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1.  Associations between the C3435T polymorphism of the ABCB1 gene and drug resistance in epilepsy: a meta-analysis 
Objective: A meta-analysis was performed to comprehensively evaluate the correlations between the C3435T polymorphism of ABCB1 (the ATP-binding cassette, subfamily B, member 1 transporter gene) and drug resistance in epilepsy. Methods: Inclusion and exclusion criteria and a strategy for searching original literature were developed and utilized to search Chinese and non-Chinese databases. Research reports discussing correlations between the ABCB1 C3435T polymorphism and patient responses to anti-epileptic drug (AED) therapy were collected. Comparisons and comprehensive quantitative analyses were conducted using an allele model (C vs. T), and a genotype model (CC vs. CT+TT). In addition, subgroup analyses were performed that divided the included studies according to the race of the study subjects (Asian or Caucasian), based on the geographical region in which each study was conducted. Results: The meta-analysis included a total of 23 publications that examined a total of 3,912 drug-resistant epileptic patients and 4,419 epileptic patients for whom drug treatment was effective. The included studies did not exhibit publication bias. Statistical analyses revealed that the C3435T polymorphism was not significantly correlated with drug resistance in epilepsy. The random-effects model comparing the C and T alleles produced an odds ratio (OR) of 1.10 with a 95% confidence interval (CI) of 0.98-1.25 and P = 0.46. Subgroup analyses suggested that in Caucasian population there are significant differences between resistance group (RN) and control group (N) in both allele model (C vsT: OR = 1.13; 95% CI: 1.03-1.25) and genotype model (CC vsCT+TT: OR = 1.27; 95% CI: 1.08-1.50). Conclusion: The ABCB1 C3435T polymorphism is associated with drug resistance in epilepsy in Caucasian population.
PMCID: PMC4276158  PMID: 25550900
Epilepsy; gene polymorphism; ATP-binding cassette; subfamily B; member 1 transporter gene (ABCB1); drug resistance; meta-analysis
2.  Kakuna taibaiensis sp. n. and a newly recorded species of Dicranotropis (Hemiptera, Fulgoroidea, Delphacidae) from China 
ZooKeys  2014;119-130.
One new species of the delphacid genus Kakuna Matsumura, Kakuna taibaiensis Ren & Qin, sp. n. is described from Mt. Taibai in Shaanxi Province, China. Dicranotropis montana (Horvath, 1897) is reported for the first time from China. Habitus photos and illustrations of male genitalia of the two species are given.
doi:10.3897/zookeys.444.7810
PMCID: PMC4205735  PMID: 25349503
Auchenorrhyncha; planthoppers; Fulgoromorpha; taxonomy; distribution
3.  Inhibition of Aurora-B suppresses HepG2 cell invasion and migration via the PI3K/Akt/NF-κB signaling pathway in vitro 
In the present study, the effect of Aurora-B inhibition on HepG2 cell invasion and migration in vitro was investigated. A recombinant plasmid targeting the Aurora-B gene (MiR-Aurora-B) was used to inhibit Aurora-B expression in HepG2 cells. Cell migration and invasion were investigated using Transwell migration and invasion assays. The results demonstrated that cell invasion and migration were suppressed by inhibiting Aurora-B. In addition, the effect of Aurora-B inhibition on the activity of the phosphoinositide 3-kinase (PI3K)/Akt/nuclear factor (NF)-κB signaling pathway was investigated by analyzing the protein expression levels of phosphorylated (p)-Akt, Akt, NF-κB p65, matrix metalloproteinase (MMP)-2 and MMP-9 using western blot analysis. The results demonstrated that the protein expression levels of p-Akt, NF-κB p65, MMP-2 and MMP-9 were reduced significantly by inhibiting Aurora-B. Therefore, inhibition of Aurora-B was shown to suppress hepatocellular carcinoma cell migration and invasion by decreasing the activity of the PI3K/Akt/NF-κB signaling pathway in vitro.
doi:10.3892/etm.2014.1844
PMCID: PMC4113576  PMID: 25120638
Aurora-B; HepG2; invasion; migration; phosphoinositide 3-kinase/Akt/nuclear factor-κB signaling pathway
4.  Plasma Sphingolipids as Potential Indicators of Hepatic Necroinflammation in Patients with Chronic Hepatitis C and Normal Alanine Aminotransferase Level 
PLoS ONE  2014;9(4):e95095.
