bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sprouty-4 Inhibits Transformed Cell Growth, Migration and Invasion, and Epithelial-Mesenchymal Transition, and Is Regulated by Wnt7A through PPARγ in Non–Small Cell Lung Cancer
Authors: Tennis Meredith A. , Van Scoyk Michelle M. , Freeman Scott V. , Vandervest Katherine M. , Nemenoff Raphael A. , Winn Robert A. 
Published: May 2010

Abstract
Sprouty proteins are potent receptor tyrosine kinase inhibitors that antagonize growth factor signaling and are involved in lung development. However, little is known about the regulation or targets of Sprouty-4 (Spry4) in lung cancer. Our study aimed to determine the role of Spry4 in non–small cell lung cancer (NSCLC). We found that Spry4 mRNA expression was decreased in NSCLC cell lines and in dysplastic lung cell lines compared with a nontransformed cell line, suggesting that Spry4 has tumor-suppressing activity. When Spry4 was stably transfected into H157 and H2122 NSCLC cell lines, decreased migration and invasion were observed. Matrix metalloproteinase-9 activity was decreased, and the expression of matrix metalloproteinase inhibitors TIMP1 and CD82 were increased. Stable expression of Spry4 led to reduced cell growth and reduced anchorage-independent growth in NSCLC cell lines, along with upregulation of tumor suppressors p53 and p21. Changes in epithelial and mesenchymal markers indicated that Spry4 expression induces a reversal of the epithelial to mesenchymal transition characteristic of tumor cells. Treatment of a nontransformed lung epithelial cell line with short hairpin RNA to Spry4 led to the decreased expression of epithelial markers and increased cell growth, supporting the concept of Spry4 acting as a tumor suppressor. We showed that the activity of the Spry4 promoter is increased by Wnt7A/Fzd9 signaling through peroxisome proliferator–activated receptor γ. These data present previously undescribed targets of Spry4 and suggest that Spry4 is a downstream target of Wnt7A/Fzd 9 signaling. Spry4 may have efficacy in the treatment of NSCLC. Mol Cancer Res; 8(6); 833–43. ©2010 AACR.
Combination Effects of Salvianolic Acid B with Low-Dose Celecoxib on Inhibition of Head and Neck Squamous Cell Carcinoma Growth In vitro and In vivo
Authors: Zhao Yuan , Hao Yubin , Ji Hongguang , Fang Yayin , Guo Yinhan , Sha Wei , Zhou Yanfei , Pang Xiaowu , Southerland William M. , Califano Joseph A. , Gu Xinbin 
Published: May 2010

Abstract
Head and neck squamous cell carcinoma (HNSCC) development is closely associated with inflammation. Cyclooxygenase-2 (COX-2) is an important mediator of inflammation. Therefore, celecoxib, a selective inhibitor of COX-2, was hailed as a promising chemopreventive agent for HNSCC. Dose-dependent cardiac toxicity limits long-term use of celecoxib, but it seems likely that this may be diminished by lowering its dose. We found that salvianolic acid B (Sal-B), isolated from Salvia miltiorrhiza Bge, can effectively suppress COX-2 expression and induce apoptosis in a variety of cancer cell lines. In this study, we report that combination of Sal-B with low-dose celecoxib results in a more pronounced anticancer effect in HNSCC than either agent alone. The combination effects were assessed in four HNSCC cell lines (JHU-06, JHU-011, JHU-013, and JHU-022) by evaluating cell viability, proliferation, and tumor xenograft growth. Cell viability and proliferation were significantly inhibited by both the combined and single-agent treatments. However, the combination treatment significantly enhanced anticancer efficacy in JHU-013 and JHU-022 cell lines compared with the single treatment regimens. A half-dose of daily Sal-B (40 mg/kg/d) and celecoxib (2.5 mg/kg/d) significantly inhibited JHU-013 xenograft growth relative to mice treated with a full dose of Sal-B or celecoxib alone. The combination was associated with profound inhibition of COX-2 and enhanced induction of apoptosis. Taken together, these results strongly suggest that combination of Sal-B, a multifunctional anticancer agent, with low-dose celecoxib holds potential as a new preventive strategy in targeting inflammatory-associated tumor development. Cancer Prev Res; 3(6); 787–96. ©2010 AACR.
Berries and Ellagic Acid Prevent Estrogen-Induced Mammary Tumorigenesis by Modulating Enzymes of Estrogen Metabolism
Authors: Aiyer Harini S. , Gupta Ramesh C. 
Published: May 2010

