bluuebunny/crossref_metadata_2025_split huggingface dataset:
No effect of meat, meat cooking preferences, meat mutagens or heme iron on lung cancer risk in the prostate, lung, colorectal and ovarian cancer screening trial
Authors: Tasevska Nataša , Cross Amanda J. , Dodd Kevin W. , Ziegler Regina G. , Caporaso Neil E. , Sinha Rashmi 
Published: March 2010

AbstractRecent epidemiological studies have suggested that red and processed meat may increase the risk of lung cancer. Possible underlying mechanisms include mutagens produced during high‐temperature cooking or preservation, or formed endogenously from heme iron in meat. We used data from 99,579 participants of both screened and nonscreened arms of the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, aged 55–74 years, to investigate whether meat type, cooking method, doneness level, intake of specific meat mutagens 2‐amino‐3,8‐dimethylimidazo[4,5‐f]quinoxaline (MeIQx), 2‐amino‐3,4,8‐trimethylimidazo[4,5‐f]quinoxaline] (DiMeIQx), 2‐amino‐1‐methyl‐6‐phenylimidazo[4,5‐b]pyridine (PhIP) and benzo(a)pyrene (B(a)P)] and heme iron are associated with lung cancer. Participants' diet was assessed prospectively using a 124‐item food frequency questionnaire and an additional meat‐cooking module. Dietary data were used in conjunction with a database to estimate intake of MeIQx, DiMeIQx, PhIP, B(a)P and heme iron. After up to 8 years of follow‐up, 782 incident lung cancer cases were ascertained. Lung cancer risk was not associated with the consumption of either red (men: HRQ5vs.Q1= 1.11, 95% CI = 0.79–1.56,Ptrend= 0.42; women: HRQ5vs.Q1= 1.30, 95% CI = 0.87–1.95,Ptrend= 0.65) or processed meat (men: HRQ5vs.Q1= 1.12, 95% CI = 0.83–1.53,Ptrend= 0.22; women: HRQ5vs.Q1= 0.98, 95% CI = 0.68–1.41,Ptrend= 0.32) in multivariable models. High‐temperature cooking methods, level of meat doneness, meat mutagens and heme iron had no effect on lung cancer risk. In this population, we found no association between meat type, cooking method, doneness level or intake of specific meat mutagens or heme iron and lung cancer risk.
Transcriptional regulation of Rex1 (zfp42) in normal prostate epithelial cells and prostate cancer cells
Authors: Lee Mi‐Young , Lu Ailan , Gudas Lorraine J. 
Published: March 2010

AbstractRex1 (zfp42) was identified by our laboratory because of its reduced expression in F9 teratocarcinoma stem cells after retinoic acid (RA) treatment. The Rex1 (Zfp42) gene is currently widely used as a marker of embryonic stem cells. We compared the transcriptional regulation of the human Rex1 gene in NTera‐2 (NT‐2) human teratocarcinoma, normal human prostate epithelial cells (PrEC), and prostate cancer cells (PC‐3) by promoter/luciferase analyses. Oct4, Sox2, Nanog, and Dax1 transcripts are expressed at higher levels in NT‐2 and PrEC cells than in PC‐3 cells. Co‐transfection analyses showed that YY1 and Rex1 are positive regulators of hRex1 transcription in NT‐2 and PrEC cells, whereas Nanog is not. Serial deletion constructs of the hRex1 promoter were created and analyzed, by which we identified a potential negative regulatory site that is located between −1 and −0.4 kb of the hRex1 promoter. We also delineated regions of the hRex1 promoter between −0.4 kb and the TSS that, when mutated, reduced transcriptional activation; these are putative Rex1 binding sites. Mutation of a putative Rex1 binding site in electrophoretic mobility shift assays (EMSA) resulted in reduced protein binding. Taken together, our results indicate that hRex1 binds to the hRex1 promoter region at −298 bp and positively regulates hRex1 transcription, but that this regulation is lost in PC‐3 human prostate cancer cells. This lack of positive transcriptional regulation by the hRex1 protein may be responsible for the lack of Rex1 expression in PC‐3 prostate cancer cells. J. Cell. Physiol. 224:17–27, 2010 © 2010 Wiley‐Liss, Inc.
Stromal cell‐derived factor 1α reduces senescence of endothelial progenitor subpopulation in lectin‐binding and DiLDL‐uptaking cell through telomerase activation and telomere elongation
Authors: Zheng Hao , Shen Cheng‐Ji , Qiu Fu‐Yu , Zhao Yan‐Bo , Fu Guo‐Sheng 
Published: March 2010

