 12-week intervention period were found on lower limb proprioception function (the rate of average trace error on right lower limb (%): control 23.50±5.50, Baduanjin 21.92±6.54, P=0.004; the rate of average trace error on left lower limb (%): control 22.32±6.62, Baduanjin 20.63±4.62, P=0.046), cardiorespiratory endurance (step test index: control 47.66±5.94, Baduanjin 50.07±9.30, P=0.025), flexibility (control 14.35±7.26cm, Baduanjin 15.39±6.43cm, P=0.009) and explosive force of lower limb (standing long jump test (m): control 1.77±0.24, Baduanjin 1.79±0.22, P=0.005 for adjustment baseline) in physical outcomes, and attention (Schulte Grid test (second): control 210.4±51.15, Baduanjin 192.4±47.14, P=0.034) in mental outcome. Lumbar muscle strength in Baduanjin group had been moderately enhanced but no significant difference compared to controls. No significant changes in other physical and mental outcomes, including vital capacity, blood pressure, heart rate, hand grip force, self-symptom intensity, stress, self-efficacy, quality of life, and quality of sleep, were found between groups. No adverse event was reported during the study period.
Regular Baduanjin exercise had an advantage for college students on improvement of lower limb proprioception, enhance of cardiorespiratory endurance, flexibility, explosive force of lower limb and attention, compared with usual exercise.
Trial Registration
Chinese Clinical Trial Registry ChiCTR-TRC-13003329
PMCID: PMC4497728  PMID: 26158769
2.  Effectiveness of Tai Chi on Physical and Psychological Health of College Students: Results of a Randomized Controlled Trial 
PLoS ONE  2015;10(7):e0132605.
To investigate the effectiveness and safety of Tai Chi Chuan (TCC) on physical and psychological health of college students.
Two hundred six college students were recruited and randomly allocated to a control group or a TCC exercise group in an equal ratio. Participants in the control group were instructed to maintain their original activity level and those in the TCC exercise group received 12 weeks of TCC exercise training based on their original activity level. Physical and psychological outcomes were evaluated at baseline, 13 weeks and 25 weeks. Intention-to-treat analysis was performed for the above outcomes.
Compared with the control group, the TCC exercise group showed significant improvements at the end of the 12-week intervention period for flexibility (length of Sit and Reach (cm): TCC group 14.09±7.40 versus control 12.88±6.57, P = 0.039 adjusted for its baseline measures using a general linear model) and balance ability (open eyes perimeter: TCC group 235.6(191~314) versus control 261(216~300); closed eyes perimeter: TCC group 370.5 (284~454) versus control 367 (293~483); P = 0.0414, 0.008, respectively, adjusted for corresponding baseline measures using a general linear model). No significant changes in other physical and mental outcomes were found between the two groups. No adverse events were reported during the study period.
TCC exercise was beneficial in college students for improving flexibility and balance capability to some extent, compared with usual exercise.
Trial Registration
Chinese Clinical Trial Registry ChiCTR-TRC-13003328
PMCID: PMC4492604  PMID: 26147842
3.  Putting a face in its place: in- and out-group membership alters the N170 response 
Two mechanisms have been proposed to account for the difficulty in recognizing faces of other racial groups (the other-race effect; ORE): perceptual expertise and social cognitive factors. Focusing on the social cognitive factors alone, we manipulated in-group and out-group memberships based on two social categories (nationality and university affiliation), and controlled for perceptual expertise by testing Caucasian participants with Caucasian faces only. Using event-related potentials (ERPs) and focusing on the N170, a brain electrical component sensitive to faces, we provide for the first time strong support for the social cognitive influence on face processing within 200 ms. After participants learned the social categories, the N170 latency differentiated between double in-group and double out-group faces, taking longer to process the latter. In comparison, without group memberships, there was no difference in N170 latency among the faces. These results are consistent with recent findings of behavioral and imaging research, providing further support for the social cognitive model and its potential for understanding ORE.
PMCID: PMC4090958  PMID: 23677488
other-race effect; social cognition; face inversion effect; ERP; N170
4.  Age-specific gender differences in early mortality following ST-segment elevation myocardial infarction in China 
Heart  2014;101(5):349-355.
To assess whether younger, but not older, women in China have higher in-hospital mortality following ST-Segment Elevation Myocardial Infarction (STEMI) compared with men, and whether this relationship varied over the last decade or across rural/urban areas.
We analysed a nationally representative sample of 11 986 patients with STEMI from 162 Chinese hospitals in 2001, 2006 and 2011, in the China PEACE-Retrospective AMI Study and compared in-hospital mortality between women and men with gender–age interactions in multivariable models.
The overall in-hospital mortality rate was higher in women compared with men (17.2% vs 9.1%, p<0.0001; unadjusted OR 2.07, 95% CI 1.85 to 2.33). The unadjusted OR for mortality in women, compared with men, was 2.20 (95% CI 1.59 to 3.04), 2.21 (95% CI 1.74 to 2.79), 1.37 (95% CI 1.15 to 1.65) and 1.25 (95% CI 0.97 to 1.63) for ages <60, 60–69, 70–79 and ≥80 years, respectively. After adjustment for patient characteristics, hospital characteristics and year of study, the OR for mortality comparing women with men was 1.69 (95% CI 1.01 to 2.83), 1.64 (95% CI 1.24 to 2.19), 1.15 (95% CI 0.90 to 1.46) and 0.82 (95% CI 0.60 to 1.11) for ages <60, 60–69, 70–79 and ≥80 years, respectively. The gender–age interaction for mortality was statistically significant (p=0.009), even after adjustment for a wide range of confounders, and did not vary over time or across rural/urban areas.