Abstract
To determine whether dietary berries and ellagic acid prevent 17β-estradiol (E2)–induced mammary tumors by altering estrogen metabolism, we randomized August-Copenhagen Irish rats (n = 6 per group) into five groups: sham implant + control diet, E2 implant + control diet (E2-CD), E2 + 2.5% black raspberry (E2-BRB), E2 + 2.5% blueberry (E2-BB), and E2 + 400 ppm ellagic acid (E2-EA). Animals were euthanized at early (6 wk), intermediate (18 wk), and late (24 wk) phases of E2 carcinogenesis, and the mammary tissue was analyzed for gene expression changes using quantitative real-time PCR. At 6 weeks, E2 treatment caused a 48-fold increase in cytochrome P450 1A1 (CYP1A1; P &lt; 0.0001), which was attenuated by both BRB and BB diets to 12- and 21-fold, respectively (P &lt; 0.001). E2 did not alter CYP1B1 levels, but both berry and EA diets significantly suppressed it by 11- and 3.5-fold, respectively, from baseline (P &lt; 0.05). There was a 5-fold increase in 17β-hydroxysteroid dehydrogenase 7 (17βHSD7), and this was moderately abrogated to ∼2-fold by all supplementation (P &lt; 0.05). At 18 weeks, CYP1A1 was elevated by 15-fold in E2-CD and only E2-BB reduced this increase to 7-fold (P &lt; 0.05). Catechol-O-methyltransferase expression was elevated 2-fold by E2 treatment (P &lt; 0.05), and all supplementation reversed this. At 24 weeks, CYP1A1 expression was less pronounced but still high (8-fold) in E2-treated rats. This increase was reduced to 3.2- and 4.6-fold by E2-BRB and E2-EA, respectively (P &lt; 0.05), but not by E2-BB. Supplementation did not alter the effect of E2 on steroid receptors. The diets also significantly suppressed mammary tumor incidence (10-30%), volume (41-67%), and multiplicity (38-51%; P &lt; 0.05). Berries may prevent mammary tumors by suppressing the levels of E2-metabolizing enzymes during the early phase of E2 carcinogenesis. Cancer Prev Res; 3(6); 727–37. ©2010 AACR.
Cytokine-activated NK cells inhibit PMN apoptosis and preserve their functional capacity
Authors: Bhatnagar Nupur , Hong Henoch S. , Krishnaswamy Jayendra K. , Haghikia Arash , Behrens Georg M. , Schmidt Reinhold E. , Jacobs Roland 
Published: May 2010

AbstractNatural killer (NK) cells and polymorphonuclear cells (PMNs) play a critical role in the first line of defense against microorganisms. Upon host infection, PMNs phagocytose invading pathogens with subsequent killing by oxidative or nonoxidative mechanisms. NK cells are known to have immunoregulatory effects on T cells, B cells, dendritic cells (DCs), and monocytes through secretion of various soluble products and cell-cell contact. However, their impact on PMN survival and function is not well known. We found that soluble factors derived from cytokine-activated NK cells delay PMN apoptosis and preserve their ability to perform phagocytosis and produce reactive oxygen species (ROS). The expression patterns of CD11b and CD62L on PMNs differed according to the cytokine combination used for NK-cell stimulation. Irrespective of the NK-cell treatment, however, PMN survival was prolonged with sustained functional capacity. We found that interferon γ, granulocyte-macrophage colony-stimulating factor, and tumor necrosis factor α produced by NK cells upon stimulation with cytokines played a crucial role in NK cell–mediated effects on PMNs. Our study demonstrates that soluble factors derived from cytokine-activated NK cells send survival signals to PMNs, which would promote their accumulation and function at the site of inflammation in vivo.
Molecular characterization of Staphylococcus aureus isolates causing skin and soft tissue infections (SSTIs)
Authors: Yao Dan , Yu Fang-you , Qin Zhi-qiang , Chen Chun , He Su-su , Chen Zeng-qiang , Zhang Xue-qing , Wang Liang-xing 
Published: May 2010