Accurate estimation of hepatic necroinflammation caused by chronic hepatitis C (CHC) is crucial for prediction of prognosis and design of therapeutic strategy, which is particularly true for CHC patients with normal alanine aminotransferase (ALT) level. Recent studies have shown that sphingolipids have a close relationship with hepatitis C virus infection. The present study aimed to identify plasma sphingolipids related to hepatic necroinflammation. We included 120 treatment-naïve CHC patients and 64/120 had normal ALT levels (<40 U/L). CHC patients who underwent liver biopsies were subjected to Scheuer scoring analysis for scope of hepatic inflammation. Plasma sphingolipids were detected by high-performance liquid chromatography tandem mass spectrometry. Our results showed 44 plasma sphingolipids were detected altogether. Of all detected sphingolipids, hexosylceramide (HexCer) (d18∶1/22∶0) and HexCer (d18∶1/24∶0) showed a significant difference among G0/G1, G2, and G3/G4 (P<0.05). For identifying hepatic necroinflammation (G≥2), after adjusting other factors, the odds ratio (OR) of HexCer (d18∶1/22∶0) reached 1.01 (95% confidence interval [CI]: 1.00–1.02). Furthermore, the area under the curve (AUC) of HexCer (d18∶1/22∶0) was 0.7 (P = 0.01) and approached that of ALT (AUC = 0.78). However, in CHC patients with normal ALT, HexCer (d18∶1/22∶0) was an independent factor (OR: 1.02, 95% CI: 1.01–1.03) to identify the hepatic necroinflammation (G≥2). HexCer (d18∶1/22∶0) not only showed the largest AUC (0.78, P = 0.001), but also exhibited the highest specificity of all indicators. These results indicate that plasma HexCer (d18∶1/22∶0) is a potential indicator to distinguish hepatic necroinflammation in CHC patients. For CHC with normal ALT, the ability of HexCer (d18∶1/22∶0) to distinguish hepatic necroinflammation might be superior to conventional serum indicators.
doi:10.1371/journal.pone.0095095
PMCID: PMC3988168  PMID: 24736528
5.  Prognostic value of M30/M65 for outcome of hepatitis B virus-related acute-on-chronic liver failure 
AIM: To determine the prognostic value of circulating indicators of cell death in acute-on-chronic liver failure (ACLF) patients with chronic hepatitis B virus (HBV) infection as the single etiology.
METHODS: Full length and caspase cleaved cytokeratin 18 (detected as M65 and M30 antigens) represent circulating indicators of necrosis and apoptosis. M65 and M30 were identified by enzyme-linked immunosorbent assay in 169 subjects including healthy controls (n = 33), patients with chronic hepatitis B (CHB, n = 55) and patients with ACLF (n = 81). According to the 3-mo survival period, ACLF patients were defined as having spontaneous recovery (n = 33) and non-spontaneous recovery which included deceased patients and those who required liver transplantation (n = 48).
RESULTS: Both biomarker levels significantly increased gradually as liver disease progressed (for M65: P < 0.001 for all; for M30: control vs CHB, P = 0.072; others: P < 0.001 for all). In contrast, the M30/M65 ratio was significantly higher in controls compared with CHB patients (P = 0.010) or ACLF patients (P < 0.001). In addition, the area under receiver operating characteristic curve (AUC) analysis demonstrated that both biomarkers had diagnostic value (AUC ≥ 0.80) in identifying ACLF from CHB patients. Interestingly, it is worth noting that the M30/M65 ratio was significantly different between spontaneous and non-spontaneous recovery in ACLF patients (P = 0.032). The prognostic value of the M30/M65 ratio was compared with the Model for End-Stage Liver Disease (MELD) and Child-Pugh scores at the 3-mo survival period, the AUC of the M30/M65 ratio was 0.66 with a sensitivity of 52.9% and the highest specificity of 92.6% (MELD:AUC = 0.71; sensitivity, 79.4%; specificity, 63.0%; Child-Pugh: AUC = 0.77; sensitivity, 61.8%; specificity, 88.9%).
CONCLUSION: M65 and M30 are strongly associated with liver disease severity. The M30/M65 ratio may be a potential prognostic marker for spontaneous recovery in patients with HBV-related ACLF.
doi:10.3748/wjg.v20.i9.2403
PMCID: PMC3942845  PMID: 24605039
Acute-on-chronic liver failure; Chronic hepatitis B virus infection; Liver disease stage; Liver disease severity; Serum M65 level; Serum M30 level; Prognostic value
6.  Oxidative stress promotes d-GalN/LPS-induced acute hepatotoxicity by increasing glycogen synthase kinase 3β activity 
Inflammation Research  2014;63(6):485-494.
Objective
Our previous studies have demonstrated that glycogen synthase kinase 3β (GSK3β) activity is increased in the progression of acute liver failure (ALF), which aggravates liver injury, while its regulatory mechanism remains elusive. This study is designated to address whether oxidative stress activates GSK3β to promote ALF.