Among a Chinese population with STEMI, gender differences in early mortality were age-dependent and greatest in the younger groups <70 years of age.
Trial registration number (NCT01624883).
PMCID: PMC4453015  PMID: 25510395
5.  TIMP-1 activated carcinoma-associated fibroblasts inhibit tumor apoptosis by activating SDF1/CXCR4 signaling in hepatocellular carcinoma 
Oncotarget  2015;6(14):12061-12079.
Tissue inhibitor of metalloproteinase 1 (TIMP-1) is an endogenous inhibitor for MMPs that regulates the remodeling and turnover of the ECM during normal development and pathological conditions. Intriguingly, recent studies have shown that TIMP-1 plays a dual role in cancer progression. In this study, we found that TIMP-1 expression in HCC tissues is associated with advanced TNM stage, intrahepatic metastasis, portal vein invasion, and vasculature invasion. Notably, TIMP-1 expression in HCC tissue is significantly related to worse overall survival for patients with HCC after liver resection. Ectopic TIMP1 expression promoted the growth of HCC xenografts in nude mice. Both co-culture with Huh7 cells with a high level of TIMP-1 and TIMP1 treatment resulted in up-regulation of hallmarks of carcinoma-associated fibroblasts (CAFs) and accelerated cell proliferation, migration and invasion in immortalized liver fibroblasts (LFs) isolated from human normal liver tissue. By co-culture with CAFs, SDF-1/CXCR4/PI3K/AKT signaling was activated and apoptosis was markedly repressed with an increased Bcl-2/BAX ratio in Huh7 cells. Taken together, our observations suggest that TIMP-1 induces the trans-differentiation of LFs into CAFs, suppresses apoptosis via SDF-1/CXCR4/PI3K/AKT signaling and then promotes HCC progression. This protein may be a potential prognostic biomarker and therapeutic target for HCC.
PMCID: PMC4494923  PMID: 25909286
TIMP-1; CAFs; HCC; apoptosis; tumor microenvironment
6.  Systematic review and meta-analysis of prophylactic abdominal drainage after pancreatic resection 
AIM: To investigate whether prophylactic abdominal drainage is necessary after pancreatic resection.
METHODS: PubMed, Web of Science, and the Cochrane Library were systematically searched to obtain relevant articles published before January 2014. Publications were retrieved if they met the selection criteria. The outcomes of interest included: mortality, morbidity, postoperative pancreatic fistula (POPF), clinically relevant pancreatic fistula (CR-PF), abdominal abscess, reoperation rate, the rate of interventional radiology drainage, and the length of hospital stay. Subgroup analyses were also performed for pancreaticoduodenectomy (PD) and for distal pancreatectomy. Begg’s funnel plot and the Egger regression test were employed to assess potential publication bias.
RESULTS: Nine eligible studies involving a total of 2794 patients were identified and included in this meta-analysis. Of the included patients, 1373 received prophylactic abdominal drainage. A fixed-effects model meta-analysis showed that placement of prophylactic drainage did not have beneficial effects on clinical outcomes, including morbidity, POPF, CR-PF, reoperation, interventional radiology drainage, and length of hospital stay (Ps > 0.05). In addition, prophylactic drainage did not significantly increase the risk of abdominal abscess. Overall analysis showed that omitting prophylactic abdominal drainage resulted in higher mortality after pancreatectomy (OR = 1.56; 95%CI: 0.93-2.92). Subgroup analysis of PD showed similar results to those in the overall analysis. Elimination of prophylactic abdominal drainage after PD led to a significant increase in mortality (OR = 2.39; 95%CI: 1.22-4.69; P = 0.01).
CONCLUSION: Prophylactic abdominal drainage after pancreatic resection is still necessary, though more evidence from randomized controlled trials assessing prophylactic drainage after PD and distal pancreatectomy are needed.
PMCID: PMC4427698  PMID: 25987799
Prophylactic abdominal drainage; Pancreatic resection; Systemic review; Meta-analysis
7.  Development and Characterization of a Novel Anti-idiotypic Monoclonal Antibody to Growth Hormone, Which Can Mimic Physiological Functions of Growth Hormone in Primary Porcine Hepatocytes 
B-32 is one of a panel of monoclonal anti-idiotypic antibodies to growth hormone (GH) that we developed. To characterize and identify its potential role as a novel growth hormone receptor (GHR) agonist, we determined that B-32 behaved as a typical Ab2β based on a series of enzyme-linked immunosorbent assay assays. The results of fluorescence-activated cell sorting, indirect immunofluorescence and competitive receptor binding assays demonstrated that B-32 specifically binds to the GHR expressed on target cells. Next, we examined the resulting signal transduction pathways triggered by this antibody in primary porcine hepatocytes. We found that B-32 can activate the GHR and Janus kinase (2)/signal transducers and activators of transcription (JAK2/STAT5) signalling pathways. The phosphorylation kinetics of JAK2/STAT5 induced by either GH or B-32 were analysed in dose-response and time course experiments. In addition, B32 could also stimulate porcine hepatocytes to secrete insulin-like growth factors-1. Our work indicates that a monoclonal anti-idiotypic antibody to GH (B-32) can serve as a GHR agonist or GH mimic and has application potential in domestic animal (pig) production.
