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1.  Aspirin Use and Risk of Age-Related Macular Degeneration: A Meta-Analysis 
PLoS ONE  2013;8(3):e58821.
Background
Age-related macular degeneration (AMD) is the main cause of blindness and the curative options are limited. The objective of this meta-analysis was to determine the association between aspirin use and risk of AMD.
Methods
A comprehensive literature search was performed in PubMed, Embase, Web of Science, and reference lists. A meta-analysis was performed by STATA software.
Results
Ten studies involving 171729 individuals examining the association between aspirin use and risk of AMD were included. Among the included studies, 2 were randomized-controlled trials (RCTs), 4 were case-control studies and 4 were cohort studies. The relative risks (RRs) were pooled using a random-effects model. Relative risks with 95% confidence intervals (CIs) of aspirin use as a risk for AMD. The pooled RR of 10 included studies between the use of aspirin and risk of AMD was 1.09 (95% CI, 0.96–1.24). The same result was detected in early and late stage AMD subgroup analysis. In the subgroup analyses, the pooled RR of RCTs, case-control studies and cohort studies were 0.81 (95% CI, 0.64–1.02), 1.02 (95% CI, 0.92–1.14) and 1.08 (95% CI, 0.91–1.28), respectively.
Conclusions
The use of aspirin was not associated with the risk of AMD.
doi:10.1371/journal.pone.0058821
PMCID: PMC3597550
2.  LAR receptor tyrosine phosphatases and HSPGs guide peripheral sensory axons to the skin 
Current Biology  2012;22(5):373-382.
Background
Peripheral axons of somatosensory neurons innervate the skin early in development to detect touch stimuli. Embryological experiments had suggested that the skin produces guidance cues that attract sensory axons, but neither the attractants nor their neuronal receptors had previously been identified.
Results
To investigate peripheral axon navigation to the skin, we combined live imaging of developing zebrafish Rohon-Beard (RB) neurons with molecular loss-of-function manipulations. Simultaneously knocking down two members of the LAR family of receptor tyrosine phosphatases expressed in RB neurons, or inhibiting their function with dominant negative proteins, misrouted peripheral axons to internal tissues. Time-lapse imaging indicated that peripheral axon guidance, rather than outgrowth or maintenance, was defective in LAR deficient neurons. Peripheral axons displayed a similar misrouting phenotype in mutants defective in heparan sulfate proteoglycan (HSPG) production and avoided regions in which HSPGs were locally degraded.
Conclusions
HSPGs and LAR family receptors are required for sensory axon guidance to the skin. Together, our results support a model in which peripheral HSPGs are attractive ligands for LAR receptors on RB neurons.
doi:10.1016/j.cub.2012.01.040
PMCID: PMC3298620  PMID: 22326027
3.  Modulating the root elongation by phosphate/nitrogen starvation in an OsGLU3 dependant way in rice 
Plant Signaling & Behavior  2012;7(9):1144-1145.
Previously, we showed that OsGLU3, a β-1,4-endoglucanase, can affect the cellulose synthesis for root elongation in rice. And the phosphate starvation induced root elongation in rice depends on the function of OsGLU3. Here, we further showed that OsGLU3 is also dispensable for nitrogen starvation induced root elongation in rice.
doi:10.4161/psb.21334
PMCID: PMC3489647  PMID: 22899054
cellulose; nitrogen starvation; root elongation
4.  The maternal folate hydrolase gene polymorphism is associated with neural tube defects in a high-risk Chinese population 
Genes & Nutrition  2012;8(2):191-197.
Folate hydrolase 1 (FOLH1) gene encodes intestinal folate hydrolase, which regulates intestinal absorption of dietary folate. Previous studies on the association between polymorphisms rs202676 and rs61886492 and the risk of neural tube defects (NTDs) were inconclusive. A case–control study of women with NTD-affected pregnancies (n = 160) and controls (n = 320) was conducted in the Chinese population of Lvliang, a high-risk area for NTDs. We genotyped the polymorphic sites rs202676 and rs61886492 and assessed maternal plasma folate and total homocysteine (tHcy). Our results showed that in case group, plasma folate concentrations were 18 % lower compared with those of control group (8.32 vs. 6.79 nmol/L, p = 0.033) and tHcy concentrations were 17 % higher (10.47 vs. 12.65 μmol/L, p = 0.047). Almost all samples had the rs61886492 GG genotype (99.78 %). The result showed that the frequency of GG genotype in rs202676 was significantly higher in group with multiple NTDs than in controls (p = 0.030, OR = 2.157, 95 % CI, 1.06–4.38). The multiple-NTD group showed higher maternal plasma concentrations of tHcy (10.47 vs. 13.96 μmol/L, p = 0.024). The GG genotype of rs202676 had a lower maternal folate and higher tHcy concentrations than other genotypes with no significant differences. The result of structural prediction indicated that this variation might change the spatial structure of the protein. These results suggested that the maternal polymorphism rs202676 was a potential risk factor for multiple NTDs in this Chinese population. The allele G might affect maternal plasma folate and tHcy concentration.