Methods
In a murine model induced by d-galactosamine (d-GalN) (700 mg/kg) and LPS (10 μg/kg), N-acetylcysteine (300 mg/kg) or SB216763 (25 mg/kg) was used to inhibit oxidative stress or GSK3β activity, respectively. Serum alanine aminotransferase and aspartate aminotransferase levels were assessed. The parameters of oxidative stress were evaluated in liver tissue. Whether GSK3β inhibition protects hepatocytes from oxidative stress-induced cell apoptosis was investigated in vitro. Moreover, the activity of GSK3β was measured in the liver of chronic hepatitis B (CHB) patients and ALF patients.
Results
In vivo, N-acetylcysteine ameliorated the d-GalN/LPS-induced hepatotoxicity and reduced GSK3β activity; GSK3β inhibition increased hepatic superoxide dismutase activity and the glutathione content, decreased malondialdehyde production in the liver tissues; while GSK3β inhibition suppressed the JNK activation in the liver and decreased cytochrome c release from mitochondria. In vitro, GSK3β inhibition lessened hepatocytes apoptosis induced by H2O2 or Antimycin A, as demonstrated by decreased LDH activity, and reduced cleavage of caspase-3 expression. Furthermore, GSK3β activity in the CHB patients was increased in the phase of ALF.
Conclusions
Results indicate that GSK3β activation contributes to liver injury by participating in oxidative stress response in ALF and is, therefore, a potential therapeutic target for ALF.
doi:10.1007/s00011-014-0720-x
PMCID: PMC4018480  PMID: 24531650
GSK3β; SB216763; Acute liver failure; Oxidative stress; N-acetylcysteine
7.  Clinical implications of tenascin-C and OX40 ligand in patients with acute coronary syndrome 
Biomedical Reports  2013;2(1):132-136.
Acute coronary syndrome (ACS) typically occurs when coronary artery disease results in the obstruction of the coronary arteries. Tenascin-C (TNC) and OX40 ligand (OX40L) were shown to be involved in the pathogenesis of atherosclerosis. In this study, 50 healthy controls and 170 patients, including 50 patients with stable angina (SA), 70 with unstable angina and 50 with acute myocardial infarction, were evaluated to assess serum TNC and plasma OX40L levels. The serum TNC levels were measured by a quantitative automated particle-enhanced immunonephelometric assay. ELISA was used to determine the expression levels of OX40L. All the coronary stenoses with a ≥30% diameter reduction were assessed by angiographic coronary stenosis morphology. The patients with ACS exhibited a significant increase in TNC expression levels (39.39±19.80 ng/ml) compared to the levels in the control and SA groups (28.65±12.32 ng/ml, P<0.01 and 31.22±18.92 ng/ml, P<0.05, respectively). The levels of OX40L were also found to be higher in patients with ACS (38.59±15.76 ng/ml) compared to those in the control and SA groups (19.42±11.19 ng/ml, P<0.001 and 21.52±10.30 ng/ml, P<0.001, respectively). The TNC and OX40L levels were positively correlated with each other (r1=0.68; P<0.001) and with fibrinogen levels (r3=0.76 and r4=0.45, respectively; P<0.001). A positive correlation was also observed between the expression of TNC and OX40L and complex coronary stenosis (r5=0.69 and r6=0.55, respectively; P<0.001). We concluded that TNC and OX40L may act synergistically in coronary plaque formation and may be also be involved in the pathogenesis of coronary lesions. Patients with ACS exhibited increased TNC and OX40L expression levels, which may have created a prothrombotic milieu, aggravating the development of atherosclerosis and the instability of atherosclerotic plaques. Therefore, the expression of TNC and OX40L may be a valuable marker for predicting the severity of ACS.
doi:10.3892/br.2013.195
PMCID: PMC3917010  PMID: 24649084
tenascin-C; OX40 ligand; acute coronary syndrome
8.  Endoplasmic Reticulum Stress Modulates Liver Inflammatory Immune Response in the Pathogenesis of Liver Ischemia and Reperfusion Injury 
Transplantation  2012;94(3):211-217.
Background
Although endoplasmic reticulum (ER) stress has been implicated in the pathophysiology of organ ischemia and reperfusion injury (IRI), the underlying mechanisms have yet to be fully elucidated. In particular, as tissue pro-inflammatory immune response is the key mediator of local IRI, how ER stress impacts liver immune cell activation cascade remains to be determined.
Methods
In vitro, ER stress in macrophages and hepatocytes were induced by pharmacological agents. Macrophage TLR4 and hepatocyte TNF-α responses were studied. In vivo, the induction of ER stress by IR and the impact of ER stress amelioration by a small molecule chaperon 4-phenyl butyric acid (PBA) on liver immune response were studied in a murine partial liver warm ischemia model.
Results
ER stressed macrophages generated a significantly enhanced pro-inflammatory immune response against TLR4 stimulation; while ER stressed hepatocyte became more susceptible to TNF-α induced cell death. IR resulted in upregulations of sXBP-1 and ATF6 levels in affected livers. Mice pre-treated with PBA were protected from liver IRI, in parallel with diminished local pro-inflammatory gene induction program.