AbstractRecent studies have suggested that reduced endothelial progenitor subpopulation in lectin‐binding and DiLDL‐uptaking cell (EPC subpopulation) number and activity was associated with EPC subpopulation senescence that involved telomerase activity and telomere length. Stromal cell‐derived factor‐1α (SDF‐1α) has been shown to augment a variety of cellular functions of EPC subpopulation and subsequently contribute to ischemic neovascularization. Therefore, we investigated whether SDF‐1α might be able to prevent senescence of EPC subpopulation and also investigated the effects of SDF‐1α on the telomerase activity and telomere length. EPC subpopulation were isolated from peripheral blood and characterized. After ex vivo prolonged cultivation, EPC subpopulation became senescent as determined by acidic β‐galactosidase staining. SDF‐1α dose‐dependently inhibited the onset of EPC subpopulation senescence. Moreover, SDF‐1α increased proliferation and colony‐forming activity of EPC subpopulation. SDF‐1α also increased telomerase activity and telomere length, which was accompanied with upregulation of the catalytic subunit, telomerase reverse transcriptase (TERT). Whereas these effects of SDF‐1α on telomerase activity and expression of hTERT mRNA were significantly attenuated by CXCR4‐specific peptide antagonist (AMD3100) and phosphoinositide 3‐kinase (PI3K) inhibitor (LY294002). In conclusions, SDF‐1α delays the onset of EPC subpopulation senescence, which may be related to the activation of telomerase and elongation of telomere length. The inhibition of EPC subpopulation senescence and induction of EPC subpopulation proliferation by SDF‐1α in vitro may importantly improve the functional activity of EPC subpopulation for potential cell therapy. J. Cell. Physiol. 223:757–763, 2010. © 2010 Wiley‐Liss, Inc.
Characterization of BAG3 cleavage during apoptosis of pancreatic cancer cells
Authors: Wang Hua‐Qin , Meng Xin , Gao Yan‐Yan , Liu Bao‐Qin , Niu Xiao‐Fang , Zhang Hai‐Yan , Du Zhen‐Xian 
Published: March 2010

AbstractCaspases are a conserved family of cell death proteases that cleave intracellular substrates at Asp residues to modify their function and promote apoptosis. In this report, we identify BAG3 as a novel caspases substrate. Here, we show that one of these BAG proteins, BAG3, is cleaved during apoptosis. BAG3 cleavage is inhibited by several different caspase inhibitors. The analysis of BAG3 cleavage by recombinant caspase proteins shows that BAG3 is efficiently cleaved by caspase‐3, to a smaller extent by caspases‐1 and ‐8, and relatively inefficient by caspase‐9. Cleavage of the BAG3 protein occurs in the C‐terminal part of the protein majorly at Asp347 (KEVD347↓S) in vitro and in pancreatic cancer SW1990 and PANC‐1 cells undergoing apoptosis. We also demonstrate that unlike cleavage of Bcl‐2 and Bcl‐XL, cleaved form of BAG3 does not result in pro‐apoptotic fragments, however, cleavage of BAG3 lead to loss its per se anti‐apoptotic property. This novel regulation of BAG3 may have important implications for its role in apoptosis. J. Cell. Physiol. 224:94–100, 2010 © 2010 Wiley‐Liss, Inc.
Growth differentiation factor 15 acts anti‐apoptotic and pro‐hypertrophic in adult cardiomyocytes
Authors: Heger J. , Schiegnitz E. , von Waldthausen D. , Anwar M.M. , Piper H.M. , Euler G. 
Published: March 2010