PMCID: PMC4341108  PMID: 25656185
Porcine Growth Hormone; Monoclonal Anti-idiotypic Antibodies (Mab2s); Porcine Hepatocytes; Janus Kinase (2)-Signal Transducers and Activators of Transcription [JAK2-STAT5]
8.  Effect of B Vitamin (Folate, B6, and B12) Supplementation on Osteoporotic Fracture and Bone Turnover Markers: A Meta-Analysis 
B vitamins (including folate, B6, and B12) supplementation can effectively and easily modify high plasma homocysteine (Hcy). However, the role of Hcy in the pathogenesis of osteoporotic fracture and bone turnover is still controversial. This meta-analysis aimed to assess the impact of B vitamin supplementation on occurrence of any osteoporotic fracture and bone turnover by pooling the results of previous studies.
Relevant randomized controlled trials (RCTs) were searched in databases. Data integration and analysis were done by using Review Manager 5.3 (the Cochrane Collaboration). The risk ratio (RR) and corresponding 95% confidence intervals (CI) of fracture (intervention vs. control) were estimated. Changes in bone turnover indicators (continuous data), weighted mean difference (WMD), and corresponding 95% (CI) were pooled for estimation.
Based on the results of 4 RCTs, this meta-analysis failed to identify a risk-reducing effect of daily supplementation of B vitamins on osteoporotic fracture in patients with vascular disease and with relatively normal plasma Hcy. In addition, we also did not find any positive effects of B vitamin supplementation on bone turnover.
B vitamin supplementation might not be effective in preventing fracture and improving bone turnover. However, the possible benefits in selective populations, such as populations with very high plasma Hcy and from regions without B vitamin fortification should be explored in the future.
PMCID: PMC4384513  PMID: 25805360
Fractures, Bone; Homocysteine; Meta-Analysis as Topic; Vitamin B Complex
9.  Maternal Gestational Smoking, Diabetes, Alcohol Drinking, Pre-Pregnancy Obesity and the Risk of Cryptorchidism: A Systematic Review and Meta-Analysis of Observational Studies 
PLoS ONE  2015;10(3):e0119006.
Maternal gestational smoking, diabetes, alcohol drinking, and pre-pregnancy obesity are thought to increase the risk of cryptorchidism in newborn males, but the evidence is inconsistent.
We conducted a systematic review and meta-analysis of studies on the association between maternal gestational smoking, diabetes, alcohol drinking, and pre-pregnancy obesity and the risk of cryptorchidism. Articles were retrieved by searching PubMed and ScienceDirect, and the meta-analysis was conducted using Stata/SE 12.0 software. Sensitivity analysis was used to evaluate the influence of confounding variables.
We selected 32 articles, including 12 case—control, five nested case—control, and 15 cohort studies. The meta-analysis showed that maternal smoking (OR = 1.17, 95% CI: 1.11–1.23) or diabetes (OR = 1.21, 95%CI: 1.00–1.46) during pregnancy were associated with increased risk of cryptorchidism. Overall, the association between maternal alcohol drinking (OR = 0.97, 95% CI: 0.87–1.07), pre-pregnancy body mass index (OR = 1.02, 95% CI: 0.95–1.09) and risk of cryptorchidism were not statistically significant. Additional analysis showed reduced risk (OR = 0.89, 95% CI: 0.82–0.96) of cryptorchidism with moderate alcohol drinking during pregnancy. No dose—response relationship was observed for increments in body mass index in the risk of cryptorchidism. Sensitivity analysis revealed an unstable result for the association between maternal diabetes, alcohol drinking and cryptorchidism. Moderate heterogeneity was detected in studies of the effect of maternal alcohol drinking and diabetes. No publication bias was detected.
Maternal gestational smoking, but not maternal pre-pregnancy overweight or obesity, was associated with increased cryptorchidism risk in the offspring. Moderate alcohol drinking may reduce the risk of cryptorchidism while gestational diabetes may be a risk factor, but further studies are needed to verify this.
PMCID: PMC4370654  PMID: 25798927
10.  Highly transparent triboelectric nanogenerator for harvesting water-related energy reinforced by antireflection coating 
Scientific Reports  2015;5:9080.
Water-related energy is an inexhaustible and renewable energy resource in our environment, which has huge amount of energy and is not largely dictated by daytime and sunlight. The transparent characteristic plays a key role in practical applications for some devices designed for harvesting water-related energy. In this paper, a highly transparent triboelectric nanogenerator (T-TENG) was designed to harvest the electrostatic energy from flowing water. The instantaneous output power density of the T-TENG is 11.56 mW/m2. Moreover, with the PTFE film acting as an antireflection coating, the maximum transmittance of the fabricated T-TENG is 87.4%, which is larger than that of individual glass substrate. The T-TENG can be integrated with silicon-based solar cell, building glass and car glass, which demonstrates its potential applications for harvesting waste water energy in our living environment and on smart home system and smart car system.
