bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of STAT3 Signaling Pathway by Nitidine Chloride Suppressed the Angiogenesis and Growth of Human Gastric Cancer
Authors: Chen Jing , Wang Jieqiong , Lin Lei , He Lijun , Wu Yuanyuan , Zhang Li , Yi Zhengfang , Chen Yihua , Pang Xiufeng , Liu Mingyao 
Published: December 2011

AbstractSTAT3 has been strongly implicated in human malignancies, and constitutive activation of STAT3 serves a crucial role in cell survival, angiogenesis, immune evasion, and inflammation. In this study, we showed that nitidine chloride, a natural phytochemical alkaloid derived from Zanthoxylum nitidum (Roxb) DC, exerts potent anticancer activity through STAT3 signaling cascade. Nitidine chloride dose dependently suppressed VEGF-induced endothelial cell proliferation, migration, and tubular structure formation in vitro and dramatically reduced VEGF-triggered neovascularization in mouse cornea and Matrigel plugs in vivo. This angiogenesis inhibition mediated by nitidine chloride was well interpreted by the suppression of Janus kinase 2/STAT3 signaling and STAT3 DNA-binding activity in endothelial cells. Furthermore, nitidine chloride suppressed the constitutively activated STAT3 protein, its DNA-binding activity, and the expression of STAT3-dependent target genes, including cyclin D1, Bcl-xL, and VEGF in human gastric cancer cells. Consistent with the earlier findings, nitidine chloride inhibited gastric tumor cell growth and induced tumor cell apoptosis in vitro and effectively suppressed the volume, weight, and microvessel density of human SGC-7901 gastric solid tumors (n = 8) at a dosage of 7 mg/kg/d (intraperitoneal injection). Immunohistochemistry and Western blot analysis further revealed that the expression of STAT3, CD31, and VEGF protein in xenografts was remarkably decreased by the alkaloid. Taken together, we propose that nitidine chloride is a promising anticancer drug candidate as a potent STAT3 signaling inhibitor. Mol Cancer Ther; 11(2); 277–87. ©2011 AACR.
Problems Closing the Energy Balance over a Homogeneous Snow Cover during Midwinter
Authors: Helgason Warren , Pomeroy John 
Published: December 2011

Abstract
Application of the energy balance approach to estimate snowmelt inherently presumes that the external energy fluxes can be measured or modeled with sufficient accuracy to reliably estimate the internal energy changes and melt rate. However, owing to difficulties in directly measuring the internal energy content of the snow during melt periods, the ability to close the energy balance is rarely quantified. To address this, all of the external energy balance terms (sensible and latent heat fluxes, shortwave and longwave radiation fluxes, and the ground heat flux) were directly measured and compared to changes of the energy content within an extensive, homogeneous, snowpack of a level field near Saskatoon, Saskatchewan, Canada. The snow was observed to lose significant amounts of energy because of a persistent longwave radiation imbalance caused by low incoming fluxes during cold, clear-sky periods, while solar heating of the snow surface caused an increase in the outgoing fluxes. The sum of the measured turbulent heat fluxes, ground heat flux, and solar radiation fluxes were insufficient to offset these losses, however the snowpack temperatures were not observed to cool. It was concluded that an unmeasured exchange of sensible heat was occurring from the atmosphere to the snowpack. The exchange mechanism for this is not known but would appear to be consistent with the concept of a windless exchange as employed to close the energy balance in various snow models. The results suggest that caution should be exercised when using the energy balance method to determine changes in internal energy in cold snowpacks.
Representing the Nation
Authors: Stock Ann Marie 
Published: December 2011