AbstractGrowth differentiation factor 15 (GDF15) is induced during heart failure development, and may influence different processes in cardiac remodeling. While its anti‐apoptotic action under conditions of ischemia–reperfusion have been shown, it remained unclear if this is a broadly protective effect applicable to other apoptotic stimuli. Furthermore, effects on cardiac hypertrophy remained obscure. Therefore, we investigated the effects of GDF15 on induction of hypertrophy and apoptosis in ventricular cardiomyocytes. GDF15 (3 ng/ml) enhanced hypertrophic growth of cardiomyocytes as determined by an increase in cell size by 27 ± 5% and rate of protein synthesis by 47 ± 15%. In addition, a time and dose‐dependent increase in SMAD‐binding affinity was found, as well as enhanced phosphorylation of R‐SMAD1. Inhibition of SMADs by transformation of cardiomyocytes with SMAD‐decoy oligonucleotides abolished the hypertrophic growth effect. Specific inhibitors of PI3K (10 µM LY290042 or 10 nM wortmannin) or ERK (10 µM PD98059) also blocked GDF15‐induced hypertrophy and SMAD activation. Apoptosis induction by three different agents, 100 nM angiotensin II, 1 ng/ml TGFβ1, or the NO‐donor SNAP (100 µM) was blocked by addition of GDF15 (3 ng/ml). Scavenging of SMADs by transformation of cardiomyocytes with SMAD‐decoy oligonucleotides abolished the anti‐apoptotic effect of GDF15. In conclusion, GDF15 protects ventricular cardiomyocytes against different apoptotic stimuli and enhances hypertrophic growth. Hypertrophic signaling is thereby mediated via the kinases PI3K and ERK and the transcription factor R‐SMAD1. Thus, GDF15 may influence cardiac remodeling via two different mechanisms, apoptosis protection and induction of hypertrophy. J. Cell. Physiol. 224:120–126, 2010 © 2010 Wiley‐Liss, Inc.
Group V secreted phospholipase A2contributes to LPS‐induced leukocyte recruitment
Authors: Lapointe Stéphanie , Brkovic Alexandre , Cloutier Isabelle , Tanguay Jean‐François , Arm Jonathan P. , Sirois Martin G. 
Published: March 2010

AbstractSecreted phospholipases A2(sPLA2s) are well known for their contribution in the biosynthesis of inflammatory eicosanoids. These enzymes also participate in the inflammatory process by regulating chemokine production and protein expression of adhesion molecules. The majority of sPLA2isoforms are up‐regulated by proinflammatory stimuli such as bacterial lipopolysaccharide (LPS), which predominantly increases the expression of group V sPLA2(sPLA2‐V). Furthermore, it has recently been shown that sPLA2‐V is a critical messenger in the regulation of cell migration during allergic airway responsiveness. Herein, we investigated the effect of sPLA2‐V on LPS‐mediated leukocyte recruitment and its capacity to modulate adhesion molecule expression. We conducted our study in the murine air pouch model, using sPLA2‐V null mice (sPLA2‐V−/−) and control wild‐type (WT) littermates. We observed that LPS (1 µg/ml)‐mediated leukocyte emigration in sPLA2‐V−/−was attenuated by 52% and 86% upon 6 and 12 h of treatment respectively, as compared to WT mice. In WT mice, treatment with the cell‐permeable sPLA2inhibitor (12‐epi‐scalaradial; SLD) reduced LPS‐mediated leukocyte recruitment by 67%, but had no additional inhibitory effect in sPLA2‐V−/−mice. Protein analyses from the air pouch skin were carried out upon LPS‐challenge, and the expression of intercellular adhesion molecule (ICAM)‐1 and vascular cell adhesion molecule (VCAM)‐1 were both significantly reduced in sPLA2‐V−/−mice as compared to control WT mice. Together, our data demonstrate the role of sPLA2‐V in LPS‐induced ICAM‐1 and VCAM‐1 protein overexpression and leukocyte recruitment, supporting the contribution of sPLA2‐V in the development of inflammatory innate immune responses. J. Cell. Physiol. 224:127–134, 2010 © 2010 Wiley‐Liss, Inc.
TGFβ mediated transition of corneal fibroblasts from a proinflammatory state to a profibrotic state through modulation of histone acetylation
Authors: Zhou Qingjun , Yang Lingling , Wang Yao , Qu Mingli , Chen Peng , Wang Ye , Xie Lixin , Zhao Jing , Wang Yiqiang 
Published: March 2010