doi:10.1007/s12263-012-0309-3
PMCID: PMC3575888  PMID: 22918695
Association study; Chinese population; FOLH1; Neural tube defects; Single-nucleotide polymorphism
6.  CA-125–indicated asymptomatic relapse confers survival benefit to ovarian cancer patients who underwent secondary cytoreduction surgery 
Background
There is no consensus regarding the management of ovarian cancer patients, who have shown complete clinical response (CCR) to primary therapy and have rising cancer antigen CA-125 levels but have no symptoms of recurrent disease. The present study aims to determine whether follow-up CA-125 levels can be used to identify the need for imaging studies and secondary cytoreductive surgery (CRS).
Methods
We identified 410 ovarian cancer patients treated at The University of Texas MD Anderson Cancer Center between 1984 and 2011. These patients had shown CCR to primary therapy. Follow-up was conducted based on the surveillance protocol of the MD Anderson Cancer Center. We used the Cox proportional hazards model and log-rank test to assess the associations between the follow-up CA-125 levels and secondary CRS and survival duration.
Results
The CA-125 level of 1.68 × nadir was defined as the indicator of recurrent disease (p < 0.001). The specificity and sensitivity of this criterion were 82.9% and 85.6%, respectively, and the median lead-time of the CA-125 biochemical progression prior to clinically-defined relapse was 31 days (ranging from 1 to 391 days). The median number of the negative imaging studies for the clinical relapse findings in patients with a CA-125 level of < 1.68 × nadir was 3 (ranging from 0 to 24 times). The increase of CA-125 level at relapse was an independent predictor of overall and progression free survival in patients who had shown CCR to primary therapy (p = 0.04 and 0.02 respectively). The overall and progression free survival durations in patients with a CA-125 level ≤ 1.68 × nadir at relapse (69.4 and 13.8 months) were longer than those with a CA-125 level > 1.68 × nadir at relapse (55.7 and 10.4 months; p = 0.04 and 0.01, respectively). The overall and progression free survival duration of patients with asymptomatic relapse and underwent a secondary CRS was longer than that of patients with symptomatic relapse (p = 0.02 and 0.04 respectively).
Conclusions
The increase of serum CA-125 levels is an early warning of clinical relapse in ovarian cancer. Using CA-125 levels in guiding the treatment of patients with asymptomatic recurrent ovarian cancer, who have shown CCR to primary therapy, can facilitate optimal secondary CRS and extend the survival duration of the patients.
doi:10.1186/1757-2215-6-14
PMCID: PMC3576242  PMID: 23402322
Epithelial ovarian cancer; CA-125; Tumor marker; Clinical relapse; Cytoreductive surgery
7.  A Robust Hybrid Approach Based on Estimation of Distribution Algorithm and Support Vector Machine for Hunting Candidate Disease Genes 
The Scientific World Journal  2013;2013:393570.
Microarray data are high dimension with high noise ratio and relatively small sample size, which makes it a challenge to use microarray data to identify candidate disease genes. Here, we have presented a hybrid method that combines estimation of distribution algorithm with support vector machine for selection of key feature genes. We have benchmarked the method using the microarray data of both diffuse B cell lymphoma and colon cancer to demonstrate its performance for identifying key features from the profile data of high-dimension gene expression. The method was compared with a probabilistic model based on genetic algorithm and another hybrid method based on both genetics algorithm and support vector machine. The results showed that the proposed method provides new computational strategy for hunting candidate disease genes from the profile data of disease gene expression. The selected candidate disease genes may help to improve the diagnosis and treatment for diseases.
doi:10.1155/2013/393570
PMCID: PMC3582165  PMID: 23476131
8.  Allergies and Risk of Head and Neck Cancer: An Original Study plus Meta-Analysis 
PLoS ONE  2013;8(2):e55138.