As the institutions charged with preserving and purveying our collective history and identity came under close scrutiny in the 1990s, the Smithsonian Institution was accused of having ignored Latino culture for decades, and it responded with a number of initiatives to right more than a century of wrongs. “Arte Latino,” one of a series of traveling exhibits launched in 1999, presented a sampling of the Latino artworks in the institution’s collection. Visits to two installations of the exhibit, one with a predominantly Latino audience and one with a predominantly non-Latino one, showed how context and reception ascribe meaning and how an emphasis on authenticity can reinforce dualities. Ethnically organized exhibits run the risk of merely placating underrepresented artists and showcasing the exotic. While cultural specificity can heighten awareness, instill pride, and redress neglect, it can also impede communication, emphasize difference and divisiveness, and undermine its own goals. Las instituciones estadounidenses a cargo de preservar la historia e identidad colectiva nacional se vieron sujetas a un profundo escrutinio durante la década de 1990, y la Smithsonian Institution fue criticada por haber ignorado la cultura latina por décadas. Respondió con una serie de inicitativas que buscaban enmendar más de un siglo de negligencia. “Arte Latino,” una de varias series de exhibiciones itinerantes inaugurada en 1999, consistió de una muestra de las obras de arte latino en la colección. Visitas a dos de las instalaciones de la exhibición, una con espectadores primordialmente latinos y otra con no latinos, dio muestra de cómo el contexto y la recepción adjudican significados y de como el énfasis en la autenticidad puede reforzar dualidades. Las exhibiciones de índole étnica corren el riesgo de no hacer más que placar artistas que cuentan con poca representación y exponer lo exótico. Mientras que la especificidad cultural puede incrementar la concientización, generar orgullo y rectificar actos de negligencia, también puede impedir la comunicación, enfatizar diferencias y divisiones, y socavar sus propias metas.
In vivo and ex vivo effects of propofol on myocardial performance in rats with obstructive jaundice
Authors: Ren Hong-Mei , Yang Li-Qun , Liu Zhi-Qiang , Chen Cai-Yang , Cheung Chi-Wai , Tao Kun-Ming , Song Jian-Gang , Chen Wu-Rong , Yu Wei-Feng 
Published: December 2011

AbstractBackgroundResponsiveness of the "jaundiced heart" to propofol is not completely understood. The purpose of this study was to evaluate the effect of propofol on myocardial performance in rats with obstructive jaundice.MethodsMale Sprague-Dawley rats (n = 40) were randomly allocated into two groups, twenty underwent bile duct ligation (BDL), and 20 underwent a sham operation. Seven days after the surgery, propofol was administered in vivo and ex vivo (Langendorff preparations). Heart rate, left ventricular end-systolic pressure (LVESP) left ventricular end-diastolic pressure (LVEDP), and maximal rate for left ventricular pressure rise and decline (± dP/dtmax) were measured to determine the influence of propofol on the cardiac function of rats.ResultsImpaired basal cardiac function was observed in the isolated BDL hearts, whereas in vivo indices of basal cardiac function (LVESP and ± dP/dt) in vivo were significantly higher in rats that underwent BDL compared with controls. With low or intermediate concentrations of propofol, these indices of cardiac function were within the normal physiologic range in both groups, and responsiveness to propofol was unaffected by BDL. When the highest concentration of propofol was administrated, a significant decline in cardiac function was observed in the BDL group.ConclusionsIn rats that underwent BDL, basal cardiac performance was better in vivo and worse ex vivo compared with controls. Low and intermediate concentrations of propofol did not appear to impair cardiac function in rats with obstructive jaundice.
Hyperglycemia in apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility
Authors: Li Jing , Wang Qian , Chai Weidong , Chen Mei-Hua , Liu Zhenqi , Shi Weibin 
Published: December 2011

Abstract

Background
Type 2 diabetes mellitus (T2DM) is associated with an increased risk of atherosclerotic vascular disease, but it is unknown whether the other way around is true too. C57BL/6 (B6) and BALB/cJ (BALB) are two mouse strains that differ markedly in their susceptibility to atherosclerosis. In this study we investigated the development of diet-induced T2DM in these two strains.