AbstractCorneal fibroblasts exhibit different phenotypes in different phases of corneal wound healing. In the inflammatory phase, the cells assume a proinflammatory phenotype and produce large amounts of cytokines and chemokines, but in the proliferative and remodeling phases, they adapt a profibrotic state, differentiate into myofibroblasts and increase extracellular matrix protein synthesis, secretion, and deposition. In the present study, the molecular mechanisms regulating the transition of corneal fibroblasts from the proinflammatory state to the profibrotic state were investigated. Corneal fibroblasts were treated with TGFβ, a known profibrotic and anti‐inflammatory factor in wound healing, in the absence or presence of trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor. The results revealed that TGFβ induced the profibrotic transition of corneal fibroblasts, including increased extracellular matrix synthesis, morphological changes, and assembly of actin filaments. Meanwhile, proinflammatory gene expressions of corneal fibroblasts were down‐regulated with the treatment of TGFβ, as confirmed by cDNA microarray, real time PCR and ELISA. Moreover, TSA reversed the TGFβ‐mediated transition of corneal fibroblasts from the proinflammatory state to the profibrotic state, as accompanied by histone hyperacetylations. In conclusion, TGFβ suppressed the production of proinflammatory factors and enhanced the expression of matrix remodeling genes of corneal fibroblasts in the transition from the proinflammatory state to the profibrotic state, and the dual roles of TGFβ on the phenotype regulations of corneal fibroblasts were mediated by altered histone acetylation. J. Cell. Physiol. 224:135–143, 2010 © 2010 Wiley‐Liss, Inc.
miR‐20b modulates VEGF expression by targeting HIF‐1α and STAT3 in MCF‐7 breast cancer cells
Authors: Cascio Sandra , D'Andrea Aleco , Ferla Rita , Surmacz Eva , Gulotta Eliana , Amodeo Valeria , Bazan Viviana , Gebbia Nicola , Russo Antonio 
Published: March 2010

AbstractMicroRNAs (miRNAs) are small non‐coding RNAs that regulate the expression of different genes, including genes involved in cancer progression. A functional link between hypoxia, a key feature of the tumor microenvironment, and miRNA expression has been documented. We investigated whether and how miR‐20b can regulate the expression of vascular endothelial growth factor (VEGF) in MCF‐7 breast cancer cells under normoxic and hypoxia‐mimicking conditions (CoCl2 exposure). Using immunoblotting, ELISA, and quantitative real‐time PCR, we demonstrated that miR‐20b decreased VEGF protein levels at 4 and 24 h following CoCl2 treatment, and VEGF mRNA at 4 h of treatment. In addition, miR‐20b reduced VEGF protein expression in untreated cells. Next, we investigated the molecular mechanism by which pre‐miR‐20b can affect VEGF transcription, focusing on hypoxia inducible factor 1 (HIF‐1) and signal transducer and activator of transcription 3 (STAT3), transcriptional inducers of VEGF and putative targets of miR‐20b. Downregulation of VEGF mRNA by miR‐20b under a 4 h of CoCl2 treatment was associated with reduced levels of nuclear HIF‐1α subunit and STAT3. Chromatin immunoprecipitation (ChIP) assays revealed that HIF‐1α, but not STAT3, was recruited to the VEGF promoter following the 4 h of CoCl2 treatment. This effect was inhibited by transfection of cells with pre‐miR‐20b. In addition, using siRNA knockdown, we demonstrated that the presence of STAT3 is necessary for CoCl2‐mediated HIF‐1α nuclear accumulation and recruitment on VEGF promoter. In summary, this report demonstrates, for the first time, that the VEGF expression in breast cancer cells is mediated by HIF‐1 and STAT3 in a miR‐20b‐dependent manner. J. Cell. Physiol. 224:242–249, 2010 © 2010 Wiley‐Liss, Inc.
3D reconstruction of histological sections: Application to mammary gland tissue
Authors: Arganda‐Carreras Ignacio , Fernández‐González Rodrigo , Muñoz‐Barrutia Arrate , Ortiz‐De‐Solorzano Carlos 
Published: March 2010