Abstract

Background

Staphylococcus aureus, particularly methicillin-resistant S. aureus (MRSA), is an important cause of pyogenic skin and soft tissue infections (SSTIs). The aim of present study is to investigate the molecular characteristic of Staphylococcus aureus isolates isolated from the pus samples from the patients with purulent skin and soft tissue infections in Wenzhou, China.

Methods
Between December 2002 and June 2008, a total of 111 nonduplicate S. aureus isolates were collected from the pus samples of the patients with SSTIs in a teaching hospital in Wenzhou, China. All the tested isolates were confirmed as S. aureus using a Staph SPA agglutination kit, Gram's stain and a Vitek-60 microbiology analyzer. The homology among the tested isolates was determined by pulsed-field gel electrophoresis (PFGE). Multilocus sequence typing (MLST) was used to determine the sequence types (STs) of the selected isolates. The genotypes of SCCmec were determined by a multiplex PCR in the MRSA isolates. Panton-Valentine leukocidin (PVL) genes and mecA were also determined by another multiplex PCR.

Results
Among the 111 S. aureus isolates, 48 and 63 isolates were community-acquired and hospital-acquired respectively. Sixty isolates were confirmed as MRSA harboring mecA detected by PCR. A total of 32 PFGE clonal types were obtained by PFGE, with 10 predominant patterns (types A to J). Twenty-five different STs including ST398 and three novel STs were found among 51 selected isolates. The main STs were ST239, ST1018, ST59, ST7 and ST88. Of 60 MRSA isolates, SCCmec II, III, IV and SCCmec V were found in three, 50, three and two isolates, respectively. The positive rates of PVL genes in overall isolates, HA-isolates, CA-isolates, MRSA isolates and MSSA isolates were 23.4% (26/111), 20.6% (13/63), 27.1% (13/48), 21.7% (13/60) and 25.5% (13/51), respectively. Eight (33.3%, 8/24) of 24 CA-MRSA isolates and 5 (13.9%, 5/36) of 36 HA-MRSA isolates were positive for PVL genes. ST239-MRSA-SCCmecIII and ST1018-MRSA-SCCmecIII clones were found to be main clones and spread between community and hospital.

Conclusion

S. aureus isolates causing SSTIs showed considerable molecular heterogeneity and harbored high prevalence of PVL genes. Clonal spread was responsible for the dissemination of the isolates of S. aureus associated with SSTIs.
Copeptin is associated with mortality and outcome in patients with acute intracerebral hemorrhage
Authors: Zweifel Christian , Katan Mira , Schuetz Philipp , Siegemund Martin , Morgenthaler Nils G , Merlo Adrian , Mueller Beat , Christ-Crain Mirjam 
Published: May 2010

