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1.  MiR-1178 Promotes the Proliferation, G1/S Transition, Migration and Invasion of Pancreatic Cancer Cells by Targeting CHIP 
PLoS ONE  2015;10(1):e0116934.
CHIP, a co-chaperone protein that interacts with Hsc/Hsp70, has been shown to be under-expressed in pancreatic cancer cells and has demonstrated a potential tumor suppressor property. Nevertheless, the underlying mechanisms of CHIP regulation in pancreatic cancer cells remain unknown. In this study, we found that miR-1178 decreased the translation of the CHIP protein by targeting the 3′-UTR region. We observed that over-expression of miR-1178 facilitated the proliferation, G1/S transition, migration and invasion of pancreatic cancer cells. Conversely, the inhibition of miR-1178 expression significantly suppressed these phenotypes. Furthermore, CHIP over-expression abrogated miR-1178-induced cell proliferation and invasion. Our data suggest that miR-1178 acts as an oncomiR in pancreatic cancer cells by inhibiting CHIP expression.
doi:10.1371/journal.pone.0116934
PMCID: PMC4312055  PMID: 25635996
2.  Developing the Psychological Strain Scales (PSS): Reliability, Validity, and Preliminary Hypothesis Tests1 
Social indicators research  2012;115(1):337-361.
Since its inception, the Strain Theory of Suicide has been tested and supported in a number of empirical studies. This social psychological theory can be employed as a complementary conceptualization to account for suicidal behaviors as well as mental disorders. However, the lack of consistent measurements of the strains limits the application of the theory in scientific research. Our research team has developed such scales for future testing of the Strain Theory of Suicide in a more systematic approach. For the initial items to measure the four strains (value, aspiration, deprivation, and coping), we solicited approximately 40 items for each strain with high face validity by about 30 fellow researchers. A preliminary examination of about 160 items for consistency and validity, with a sample of about 300 college students, yielded 20 consistent items for each of the four strain scales. Then, a second study was conducted at a different university with approximately 500 students to further streamline each of the four strain scales and test the validity of each with corresponding established scales and variables. As a result, 15 items were selected for each of the four Psychological Strain Scales (PSS). In correlation and multiple regression analyses, we found support for the hypotheses regarding the positive associations between psychological strains measured by the PSS and psychopathology including suicidal ideation. Follow up research with the new scales needs to be carried out in order to test the effects of psychological strains on suicide and mental disorders for various populations.
doi:10.1007/s11205-012-0222-6
PMCID: PMC3891678  PMID: 24443628
Psychological Strain; Reliability; Validity; Mental Disorder; Suicide
3.  Molecular Variation and Horizontal Gene Transfer of the Homocysteine Methyltransferase Gene mmuM and its Distribution in Clinical Pathogens 
The homocysteine methyltransferase encoded by mmuM is widely distributed among microbial organisms. It is the key enzyme that catalyzes the last step in methionine biosynthesis and plays an important role in the metabolism process. It also enables the microbial organisms to tolerate high concentrations of selenium in the environment. In this research, 533 mmuM gene sequences covering 70 genera of the bacteria were selected from GenBank database. The distribution frequency of mmuM is different in the investigated genera of bacteria. The mapping results of 160 mmuM reference sequences showed that the mmuM genes were found in 7 species of pathogen genomes sequenced in this work. The polymerase chain reaction products of one mmuM genotype (NC_013951 as the reference) were sequenced and the sequencing results confirmed the mapping results. Furthermore, 144 representative sequences were chosen for phylogenetic analysis and some mmuM genes from totally different genera (such as the genes between Escherichia and Klebsiella and between Enterobacter and Kosakonia) shared closer phylogenetic relationship than those from the same genus. Comparative genomic analysis of the mmuM encoding regions on plasmids and bacterial chromosomes showed that pKF3-140 and pIP1206 plasmids shared a 21 kb homology region and a 4.9 kb fragment in this region was in fact originated from the Escherichia coli chromosome. These results further suggested that mmuM gene did go through the gene horizontal transfer among different species or genera of bacteria. High-throughput sequencing combined with comparative genomics analysis would explore distribution and dissemination of the mmuM gene among bacteria and its evolution at a molecular level.
doi:10.7150/ijbs.10320
PMCID: PMC4278250  PMID: 25552925
comparative genomics; homocysteine methyltransferase gene; horizontal gene transfer; molecular variation
4.  Section Curve Reconstruction and Mean-Camber Curve Extraction of a Point-Sampled Blade Surface 
PLoS ONE  2014;9(12):e115471.