PMCID: PMC4357854  PMID: 25765205
11.  Poly(I:C) Treatment Leads to Interferon-Dependent Clearance of Hepatitis B Virus in a Hydrodynamic Injection Mouse Model 
Journal of Virology  2014;88(18):10421-10431.
We have previously shown that poly(I:C) activates murine hepatic cells to produce interferon (IFN) and suppresses hepatitis B virus (HBV) replication in vitro. Therefore, we addressed whether poly(I:C) is able to induce the clearance of HBV in vivo. The chronic HBV replication mouse model was established by the hydrodynamic injection (HI) of pAAV-HBV1.2 into the tail veins of wild-type and IFN-α/βR-, IFN-γ-, and CXCR3-deficient C57BL/6 mice. Fourteen days post-HI of pAAV-HBV1.2, mice were administered poly(I:C) by intraperitoneal injection, intramuscular injection, or HI. Only treatment of poly(I:C) by HI led to HBV clearance in wild-type C57BL/6 mice. Serum HBsAg disappeared within 40 days postinfection (dpi) in mice that received poly(I:C) by HI, and this was accompanied by the appearance of anti-HBs antibodies. HBV-specific T-cell and antibody responses were significantly enhanced by HI of poly(I:C). HBV replication intermediates and HBcAg-positive hepatocytes were eliminated in the liver. HI of poly(I:C) induced the production of IFNs in mice and enhanced the levels of cytokines, IFN-stimulated genes, and T-cell markers in the liver. Importantly, poly(I:C)-induced HBV clearance was impaired in IFN-α/βR-, IFN-γ-, and CXCR3-deficient mice, indicating that the induction of type I IFN and the stimulation and recruitment of T cells into the liver are essential for HBV clearance in this model. Taken together, the application of poly(I:C) by HI into the liver enhances innate and adaptive immune responses and leads to HBV clearance in an HBV mouse model, implicating the potential of intrahepatic Toll-like receptor 3 (TLR3) activation for the treatment of chronic hepatitis B patients.
IMPORTANCE It has become well accepted that immunomodulation is a potentially useful approach to treat chronic viral infection. Recently, combinations of antiviral treatment and therapeutic vaccinations were evaluated for therapies of chronic hepatitis B virus (HBV) infection. Activation of the innate immune branch may also be important for viral control and contributes to HBV clearance. Our present study demonstrated that hepatic TLR3 activation led to clearance of hepatitis B virus in an HBV mouse model. For the first time, we showed that HBV clearance in this model is dependent not only on type I interferon (IFN) but also on type II IFN, indicating a coordinated action of innate and adaptive immune responses. T-cell recruitment appeared to be critical for the success of TLR3-mediated antiviral action. These findings implicate the potential of intrahepatic TLR3 activation for the treatment of chronic HBV infection.
PMCID: PMC4178898  PMID: 24920792
12.  Design and fabrication of far ultraviolet filters based on π-multilayer technology in high-k materials 
Scientific Reports  2015;5:8503.
Application of π-multilayer technology is extended to high extinction coefficient materials, which is introduced into metal-dielectric filter design. Metal materials often have high extinction coefficients in far ultraviolet (FUV) region, so optical thickness of metal materials should be smaller than that of the dielectric material. A broadband FUV filter of 9-layer non-periodic Al/MgF2 multilayer was successfully designed and fabricated and it shows high reflectance in 140–180 nm, suppressed reflectance in 120–137 nm and 181–220 nm.
PMCID: PMC4330531  PMID: 25687255
13.  An Antagonist Mutant IL-15/Fc Promotes Transplant Tolerance 
Transplantation  2006;81(1):109-116.
IL-15 is a proinflammatory and antiapoptotic T-cell growth factor that plays an important role in a variety of autoimmune disorders and transplant rejection. To inhibit IL-15 function and to target IL-15 receptor (IL-15R) bearing cells, we have generated a unique lytic antagonistic mutant IL-15/Fc fusion protein (mIL-15/Fc).
In this study, we further examined the efficacy of mIL-15/Fc in preventing allograft rejection cross minor and major histocompatibility barriers.
A short-course treatment with mIL-15/Fc fusion protein is sufficient to prevent cardiac allograft rejection and induce antigen-specific tolerance in minor histocompatibility complex-mismatched recipients, and permit prolonged cardiac allograft survival in fully MHC mismatched recipients. In addition, mIL-15/Fc treatment, in combination with a suboptimal dose of anti-CD154 antibody, confers permanent cardiac allograft engraftment in a fully MHC-mismatched mouse strain combination. In a murine islet allograft model, mIL-15/Fc monotherapy is capable to permit permanent allograft survival in 50% fully MHC-mismatched recipients.
Immunochemistry studies demonstrated that prolonged graft survival was accompanied by reduced intragraft mononuclear cell infiltration and pro-inflammatory cytokine gene expression in the mIL-15/Fc treated recipients. Moreover, parallel experiments employing a mutated nonlytic IgG2a Fc demonstrate that the Fc portion of mIL-15/Fc contributes to the overall efficacy of the molecule in vivo.