Background
Although the relationship between allergy and cancer has been investigated extensively, the role of allergy in head and neck cancer (HNC) appears less consistent. It is not clear whether allergies can independently influence the risk of HNC in the presence of known strong environmental risk factors, including consumption of alcohol, betel quid, and cigarette.
Methods
The current paper reports results from: 1) an original hospital-based case-control study, which included 252 incident cases of HNC and 236 controls frequency-matched to cases on sex and age; and 2) a meta-analysis combining the results of the current case-control study and 13 previously published studies (9 cohort studies with 727,569 subjects and 550 HNC outcomes and 5 case-control studies with 4,017 HNC cases and 10,928 controls).
Results
In the original case-control study, we observed a strong inverse association between allergies and HNC [odds ratio = 0.41, 95% confidence interval (CI): 0.27–0.62]. The meta-analysis also indicated a statistically significant inverse association between HNC and allergies [meta-relative risk (RR) = 0.76, 95% CI: 0.63–0.91], particularly strong for allergic rhinitis (meta-RR = 0.55, 95% CI: 0.40–0.76). In addition, the inverse association between allergies and HNC was observed only among men (meta-RR = 0.67, 95% CI: 0.54–0.84) but not among women (meta-RR = 0.98, 95% CI: 0.81–1.18).
Conclusions
These findings suggest that immunity plays an influential role in the risk of HNC. Future studies investigating immune biomarkers, including cytokine profiles and genetic polymorphisms, are warranted to further delineate the relationship between allergies and HNC. Understanding the relationship between allergies and HNC may help devise effective strategies to reduce and treat HNC.
doi:10.1371/journal.pone.0055138
PMCID: PMC3562357  PMID: 23383309
9.  Serum osteocalcin level and its association with carotid atherosclerosis in patients with type 2 diabetes 
Objective
To investigate the association of serum osteocalcin with carotid atherosclerosis in patients with type 2 diabetes.
Methods
We performed a cross-sectional community-based study in metropolitan area. Serum total osteocalcin was measured by radioimmunoassay in 382 men and 435 postmenopausal women. The carotid artery intima-media thickness (IMT) and carotid plaques (PLQ) were measured by B-mode ultrasound.
Results
The crude mean of serum osteocalcin concentrations were 4.52±2.43 ng/ml for men and 5.75±2.92 ng/ml for postmenopausal women (P <0.001), respectively. Osteocalcin levels were associated inversely with age, fasting serum insulin, HOMA-IR, ALT, triglycerides, total cholesterol, LDL- cholesterol, CRP (all P<0.001) and positively with adiponectin and HOMA-B (all P<0.05). After multiple adjustment, the odds ratios (ORs) were substantially higher risk for carotid plaques (OR 1.77 for 1 SD decrease in osteocalcin, 95% CI 1.23-2.76, p=0.005). These associations remained significant after further adjustment for potential confounder.
Conclusions
Serum osteocalcin levels is an independent risk factor for carotid atherosclerosis in patients with type 2 diabetes.
doi:10.1186/1475-2840-12-22
PMCID: PMC3558414  PMID: 23342952
Osteocalcin; Intima-media thickness; Carotid atherosclerotic plaques; Atherosclerosis
10.  The Effects of Qigong on Anxiety, Depression, and Psychological Well-Being: A Systematic Review and Meta-Analysis 
Introduction. The effect of Qigong on psychological well-being is relatively unknown. This study systematically reviewed the effects of Qigong on anxiety, depression, and psychological well-being. Methods. Using fifteen studies published between 2001 and 2011, a systematic review was carried out and meta-analyses were performed on studies with appropriate homogeneity. The quality of the outcome measures was also assessed. Results. We categorized these studies into three groups based on the type of subjects involved as follows: (1) healthy subjects, (2) subjects with chronic illnesses, and (3) subjects with depression. Based on the heterogeneity assessment of available studies, meta-analyses were conducted in three studies of patients with type II diabetes in the second group, which suggested that Qigong was effective in reducing depression (ES = −0.29; 95% CI, −0.58–0.00) and anxiety (ES = −0.37; 95% CI, −0.66–0.08), as measured by Symptom Checklist 90, and in improving psychological well-being (ES = −0.58; 95% CI, −0.91–0.25) as measured by Diabetes Specific Quality of Life Scale. Overall, the quality of research methodology of existing studies was poor. Conclusions. Preliminary evidence suggests that Gigong may have positive effects on psychological well-being among patients with chronic illnesses. However the published studies generally had significant methodological limitations. More high-quality studies are needed.