Conclusions
Our study documents a potential immune regulatory role of ER stress in the mechanism of liver IRI, and provides a rationale for targeting stress response as a new therapeutic means to ameliorate tissue inflammation in organ transplant recipients.
doi:10.1097/TP.0b013e318259d38e
PMCID: PMC3414672  PMID: 22790388
ER stress; Liver ischemia; TLR4; Inflammation
9.  The ion implantation-induced properties of one-dimensional nanomaterials 
Nanoscale Research Letters  2013;8(1):175.
Nowadays, ion implantation is an extensively used technique for material modification. Using this method, we can tailor the properties of target materials, including morphological, mechanical, electronic, and optical properties. All of these modifications impel nanomaterials to be a more useful application to fabricate more high-performance nanomaterial-based devices. Ion implantation is an accurate and controlled doping method for one-dimensional nanomaterials. In this article, we review recent research on ion implantation-induced effects in one-dimensional nanostructure, such as nanowires, nanotubes, and nanobelts. In addition, the optical property of single cadmium sulfide nanobelt implanted by N+ ions has been researched.
doi:10.1186/1556-276X-8-175
PMCID: PMC3668221  PMID: 23594476
Nanomaterials; Ion implantation; Doping
10.  The Brassica napus Calcineurin B-Like 1/CBL-interacting protein kinase 6 (CBL1/CIPK6) component is involved in the plant response to abiotic stress and ABA signalling 
Journal of Experimental Botany  2012;63(17):6211-6222.
A CBL-interacting protein kinase (CIPK) gene, BnCIPK6, was isolated in Brassica napus. Through yeast two-hybrid screening, 27 interaction partners (including BnCBL1) of BnCIPK6 were identified in Brassica napus. Interaction of BnCIPK6 and BnCBL1 was further confirmed by BiFC (bimolecular fluorescence complementation) in plant cells. Expressions of BnCIPK6 and BnCBL1 were significantly up-regulated by salt and osmotic stresses, phosphorous starvation, and abscisic acid (ABA). Furthermore, BnCIPK6 promoter activity was intensively induced in cotyledons and roots under NaCl, mannitol, and ABA treatments. Transgenic Arabidopsis plants with over-expressing BnCIPK6, its activated form BnCIPK6M, and BnCBL1 enhanced high salinity and low phosphate tolerance, suggesting that the functional interaction of BnCBL1 and BnCIPK6 may be important for the high salinity and phosphorous deficiency signalling pathways. In addition, activation of BnCIPK6 confers Arabidopsis plants hypersensitive to ABA. On the other hand, over-expression of BnCIPK6 in Arabidopsis cipk6 mutant completely rescued the low-phosphate-sensitive and ABA-insensitive phenotypes of this mutant, further suggesting that BnCIPK6 is involved in the plant response to high-salinity, phosphorous deficiency, and ABA signalling.
doi:10.1093/jxb/ers273
PMCID: PMC3481211  PMID: 23105131
Abiotic stress tolerance; abscisic acid (ABA); Brassica napus; BnCBL1; BnCIPK6; interaction; regulation of gene expression
11.  Inhibition of Glycogen Synthase Kinase 3β Ameliorates D-GalN/LPS-Induced Liver Injury by Reducing Endoplasmic Reticulum Stress-Triggered Apoptosis 
PLoS ONE  2012;7(9):e45202.
Background
Glycogen synthase kinase 3β(GSK3β) is a ubiquitous serine-threonine protein kinase that participates in numerous cellular processes and disease pathophysiology. We aimed to determine therapeutic potential of GSK3β inhibition and its mechanism in a well-characterized model of lipopolysaccharide (LPS)-induced model of acute liver failure (ALF).
Methodology
In a murine ALF model induced by D-GalN(700 mg/kg)/LPS(10 µg/kg), we analyzed GSK3β mechanisms using a specific chemical inhibitor, SB216763, and detected the role of endoplasmic reticulum stress (ERS). Mice were administered SB216763 at 2 h before or after D-GalN/LPS injection, respectively, and then sacrificed 6 h after D-GalN/LPS treatment to evaluate its prophylactic and therapeutic function. The lethality rate, liver damage, ERS, cytokine expression, MAP kinase, hepatocyte apoptosis and expression of TLR 4 were evaluated, respectively. Whether the inhibition of GSK3β activation protected hepatocyte from ERS-induced apoptosis was investigated in vitro.