The blade is one of the most critical parts of an aviation engine, and a small change in the blade geometry may significantly affect the dynamics performance of the aviation engine. Rapid advancements in 3D scanning techniques have enabled the inspection of the blade shape using a dense and accurate point cloud. This paper proposes a new method to achieving two common tasks in blade inspection: section curve reconstruction and mean-camber curve extraction with the representation of a point cloud. The mathematical morphology is expanded and applied to restrain the effect of the measuring defects and generate an ordered sequence of 2D measured points in the section plane. Then, the energy and distance are minimized to iteratively smoothen the measured points, approximate the section curve and extract the mean-camber curve. In addition, a turbine blade is machined and scanned to observe the curvature variation, energy variation and approximation error, which demonstrates the availability of the proposed method. The proposed method is simple to implement and can be applied in aviation casting-blade finish inspection, large forging-blade allowance inspection and visual-guided robot grinding localization.
doi:10.1371/journal.pone.0115471
PMCID: PMC4281077  PMID: 25551467
5.  β-catenin SUMOylation is involved in the dysregulated proliferation of myeloma cells 
Over-activation of SUMOylation is correlated with poor prognosis in multiple myeloma (MM), with the mechanism unclear. Wnt signaling is one of the aberrantly regulated pathways related to cancer tumorigenesis and progression. Whether SUMOylation is involved in regulating the activity of Wnt/β-catenin pathway, however, has not been reported in MM. Here we found that the TOPflash reporter activity and the expression of Wnt/β-catenin target genes can be down-regulated after interference with SUMOylation through SUMO-1 small interfering RNA (siRNA). SUMOylation inhibition down-regulated β-catenin at protein level via promotion of ubiquitin-proteasomal mediated degradation. Furthermore, over-expression of β-catenin rescued Wnt/β-catenin pathway activity and partially prevented increased apoptosis and growth inhibition induced by SUMOylation inhibition, indicating that β-catenin was responsible for the observed effect on Wnt/β-catenin pathway. To gain a clearer view, we exploited the inter-protein interactions of β-catenin and SUMO-1 in myeloma cell lines. Immunoprecipitation and immunofluorescence assay proved that β-catenin is subjected to SUMOylation in vivo, which may, at least partially explain the impact of SUMOylation inhibition on β-catenin. The association of SUMO-1 and β-catenin was confirmed in myeloma patient samples. Taken together, our data proved that SUMOylation inhibition down-regulates Wnt/β-catenin pathway by promoting the ubiquitin-proteasomal mediated degradation of β-catenin. SUMOylation of β-catenin is part of the mechanisms involved in the dysregulated proliferation of myeloma cells.
PMCID: PMC4300696  PMID: 25628940
Multiple myeloma; SUMO-1; SUMOylation; Wnt/β-catenin
6.  Anti-inflammatory activity of leaf essential oil from Cinnamomum longepaniculatum (Gamble) N. Chao 
The anti-inflammatory activity of the essential oil from C. longepaniculatum was evaluated by three experimental models including the dimethyl benzene-induced ear edema in mice, the carrageenan-induced paw edema in rat and the acetic acid-induced vascular permeability in mice. The influence of the essential oil on histological changes and prostaglandin E2 (PGE2), histamine and 5-hydroxytryptamine (5-HT) production associated with carrageenan-induced rat paw edema was also investigated. The essential oil (0.5, 0.25, 0.13 ml/kg b.w.) showed significantly inhibition of inflammation along with a dose-dependent manner in the three experimental models. The anti-inflammatory activity of essential oil was occurred both in early and late phase and peaked at 4 h after carrageenan injection. The essential oil resulted in a dose dependent reduction of the paw thickness, connective tissue injury and the infiltration of inflammatory cell. The essential oil also significantly reduced the production of PGE2, histamine and 5-HT in the exudates of edema paw induced by carrageenan. Both the essential oil and indomethacin resulted relative lower percentage inhibition of histamine and 5-HT than that of PGE2 at 4 h after carrageenan injection.
PMCID: PMC4307527  PMID: 25664080
Cinnamomum longepaniculatum; essential oil; anti-inflammatory activity
7.  Blocking and reversing hepatic fibrosis in patients with chronic hepatitis B treated by traditional Chinese medicine (tablets of biejia ruangan or RGT): study protocol for a randomized controlled trial 
Trials  2014;15(1):438.
Background
Chronic hepatitis B (CHB) can progress to cirrhosis, hepatocellular carcinoma (HCC) and ultimately liver-related death. Although oral antiviral therapy for patients with CHB reduces the risk of such complications, once cirrhosis is established, the benefits of antiviral therapy are not robustly demonstrated. According to traditional Chinese medicine (TCM), some Chinese herbal medicines promote blood circulation and soften hard masses, and therefore they may block and reverse hepatic fibrosis. The aim of this study is to evaluate the effects of TCM tablets of the compound biejia ruangan (RGT) administered for fibrosis, and entecavir (ETV), on the development of HCC in patients with CHB or hepatitis B virus (HBV)-related compensated cirrhosis.
Methods/design
This multicenter, centrally randomized, double-blind, placebo-controlled, parallel-group study is planned to complete within 5 years. For the study, 1,000 with CHB or HBV-related compensated cirrhosis are randomly assigned in a 1:1 ratio to a treatment group (0.5 mg ETV once daily; 2 g RGT three times daily) or a control group (0.5 mg ETV once daily; 2 g RGT dummy agent three times daily). The primary end points are the development of HCC and liver-related death. Secondary end points include disease progression and overall survival.