Methods and Results
When deficient in apolipoprotein E (apoE-/-) and fed a Western diet for 12 weeks, atherosclerosis-susceptible B6 mice developed significant hyperglycemia. In contrast, atherosclerosis-resistant BALB apoE-/- mice had much lower plasma glucose levels than B6.apoE-/- mice on either chow or Western diet and during an intraperitoneal glucose tolerance test. In response to glucose BALB.apoE-/- mice displayed both the first and second phases of insulin secretion but the second phase of insulin secretion was absent in B6.apoE-/- mice. In response to insulin B6.apoE-/- mice showed a deeper and longer-lasting fall in blood glucose levels while BALB.apoE-/- mice showed little reduction in glucose levels. Pancreatic islet area of BALB.apoE-/- mice on light microscopy nearly doubled the area of B6.apoE-/- mice. Most circulating proinflammatory cytokines were lower in BALB.apoE-/- than in B6.apoE-/- mice on the Western diet, as determined by protein arrays. Increased macrophage infiltration in islets was observed in B6.apoE-/- mice by immunostaining for Mac2 and also by flow cytometry.

Conclusion
This study demonstrates that defects in insulin secretion rather than defects in insulin resistance explain the marketed difference in susceptibility to T2DM in the B6.apoE-/- and BALB.apoE-/- mouse model. A smaller islet mass and more prominent islet inflammation may explain the vulnerability of B6.apoE-/- mice to diet-induced diabetes.
The signaling pathway of Campylobacter jejuni-induced Cdc42 activation: Role of fibronectin, integrin beta1, tyrosine kinases and guanine exchange factor Vav2
Authors: Krause-Gruszczynska Malgorzata , Boehm Manja , Rohde Manfred , Tegtmeyer Nicole , Takahashi Seiichiro , Buday Laszlo , Oyarzabal Omar A , Backert Steffen 
Published: December 2011

Abstract

Background
Host cell invasion by the foodborne pathogen Campylobacter jejuni is considered as one of the primary reasons of gut tissue damage, however, mechanisms and key factors involved in this process are widely unclear. It was reported that small Rho GTPases, including Cdc42, are activated and play a role during invasion, but the involved signaling cascades remained unknown. Here we utilised knockout cell lines derived from fibronectin-/-, integrin-beta1-/-, focal adhesion kinase (FAK)-/- and Src/Yes/Fyn-/- deficient mice, and wild-type control cells, to investigate C. jejuni-induced mechanisms leading to Cdc42 activation and bacterial uptake.

Results
Using high-resolution scanning electron microscopy, GTPase pulldowns, G-Lisa and gentamicin protection assays we found that each studied host factor is necessary for induction of Cdc42-GTP and efficient invasion. Interestingly, filopodia formation and associated membrane dynamics linked to invasion were only seen during infection of wild-type but not in knockout cells. Infection of cells stably expressing integrin-beta1 variants with well-known defects in fibronectin fibril formation or FAK signaling also exhibited severe deficiencies in Cdc42 activation and bacterial invasion. We further demonstrated that infection of wild-type cells induces increasing amounts of phosphorylated FAK and growth factor receptors (EGFR and PDGFR) during the course of infection, correlating with accumulating Cdc42-GTP levels and C. jejuni invasion over time. In studies using pharmacological inhibitors, silencing RNA (siRNA) and dominant-negative expression constructs, EGFR, PDGFR and PI3-kinase appeared to represent other crucial components upstream of Cdc42 and invasion. siRNA and the use of Vav1/2-/- knockout cells further showed that the guanine exchange factor Vav2 is required for Cdc42 activation and maximal bacterial invasion. Overexpression of certain mutant constructs indicated that Vav2 is a linker molecule between Cdc42 and activated EGFR/PDGFR/PI3-kinase. Using C. jejuni mutant strains we further demonstrated that the fibronectin-binding protein CadF and intact flagella are involved in Cdc42-GTP induction, indicating that the bacteria may directly target the fibronectin/integrin complex for inducing signaling leading to its host cell entry.

Conclusion
Collectively, our findings led us propose that C. jejuni infection triggers a novel fibronectin→integrin-beta1→FAK/Src→EGFR/PDGFR→PI3-kinase→Vav2 signaling cascade, which plays a crucial role for Cdc42 GTPase activity associated with filopodia formation and enhances bacterial invasion.
Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders
Authors: Mader Simone , Gredler Viktoria , Schanda Kathrin , Rostasy Kevin , Dujmovic Irena , Pfaller Kristian , Lutterotti Andreas , Jarius Sven , Di Pauli Franziska , Kuenz Bettina , Ehling Rainer , Hegen Harald , Deisenhammer Florian , Aboul-Enein Fahmy , Storch Maria K , Koson Peter , Drulovic Jelena , Kristoferitsch Wolfgang , Berger Thomas , Reindl Markus 
Published: December 2011

Abstract

Background
Serum autoantibodies against the water channel aquaporin-4 (AQP4) are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO). However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM) and multiple sclerosis (MS) patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM) remains unresolved.