Principal Findings
GSK3β became quickly activated (dephosphorylated) upon D-GalN/LPS exposure. Administration of SB216763 not only ameliorated liver injury, as evidenced by reduced transaminase levels, and well-preserved liver architecture, but also decreased lethality. Moreover, GSK3β inhibition resulted in down-regulation of pro-apoptotic proteins C/EBP–homologous protein(CHOP) and caspase-12, which are related to ERS. To further demonstrate the role of ERS, we found that GSK3β inhibition protected hepatocyte from ERS-induced cell death. GSK3β inhibition down-regulated the MAPK pathways, reduced expression of inflammatory cytokines and decreased expression of TLR4.
Conclusions
Our findings demonstrate the key function of GSK3β signaling in the pathophysiology of ALF, especially in regulating the ERS, and provide a rationale for targeting GSK3β as a potential therapeutic strategy to ameliorate ALF.
doi:10.1371/journal.pone.0045202
PMCID: PMC3461002  PMID: 23028846
12.  Brassica napus PHR1 Gene Encoding a MYB-Like Protein Functions in Response to Phosphate Starvation 
PLoS ONE  2012;7(8):e44005.
Phosphorus (P) is one of the essential nutrient elements for plant development. In this work, BnPHR1 encoding a MYB transcription activator was isolated from Brassica napus. The characterization of nuclear localization and transcription activation ability suggest BnPHR1 is a transcriptional activator. The tissue expression and histochemical assay showed that BnPHR1 was predominantly expressed in roots and modulated by exogenous Pi in transcriptional level in roots under Pi deficiency conditions. Furthermore, overexpression of BnPHR1 in both Arabidopsis and B. napus remarkably enhanced the expression of the Pi-starvation-induced genes including ATPT2 and BnPT2 encoding the high-affinity Pi transporter. Additionally, BnPHR1 can in vivo bind the promoter sequence of ATPT2 and BnPT2 in both Arabidopsis and B. napus. Possibly, due to the activation of ATPT2 and BnPT2, or even more high-affinity Pi transporters, the excessive Pi was accumulated in transgenic plants, resulting in the crucially Pi toxicity to cells and subsequently retarding plant growth. Given the data together, BnPHR1, as crucial regulator, is regulated by exogenous Pi and directly activates those genes, which promote the uptake and homeostasis of Pi for plant growth.
doi:10.1371/journal.pone.0044005
PMCID: PMC3430610  PMID: 22952851
13.  The Inhibition of Glycogen Synthase Kinase 3 beta Ameliorates Liver Ischemia Reperfusion Injury via an IL-10-mediated Immune Regulatory Mechanism 
Hepatology (Baltimore, Md.)  2011;54(2):687-696.
The ubiquitous serine/threnine kinase glycogen synthase kinase 3β (Gsk3β) differentially regulates macrophage TLR-triggered pro- and anti-inflammatory cytokine programs. This study was designed to determine in vivo role and therapeutic potential of Gsk3β modulation in tissue inflammation and injury in a murine model of liver partial warm ischemia/reperfusion (IRI). As a constitutively activated liver kinase, Gsk3β became quickly inactivated (phosphorylated) following IR. The active Gsk3β, however, was essential for the development of IRI pathology, as administration of its specific inhibitor SB216763, ameliorated the hepatocellular damage, evidenced by reduced sALT levels and well-preserved liver architecture, compared with controls. The liver protective effect of Gsk3β inhibition was dependent on an immune regulatory mechanism, rather than direct cytoprotection via mitochondria permeability transition pores (MPTP). Indeed: (a) co-administration of SB216763 and atractyloside (MPTP opener) failed to abrogate local cytoprotective Gsk3β inhibition effect; (b) SB216763 selectively inhibited IR-triggered liver pro-inflammatory, but spared IL-10, gene induction program; and (c) IL-10 neutralization restored liver inflammation and IRI in SB216763-treated mice. Gsk3β inactivation by IR was a self-regulatory mechanism in liver homeostasis, critically dependent on phosphoinositide 3 (PI3)-kinase activation, as administration of PI3 kinase inhibitor, wortmannin, reduced Gsk3 phosphorylation and augmented liver damage. In vitro, IL-10 was critical for the suppression of pro-inflammatory gene programs by Gsk3 inhibition in bone marrow-derived macrophages in response to TLR4 stimulation. Our novel findings document the key immune regulatory function of Gsk3β signaling in the pathophysiology of liver IRI, and provide the rationale to target Gsk3β as a refined therapeutic strategy to ameliorate liver IRI.
doi:10.1002/hep.24419
PMCID: PMC3145016  PMID: 21567437
14.  Enhanced photocatalysis by coupling of anatase TiO2 film to triangular Ag nanoparticle island 
Nanoscale Research Letters  2012;7(1):239.