Discussion
Although antiviral therapy can achieve sustained suppression of HBV replication, thereby preventing cirrhosis, patients with CHB treated with nucleos(t)ide analogs (NUCs) retain a higher risk for HCC compared with patients with inactive disease. Although previous clinical trials with RGT have confirmed the efficacy of blocking and reversing hepatic fibrosis in patients with CHB or compensated cirrhosis, the long-term risk for HCC or disease progression in these patients treated with combination of RGT and NUCs compared with NUCs alone is unclear. Therefore, it is necessary to investigate the effects of the RGT blockade and reversal of hepatic fibrosis on the development of HCC in patients with CHB or HBV-related compensated cirrhosis in large, prospective, multicenter, double-blind, randomized, controlled trials in China.
Trial registration
ClinicalTrials.gov Identifier: NCT01965418. Date registered: 17 October 2013
doi:10.1186/1745-6215-15-438
PMCID: PMC4234899  PMID: 25381721
Compound biejia ruangan tablet; multicenter randomized controlled trial; chronic hepatitis B; hepatocellular carcinoma; hepatic fibrosis
8.  Therapeutic Effect of Esophageal Foreign Body Extraction Management: Flexible versus Rigid Endoscopy in 216 Adults of Beijing 
Background
The aim of this study was to assess the effectiveness and complications of rigid endoscopy (RE) and flexible endoscopy (FE) for the extraction of esophageal foreign bodies (FB) in adults.
Material/Methods
A retrospective analysis was conducted on the medical records of 216 adult patients with esophageal FB impaction treated at Peking University Third Hospital, Beijing, China, between January 2008 and December 2012.
Results
The success rate of FB extraction was 100% (142/142) in patients treated with RE compared to 97.3% (72/74) in those treated with FE (P=0.045). The total incidence of complications in RE-treated patients was lower than that in FE-treated patients (28.2% vs. 45.9%, P=0.009), but the perforation rate was higher (5.6% vs. 1.4%, P=0.135). The incidences of total complications and perforation were associated with the duration of FB impaction in patients who underwent RE (both P<0.05) but not in patients who underwent FE. RE was more frequently used in extraction of FBs located in the upper esophagus (88.7%, 126/142) compared to FE (60.8%, 45/74) (P<0.05). The size of extracted FB was significantly larger in patients treated with FE compared to those treated with RE (P<0.05).
Conclusions
Both RE and FE were effective in the extraction of esophageal FB. However, the perforation rate and the need for general anesthesia were higher in RE-associated extraction. FE may be the preferred endoscopic treatment for the extraction of esophageal FB, except possibly for those impacted in the upper esophagus. FB extraction may produce better outcomes if endoscopy is employed early.
doi:10.12659/MSM.889758
PMCID: PMC4214697  PMID: 25349897
esophagus; foreign body; flexible endoscopy; rigid endoscopy; adult
9.  CYP2E1 gene rs6413420 polymorphism was first found in the Bouyei ethnic group of China 
Background: China is a multinational country. The relationship between gene polymorphisms of xenobiotic metabolizing enzymes and national ethnicity has not previously investigated among Chinese people. The aim of this study was to investigate distributions of CYP1A1 and CYP2E1 gene polymorphisms in five ethnic groups of China. Methods: 829 blood samples were collected from five ethnic groups (Han, Shui, Miao, Zhuang, Bouyei). Taqman-MGB probe was used in Real-time PCR to test the gene polymorphisms of CYP1A1 (rs1048943 and rs4646903) and CYP2E1 (rs2031920 and rs6413420). We further validate the SNP genotyping results through DNA sequencing. Results: The genotype distribution of all four SNPs was in accordance with Hardy-Weinberg equilibrium except the genotype distribution of rs4646903 in Han and Bouyei ethnic groups (p=0.013 and 0.0005, respectively). CYP2E1 gene rs6413420 polymorphism was first found in the Bouyei ethnic group in China. The results of DNA sequencing were entirely in line with the SNP genotyping assay. Conclusions: The CYP1A1 and CYP2E1 genetic polymorphisms were different in different ethnic groups in China. CYP2E1 gene rs6413420 polymorphism was first found in the Bouyei ethnic group of China.
PMCID: PMC4238488  PMID: 25419409
CYP1A1; CYP2E1; Taqman-MGB probe; Real-time PCR; SNPs
10.  Biomarkers for cancer-related fatigue and adverse reactions to chemotherapy in lung cancer patients 
Molecular and Clinical Oncology  2014;3(1):163-166.
This study was conducted to investigate the biomarkers that appear to be correlated with cancer-related fatigue (CRF) and the adverse reactions (ADRs) to chemotherapy. A total of 100 lung cancer patients were selected and CRF prior to and following chemotherapy was evaluated. The plasma levels of tumor necrosis factor (TNF)-α and interleukin (IL)-1 and the level of 17-hydroxycorticosteroid (17-OHCS) in the urine were analyzed and correlated with CRF and the ADRs associated with chemotherapy. The incidence of CRF was found to be 88.0% and ADRs following chemotherapy occurred in 15.0% of the patients. An increase in the TNF-α and IL-1 levels was detected in patients with CRF. The level of 17-OHCS in the urine was found to be elevated in cases that experienced ADRs following chemotherapy. In conclusion, CRF is closely correlated with increased plasma levels of TNF-α and IL-1. Furthermore, an abnormally elevated 17-OHCS level in the urine may be an important indicator predicting ADR development following chemotherapy.
doi:10.3892/mco.2014.439
PMCID: PMC4251268  PMID: 25469288
lung cancer; cancer-related fatigue; adverse reactions to chemotherapy; tumor necrosis factor-α; interleukin 1; 17-hydroxycorticosteroid
11.  Simultaneous Detection of Five Enteric Viruses Associated with Gastroenteritis by Use of a PCR Assay: a Single Real-Time Multiplex Reaction and Its Clinical Application 
Journal of Clinical Microbiology  2014;52(4):1266-1268.