PMCID: PMC4329733  PMID: 16421485
Transplantation; Heart; Islet; Cytokines; Rejection
14.  Influence of direct and indirect allorecognition pathways on CD4+CD25+ regulatory T-cell function in transplantation 
While both direct and indirect allorecognition are involved in allograft rejection, evidence to date suggests that tolerance is primarily dependent on indirect pathway-triggered CD4+CD25+ T cell-mediated immunoregulation. However, the precise influence of these two pathways on CD4+CD25+ T-cell function has not been addressed. In the current study, we have utilized an adoptive transfer model to assess selectively how the absence of either direct or indirect allorecognition affects CD4+CD25+ T-cell function. The effects of the loss of the direct pathway were assessed by transplanting skin grafts from minor histocompatibility mismatched B10.D2 (H-2d) donors onto Balb/c (H-2d) recipients, or by placing bone marrow chimeric DBA/2 (H-2d/H-2b) allografts onto C57BL/6 (H-2b) hosts. The requirement for indirect allorecognition was tested by grafting DBA/2 skin allografts onto either C57BL/6- or MHC-II-deficient C57BL/6 recipients. We report here that although CD4+CD25+ regulatory T cells can suppress both directly and indirectly generated alloresponses, immunoregulation is favored when indirect presentation is the sole mechanism of allorecognition. Hence, in the absence of indirect presentation, net CD4+CD25+ T cell-dependent immunoregulation is weak, and high ratios of CD4+CD25+ to CD4+CD25− T cells are required to ensure graft survival.
PMCID: PMC4329766  PMID: 17362475
allorecognition; immunoregulation; regulatory T cells; tolerance
15.  Novel impurity-free hexagonal hydroxyapatite nanotubes for local delivery of antibiotics in orthopedic surgery: in vitro release validation 
Hydroxyapatite (HA) has been studied recently as a drug carrier in prevent implant infections due to its biocompatibility and osteoconductive properties, but most of these studies failed to control infection. The aim of the present study was to evaluate the potential of this impurity-free novel HA nanotube as a carrier for drug delivery in a controlled manner. Gentamicin was selected as an antibiotic to study the drug-carrier properties of this novel HA nanotube. Gentamicin was introduced into the HA nanotubes through immersion and evaporation process. Gentamicin-loaded HA nanotubes were then placed in phosphate buffered saline (PBS) and drug release profile was then monitored by measuring free genntamicin in the solution. An initial burst release of the drug occurred in the first 24 hours; subsequently, 84.7% of the drug was released from the nanotubes in 9 days. After 13 d, the concentrations of released drug were measured close to 2 μg/ml. The porosity of the gentamicin-loaded HA nanotubes was also observed using a Hitachi s-4800 high-resolution SEM, further confirming the drug-carrier property of HA nanotubes. Our novel bone substitute is an effective prophylactic tool for the local delivery of gentamicin to prevent periprosthetic infections.
PMCID: PMC4402858  PMID: 25932211
Drug release; gentamicin; hydroxyapatite; nanotube
16.  CtBP2 is an independent prognostic marker that promotes GLI1 induced epithelial-mesenchymal transition in hepatocellular carcinoma 
Oncotarget  2015;6(6):3752-3769.
C-terminal binding protein 2 (CtBP2) is a transcriptional co-repressor that promotes cancer cell migration and invasion by inhibiting multiple tumor suppressor genes that contribute to cell mobility and adhesion. In this investigation, we showed thatCtBP2 expression was increased significantly in HCC tissues when compared to matched normal adjacent liver tissues. We also showed that CtBP2 expression is associated with worse HCC patient prognosis after liver resection. CtBP2 over-expression induced epithelial-mesenchymal transition (EMT) in Huh7 cells and, correspondingly, silencing CtBP2 suppressed EMT in MHCC97H cells. ChIP assays revealed that GLI1 increased CtBP2 transcription by directly binding its promoter. Furthermore, interaction of CtBP2 and Snail Family Zinc Finger 1 (SNAI1), both of which were found to be positively regulated by GLI1, was confirmed by Co-IP assay. SNAI1 knockdown revealed that SNAI1 was essential for CtBP2 induction of the EMT phenotype of HCC cells, and CtBP2 knockdown reversed GLI1-SNAI1 driven EMT in Huh7 cells. Finally, in vivo experiments demonstrated that enhanced CtBP2expression promoted HCC xenograft growth and induced EMT. In conclusion, CtBP2 may serve as a prognostic marker for post liver resection HCC and may play a role during GLI1-driven EMT as a transcriptional co-repressor of SNAI1.
PMCID: PMC4414151  PMID: 25686837
C-terminal binding protein 2; CtBP2; GLI family zinc finger 1; GLI1; Snail Family Zinc Finger 1; epithelial-mesenchymal transition; EMT; Hepatocellular carcinoma; HCC
17.  Increasing expression of substance P and calcitonin gene-related peptide in synovial tissue and fluid contribute to the progress of arthritis in developmental dysplasia of the hip 
Developmental dysplasia of the hip (DDH) is a common musculoskeletal disorder that has pain and loss of joint function as major pathological features. In the present study, we explored the mechanisms of possible involvement and regulation of substance P (SP) and calcitonin gene-related peptide (CGRP) in the pathological and inflammatory processes of arthritis in DDH.