Results
We analyzed patients with definite NMO (n = 45), HR-NMO (n = 53), ADEM (n = 33), clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32), MS (n = 71) and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects) for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC). AQP4-IgG was found in patients with NMO (n = 43, 96%), HR-NMO (n = 32, 60%) and in one CIS patient (3%), but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%), NMO (n = 3, 7%), HR-NMO (n = 7, 13%, 5 rON and 2 LETM), CIS (n = 2, 6%), MS (n = 2, 3%) and controls (n = 3, 3%, two SLE and one OND). Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33%) AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able to mediate CDC at high-titer levels.

Conclusions
We could show for the first time that a subset of AQP4-IgG seronegative patients with NMO and HR-NMO exhibit a MOG-IgG mediated immune response, whereas MOG is not a target antigen in cases with an AQP4-directed humoral immune response.
Transgenic neuronal overexpression reveals that stringently regulated p23 expression is critical for coordinated movement in mice
Authors: Gong Ping , Roseman Jelita , Fernandez Celia G , Vetrivel Kulandaivelu S , Bindokas Vytautas P , Zitzow Lois A , Kar Satyabrata , Parent Angèle T , Thinakaran Gopal 
Published: December 2011

AbstractBackgroundp23 belongs to the highly conserved p24 family of type I transmembrane proteins, which participate in the bidirectional protein transport between the endoplasmic reticulum and Golgi apparatus. Mammalian p23 has been shown to interact with γ-secretase complex, and modulate secretory trafficking as well as intramembranous processing of amyloid precursor protein in cultured cells. Negative modulation of β-amyloid production by p23 in cultured cell lines suggested that elevation of p23 expression in neurons might mitigate cerebral amyloid burden.ResultsWe generated several lines of transgenic mice expressing human p23 in neurons under the control ofThy-1.2promoter. We found that even a 50% increase in p23 levels in the central nervous system of mice causes post-natal growth retardation, severe neurological problems characterized by tremors, seizure, ataxia, and uncoordinated movements, and premature death. The severity of the phenotype closely correlated with the level of p23 overexpression in multiple transgenic lines. While the number and general morphology of neurons in Hup23 mice appeared to be normal throughout the brain, abnormal non-Golgi p23 localization was observed in a subset of neurons with high transgene expression in brainstem. Moreover, detailed immunofluorescence analysis revealed marked proliferation of astrocytes, activation of microglia, and thinning of myelinated bundles in brainstem of Hup23 mice.ConclusionsThese results demonstrate that proper level of p23 expression is critical for neuronal function, and perturbing p23 function by overexpression initiates a cascade of cellular reactions in brainstem that leads to severe motor deficits and other neurological problems, which culminate in premature death. The neurological phenotype observed in Hup23 mice highlights significant adverse effects associated with manipulating neuronal expression of p23, a previously described negative modulator of γ-secretase activity and β-amyloid production. Moreover, our report has broader relevance to molecular mechanisms in several neurodegenerative diseases as it highlights the inherent vulnerability of the early secretory pathway mechanisms that ensure proteostasis in neurons.
Unraveling the biological functions of Smad7 with mouse models
Authors: Zhu Lu , Chen Susie , Chen Yan 
Published: December 2011