We developed a highly sensitive reverse transcription and multiplex real-time PCR (rtPCR) assay that can identify five viruses, including six genogroups, in a single reaction: norovirus genogroups I and II; sapovirus genogroups I, II, IV, and V; human rotavirus A; adenovirus serotypes 40 and 41; and human astrovirus. In comparison to monoplex rtPCR assays, the sensitivities and specificities of the multiplex rtPCR ranged from 75% to 100% and from 99% to 100%, respectively, evaluated on 812 clinical stool specimens.
doi:10.1128/JCM.00245-14
PMCID: PMC3993471  PMID: 24478418
12.  The Effect of Pylorus Removal on Delayed Gastric Emptying after Pancreaticoduodenectomy: A Meta-Analysis of 2,599 Patients 
PLoS ONE  2014;9(10):e108380.
Background
Delayed gastric emptying is a serious complication of pancreaticoduodenectomy. The effect of pylorus removal on delayed gastric emptying has not been well evaluated.
Study Design
We searched five databases (PubMed, EMBASE and the Cochrane Central Register of Controlled Trials, Scopus and Web of Science) up to July 2014. The meta-regression analysis was performed to evaluate any factors accountable for the heterogeneity. Publication bias was assessed by Egger's test, and corrected by Duval's trim and fill method. Subgroup analyses were conducted for different surgical techniques of pyloric removal. Other intraoperative and postoperative parameters were compared between two groups.
Results
We included 27 studies involving 2,599 patients, with a moderate-high heterogeneity for primary outcome (I2 = 63%). Meta-regression analysis showed that four variables primarily contributed to the heterogeneity, namely nasogastric tube intubation time, solid food start time, preoperative diabetes percentage and the number of patients in pylorus-preserving group. After excluding four studies, the remaining twenty-three studies showed reduced heterogeneity (I2 = 51%). Then we used Duval's trim and fill method to correct publication bias. The corrected MH odds ratio was 0.78 (95% CI: 0.52–1.17). A subgroup analysis showed that pylorus removal tends to reduce delayed gastric emptying incidence for subtotal stomach-preserving pancreaticoduodenectomy or pylorus-resecting pancreaticoduodenectomy, compared with pylorus-preserving group. However, standard Whipple procedure failed to show any significant reduction of DGE compared with pylorus-removal group. No significant differences were observed in terms of length of hospital stay, infection and pancreatic fistula; however, pylorus removal resulted in longer operation time, more blood loss and higher mortality.
Conclusion
The pylorus removal does not significantly reduce the overall incidence of delayed gastric emptying. Subtotal stomach-preserving pancreaticoduodenectomy or pylorus-resecting pancreaticoduodenectomy tends to reduce delayed gastric emptying incidence, but needs further validation.
doi:10.1371/journal.pone.0108380
PMCID: PMC4182728  PMID: 25272034
13.  Efficient Preparation of Enantiopure D-Phenylalanine through Asymmetric Resolution Using Immobilized Phenylalanine Ammonia-Lyase from Rhodotorula glutinis JN-1 in a Recirculating Packed-Bed Reactor 
PLoS ONE  2014;9(9):e108586.
An efficient enzymatic process was developed to produce optically pure D-phenylalanine through asymmetric resolution of the racemic DL-phenylalanine using immobilized phenylalanine ammonia-lyase (RgPAL) from Rhodotorula glutinis JN-1. RgPAL was immobilized on a modified mesoporous silica support (MCM-41-NH-GA). The resulting MCM-41-NH-GA-RgPAL showed high activity and stability. The resolution efficiency using MCM-41-NH-GA-RgPAL in a recirculating packed-bed reactor (RPBR) was higher than that in a stirred-tank reactor. Under optimal operational conditions, the volumetric conversion rate of L-phenylalanine and the productivity of D-phenylalanine reached 96.7 mM h−1 and 0.32 g L−1 h−1, respectively. The optical purity (eeD) of D-phenylalanine exceeded 99%. The RPBR ran continuously for 16 batches, the conversion ratio did not decrease. The reactor was scaled up 25-fold, and the productivity of D-phenylalanine (eeD>99%) in the scaled-up reactor reached 7.2 g L−1 h−1. These results suggest that the resolution process is an alternative method to produce highly pure D-phenylalanine.
doi:10.1371/journal.pone.0108586
PMCID: PMC4182499  PMID: 25268937
14.  Serum Amyloid A and Clusterin as Potential Predictive Biomarkers for Severe Hand, Foot and Mouth Disease by 2D-DIGE Proteomics Analysis 
PLoS ONE  2014;9(9):e108816.