Blood, synovial tissue and fluid samples were collected from patients diagnosed with different severities of DDH and from patients with femoral neck fracture. Levels of SP, CGRP and inflammatory cytokines in synovium and synovial fluid (SF) in the different groups were evaluated by immunohistochemistry, real-time PCR and enzyme-linked immunosorbent assay (ELISA). Correlations between neuropeptides and inflammatory cytokines in SF were evaluated by partial correlation analysis. The proinflammatory effects of SP and CGRP on synoviocytes obtained from patients with moderate DDH were investigated in vitro by real-time PCR and ELISA. The mechanisms of those effects were evaluated by Western blot analysis and nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) DNA binding assay.
Significantly increased levels of neuropeptides and inflammatory cytokines were observed in synovium and SF from patients in the severe DDH group compared with the moderate DDH and control groups. In moderate DDH samples, SP in SF correlated with tumor necrosis factor (TNF)-α, and CGRP in SF correlated with TNF-α and interleukin (IL)-10. In the severe DDH group, SP in SF correlated with interleukin (IL)-1β, TNF-α and IL-10. CGRP in SF correlated with TNF-α. Additionally, SP might have had obvious proinflammatory effects on synoviocytes through the activation of NF-κB.
The upregulation of SP and CGRP in synovium and SF might participate in the inflammatory process of arthritis in DDH. The activation of the NF-κB pathway seems indispensable in the proinflammatory effect of SP on synoviocytes. This original discovery may indicate a potential clinical drug target and the development of innovative therapies for DDH.
PMCID: PMC4320827  PMID: 25578529
18.  Structural white matter changes in descending motor tracts correlate with improvements in motor impairment after undergoing a treatment course of tDCS and physical therapy 
Motor impairment after stroke has been related to the structural and functional integrity of corticospinal tracts including multisynaptic motor fibers and tracts such as the cortico-rubral-spinal and the cortico-tegmental-spinal tract. Furthermore, studies have shown that the concurrent use of transcranial direct current stimulation (tDCS) with peripheral sensorimotor activities can improve motor impairment. We examined microstructural effects of concurrent non-invasive bihemispheric stimulation and physical/occupational therapy for 10 days on the structural components of the CST as well as other descending motor tracts which will be referred to here as alternate motor fibers (aMF). In this pilot study, ten chronic patients with a uni-hemispheric stroke underwent Upper-Extremity Fugl-Meyer assessments (UE-FM) and diffusion tensor imaging (DTI) for determining diffusivity measures such as fractional anisotropy (FA) before and after treatment in a section of the CST and aMF that spanned between the lower end of the internal capsule (below each patient’s lesion) and the upper pons region on the affected and unaffected hemisphere. The treated group (tDCS + PT/OT) showed significant increases in the proportional UE-FM scores (+21%; SD 10%), while no significant changes were observed in an untreated comparison group. Significant increases in FA (+0.007; SD 0.0065) were found in the ipsilesional aMF in the treated group while no significant changes were found in the contralesional aMF, in either CST, or in any tracts in the untreated group. The FA changes in the ipsilesional aMF significantly correlated with the proportional change in the UE-FM (r = 0.65; p < 0.05). The increase in FA might indicate an increase in motor fiber alignment, myelination, and overall fiber integrity. Crossed and uncrossed fibers from multiple cortical regions might be one reason why the aMF fiber system showed more plastic structural changes that correlate with motor improvements than the CST.
PMCID: PMC4415397  PMID: 25983684
diffusion tensor imaging; motor recovery; rehabilitation; brain stimulation; tDCS; plasticity
19.  Antiviral therapy for chronic hepatitis B in China 
The vaccination program against hepatitis B virus (HBV) has greatly reduced the incidence of HBV infection. However, almost one-fourth of the HBV infected patients worldwide are still located in China. The healthcare burden from chronic HBV infection is a big challenge for the Chinese government and clinicians. Antiviral therapy plays a central role in controlling chronic HBV infection and preventing the disease progression. However, due to the specific economic and medical system issues, the first-line antiviral agents recommended by the AASLD and EASL have not been widely used for Chinese patients. In this review, we will discuss some key issues in the area of antiviral treatment for chronic hepatitis B in China.
PMCID: PMC4305090  PMID: 25540038
Chronic hepatitis B; Antiviral therapy; Drug resistance; China
20.  Accelerated endochondral growth in adolescents with idiopathic scoliosis: a preliminary histomorphometric study 
Abnormal longitudinal growth has been identified in the early pubertal stage of idiopathic scoliosis (IS) and is thought to contribute to the development of scoliosis. This phenotype may be caused by abnormal endochondral ossification, but histological evidence is lacking. The aim of this study was to investigate whether there is abnormal endochondral ossification in IS patients at early stage of puberty by histomorphometric analysis of their iliac cartilage.