AbstractBackgroundSpontaneous intracerebral hemorrhage (ICH) accounts for a high mortality and morbidity. Early prediction of outcome is crucial for optimized care and treatment decision. Copeptin, the C-terminal part of provasopressin, has emerged as a new prognostic marker in a variety of diseases, but its prognostic value in ICH is unknown.MethodsIn 40 consecutive patients who were admitted to the hospital within 72 hours after a spontaneous ICH, the plasma copeptin level was measured with a sandwich immunoassay upon admission. The prognostic value of copeptin to predict 30 day mortality and functional outcome after 90 days was assessed. A favorable outcome was defined as a Barthel score above 85 and a score below 3 on the Modified Rankin Scale.ResultsCopeptin correlated positively with hematoma volume (r = 0.32, p < 0.05) and negatively with the Glasgow Coma Scale (GCS) on admission (r = -0.35, p < 0.05). Copeptin levels were higher in patients who died within 30 days than in 30-day survivors (179.0 pmol/l (IQR 33.7- 566.0) vs. 12.9 pmol/l (IQR 5.2 - 42.8), p = 0.003). Copeptin levels were also higher in patients with an unfavorable functional outcome at 90 days compared to patients with a favorable outcome (32.4 pmol/l (IQR 9.5-97.8) vs. 11.9 pmol/l (IQR 3.2-19.8), p = 0.04). For the prediction of death, receiver-operating-characteristics analysis revealed an area under the curve (AUC) for copeptin of 0.88 (95%CI 0.75-1.00). The predictive value of the copeptin concentration was thus similar to that of GCS (AUC 0.82 (95%CI 0.59-1.00) p = 0.53), of the ICH Score (AUC 0.89, (95%CI 0.76-1.00), p = 0.94) and the ICH Grading Scale (AUC 0.86 (95%CI 0.69-1.00), p = 0.81).ConclusionsCopeptin is a new prognostic marker in patients with an ICH. If this finding can be confirmed in larger studies, copeptin might be an additional valuable tool for risk stratification and decision-making in the acute phase of ICH.Trial Registration(Clinical Trial Registration: ISCTRN00390962)
Healthcare costs associated with progressive diabetic retinopathy among National Health Insurance enrollees in Taiwan, 2000-2004
Authors: Woung Lin-Chung , Tsai Ching-Yao , Chou Hsin-Kai , Tsai Ming-Tsu , Tsai Wei-Her , Chou Pesus , Shen Shih-Tsuo 
Published: May 2010

Abstract

Background
Diabetic retinopathy is one of the most common microvascular complications of diabetes and one of the major causes of adult visual impairment in national surveys in Taiwan. This study aimed to identify the healthcare costs of Taiwan's National Health Insurance program on behalf of diabetic patients with stable or progressive retinopathy.

Methods
A retrospective cohort study was conducted with 4,988 medication-using diabetic retinopathy subjects ≥ 40 years of age under National Health Insurance Program coverage between 2000 and 2004. Study cohort subjects were recorded as having diabetic retinopathy according to ICD-9-CM codes. States of diabetic retinopathy were strategically divided into stable and progressive categories according to subjects' conditions at follow-up in 2004. Expenditures were calculated and compared for the years 2000 and 2004.

Results
During the 4-year follow-up (2000 through 2004), 4,116 subjects (82.5%) of 4,988 diabetic subjects were in the stable category, and 872 (17.5%) were in the progressive category. Average costs of those in the normal category increased by US $48 from US $1921 in 2000 to US $1969 in 2004 (p = 0.594), whereas costs for those progressing from normal to non-proliferative diabetic retinopathy (NPDR) or proliferative diabetic retinopathy (PDR) increased by US $1760, from US $1566 in 2000 to US $3326 in 2004 (p < 0.001). The PDR category had the highest average costs at US $3632 in 2000. The NPDR-to-PDR category experienced the greatest increase in costs at US $3482, from US $2723 in 2000 to US $6204 in 2004 (p = 0.042), and the greatest percentage of increase at 2.3% (2.2% when adjusted by comparing to normal category).

Conclusions
This large-scale longitudinal study provides evidence that increased healthcare costs are associated with progressive diabetic retinopathy among diabetic NHI enrollees in Taiwan.
Decreased paraoxonase-1 activity is associated with alterations of high-density lipoprotein particles in chronic liver impairment
Authors: Marsillach Judit , Aragonès Gerard , Mackness Bharti , Mackness Michael , Rull Anna , Beltrán-Debón Raúl , Pedro-Botet Juan , Alonso-Villaverde Carlos , Joven Jorge , Camps Jordi 
Published: May 2010

Abstract

Background
Paraoxonase-1 (PON1), a lactonase synthesized by the liver, circulates in blood bound to high-density lipoproteins (HDL). This enzyme is thought to degrade oxidized phospholipids and play an important role in the organism's antioxidant and anti-inflammatory system. Chronic liver diseases are characterized by decreased serum PON1 activity. The aim of the present study was to investigate the compositional changes in HDL that could influence PON1 activity in liver impairment.