Hand, foot, and mouth disease (HFMD) affects more than one million children, is responsible for several hundred child deaths every year in China and is the cause of widespread concerns in society. Only a small fraction of HFMD cases will develop further into severe HFMD with neurologic complications. A timely and accurate diagnosis of severe HFMD is essential for assessing the risk of progression and planning the appropriate treatment. Human serum can reflect the physiological or pathological states, which is expected to be an excellent source of disease-specific biomarkers. In the present study, a comparative serological proteome analysis between severe HFMD patients and healthy controls was performed via a two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy. Fifteen proteins were identified as differentially expressed in the sera of the severe HFMD patients compared with the controls. The identified proteins were classified into different groups according to their molecular functions, biological processes, protein classes and physiological pathways by bioinformatics analysis. The up-regulations of two identified proteins, serum amyloid A (SAA) and clusterin (CLU), were confirmed in the sera of the HFMD patients by ELISA assay. This study not only increases our background knowledge about and scientific insight into the mechanisms of HFMD, but also reveals novel potential biomarkers for the clinical diagnosis of severe HFMD.
doi:10.1371/journal.pone.0108816
PMCID: PMC4182520  PMID: 25268271
15.  Immune Modulatory Effects of IL-22 on Allergen-Induced Pulmonary Inflammation 
PLoS ONE  2014;9(9):e107454.
IL-22 is a Th17/Th22 cytokine that is increased in asthma. However, recent animal studies showed controversial findings in the effects of IL-22 in allergic asthma. To determine the role of IL-22 in ovalbumin-induced allergic inflammation we generated inducible lung-specific IL-22 transgenic mice. Transgenic IL-22 expression and signaling activity in the lung were determined. Ovalbumin (OVA)-induced pulmonary inflammation, immune responses, and airway hyperresponsiveness (AHR) were examined and compared between IL-22 transgenic mice and wild type controls. Following doxycycline (Dox) induction, IL-22 protein was readily detected in the large (CC10 promoter) and small (SPC promoter) airway epithelial cells. IL-22 signaling was evidenced by phosphorylated STAT3. After OVA sensitization and challenge, compared to wild type littermates, IL-22 transgenic mice showed decreased eosinophils in the bronchoalveolar lavage (BAL), and in lung tissue, decreased mucus metaplasia in the airways, and reduced AHR. Among the cytokines and chemokines examined, IL-13 levels were reduced in the BAL fluid as well as in lymphocytes from local draining lymph nodes of IL-22 transgenic mice. No effect was seen on the levels of serum total or OVA-specific IgE or IgG. These findings indicate that IL-22 has immune modulatory effects on pulmonary inflammatory responses in allergen-induced asthma.
doi:10.1371/journal.pone.0107454
PMCID: PMC4177833  PMID: 25254361
16.  Connexin 32 and 43 promoter methylation in Helicobacter pylori-associated gastric tumorigenesis 
World Journal of Gastroenterology : WJG  2014;20(33):11770-11779.
AIM: To explore the mechanism of abnormal Connexin (Cx) 32 and Cx43 expression in the gastric mucosa after Helicobacter pylori (H. pylori) infection.
METHODS: Biopsy specimens of gastric mucosa in different gastric carcinogenesis stages with H. pylori infection, that is, non-atrophic gastritis (NAG; n = 24), chronic atrophic gastritis (CAG; n = 25), intestinal metaplasia (IM; n = 28), dysplasia (DYS; n = 24), and gastric cancer (GC; n = 30), as well as specimens of normal gastric mucosa without H. pylori infection (NGM; n = 25), were confirmed by endoscopy and pathological examination. Cx32 and Cx43 mRNA expression was detected by real-time polymerase chain reaction (PCR). Cx32 and Cx43 promoter CpG island methylation status was determined by methylation-specific PCR (MSP), bisulfite PCR sequencing (BSP) and MassArray methods.
RESULTS: The relative mRNA expression levels in the gastric mucosa of patients with NGM, NAG, CAG, IM, DYS and GC were 0.146 ± 0.011, 0.133 ± 0.026, 0.107 ± 0.035, 0.039 ± 0.032, 0.037 ± 0.01 and 0.03 ± 0.011 for Cx32; and 0.667 ± 0.057, 0.644 ± 0.051, 0.624 ± 0.049, 0.555 ± 0.067, 0.536 ± 0.058 and 0.245 ± 0.121 for Cx43, respectively, which were gradually decreasing and significantly different (GC vs NGM: P < 0.001 for Cx32, P < 0.001 for Cx43). The promoter methylation levels in the gastric mucosa from NGM to GC stages by MSP were 38.8% ± 9.0%, 43.1% ± 9.4%, 56.5% ± 3.1%, 64.4% ± 9.7%, 72.5% ± 4.2% and 79.6% ± 6.8% for Cx32; and 49.0% ± 3.9%, 58.1% ± 5.0%, 66.5% ± 7.9%, 74.0% ± 8.8%, 78.3% ± 3.6% and 88.7% ± 6.2% for Cx43, respectively, which were gradually increasing and significantly different (P = 0.039, P = 0.019). The promoter methylation levels by BSP and MassArray exhibited similar trends. Cx32 and Cx43 mRNA expression was negatively correlated with promoter methylation status and gastric carcinogenesis stages (P < 0.001, P = 0.016).