Fifty-two patients with IS and 19 controls were recruited and grouped according to their Risser grade (Group A: Risser grade 0 with Oxford stage 2–3; Group B: Risser grade 2). Group A consisted of 20 IS patients (mean age: 12.3 years) and 9 controls (mean age: 12.0 years), while Group B included 32 IS patients (mean age: 13.8 years) and 10 controls (mean age: 13.7 years). Biopsies of the iliac cartilage were harvested intra-operatively and prepared using routine histological methods. Histomorphometric analysis was performed to quantify the thickness of the hypertrophic zone, the area and number of chondrocytes in the cell-nest, and the number of chondrocytes in the proliferative zone using Image-Pro Plus software.
In Group A, a significantly thicker hypertrophic zone and larger cell-nest area and number of cells within the cell-nest, and in the proliferative zone, were found in iliac cartilages from IS patients compared with those of controls (all P < 0.05). In group B however, there were no significant differences in histomorphometric parameters between IS patients and the controls.
The differences in the histomorphometric results between IS patients and their controls for patients with Risser grade 0 and Oxford grades 2 & 3, but not in those with Risser grade 2, indicated a pattern of accelerated endochondral growth in IS at the early stage of puberty, but not at the late stage.
Trial registration
Current Controlled Trials: ChiCTR-CCC-13003988. Registered 17 December 2013.
PMCID: PMC4301996  PMID: 25494722
Idiopathic scoliosis; Growth plate; Iliac cartilage; Endochondral ossification
21.  Fibulin-5 inhibits hepatocellular carcinoma cell migration and invasion by down-regulating matrix metalloproteinase-7 expression 
BMC Cancer  2014;14:938.
Fibulin-5 has been considered as a tumor suppressor through inhibiting tumor growth and invasion. Reduced expression of Fibulin-5 is frequently observed in various human cancers. In this study, we investigate the clinical significance of Fibulin-5 and its role in hepatocellular carcinoma (HCC) cell migration and invasion.
The expression of Fibulin-5 was evaluated by qRT-PCR and immunoblotting in HCC and matched noncancerous tissues. Fibulin-5 was over-expressed or knocked down by a retrovirus-mediated expression plasmid or a specific siRNA in HCC cells. Boyden chamber and Transwell assays were used to test HCC cell migration and invasion. Immunostaining was performed to determine matrix metalloproteinase-7 (MMP-7) expression in HCC specimens. MMP-7 retroviruses and siRNA were used to alter MMP-7 expression in HCC cells.
In our study, the expression levels of Fibulin-5 protein and mRNA were down-regulated in HCC tissues as compared with those in matched noncancerous tissues. Reduced expression of Fibulin-5 was observed in all HCC cell lines (HepG2, SMMC-7721, MHCC97L, Hep3B, MHCC97H and HCC-LM3) as compare with that in a non-transformed hepatic cell line (LO2). Low expression of Fibulin-5 was significantly correlated with poor prognostic features including multiple tumor nodes, venous infiltration, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage. Furthermore, we demonstrated that Fibulin-5 was a novel independent prognostic marker for predicting 5-year survival of HCC patients. Our in vitro studies showed that Fibulin-5 overexpression inhibited HCC cell migration and invasion. While Fibulin-5 knockdown increased the number of migrated and invaded HCC cells. Fibulin-5 negatively regulated MMP-7 abundance in HCC cells. Moreover, the inverse correlation between Fibulin-5 and MMP-7 expressions was observed in HCC tissues. Mechanistically, we disclosed that MMP-7 knockdown reduced the number of migrated and invaded HCC cells. Restoring MMP-7 expression abrogated the suppressive effect of Fibulin-5 on HCC cell migration and invasion in vitro, suggesting that Fibulin-5 exerted its anti-metastatic function, at least in part, by down-regulating the expression of MMP-7 in HCC cells.
These results indicate that Fibulin-5 may serve as a prognostic biomarker and inhibits HCC invasion and metastasis by suppressing MMP-7 expression.
PMCID: PMC4295477  PMID: 25494879
Fibulin-5; Hepatocellular carcinoma; Migration; Invasion; MMP-7
22.  MicroRNA-130b Promotes Cell Aggressiveness by Inhibiting Peroxisome Proliferator-Activated Receptor Gamma in Human Hepatocellular Carcinoma 
MircroRNA-130b (miR-130b) is proposed as a novel tumor-related miRNA and has been found to be significantly dysregulated in tumors. In this study, the expression level of miR-130b was found to be obviously higher in hepatocellular carcinoma (HCC) tissues than that in nontumor tissues. Further, miR-130b was expressed at significantly higher levels in aggressive and recurrent tumor tissues. Clinical analysis indicated that high-expression of miR-130b was prominently correlated with venous infiltration, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage in HCC. Elevated miR-130b expression was observed in all HCC cell lines (HepG2, SMMC-7721, Huh7, Hep3B and MHCC97H) as compared with that in a nontransformed hepatic cell line (LO2). Furthermore, an inverse correlation between miR-130b and E-cadherin and a positive correlation between miR-130b and Vimentin were observed in HCC tissues. Down-regulation of miR-130b expression reduced invasion and migration in both Hep3B and MHCC97H cells. Peroxisome proliferator-activated receptor gamma (PPAR-γ) was inversely correlated with miR-130b expression in HCC tissues. In addition, down-regulation of miR-130b restored PPAR-γ expression and subsequently suppressed epithelial-mesenchymal transition (EMT) in HCC cells. We identified PPARγ as a direct target of miR-130b in HCC in vitro. Notably, PPAR-γ knockdown abolished down-regulation of miR-130b-inhibited EMT in MHCC97H cells. In conclusion, miR-130b may promote HCC cell migration and invasion by inhibiting PPAR-γ and subsequently inducing EMT.