Methods
The study was performed in samples from five patients with advanced liver cirrhosis and with preserved renal function, chosen on the basis of having low serum PON1 activity and high serum PON1 concentration. As a control group, we accessed five healthy volunteers from among our hospital staff. Lipid and protein compositional analysis of lipoprotein particles were done by high-performance liquid chromatography, gel electrophoresis, and Western-Blot.

Results
HDL particles from cirrhotic patients had an increased phospholipid content that was inversely correlated to PON1 activity. The HDL particles contained high levels of PON1 that corresponded, in part, to an immunoreactive protein of high molecular weight (55 kDa) not present in control subjects. This protein was identified as glycosylated PON1 and was also present in biopsies from patients with steatosis and from rats with CCl4-induced hepatic impairment. These changes were associated with an increased plasma concentration of markers of oxidative stress, inflammation and fibrogenesis.

Conclusion
Abnormalities in the composition of lipids and proteins of HDL particles, including PON1 glycosylation, are associated with the decrease in serum PON1 activity in patients with liver disease. These alterations may adversely affect the protective role of HDL against oxidative stress and inflammation in these patients.
Changes in the SF-8 scores among healthy non-smoking school teachers after the enforcement of a smoke-free school policy: a comparison by passive smoke status
Authors: Kiyohara Kosuke , Itani Yuri , Kawamura Takashi , Matsumoto Yoshitaka , Takahashi Yuko 
Published: May 2010

Abstract

Background
The effects of the enforcement of a smoke-free workplace policy on health-related quality of life (HRQOL) among a healthy population are poorly understood. The present study was undertaken to examine the effects of the enforcement of a smoke-free school policy on HRQOL among healthy non-smoking schoolteachers with respect to their exposure to passive smoke.

Methods
Two self-reported questionnaire surveys were conducted, the first before and the second after the enforcement of a total smoke-free public school policy in Nara City. A total of 1534 teachers were invited from 62 schools, and their HRQOL was assessed using six domains extracted from the Medical Outcomes Survey Short Form-8 questionnaire (SF-8): general health perception (GH), role functioning-physical (RP), vitality (VT), social functioning (SF), mental health (MH), and role functioning-emotional (RE). The participants were divided into two groups according to their exposure to environmental tobacco smoke (ETS) at baseline: participants not exposed to ETS at school (non-smokers), and participants exposed to ETS at school (passive smokers). Changes in each SF-8 score were evaluated using paired t-tests for each group, and their inter-group differences were evaluated using multiple linear regression analyses adjusted for sex, age, school type, managerial position, and attitude towards a smoke-free policy.

Results
After ineligible subjects were excluded, 689 teachers were included in the analyses. The number of non-smokers and passive smokers was 447 and 242, respectively. Significant changes in SF-8 scores were observed for MH (0.9; 95% confidence interval [CI], 0.2-1.5) and RE (0.7; 95% CI, 0.0-1.3) in non-smokers, and GH (2.2; 95% CI, 1.2-3.1), VT (1.8; 95% CI, 0.9-2.7), SF (2.7; 95% CI, 1.6-3.8), MH (2.0; 95% CI, 1.0-2.9), and RE (2.0; 95% CI, 1.2-2.8) in passive smokers. In the multiple linear regression analyses, the net changes in the category scores of GH (1.8; 95% CI, 0.7-2.9), VT (1.4, 95% CI, 0.3-2.5), SF (2.5; 95% CI, 1.1-3.9), MH (1.2; 95% CI, 0.1-2.4) and RE (1.6; 95% CI, 0.5-2.7) in passive smokers significantly exceeded those in non-smokers.