CONCLUSION: Cx32 and Cx43 mRNA expression decreased gradually during H. pylori infection-associated gastric carcinogenesis, and it is associated with hypermethylation of these genes’ promoter.
doi:10.3748/wjg.v20.i33.11770
PMCID: PMC4155367  PMID: 25206281
Gastric cancer; Helicobacter pylori; Cx32; Cx43; DNA methylation
17.  Coarctation of the aorta associated with Dandy–Walker variant 
This article reports a rare case of coarctation of the aorta associated with Dandy–Walker variant in a 17-year-old girl. Differential diagnoses of coarctation of the aorta and Dandy–Walker variant are extensively discussed. In addition, standard surgical treatment of coarctation as well as new approaches such as endovascular stenting are described in detail to provide therapeutic insights into her management. Although surgical or endovascular repair of coarctation results in significant improvement of systemic hypertension and is associated with better survival, cardiovascular complications are still very common. Thus, long-term follow-up after repair is required, and high-quality imaging studies such as echocardiography, CT and MRI are warranted.
doi:10.1016/j.jcdr.2013.06.002
PMCID: PMC3849293  PMID: 24396258
Coarctation of the aorta; Dandy–Walker variant; Hypertension; Surgical repair; Endovascular stent
18.  Astroglial cells regulate the developmental timeline of human neurons differentiated from induced pluripotent stem cells 
Stem cell research  2013;11(2):743-757.
Neurons derived from human induced-pluripotent stem cells (hiPSCs) have been used to model a variety of neurological disorders. Different protocols have been used to differentiate hiPSCs into neurons, but their functional maturation process has varied greatly among different studies. Here, we demonstrate that laminin, a commonly used substrate for iPSC cultures, was inefficient to promote fully functional maturation of hiPSC-derived neurons. In contrast, astroglial substrate greatly accelerated neurodevelopmental processes of hiPSC-derived neurons. We have monitored the neural differentiation and maturation process for up to two months after plating hiPSC-derived neuroprogenitor cells (hNPCs) on laminin or astrocytes. We found that one week after plating hNPCs, there were 21-fold more newly differentiated neurons on astrocytes than on laminin. Two weeks after plating hNPCs, there were 12-fold more dendritic branches in neurons cultured on astrocytes than on laminin. Six weeks after plating hNPCs, the Na+ and K+ currents, as well as glutamate and GABA receptor currents, were 3-fold larger in neurons cultured on astrocytes than on laminin. And two months after plating hNPCs, the spontaneous synaptic events were 8-fold more in neurons cultured on astrocytes than on laminin. These results highlight a critical role of astrocytes in promoting neural differentiation and functional maturation of human neurons derived from hiPSCs. Moreover, our data presents a thorough developmental timeline of hiPSC-derived neurons in culture, providing important benchmarks for future studies on disease modeling and drug screening.
doi:10.1016/j.scr.2013.05.002
PMCID: PMC3979966  PMID: 23759711
19.  Evaluating standard terminologies for encoding allergy information 
Objective
Allergy documentation and exchange are vital to ensuring patient safety. This study aims to analyze and compare various existing standard terminologies for representing allergy information.
Methods
Five terminologies were identified, including the Systemized Nomenclature of Medical Clinical Terms (SNOMED CT), National Drug File–Reference Terminology (NDF-RT), Medication Dictionary for Regulatory Activities (MedDRA), Unique Ingredient Identifier (UNII), and RxNorm. A qualitative analysis was conducted to compare desirable characteristics of each terminology, including content coverage, concept orientation, formal definitions, multiple granularities, vocabulary structure, subset capability, and maintainability. A quantitative analysis was also performed to compare the content coverage of each terminology for (1) common food, drug, and environmental allergens and (2) descriptive concepts for common drug allergies, adverse reactions (AR), and no known allergies.
Results
Our qualitative results show that SNOMED CT fulfilled the greatest number of desirable characteristics, followed by NDF-RT, RxNorm, UNII, and MedDRA. Our quantitative results demonstrate that RxNorm had the highest concept coverage for representing drug allergens, followed by UNII, SNOMED CT, NDF-RT, and MedDRA. For food and environmental allergens, UNII demonstrated the highest concept coverage, followed by SNOMED CT. For representing descriptive allergy concepts and adverse reactions, SNOMED CT and NDF-RT showed the highest coverage. Only SNOMED CT was capable of representing unique concepts for encoding no known allergies.
Conclusions
The proper terminology for encoding a patient's allergy is complex, as multiple elements need to be captured to form a fully structured clinical finding. Our results suggest that while gaps still exist, a combination of SNOMED CT and RxNorm can satisfy most criteria for encoding common allergies and provide sufficient content coverage.
doi:10.1136/amiajnl-2012-000816
PMCID: PMC3756252  PMID: 23396542
Terminology; Standards; Vocabulary, Controlled; Allergy; Hypersensitivity; Drug Intolerance
20.  Clinical features and therapeutic strategies of obstructive azoospermia in patients treated by bilateral inguinal hernia repair in childhood 
Asian Journal of Andrology  2014;16(5):745-748.