In order to overcome the low utilization ratio of solar light and high electron-hole pair recombination rate of TiO2, the triangular Ag nanoparticle island is covered on the surface of the TiO2 thin film. Enhancement of the photocatalytic activity of the Ag/TiO2 nanocomposite system is observed. The increase of electron-hole pair generation is caused by the enhanced near-field amplitudes of localized surface plasmon of the Ag nanoparticles. The efficiently suppressed recombination of electron-hole pair caused by the metal-semiconductor contact can also enhance the photocatalytic activity of the TiO2 film.
doi:10.1186/1556-276X-7-239
PMCID: PMC3432611  PMID: 22548875
plasmon; photocatalysis; nanospheres lithography; Ag nanoparticle island
15.  Expression and subcellular localization of menin in human cancer cells 
The aim of this study was to elucidate the expression and localization of menin, a protein encoded by the multiple endocrine neoplasia type I (MEN1) gene, in 13 human cancer cell lines. Reverse transcription-polymerase chain reaction (RT-PCR) was used to determine the expression of the menin gene. The localization of the menin protein was detected by immunofluorescence microscopy. Western blotting was used to determine the quantity of menin in the nucleus, cytosol and membrane of the cells. RT-PCR revealed that menin was expressed in all the cell lines examined in this study. Immunofluorescence microscopy revealed that menin was located primarily in the nucleus. In the GES-1 (transformed human gastric epithelium), MCF-7 (breast cancer), SGH44 (brain glioma) and HeLa (cervical cancer) cell lines, menin was also found to be localized to the membrane, cytosol and nucleus. Moreover, in SGH44 cells more menin was located in the cytosol than the nucleus. Similar findings were obtained by western blotting. In the GES-1 and MKN-28 cells undergoing octreotide treatment, cytoplasmic menin was significantly increased compared with the control groups. Therefore, we suggest that menin is expressed in a number of human cancer cell lines and that the cytosolic distribution increases when the cells undergo octreotide treatment, indicating a new role for menin.
doi:10.3892/etm.2012.530
PMCID: PMC3438647  PMID: 22970022
menin; cancer cells; subcellular localization; nucleus
16.  Manipulation of the Complement System for Benefit in Sepsis 
There is evidence in sepsis, both in rodents and in humans, that activation of the complement system results in excessive production of C5a, which triggers a series of events leading to septic shock, multiorgan failure, and lethality. In rodents following cecal ligation and puncture (CLP), which induces polymicrobial sepsis, in vivo blockade of C5a using neutralizing antibodies dramatically improved survival, reduced apoptosis of lymphoid cells, and attenuated the ensuing coagulopathy. Based on these data, it seems reasonable to consider therapeutic blockade of C5a in humans entering into sepsis and septic shock. Strategies for the development of such an antibody for use in humans are presented.
doi:10.1155/2012/427607
PMCID: PMC3303540  PMID: 22482043
17.  Osseous metastasis of cutaneous squamous cell carcinoma treated successfully with oxaliplatin, tegafur and leucovorin combination chemotherapy: a case report 
Bone metastasis from cutaneous squamous cell carcinoma (SCC) is rare. We report a case of cutaneous SCC which was diagnosed by the presence of bone metastasis and treated with combination chemotherapy. A 53 year male had tissue contusion and persistent ulcer in the multiple regions of body for about 30 years and treat with Chinese Herbal Drugs in several hospitals, however, did not thorough cure. He was referred to our hospital for a dermatological examination in March 2009. Excisional biopsy and positron emission tomography-computed tomography (PET-CT) scan showed an invasive cutaneous SCC concomitant bone metastasis. Surgical treatment is limited, because of multiple cancerous ulcer and metastatic spreading. Therefore, we proceed to treat with oxaliplatin, tegafur and leucovorin (LV) combination chemotherapy and other adjuvant therapy. About 5 months following chemotherapy, the general situation of the patient was improved. Further cycle of chemotherapy resulted in complete disappearance of the tumor masses (confirmed by PET-CT). So far, there was no evidence of local recurrence or distant metastasis. This report indicates that the combination chemotherapy of oxaliplatin, tegafur and LV seems to have a considerable therapeutic effect for cutaneous SCC concomitant malignant bone metastasis.
PMCID: PMC3272691  PMID: 22328953
Cutaneous squamous cell carcinoma; bone metastasis; chemotherapy; PET-CT
18.  Polymorphisms of mismatch repair gene hMLH1 and hMSH2 and risk of gastric cancer in a Chinese population 
Oncology Letters  2011;3(3):591-598.