Conclusions
A smoke-free school policy would improve the HRQOL of healthy non-smoking teachers who are exposed to ETS.
Fishing for Allergens: Bloodworm-Induced Asthma
Authors: Wu Keith CP , Räsänen Katja , Hudson Thomas J 
Published: May 2010

Abstract
Hypersensitivity to bloodworms (chironomid larvae) leading to asthma and other related allergic disorders is becoming common in individuals who keep or work with fish due to the increased use of bloodworms as fish food or bait.
Subcutaneous Immunoglobulin-G Replacement Therapy with Preparations Currently Available in the United States for Intravenous or Intramuscular Use: Reasons and Regimens
Authors: Chouksey Akhilesh , Duff Kimberly , Wasserbauer Nancy , Berger Melvin 
Published: May 2010

AbstractFor patients who require replacement therapy for primary immunodeficiency, subcutaneous infusions of immunoglobulin G (IgG) may be preferable to intravenous infusions for several reasons. However, at present, there is no preparation marketed for use by this route in North America. In this article, we describe the reasons patients have selected this route of therapy and the range of treatment regimens used. Approximately 20% of our patients have chosen the subcutaneous route, mainly because of adverse effects from intravenous (IV) infusions or difficulties with venous access. Unit dose regimens using whole bottles of currently available 16% intramuscular preparations or sucrose-containing lyophilized preparations intended for IV use but reconstituted to 15% IgG for subcutaneous administration were individually tailored to each patient. In most cases, self-infusions or home infusions were administered once or twice a week, most commonly requiring two subcutaneous sites and 2 to 3 hours per infusion. On average, patients took 0.18 mL of IgG per kilogram of body weight per site per hour. There were no systemic adverse effects. In patients for whom comparative data were available, trough serum IgG levels were higher with subcutaneous therapy than with IV therapy.
Proteome changes of lungs artificially infected with H-PRRSV and N-PRRSV by two-dimensional fluorescence difference gel electrophoresis
Authors: Xiao Shuqi , Wang Qiwei , Jia Jianyu , Cong Peiqing , Mo Delin , Yu Xiangchun , Qin Limei , Li Anning , Niu Yuna , Zhu Kongju , Wang Xiaoying , Liu Xiaohong , Chen Yaosheng 
Published: May 2010

AbstractBackgroundPorcine reproductive and respiratory syndrome with PRRS virus (PRRSV) infection, which causes significant economic losses annually, is one of the most economically important diseases affecting swine industry worldwide. In 2006 and 2007, a large-scale outbreak of highly pathogenic porcine reproductive and respiratory syndrome (PRRS) happened in China and Vietnam. However little data is available on global host response to PRRSV infection at the protein level, and similar approaches looking at mRNA is problematic since mRNA levels do not necessarily predict protein levels. In order to improve the knowledge of host response and viral pathogenesis of highly virulent Chinese-type PRRSV (H-PRRSV) and Non-high-pathogenic North American-type PRRSV strains (N-PRRSV), we analyzed the protein expression changes of H-PRRSV and N-PRRSV infected lungs compared with those of uninfected negative control, and identified a series of proteins related to host response and viral pathogenesis.ResultsAccording to differential proteomes of porcine lungs infected with H-PRRSV, N-PRRSV and uninfected negative control at different time points using two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) and mass spectrometry identification, 45 differentially expressed proteins (DEPs) were identified. These proteins were mostly related to cytoskeleton, stress response and oxidation reduction or metabolism. In the protein interaction network constructed based on DEPs from lungs infected with H-PRRSV, HSPA8, ARHGAP29 and NDUFS1 belonged to the most central proteins, whereas DDAH2, HSPB1 and FLNA corresponded to the most central proteins in those of N-PRRSV infected.ConclusionsOur study is the first attempt to provide the complex picture of pulmonary protein expression during H-PRRSV and N-PRRSV infection under the in vivo environment using 2D-DIGE technology and bioinformatics tools, provides large scale valuable information for better understanding host proteins-virus interactions of these two PRRSV strains.