Childhood inguinal herniorrhaphy is one common cause of seminal tract obstruction. Vasovasostomy (VV) can reconstruct seminal deferens and result in appearance of sperm and natural pregnancy in some patients. Secondary epididymal obstruction caused by a relatively long-term vasal obstruction is a common cause of lower patency compared with VV due to vasectomy in adults. From July 2007 to June 2012, a total of 62 patients, with history of childhood inguinal herniorrhaphy and diagnosed as obstructive azoospermia were treated in our center. The overall patency rate and natural pregnancy rate were 56.5% (35/62) and 25.8% (16/62), respectively. 48.4% (30/62) of the patients underwent bilateral VV in the inguinal region, with a patency rate of 76.7% (23/30) and a natural pregnancy rate of 36.7% (11/30), respectively. 30.6% (19/62) of the patients underwent bilateral VV and unilateral or bilateral vasoepididymostomies due to ipsilateral epididymal obstruction with the patency and natural pregnancy rate decreasing to 63.2% (12/19) and 26.3% (5/19). 21.0% (13/62) of the patients merely underwent vasal exploration without reconstruction due to failure to find distal vasal stump, etc. Our study indicate that microsurgical reanastomosis is an effective treatment for some patients with seminal tract obstruction caused by childhood inguinal herniorrhaphy.
doi:10.4103/1008-682X.131710
PMCID: PMC4215684  PMID: 24994783
azoospermia; inguinal herniorrhaphy; microsurgical reanastomosis
21.  P300-dependent STAT3 acetylation is necessary for angiotensin II-induced pro-fibrotic responses in renal tubular epithelial cells 
Acta Pharmacologica Sinica  2014;35(9):1157-1166.
Aim:
To explore the signal transducer and activator of transcription 3 (STAT3) signaling pathway, especially STAT3 acetylation, in angiotensin II (Ang II)-induced pro-fibrotic responses in renal tubular epithelial cells.
Methods:
Rat renal tubular epithelial cell line (NRK-52E) was used. STAT3 acetylation and phosphorylation, as well as the expression of fibronectin, collagen IV and transforming growth factor-β1 (TGF-β1) were examined using Western blotting. The level and localization of STAT3 phosphorylation on Tyr705 were detected with fluorescence immunocytochemistry. The cells were transfected with a plasmid vector carrying p300 gene or siRNA targeting p300 to regulate p300 expression.
Results:
Overexpression of p300 significantly increased STAT3 acetylation on Lys685, STAT3 phosphorylation on Tyr705, and the expression of TGF-β1, collagen IV and fibronectin in the cells. Treatment of the cells with Ang II (1 μmol/L) significantly increased STAT3 phosphorylation on Tyr705 through JAK2 activation, and dose-dependently increased the expression of fibronectin, collagen IV and TGF-β1. Pretreatment with curcumin, an inhibitor of JAK2 and p300, blocked Ang II-induced effects. Knockdown of p300 significantly decreased STAT3 acetylation on Lys685, and abolished Ang II-stimulated STAT3 phosphorylation on Tyr705, whereas pretreatment of the cells with C646, a selective inhibitor of p300, inhibited Ang II-induced STAT3 nuclear translocation and the expression of TGF-β1, collagen IV and fibronectin. Pretreatment of the cells with AG490, a JAK2 inhibitor, markedly inhibited Ang II-induced STAT3 phosphorylation on Tyr705 and fibronectin expression.
Conclusion:
p300-dependent STAT3 acetylation is necessary for Ang II-induced STAT3 phosphorylation and the consequent pro-fibrotic responses in renal tubular epithelial cells in vitro.
doi:10.1038/aps.2014.54
PMCID: PMC4155527  PMID: 25088002
renal fibrosis; angiotensin II; renal tubular epithelial cells; STAT3; JAK2; extracellular matrix; p300; curcumin; C646; AG490
22.  ProBDNF and its receptors are upregulated in glioma and inhibit the growth of glioma cells in vitro 
Neuro-Oncology  2013;15(8):990-1007.
Background
High-grade glioma is incurable, with a short survival time and poor prognosis. The increased expression of p75 neurotrophin receptor (NTR) is a characteristic of high-grade glioma, but the potential significance of increased p75NTR in this tumor is not fully understood. Since p75NTR is the receptor for the precursor of brain-derived neurotrophic factor (proBDNF), it is suggested that proBDNF may have an impact on glioma.
Methods
In this study we investigated the expression of proBDNF and its receptors p75NTR and sortilin in 52 cases of human glioma and 13 cases of controls by immunochemistry, quantitative real-time PCR, and Western blot methods. Using C6 glioma cells as a model, we investigated the roles of proBDNF on C6 glioma cell differentiation, growth, apoptosis, and migration in vitro.
Results
We found that the expression levels of proBDNF, p75NTR, and sortilin were significantly increased in high-grade glioma and were positively correlated with the malignancy of the tumor. We also observed that tumors expressed proBDNF, p75NTR, and sortilin in the same cells with different subcellular distributions, suggesting an autocrine or paracrine loop. The ratio of proBDNF to mature BDNF was decreased in high-grade glioma tissues and was negatively correlated with tumor grade. Using C6 glioma cells as a model, we found that proBDNF increased apoptosis and differentiation and decreased cell growth and migration in vitro via p75NTR.