doi:10.1155/2013/152738
PMCID: PMC3557628  PMID: 23401706
11.  Transcript Profile Analyses of Maize Silks Reveal Effective Activation of Genes Involved in Microtubule-Based Movement, Ubiquitin-Dependent Protein Degradation, and Transport in the Pollination Process 
PLoS ONE  2013;8(1):e53545.
Pollination is the first crucial step of sexual reproduction in flowering plants, and it requires communication and coordination between the pollen and the stigma. Maize (Zea mays) is a model monocot with extraordinarily long silks, and a fully sequenced genome, but little is known about the mechanism of its pollen–stigma interactions. In this study, the dynamic gene expression of silks at four different stages before and after pollination was analyzed. The expression profiles of immature silks (IMS), mature silks (MS), and silks at 20 minutes and 3 hours after pollination (20MAP and 3HAP, respectively) were compared. In total, we identified 6,337 differentially expressed genes in silks (SDEG) at the four stages. Among them, the expression of 172 genes were induced upon pollination, most of which participated in RNA binding, processing and transcription, signal transduction, and lipid metabolism processes. Genes in the SDEG dataset could be divided into 12 time-course clusters according to their expression patterns. Gene Ontology (GO) enrichment analysis revealed that many genes involved in microtubule-based movement, ubiquitin-mediated protein degradation, and transport were predominantly expressed at specific stages, indicating that they might play important roles in the pollination process of maize. These results add to current knowledge about the pollination process of grasses and provide a foundation for future studies on key genes involved in the pollen–silk interaction in maize.
doi:10.1371/journal.pone.0053545
PMCID: PMC3536752  PMID: 23301084
12.  Identification and expansion of cancer stem cells in tumor tissues and peripheral blood derived from gastric adenocarcinoma patients 
Cell Research  2011;22(1):248-258.
Gastric cancer is the fourth most common cancer worldwide, with a high rate of death and low 5-year survival rate. To date, there is a lack of efficient therapeutic protocols for gastric cancer. Recent studies suggest that cancer stem cells (CSCs) are responsible for tumor initiation, invasion, metastasis, and resistance to anticancer therapies. Thus, therapies that target gastric CSCs are attractive. However, CSCs in human gastric adenocarcinoma (GAC) have not been described. Here, we identify CSCs in tumor tissues and peripheral blood from GAC patients. CSCs of human GAC (GCSCs) that are isolated from tumor tissues and peripheral blood of patients carried CD44 and CD54 surface markers, generated tumors that highly resemble the original human tumors when injected into immunodeficient mice, differentiated into gastric epithelial cells in vitro, and self-renewed in vivo and in vitro. Our findings suggest that effective therapeutic protocols must target GCSCs. The capture of GCSCs from the circulation of GAC patients also shows great potential for identification of a critical cell population potentially responsible for tumor metastasis, and provides an effective protocol for early diagnosis and longitudinal monitoring of gastric cancer.
doi:10.1038/cr.2011.109
PMCID: PMC3351913  PMID: 21727908
cancer stem cells; gastric adenocarcinoma; CD44; CD54; circulating tumor cells
13.  Risk of Eye Damage from the Wavelength-Dependent Biologically Effective UVB Spectrum Irradiances 
PLoS ONE  2012;7(12):e52259.