AbstractIn this article, we present a novel method for the automatic 3D reconstruction of thick tissue blocks from 2D histological sections. The algorithm completes a high‐content (multiscale, multifeature) imaging system for simultaneous morphological and molecular analysis of thick tissue samples. This computer‐based system integrates image acquisition, annotation, registration, and three‐dimensional reconstruction. We present an experimental validation of this tool using both synthetic and real data. In particular, we present the 3D reconstruction of an entire mouse mammary gland and demonstrate the integration of high‐resolution molecular data. Microsc. Res. Tech. 73:1019–1029, 2010. © 2010 Wiley‐Liss, Inc.
Structural and functional consequences of poly(ethylene glycol) inclusion on DNA condensation for gene delivery
Authors: Millili Peter G. , Selekman Joshua A. , Blocker Kory M. , Johnson David A. , Naik Ulhas P. , Sullivan Millicent O. 
Published: March 2010

AbstractPolycationic polymers have been used to condense therapeutic DNA into submicron particles, offering protection from shear‐induced or enzymatic degradation. However, the spontaneous nature of this self‐assembly process gives rise to the formation of multimolecular aggregates, resulting in significant polyplex heterogeneity. Additionally, cytotoxicity issues and serum instability have limited the in vivo efficacy of such systems. One way these issues can be addressed is through the inclusion of poly(ethylene glycol) (PEG). PEG has known steric effects that inhibit polyplex self‐aggregation. A variety of PEGylated gene delivery formulations have been previously pursued in an effort to take advantage of this material's benefits. Because of such interest, our aim was to further explore the consequences of PEG inclusion on the structure and activity of gene delivery vehicle formulations. We explored the complexation of plasmid DNA with varying ratios of a PEGylated trilysine peptide (PEG‐K3) and 25‐kDa polyethylenimine (PEI). Atomic force and scanning electron microscopy were utilized to assess the polyplex size and shape and revealed that a critical threshold of PEG was necessary to promote the formation of homogeneous polyplexes. Flow cytometry and fluorescence microscopy analyses suggested that the presence of PEG inhibited transfection efficiency as a consequence of changes in intracellular trafficking and promoted an increased reliance on energy‐independent mechanisms of cellular uptake. These studies provide new information on the role of PEG in delivery vehicle design and lay the foundation for future work aimed at elucidating the details of the intracellular transport of PEGylated polyplexes. Microsc. Res. Tech. 73:866–877, 2010. © 2010 Wiley‐Liss, Inc.
Two and three‐dimensional gene transfer from enzymatically degradable hydrogel scaffolds
Authors: Lei Yuguo , Ng Quinn K.T. , Segura Tatiana 
Published: March 2010