The purpose of this study was to determine the genotype and allele frequencies of hMLH1 (-93G>A and I219V) and hMSH2 (-118T>C and IVS12-6T>C) polymorphisms in patients with gastric carcinoma and normal controls, and to evaluate the association between these polymorphisms and the risk of gastric cancer in a hospital-based Chinese population. Genomic DNA was extracted from peripheral blood lymphocytes. A TaqMan assay was used to determine the genotype and allele frequencies of hMLH1 and hMSH2 polymorphisms in data obtained from 554 gastric cancer cases and 592 controls. Unconditional logistic regression was used to assess the association between the four single nucleotide polymorphisms (SNPs) and gastric carcinoma risk. No evidence of an association among any of the four polymorphisms and the risk of gastric cancer was observed. However, when gastric cancer patients were further stratified by age, gender, smoking status, alcohol use and clinicopathological characteristics, and compared with the control populations, the combined variant genotype hMSH2 -118T>C (TC+CC) was not only associated with an increased risk of gastric cancer in subgroups of younger subjects [ages ≤63years; adjusted odds ratio (OR)=1.51, 95% confidence interval (CI), 1.05–2.16], but also with diffuse tumors (adjusted OR=1.41, 95% CI, 1.01–1.96). These data indicate that the polymorphisms of -93G>A, I219V and IVS12-6T>C are not associated with the risk of gastric cancer. However, hMSH2-118T>C combined with variant genotypes (TC+CC) may confer a potential risk of gastric cancer in the Chinese population.
doi:10.3892/ol.2011.517
PMCID: PMC3362438  PMID: 22740958
gastric cancer; polymorphism; hMLH1; hMSH2
19.  Facile method to synthesize magnetic iron oxides/TiO2 hybrid nanoparticles and their photodegradation application of methylene blue 
Nanoscale Research Letters  2011;6(1):533.
Many methods have been reported to improving the photocatalytic efficiency of organic pollutant and their reliable applications. In this work, we propose a facile pathway to prepare three different types of magnetic iron oxides/TiO2 hybrid nanoparticles (NPs) by seed-mediated method. The hybrid NPs are composed of spindle, hollow, and ultrafine iron oxide NPs as seeds and 3-aminopropyltriethyloxysilane as linker between the magnetic cores and TiO2 layers, respectively. The composite structure and the presence of the iron oxide and titania phase have been confirmed by transmission electron microscopy, X-ray diffraction, and X-ray photoelectron spectra. The hybrid NPs show good magnetic response, which can get together under an external applied magnetic field and hence they should become promising magnetic recovery catalysts (MRCs). Photocatalytic ability examination of the magnetic hybrid NPs was carried out in methylene blue (MB) solutions illuminated under Hg light in a photochemical reactor. About 50% to 60% of MB was decomposed in 90 min in the presence of magnetic hybrid NPs. The synthesized magnetic hybrid NPs display high photocatalytic efficiency and will find recoverable potential applications in cleaning polluted water with the help of magnetic separation.
doi:10.1186/1556-276X-6-533
PMCID: PMC3212071  PMID: 21961891
magnetic iron oxide nanoparticles; TiO2; hybrid structure; photocatalyst; methylene blue
20.  Synthesis of L-Kedarosamine in Protected Form and Its Efficient Incorporation into an Advanced Intermediate to Kedarcidin Chromophore 
Organic letters  2007;9(10):1923-1925.
An efficient route to the complex L-kedarosamine α-glycosidic ether 2, a synthetic precursor to kedarcidin chromophore, is described. Central to the route, which is suitable for the preparation of multi-gram amounts of material, is a short synthetic sequence from D-threonine to protected L-kedarosamine derivatives and methodology for their α-selective coupling with appropriate hydroxyl acceptors.
doi:10.1021/ol070450x
PMCID: PMC3176327  PMID: 17439225
21.  Kedarcidin Chromophore–Synthesis of Its Proposed Structure and Evidence for a Stereochemical Revision 
A convergent, enantioselective synthesis of the proposed structure of kedarcidin chromophore (1) is described. The route is 24 steps in the longest linear sequence (beginning with the commercial reagent 2,3-O-isopropylidene-d-erythronolactone) with an average yield of 75% per step (overall yield: 0.1%). Our 1H NMR data for 1 do not coincide with the data reported for kedarcidin chromophore. We have re-analyzed the original data and here propose a stereochemical revision at position C10, the site of attachment of the l-mycarose carbohydrate residue to the chromophore core (structure 2).
doi:10.1021/ja071205b
PMCID: PMC3174495  PMID: 17417855
22.  Runx3 expression in lymph nodes with metastasis is associated with the outcome of gastric cancer patients 
Oncology Letters  2011;2(6):1275-1279.