A number of previous studies have discussed the risk of eye damage from broadband ultraviolet (UV) radiation. As the biologically damaging effectiveness of UV irradiation on the human body is known to be wavelength-dependent, it is necessary to study the distribution of the UV spectral irradiance. In order to quantify the ocular biologically effective UV (UVBE) irradiance exposure of different wavelengths and assess the risk of eye damage, UV exposure values were measured at Sanya, China (18.4° N, 109.7°E, altitude 18 m), using a manikin and a dual-detector spectrometer to measure simultaneously the ocular exposure and ambient UV spectral irradiance data and solar elevation angle (SEA) range (approximately 7°–85°). The present study uses the ocular UV spectral irradiance exposure weighted with the action spectra for photokeratitis, photoconjunctivitis and cataracts to calculate the ocular UVBE irradiance exposure for photokeratitis (UVBEpker), photoconjunctivitis (UVBEpcon) and cataracts (UVBEcat). We found that the ocular exposure to UV irradiance is strongest in the 30°–60° SEA range when ∼50% of ocular exposure to UV irradiance on a summer’s day is received. In the 7°–30° SEA range, all the biologically highly effective wavelengths of UVBEpker, UVBEpcon and UVBEcat irradiances are at 300 nm. However, in other SEA ranges the biologically highly effective wavelengths of UVBEpker, UVBEpcon and UVBEcat irradiances are different, corresponding to 311 nm, 300 nm and 307 nm, respectively.
doi:10.1371/journal.pone.0052259
PMCID: PMC3527526  PMID: 23284960
15.  Hepatoprotective effects of baicalein against CCl4-induced acute liver injury in mice 
AIM: To investigate the hepatoprotective effect of baicalein against carbon tetrachloride (CCl4)-induced liver damage in mice.
METHODS: Mice were orally administered with baicalein after CCl4 injection, and therapeutic baicalein was given twice a day for 4 d. The anti-inflammation effects of baicalein were assessed directly by hepatic histology and serum alanine aminotranferease and aspartate aminotransferase measurement. Proliferating cell nuclear antigen was used to evaluate the effect of baicalein in promoting hepatocyte proliferation. Serum interleukin (IL)-6, IL-1β and tumor necrosis factor-α (TNF-α) levels were measured by enzyme-linked immunosorbent assay and liver IL-6, TNF-α, transforming growth factor-α (TGF-α), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) genes expression were determined by quantitative real-time polymerase chain reaction.
RESULTS: CCl4-induced acute liver failure model offers a survival benefit in baicalein-treated mice. The data indicated that the mRNA levels of IL-6 and TNF-α significantly increased within 12 h after CCl4 treatment in baicalein administration groups, but at 24, 48 and 72 h, the expression of IL-6 and TNF-α was kept at lower levels compared with the control. The expression of TGF-α, HGF and EGF was enhanced dramatically in baicalein administration group at 12, 24, 48 and 72 h. Furthermore, we found that baicalein significantly elevated the serum level of TNF-α and IL-6 at the early phase, which indicated that baicalein could facilitate the initiating events in liver regeneration.
CONCLUSION: Baicalein may be a therapeutic candidate for acute liver injury. Baicalein accelerates liver regeneration by regulating TNF-α and IL-6 mediated pathways.
doi:10.3748/wjg.v18.i45.6605
PMCID: PMC3516202  PMID: 23236235
Baicalein; Carbon tetrachloride; Liver injury; Liver regeneration; Hepatocyte proliferation
16.  A bronchofiberoscopy-associated outbreak of multidrug-resistant Acinetobacter baumannii in an intensive care unit in Beijing, China 
BMC Infectious Diseases  2012;12:335.
Background
Bronchofiberscopy, a widely used procedure for the diagnosis of various pulmonary diseases within intensive care units, has a history of association with nosocomial infections. Between September and November 2009, an outbreak caused by multidrug-resistant Acinetobacter baumannii (MDR-Ab) was observed in the intensive care unit of a tertiary care hospital in Beijing, China. This study is aimed to describe the course and control of this outbreak and investigate the related risk factors.
Methods
Clinical and environmental sampling, genotyping with repetitive extragenic palindromic polymerase chain reaction (REP-PCR), and case–control risk factor analysis were performed in the current study.
Results
During the epidemic period, 12 patients were infected or colonized with MDR-Ab. Sixteen (72.7%) of twenty-two MDR-Ab isolates from the 12 patients and 22 (84.6%) of 26 MDR-Ab isolates from the bronchofiberscope and the healthcare-associated environment were clustered significantly into a major clone (outbreak MDR-Ab strain) by REP-PCR typing. Seven patients carrying the outbreak MDR-Ab strain were defined as the cases. Six of the seven cases (83%) received bronchofiberscopy versus four of the 19 controls (21%) (odds ratio, 22.5; 95% confidence interval, 2.07–244.84; P = 0.005). Several potential administrative and technical problems existed in bronchofiberscope reprocessing.