AbstractThe ability to genetically modify mesenchymal stem cells (MSCs) seeded inside synthetic hydrogel scaffolds would offer an alternative approach to guide MSC differentiation. In this report, we explored gene transfer to MSCs seeded on top or inside matrix metalloproteinase (MMP) degradable hydrogels that were loaded with DNA/poly(ethylene imine) (PEI) polyplexes. DNA/PEI polyplexes were encapsulated inside poly(ethylene glycol) (PEG) hydrogels crosslinked with MMP degradable peptides via Michael Addition chemistry. Gene transfer was visualized and quantified through using a vector encoding for green fluorescent protein and luciferase. We found that gene transfer to MSCs was possible for cells seeded both in two and three dimensions. The amount of luciferase expression was similar for cells seeded in two and three dimensions even though the number of cells in three dimensions is significantly higher, indicating that gene transfer to cells seeded in two dimensions is more efficient than for cells seeded in three dimensions. The use of hydrogel scaffolds that allow cellular infiltration to deliver DNA may result in long‐lasting signals in vivo, which are essential for the regeneration of functional tissues. Microsc. Res. Tech. 73:910–917, 2010. © 2010 Wiley‐Liss, Inc.
Imaging multiple intermediates of single‐virus membrane fusion mediated by distinct fusion proteins
Authors: Joo Kye‐Il , Tai April , Lee Chi‐Lin , Wong Clement , Wang Pin 
Published: March 2010

AbstractMembrane fusion plays an essential role in the entry of enveloped viruses into target cells. The merging of viral and target cell membranes is catalyzed by viral fusion proteins, which involves multiple sequential steps in the fusion process. However, the fusion mechanisms mediated by different fusion proteins involve multiple transient intermediates that have not been well characterized. Here, we report a synthetic virus platform that allows us to better understand the different fusion mechanisms driven by the diverse types fusion proteins. The platform consists of lentiviral particles coenveloped with a surface antibody, which serves as the binding protein, along with a fusion protein derived from either influenza virus (HAmu) or Sindbis virus (SINmu). By using a single virus tracking technique, we demonstrated that both HAmu‐ and SINmu‐bearing viruses enter cells through clathrin‐dependent endocytosis, but they required different endosomal trafficking routes to initiate viral fusion. Direct observation of single viral fusion events clearly showed that hemifusion mediated by SINmu upon exposure to low pH occurs faster than that mediated by HAmu. Monitoring sequential fusion processes by dual labeling the outer and inner leaflets of viral membranes also revealed that the SINmu‐mediated hemifusion intermediate is relatively long‐lived as compared with that mediated by HAmu. Taken together, we have demonstrated that the combination of this versatile viral platform with the techniques of single virus tracking can be a powerful tool for revealing molecular details of fusion mediated by various fusion proteins. Microsc. Res. Tech. 73:886–900, 2010. © 2010 Wiley‐Liss, Inc.
Multiscale observation of biological interactions of nanocarriers: From nano to macro
Authors: Jin Su‐Eon , Bae Jin Woo , Hong Seungpyo 
Published: March 2010

AbstractMicroscopic observations have played a key role in recent advancements in nanotechnology‐based biomedical sciences. In particular, multiscale observation is necessary to fully understand the nano‐bio interfaces where a large amount of unprecedented phenomena have been reported. This review describes how to address the physicochemical and biological interactions of nanocarriers within the biological environments using microscopic tools. The imaging techniques are categorized based on the size scale of detection. For observation of the nanoscale biological interactions of nanocarriers, we discuss atomic force microscopy (AFM), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). For the micro to macro‐scale (in vitro and in vivo) observation, we focus on confocal laser scanning microscopy (CLSM) as well as in vivo imaging systems such as magnetic resonance imaging (MRI), superconducting quantum interference devices, and IVIS®. Additionally, recently developed combined techniques such as AFM‐CLSM, correlative light and electron microscopy (CLEM), and SEM spectroscopy are also discussed. In this review, we describe how each technique helps elucidate certain physicochemical and biological activities of nanocarriers such as dendrimers, polymers, liposomes, and polymeric/inorganic nanoparticles, thus providing a toolbox for bioengineers, pharmaceutical scientists, biologists, and research clinicians. Microsc. Res. Tech. 73:813–823, 2010. © 2010 Wiley‐Liss, Inc.