Accumulating evidence shows that runt-related transcription factor 3 (Runx3) is a putative tumor suppressor in various types of cancer, the lower levels of which are associated with a less favorable cancer outcome. However, these studies were restricted to primary cancer lesions. Lymph node metastasis (LNM) is a significant factor in determining the prognosis of patients with gastric cancer and is a frequent target of chemotherapy. In the present study, we investigated the expression of Runx3 in the lymph nodes (LNs) of stomach carcinoma and the association of Runx3 expression with the prognosis of patients. The expression of Runx3 in LNs with and without metastasis was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. The positive rate of Runx3 mRNA in LNM specimens was significantly lower (28.4%, 21 out of 74) compared to that of the non-metastatic samples (33.3%, 9 out of 27, P<0.05). Similar findings were obtained by Western blotting. Univariate analysis revealed that the loss of Runx3 expression in LNs was not only associated with poor clinicopathological factors, such as LNM, distant organ metastasis, later clinicopathological stages and deep infiltration, but also with a lower 5-year survival rate and poorer prognosis. These results strongly suggest a potential diagnostic value of Runx3 expression in LNs and multiple pathways contributing to the outcome of patients with gastric cancer.
doi:10.3892/ol.2011.381
PMCID: PMC3406507  PMID: 22848301
stomach neoplasms; lymph node metastasis; Runx3; prognosis
23.  Analysis of 19-nortestosterone residue in animal tissues by ion-trap gas chromatography-tandem mass spectrometry*  
A rapid sample treatment procedure for the gas chromatography-tandem mass spectrometry (GC-MS) determination of 19-nortestosterone (19-NT) in animal tissues has been developed. In our optimized procedures, enzymatic hydrolysis with β-glucuronidase from Escherichia coli was performed in an acetate buffer (pH 5.2, 0.2 mol/L). Next, the homogenate was mixed with methanol and heated at 60 °C for 15 min, then placed in an ice-bath at −18 °C for 2 h. After liquid-liquid extraction with n-hexane, the analytes were subjected to a normal-phase solid phase extraction (SPE) C18 cartridge for clean-up. The dried organic extracts were derivatized with heptafluorobutyric anhydride (HFBA), and then the products were injected into GC-MS. Using electron impact mass spectrometry (EI-MS) with positive chemical ionization (PCI), four diagnostic ions (m/z 666, 453, 318, and 306) were determined. A standard calibration curve over the concentration range of 1–20 ng/g was reached, with Y=467 084X−68 354 (R 2=0.999 7) for 19-NT, and the detection limit was 0.3 ng. When applied to spiked samples collected from bovine and ovine, the recoveries ranged from 63% to 101% with relative standard deviation (RSD) between 2.7% and 8.9%. The procedure is a highly efficient, sensitive, and more economical method which offers considerable potential to resolve cases of suspected nandrolone doping in husbandry animals.
doi:10.1631/jzus.B1000301
PMCID: PMC3109148  PMID: 21634039
19-Nortestosterone (19-NT); Gas chromatography-tandem mass spectrometry (GC-MS); Animal tissues
24.  Solar light-driven photocatalytic hydrogen evolution over ZnIn2S4 loaded with transition-metal sulfides 
Nanoscale Research Letters  2011;6(1):290.
A series of Pt-loaded MS/ZnIn2S4 (MS = transition-metal sulfide: Ag2S, SnS, CoS, CuS, NiS, and MnS) photocatalysts was investigated to show various photocatalytic activities depending on different transition-metal sulfides. Thereinto, CoS, NiS, or MnS-loading lowered down the photocatalytic activity of ZnIn2S4, while Ag2S, SnS, or CuS loading enhanced the photocatalytic activity. After loading 1.0 wt.% CuS together with 1.0 wt.% Pt on ZnIn2S4, the activity for H2 evolution was increased by up to 1.6 times, compared to the ZnIn2S4 only loaded with 1.0 wt.% Pt. Here, transition-metal sulfides such as CuS, together with Pt, acted as the dual co-catalysts for the improved photocatalytic performance. This study indicated that the application of transition-metal sulfides as effective co-catalysts opened up a new way to design and prepare high-efficiency and low-cost photocatalysts for solar-hydrogen conversion.
doi:10.1186/1556-276X-6-290
PMCID: PMC3211356  PMID: 21711804
25.  Preparation and characterization of spindle-like Fe3O4 mesoporous nanoparticles 
Magnetic spindle-like Fe3O4 mesoporous nanoparticles with a length of 200 nm and diameter of 60 nm were successfully synthesized by reducing the spindle-like α-Fe2O3 NPs which were prepared by forced hydrolysis method. The obtained samples were characterized by transmission electron microscopy, powder X-ray diffraction, attenuated total reflection fourier transform infrared spectroscopy, field emission scanning electron microscopy, vibrating sample magnetometer, and nitrogen adsorption-desorption analysis techniques. The results show that α-Fe2O3 phase transformed into Fe3O4 phase after annealing in hydrogen atmosphere at 350°C. The as-prepared spindle-like Fe3O4 mesoporous NPs possess high Brunauer-Emmett-Teller (BET) surface area up to ca. 7.9 m2 g-1. In addition, the Fe3O4 NPs present higher saturation magnetization (85.2 emu g-1) and excellent magnetic response behaviors, which have great potential applications in magnetic separation technology.
doi:10.1186/1556-276X-6-89
PMCID: PMC3212238  PMID: 21711591

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