Conclusions
Our data indicate that proBDNF and its receptors are upregulated in high-grade glioma and might play an inhibitory effect on glioma.
doi:10.1093/neuonc/not039
PMCID: PMC3714150  PMID: 23576602
brain-derived neurotrophic factor; glioma; human; proBDNF; p75NTR; sortilin
23.  Protective effect of indomethacin in renal ischemia-reperfusion injury in mice*  
Objective: To evaluate the renoprotection effects of non-steroidal anti-inflammatory drugs (NSAIDs) in renal ischemia-reperfusion injury (IRI) and the cyclooxygenase (COX)-1/2 blockade association by indomethacin (IMT) in the mice model. Methods: After the left renal pedicle of mice was clamped, IMT was administrated by intraperitoneal injection with four doses: 1, 3, 5, and 7 mg/kg. Blood and kidney samples were collected 24 h after IRI. The renal functions were assayed by the cytokines and serum creatinine (SCr) using enzyme-linked immunosorbent assay (ELISA) kits. Kidney samples were analyzed by hematoxylin and eosin (H&E) and immunohistochemistry stainings. Results: The mice administered with 5 mg/kg IMT had a marked reduction in SCr and significantly less tubular damage. The tumor necrosis factor α (TNF-α) activity in renal homogenates and interleukin 6 (IL-6) activity in serum had a marked reduction at doses of 5 and 7 mg/kg IMT. The administration of 3 and 5 mg/kg IMT had a marked reduction in the ratio of thromboxane B2 to 6-keto-prostaglandin F1α. COX-1 and COX-2 stainings were weaker in 5 mg/kg IMT groups than that in the other groups. Conclusions: There was a dose response in the IMT function of renal IRI in mice, and IMT had a protective effect in a certain dose range. The effect of IMT on mice IRI was related to COX-1/2 blockades.
doi:10.1631/jzus.B1300196
PMCID: PMC4129094  PMID: 25091992
Non-steroidal anti-inflammatory drug (NSAID); Indomethacin (IMT); Ischemia-reperfusion injury (IRI); Dosage; Protective effect
24.  MiR-497 downregulation contributes to the malignancy of pancreatic cancer and associates with a poor prognosis 
Oncotarget  2014;5(16):6983-6993.
Chemoresistance is one of the causes of poor prognosis in pancreatic cancer patients. However, the mechanisms of resistance remain unclear. Here we screened miRNAs associated with drug resistance in pancreatic cancer, and identified a panel of miRNAs dysregulated in gemcitabine-resistance pancreatic cancer cells, including 13 downregulated miRNAs and 20 upregulated miRNAs. Further studies focusing on miR-497 demonstrated that miR-497 suppressed cells proliferation, decreased the percentage of S phase cells, re-sensitized cells to gemcitabine and erlotinib, and attenuated migration and invasion capacities. Furthermore, fibroblast growth factor 2 and fibroblast growth factor receptor 1 were confirmed as miR-497 targets. Overexpression of miR-497 inhibited tumor growth in vivo. Additionally, miR-497 expression was significantly downregulated in pancreatic cancer tissues compared with tumor-adjacent samples (P=0.000). Low expression of miR-497 was an independent adverse prognostic factor of pancreatic cancer (P=0.01, hazard ratio=2.762, 95% confidence interval: 1.159–6.579). Together these results indicate that miR-497 could be a new therapeutic target and prognostic marker of pancreatic cancer.
PMCID: PMC4196178  PMID: 25149530
pancreatic cancer; miRNA; chemoresistance; prognosis
25.  Moyamoya syndrome associated with Graves’ disease: a case series study 
Objective
The aim of this study was to describe the clinical and radiological findings of patients with moyamoya syndrome and Graves’ disease. Possible mechanisms predisposing these individuals to ischemic stroke are discussed.
Methods
We retrospectively analyzed 12 consecutive patients with both moyamoya syndrome and Graves’ disease. Moyamoya vasculopathy was diagnosed by digital subtract angiography or magnetic resonance angiography (MRA). The clinical characteristics, laboratory data, vascular radiological characteristics and outcome were reported.
Results
All patients were female and mean age was 33.33±12.65 years. Stenosis or occlusion of bilateral terminal internal carotid artery and/or proximal anterior/middle cerebral arteries was found in nine patients. Among them, three patients displayed asymmetrical stenosis. In addition, there were three patients with probable unilateral moamoya syndrome. Eleven patients presented with ischemic stroke and/or transient ischemic attack (TIA) and one with dizziness. Thyroid function tests demonstrated elevated thyroid hormone levels and suppressed thyroid stimulating hormone levels in all the patients with ischemic events. All patients received anti-thyroid therapy and two had recurrent ischemic attack after drug withdrawal.
Conclusions
Moyamoya syndrome associated Graves’ disease often presented with asymmetric stenosis or occlusion. We hypothesize cerebrovascular hemodynamic changes due to thyrotoxicosis contribute to the ischemic events.
doi:10.3978/j.issn.2305-5839.2014.08.03
PMCID: PMC4200642  PMID: 25333052
Moyamoya syndrome; Graves’ disease; thyrotoxicosis; treatment

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