Conclusions
Bronchofiberscopy was associated with this MDR-Ab outbreak. Infection control precautions including appropriate bronchofiberscope reprocessing and environmental decontamination should be strengthened.
doi:10.1186/1471-2334-12-335
PMCID: PMC3562511  PMID: 23198973
Outbreak; Bronchofiberscopy; Multidrug-resistant Acinetobacter baumannii
17.  On the Nature of C-H…F-C Interactions in Hindered CF3-C(sp3) Bond Rotations 
doi:10.1002/anie.201105288
PMCID: PMC3439535  PMID: 21984045
conformational isomerism; hydrogen bondings; steric hindrance; cinchona alkaloids; fluorine
18.  A new species of Coccus (Hemiptera, Coccoidea, Coccidae) from China  
ZooKeys  2012;59-65.
A new species of soft scale, Coccus multisetus Wang & Feng, sp. n. is described and illustrated from Yunnan, China. A key to adult females of all Coccusknown from China is provided.
doi:10.3897/zookeys.244.4045
PMCID: PMC3520103  PMID: 23275744
Hemiptera; Coccoidea; soft scale; new species; China
19.  Different Distribution Patterns between Putative Ercoid Mycorrhizal and Other Fungal Assemblages in Roots of Rhododendron decorum in the Southwest of China 
PLoS ONE  2012;7(11):e49867.
Fungal diversity within plant roots is affected by several factors such as dispersal limitation, habitat filtering, and plant host preference. Given the differences in life style between symbiotic and non-symbiotic fungi, the main factors affecting these two groups of fungi may be different. We assessed the diversity of root associated fungi of Rhododendron decorum using internal transcribed spacer (ITS) sequencing and terminal restriction fragment length polymorphism (T-RFLP) analysis, and our aim was to evaluate the role of different factors in structuring ericoid mycorrhizal (ERM) and non-ericoid mycorrhizal (NEM) fungal communities. Thirty-five fungal operational taxonomic units (OTUs) were found in roots of R. decorum, of which 25 were putative ERM fungal species. Of the two main groups of known ERM, helotialean fungi were more abundant and common than sebacinalean species. Geographic and host patterning of the fungal assemblages were different for ERM and NEM. The distribution of putative ERM fungal terminal restriction fragments (TRFs) showed that there were more common species within ERM than in the NEM fungal assemblages. Results of Mantel tests indicated that the composition of NEM fungal assemblages correlated with geographic parameters while ERM fungal assemblages lacked a significant geographic pattern and instead were correlated with host genotype. Redundancy analysis (RDA) showed that the NEM fungal assemblages were significantly correlated with latitude, longitude, elevation, mean annual precipitation (MAP), and axis 2 of a host-genetic principle component analysis (PCA), while ERM fungal assemblages correlated only with latitude and axis 1 of the host-genetic PCA. We conclude that ERM and NEM assemblages are affected by different factors, with the host genetic composition more important for ERM and geographic factors more important for NEM assemblages. Our results contribute to understanding the roles of dispersal limitation, abiotic factors and biotic interactions in structuring fungal communities in plant roots.
doi:10.1371/journal.pone.0049867
PMCID: PMC3504031  PMID: 23185466
20.  Targeting Multiple Conformations Leads to Small Molecule Inhibitors of the uPAR·uPA Protein-Protein Interaction that Block Cancer Cell Invasion 
ACS chemical biology  2011;6(11):1232-1243.
Interaction of the urokinase receptor (uPAR) with its binding partners including the urokinase-type plasminogen activator (uPA) at the cell surface triggers a series of proteolytic and signaling events that promote invasion and metastasis. Here, we report the discovery of a small molecule (IPR-456) and its derivatives that inhibit the tight uPAR·uPA protein-protein interaction. IPR-456 was discovered by virtual screening against multiple conformations of uPAR sampled from explicit-solvent molecular dynamics simulations. Biochemical characterization reveal that the compound binds to uPAR with sub-micromolar affinity (Kd = 310 nM) and inhibits the tight protein-protein interaction with an IC50 of 10 μM. Free energy calculations based on explicit-solvent molecular dynamics simulations suggested the importance of a carboxylate moiety on IPR-456, which was confirmed by the activity of several derivatives including IPR-803. Immunofluorescence imaging showed that IPR-456 inhibited uPA binding to uPAR of breast MDA-MB-231 tumor cells with an IC50 of 8 μM. The compounds blocked MDA-MB-231 cell invasion, but IPR-456 showed little effect on MDA-MB-231 migration, and no effect on adhesion, suggesting that uPAR mediates these processes through its other binding partners.