Abstract
Smad7 is a key negative regulator of the transforming growth factor β (TGF-β) signaling and plays an important role in modulating a large array of biological processes. The physiological actions of Smad7 have been extensively investigated by using various mouse models. These studies have pinpointed numerous important in vivo functions of Smad7, including its activity in early embryonic development, fibrosis of many organs, skin cell differentiation, regulation of immune response and inflammation, tumorigenesis, and metabolic control. As most biological activities modulated by Smad7 are closely related to human disorders, it is anticipated that Smad7 will continue to be an intriguing molecule that will be vigorously investigated in the future to strengthen our understanding about the pathogenesis of human diseases.
Effect of Early Palliative Care on Chemotherapy Use and End-of-Life Care in Patients With Metastatic Non–Small-Cell Lung Cancer
Authors: Greer Joseph A. , Pirl William F. , Jackson Vicki A. , Muzikansky Alona , Lennes Inga T. , Heist Rebecca S. , Gallagher Emily R. , Temel Jennifer S. 
Published: December 2011

Purpose Prior research shows that introducing palliative care soon after diagnosis for patients with metastatic non–small-cell lung cancer (NSCLC) is associated with improvements in quality of life, mood, and survival. We sought to investigate whether early palliative care also affects the frequency and timing of chemotherapy use and hospice care for these patients. Patients and Methods This secondary analysis is based on a randomized controlled trial of 151 patients with newly diagnosed metastatic NSCLC presenting to an outpatient clinic at a tertiary cancer center from June 2006 to July 2009. Participants received either early palliative care integrated with standard oncology care or standard oncology care alone. By 18-month follow-up, 133 participants (88.1%) had died. Outcome measures included: first, number and types of chemotherapy regimens, and second, frequency and timing of chemotherapy administration and hospice referral. Results The overall number of chemotherapy regimens did not differ significantly by study group. However, compared with those in the standard care group, participants receiving early palliative care had half the odds of receiving chemotherapy within 60 days of death (odds ratio, 0.47; 95% CI, 0.23 to 0.99; P = .05), a longer interval between the last dose of intravenous chemotherapy and death (median, 64.00 days [range, 3 to 406 days] v 40.50 days [range, 6 to 287 days]; P = .02), and higher enrollment in hospice care for longer than 1 week (60.0% [36 of 60 patients] v 33.3% [21 of 63 patients]; P = .004). Conclusion Although patients with metastatic NSCLC received similar numbers of chemotherapy regimens in the sample, early palliative care optimized the timing of final chemotherapy administration and transition to hospice services, key measures of quality end-of-life care.
Use of Topical Tranexamic Acid or Aminocaproic Acid to Prevent Bleeding After Major Surgical Procedures
Authors: Ipema Heather J , Tanzi Maria G 
Published: December 2011

OBJECTIVE: To evaluate the literature describing topical use of tranexamic acid or aminocaproic acid for prevention of postoperative bleeding after major surgical procedures. DATA SOURCES: Literature was retrieved through MEDLINE (1946-September 2011) and International Pharmaceutical Abstracts(1970-September 2011) using the terms tranexamic acid, aminocaproic acid, antifibrinolytic, topical, and surgical. In addition, reference citations from publications identified were reviewed. STUDY SELECTION AND DATA EXTRACTION: All identified articles in English were evaluated. Clinical trials, case reports, and meta-analyses describing topical use of tranexamic acid or aminocaproic acid to prevent postoperative bleeding were included. DATA SYNTHESIS: A total of 16 publications in the setting of major surgical procedures were included; the majority of data were for tranexamic acid. For cardiac surgery, 4 trials used solutions containing tranexamic acid (1-2.5 g in 100-250 mL of 0.9% NaCl), and 1 trial assessed a solution containing aminocaproic acid (24 g in 250 mL of 0.9% NaCl). These solutions were poured into the chest cavity before sternotomy closure. For orthopedic procedures, all of the data were for topical irrigation solutions containing tranexamic acid (500 mg-3 g in 50-100 mL of 0.9% NaCl) or for intraarticular injections of tranexamic acid (250 mg to 2 g in 20-50 mL of 0.9% sodium chloride, with or without carbazochrome sodium sulfate). Overall, use of topical tranexamic acid or aminocaproic acid reduced postoperative blood loss; however, few studies reported a significant reduction in the number of packed red blood cell transfusions or units given, intensive care unit stay, or length of hospitalization. CONCLUSIONS: Topical application of tranexamic acid and aminocaproic acid to decrease postsurgical bleeding after major surgical procedures is a promising strategy. Further data are needed regarding the safety of this hemostatic approach.