PMCID: PMC4264179  PMID: 25387077
microRNA-130b; hepatocellular carcinoma; PPAR-γ (peroxisome proliferator-activated receptor gamma); invasion; tumor metastasis
23.  Intracellular Signaling Transduction Pathways Triggered by a Well-Known Anti-GHR Monoclonal Antibody, Mab263, in Vitro and in Vivo 
A series of studies have reported that monoclonal antibody 263 (Mab263), a monoclonal antibody against the growth hormone receptor (GHR), acts as an agonist in vitro and in vivo. However, the intracellular signaling pathways triggered by Mab263 have not yet been delineated. Therefore, we examined the intracellular signaling pathways induced by Mab263 in vivo and in vitro in the present study. The results show that this antibody activated janus kinase 2 (JAK2), signal transducer and activator of transcription 3 (STAT3), STAT1 and extracellular signal-regulated kinase 1/2 (ERK1/2), but not STAT5. The phosphorylation kinetics of JAK2, STAT3/1 and ERK1/2 induced by Mab263 were subsequently analyzed in dose-response and time course experiments. Our observations indicate that Mab263 induced different intracellular signaling pathways than GH, which indicates that Mab263 is a signal-specific molecule and that Mab263 may be a valuable biological reagent to study the mechanism(s) of GHR-mediated intracellular signaling pathways.
PMCID: PMC4264182  PMID: 25391041
monoclonal antibody 263 (Mab263); growth hormone receptor; signal transduction pathway
24.  Upregulated UHRF1 Promotes Bladder Cancer Cell Invasion by Epigenetic Silencing of KiSS1 
PLoS ONE  2014;9(10):e104252.
Ubiquitin-like with PHD and RING finger domains 1 (UHRF1), as an epigenetic regulator, plays important roles in the tumorigenesis and cancer progression. KiSS1 functions as a metastasis suppressor in various cancers, and epigenetic silencing of KiSS1 increases the metastatic potential of cancer cells. We therefore investigated whether UHRF1 promotes bladder cancer cell invasion by inhibiting KiSS1. The expression levels of UHRF1 and KiSS1 were examined by quantitative real-time PCR assay in vitro and in vivo. The role of UHRF1 in regulating bladder cancer metastasis was evaluated in bladder cancer cell. We found that UHRF1 levels are upregulated in most clinical specimens of bladder cancer when compared with paired normal tissues, and UHRF1 expression levels are significantly increased in primary tumors that subsequently metastasized compared with non-metastatic tumors. Forced expression of UHRF1 promotes bladder cancer cell invasion, whereas UHRF1 knockdown decreases cell invasion. Overexpression of UHRF1 increases the methylation of CpG nucleotides and reduces the expression of KiSS1. UHRF1 and KiSS1 expression level is negatively correlated in vivo and in vitro. Knockdown of KiSS1 promotes bladder cancer cell invasion. Importantly, forced expression of KiSS1 partly abrogates UHRF1-induced cell invasion. These data demonstrated that upregulated UHRF1 increases bladder cancer cell invasion by epigenetic silencing of KiSS1.
PMCID: PMC4182677  PMID: 25272010
25.  Network analysis of ChIP-Seq data reveals key genes in prostate cancer 
Prostate cancer (PC) is the second most common cancer among men in the United States, and it imposes a considerable threat to human health. A deep understanding of its underlying molecular mechanisms is the premise for developing effective targeted therapies. Recently, deep transcriptional sequencing has been used as an effective genomic assay to obtain insights into diseases and may be helpful in the study of PC.
In present study, ChIP-Seq data for PC and normal samples were compared, and differential peaks identified, based upon fold changes (with P-values calculated with t-tests). Annotations of these peaks were performed. Protein–protein interaction (PPI) network analysis was performed with BioGRID and constructed with Cytoscape, following which the highly connected genes were screened.
We obtained a total of 5,570 differential peaks, including 3,726 differentially enriched peaks in tumor samples and 1,844 differentially enriched peaks in normal samples. There were eight significant regions of the peaks. The intergenic region possessed the highest score (51%), followed by intronic (31%) and exonic (11%) regions. The analysis revealed the top 35 highly connected genes, which comprised 33 differential genes (such as YWHAQ, tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein and θ polypeptide) from ChIP-Seq data and 2 differential genes retrieved from the PPI network: UBA52 (ubiquitin A-52 residue ribosomal protein fusion product 1) and SUMO2 (SMT3 suppressor of mif two 3 homolog 2) .
Our findings regarding potential PC-related genes increase the understanding of PC and provides direction for future research.
Electronic supplementary material
The online version of this article (doi:10.1186/s40001-014-0047-7) contains supplementary material, which is available to authorized users.
PMCID: PMC4171560  PMID: 25183411
ChIP-Seq; Highly connected genes; Network analysis; Prostate cancer

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