doi:10.1021/cb200180m
PMCID: PMC3220747  PMID: 21875078
Virtual screening; small molecule; protein-protein interaction; inhibitor; urokinase receptor; invasion; migration; metastasis; MDA-MB-231; cancer; breast cancer; urokinase-type plasminogen activator; uPAR; uPA; docking; scoring; flexible docking
21.  Indocyanine Green-Assisted Internal Limiting Membrane Peeling in Macular Hole Surgery: A Meta-Analysis 
PLoS ONE  2012;7(11):e48405.
Background
The opinion of application of indocyanine green (ICG) in the macular hole surgery was contradictory. Here we conducted a meta-analysis to evaluate the effect of in internal limiting membrane (ILM) peeling for macular hole surgery.
Methods and Findings
We searched electronic databases for comparative studies published before July 2012 of ILM peeling with and without ICG. Twenty-two studies including 1585 eyes were included. Visual acuity (VA) improvement, including the postoperative rate of ≥20/40 VA gained (OR, 0.65; 95% CI, 0.43 to 0.97; P = 0.033) and increased LogMAR (WMD, −0.09; 95% CI, −0.16 to −0.02; P = 0.011), was less in the ICG group. The risk of visual field defects was greater in the ICG group than in the non-ICG group. There was no significant difference in the rate of anatomical outcomes between ILM peeling procedures performed with and without ICG. RPE changes and other postoperative complications were not significantly different between the ICG and non-ICG groups. An additional analysis showed that the VA improvement of the ICG group was less than the non-ICG group only within the first year of follow up. A subgroup analysis showed that the rate of VA improvement was lower in the ICG group than in other adjuncts group. A higher rate of secondary closure and less VA improvement were observed in a high proportion (>0.1%) of the ICG group. A sensitivity analysis after the randomized-controlled trials were excluded from the meta-analysis demonstrated no differences compared with the overall results.
Conclusions
This meta-analysis demonstrated that there is no evidence of clinical superiority in outcomes for ICG-assisted ILM peeling procedure over the non-ICG one. The toxicity of ICG should be considered when choosing the various staining methods.
doi:10.1371/journal.pone.0048405
PMCID: PMC3492355  PMID: 23144875
22.  Virtual Screening Targeting the Urokinase Receptor, Biochemical and Cell-Based Studies, Synthesis, Pharmacokinetic Characterization, and Effect on Breast Tumor Metastasis 
Journal of Medicinal Chemistry  2011;54(20):7193-7205.
Virtual screening targeting the urokinase receptor (uPAR) led to (3R)-4-cyclohexyl-3-(hexahydrobenzo[d][1,3]dioxol-5-yl)-N-((hexahydrobenzo[d][1,3]dioxol-5-yl)methyl)butan-1-aminium 1 (IPR-1) and 4-(4-((3,5-dimethylcyclohexyl)carbamoyl)-2-(4-isopropylcyclohexyl)pyrazolidin-3-yl)piperidin-1-ium 3 (IPR-69). Synthesis of an analog of 1, namely 2 (IPR-9), and 3 led to breast MDA-MB-231 invasion, migration and adhesion assays with IC50 near 30 μM. Both compounds blocked angiogenesis with IC50 of 3 μM. Compounds 2 and 3 inhibited cell growth with IC50 of 6 and 18 μM and induced apoptosis. Biochemical assays revealed lead-like properties for 3, but not 2. Compound 3 administered orally reached peak concentration of nearly 40 μM with a half-life of about 2 hours. In NOD-SCID mice inoculated with breast TMD-231 cells in their mammary fat pads, compound 3 showed a 20% reduction in tumor volumes and less extensive metastasis was observed for the treated mice. The suitable pharmacokinetic properties of 3 and the encouraging preliminary results in metastasis make it an ideal starting point for next generation compounds.
doi:10.1021/jm200782y
PMCID: PMC3280887  PMID: 21851064
23.  Antioxidant Activities of Stilbenoids from Rheum emodi Wall 
Rheum emodi Wall has been reported to possess protective effect in many inflammatory diseases and oxidative stress-related injuries. This study aims to investigate antioxidant power of stilbenoids from R. emodi and then explore the material basis for its antioxidant potential. The most abundant stilbenoid piceatannol-4′-O-β-D-glucopyranoside (PICG) and its aglycon piceatannol (PICE) were isolated from R. emodi rhizome. Using well-accepted antioxidant chemicals as reference, antioxidant activity of these stilbenoids was examined by measuring DPPH and superoxide anion radical scavenging, ferric reducing power, and inhibition of lipid peroxidation in vitro. Both PICG and PICE displayed promising antioxidant activity in all the four assays. Comparisons among the tested compounds indicated that PICE has the most potent antioxidant activity and the presence of 3′-hydroxyl group may enhance antioxidant activity of stilbenoids. The antioxidative effect of PICE at the cellular level was further demonstrated on the model of hydrogen-peroxide-induced H9c2 rat cardiomyoblasts injury. Taking into account the rapid in vivo metabolic transformation of PICG into PICE it can be inferred that the most abundant stilbenoid PICG may be an important constituent responsible for the antioxidant potential of R. emodi and promising to be developed as an antioxidant agent for supplementary or therapeutic use.
doi:10.1155/2012/603678
PMCID: PMC3488939  PMID: 23193425
24.  Interleukin-29 modulates proinflammatory cytokine production in synovial inflammation of rheumatoid arthritis 
Arthritis Research & Therapy  2012;14(5):R228.
Introduction
The immunoregulatory function of interleukin (IL)-29 has recently been recognized. However, little is known about the involvement of IL-29 in the pathogenesis of rheumatoid arthritis (RA). This study aimed to examine the expression profiles of IL-29 in blood, synovial fluid (SF) and synovium in RA patients and investigate the effect of IL-29 on cytokines production in RA synovial fibroblasts.
Methods
The transcript levels of IL-29 and its specific receptor IL-28Rα in peripheral blood mononuclear cells (PBMC) and synovium were determined by real-time reverse transcription-polymerase chain reaction (real-time PCR). The concentrations of IL-29 in serum and synovial fluid (SF) were quantified by enzyme-linked immunoassay (ELISA), and the correlation of serum IL-29 levels with disease activity in RA patients was investigated. Furthermore, the expression of IL-29 in RA synovium was examined by immunohistochemistry and double immunofluorescence analysis. Finally, the expression of IL-6, IL-8, IL-10, IL-17 and matrix metalloproteinase-3 (MMP-3) in synovial fibroblasts upon IL-29 stimulation was determined by real-time PCR.
Results
IL-29 and IL-28Rα mRNA expression in PBMC was significantly increased in patients with RA compared with healthy controls (HC). The serum levels of circulating IL-29 were higher in RA than those in HC. Increased IL-29 levels were detected in RA SF when compared with osteoarthritis (OA) SF. However, serum IL-29 levels showed no significant correlation with RA disease activity. IL-29 was mostly expressed in the lining region of RA synovium. Moreover, IL-29 was expressed predominately in synovial macrophages and fibroblasts. RA synovial fibroblasts exposed to IL-29 specifically upregulated IL-6, -8 and MMP-3 but downregulated IL-10.
Conclusions
The findings in the present study indicate, for the first time, that IL-29 is dysregulated in patients with RA, which may contribute to the RA pathogenesis via inducing the production of proinflammatory cytokines, chemokines or matrix metalloproteinases in synovial fibroblasts.
doi:10.1186/ar4067
PMCID: PMC3580539  PMID: 23078630
25.  A review of the genus Megapulvinaria Young (Hemiptera, Coccoidea, Coccidae) from China, with a description of a new species  
ZooKeys  2012;59-68.
Prior to this study, only Megapulvinaria maxima (Green) was known from China. However, a new species Megapulvinaria beihaiensis Wang & Feng, sp. n. is described below and Megapulvinaria maxima is redescribed. A key is provided for the five species now placed in this genus.
doi:10.3897/zookeys.228.3211
PMCID: PMC3487642  PMID: 23166471
Hemiptera; Coccoidea; soft scale; taxonomy; China

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