bluuebunny/crossref_metadata_2025_split huggingface dataset:
Raloxifene induces cell death and inhibits proliferation through multiple signaling pathways in prostate cancer cells expressing different levels of estrogen receptorα and β
Authors: Rossi V. , Bellastella G. , De Rosa C. , Abbondanza C. , Visconti D. , Maione L. , Chieffi P. , Della Ragione F. , Prezioso D. , De Bellis A. , Bellastella A. , Sinisi A.A. 
Published: October 2010

AbstractRaloxifene (RAL), a selective estrogen receptor (ER) modulator (SERM) seems to induce apoptosis in both androgen‐dependent and ‐independent prostate cell (PC) lines via activation of ERβ and an antagonistic effect on ERα. In this study, we evaluated the effects of RAL on epithelial PC growth using the two following in vitro models: the androgen‐dependent cell line EPN which expressed both ERs; and a stabilized epithelial cell line derived from a prostate cancer specimen (CPEC), which expressed low levels of ERβ and lacked ERα. In EPN cells, there was an increase in the pre‐G1 apoptotic peak and a reduction in the S phase of the cell cycle with G0/G1 arrest after E2 or RAL treatment;bcl‐2mRNA and Bcl‐2 protein levels were significantly reduced, while activated caspase‐3 and Par‐4 levels increased significantly after either E2 or RAL treatment; in addition, c‐myc transcript was inhibited after 10−6 M RAL treatment. A dose‐dependent increase of metallothionein II gene RNA level was also induced by RAL in EPN. In CPEC, there was only a weak apoptotic peak associated with caspase‐3 activation and Par‐4 increase after either E2 or RAL treatment; while c‐myc transcript level increased. RAL induced a rapid but transient phosphorylation of ERK 1/2 in EPN cells but generated a sustained effect in CPEC. These findings suggest that RAL effects on PC growth control in vitro are cell‐specific, depending on ERβ or ERβ/ERα relative expression levels. Moreover, this study demonstrated that RAL affected both transcriptional regulation and non‐genomic signals, which resulted in the modulation of multiple signaling pathways of apoptosis and of cell cycle progression. J. Cell. Physiol. 226: 1334–1339, 2011. © 2010 Wiley‐Liss, Inc.
Urinary 8‐OHdG elevations in a partial lesion rat model of parkinson's disease correlate with behavioral symptoms and nigrostriatal dopaminergic depletion
Authors: Kikuchi Yoichiro , Yasuhara Takao , Agari Takashi , Kondo Akihiko , Kuramoto Satoshi , Kameda Masahiro , Kadota Tomohito , Baba Tanefumi , Tajiri Naoki , Wang Feifei , Tayra Judith T. , Liang Hanbai , Miyoshi Yasuyuki , Borlongan Cesario V. , Date Isao 
Published: October 2010

AbstractIncreased oxidative stress contributes to pathogenesis of Parkinson's disease (PD). 8‐hydroxy‐2'‐deoxyguanosine (8‐OHdG) is the oxidation product most frequently measured as an indicator of oxidative DNA damage. Several studies have shown increased 8‐OHdG in PD patients. There are few basic laboratory data examining 8‐OHdG levels in animal models of PD. In this study, we utilized hemiparkinsonian model of rats induced by intrastriatal injection of 6‐hydroxydopamine (6‐OHDA). The urinary 8‐OHdG level was measured in relation to behavioral and pathological deficits arising from 6‐OHDA‐induced neurotoxic effects on the nigrostriatal dopaminergic pathway. All rats were subjected to a series of behavioral tests for 42 days after 6‐OHDA injection. We collected urine samples with subsequent measurement of 8‐OHdG level using ELISA kits. For immunohistochemical evaluation, tyrosine hydroxylase (TH) staining was performed. Significant increments in urinary 8‐OHdG level were observed continuously from day 7 until day 35 compared to control group, which showed a trend of elevation as early as day 3. Such elevated urinary 8‐OHdG level significantly correlated with all of the behavioral deficits measured here, suggesting that urinary 8‐OHdG level provides a good index of severity of parkinsonism. Urinary 8‐OHdG level also had a significant positive correlation with the survival rate of dopaminergic fibers or neurons, advancing the concept that oxidative stress during the early phase of 6‐OHDA neurotoxicity may correspond to disease progression closely approximating neuronal degeneration in the nigrostriatal dopaminergic system. The present results demonstrate that alterations in urinary 8‐OHdG level closely approximate onset and disease progression in PD. J. Cell. Physiol. 226: 1390–1398, 2011. © 2010 Wiley‐Liss, Inc.
Dicer is required for the formation of white but not brown adipose tissue
Authors: Mudhasani Rajini , Puri Vishwajeet , Hoover Kathleen , Czech Michael P. , Imbalzano Anthony N. , Jones Stephen N. 
Published: October 2010

AbstractDicer, an enzyme involved in microRNA maturation, is required for proper embryo gastrulation and tissue morphogenesis during mammalian development. Using primary cultures of fibroblasts and pre‐adipocytes, we have previously shown that Dicer is essential for early stages of adipogenic cell differentiation. In this study, we have utilized Dicer‐conditional mice to explore a role for Dicer and microRNA biogenesis in the terminal differentiation of adipocytes in vivo and in the formation of white and brown adipose tissue. Deletion of Dicer in differentiated adipocytes in Dicer‐conditional, aP2‐Cre transgenic mice reduced the level of various adipogenic‐associated transcripts and inhibited lipogenesis in white adipocytes, resulting in a severe depletion of white adipose tissue in mice. In contrast, Dicer was not required in vivo for lipogenesis in brown adipose or for brown fat formation. However, Dicer deletion in brown adipose did decrease the expression of genes involved in thermoregulation. The results of our study provide genetic evidence of a role for microRNA molecules in regulating adipogenesis and reveal distinct requirements for Dicer in the formation of white and brown adipose tissue. J. Cell. Physiol. 226: 1399–1406, 2011. © 2010 Wiley‐Liss, Inc.
MicroRNA‐24 regulates the processing of latent TGFβ1 during cyclic mechanical stress in human trabecular meshwork cells through direct targeting of FURIN
Authors: Luna Coralia , Li Guorong , Qiu Jianming , Epstein David L. , Gonzalez Pedro 
Published: October 2010

AbstractCyclic mechanical stress (CMS) leads to alterations of cellular functions in the trabecular meshwork (TM), including the up‐regulation of transforming growth factor beta 1 (TGFβ1), that can potentially contribute to the pathogenesis of glaucoma. Although microRNAs (miRNAs) are known to play important roles in many biological functions, little is known about their potential involvement in the cellular responses elicited by mechanical stress. Here we analyzed changes in miRNA expression induced by CMS, and examined the possible role of miR‐24 in the response of human TM cells to CMS. CMS induced the expression of miR‐24 that led to the down regulation of the subtilisin‐like proprotein convertase FURIN, which is known to play a major role in the processing of TGFβ1. FURIN was confirmed as a novel target of miR‐24 by 3' UTR luciferase assay and western blot. Overexpression of miR‐24 resulted in a significant decrease in activated TGFβ1. This effect was mimicked by down regulation of FURIN by siRNA. Conversely, inhibition of miR‐24 expression with a specific antagomir led to a small but significant increase in TGFβ1. Furthermore, the increase in active TGFβ1 induced by CMS in HTM cells was prevented by miR‐24. Altogether, our results suggest that miRNAs might contribute to the regulation of responses to CMS in TM cells. Specifically, miR‐24 might play an important role in modulating the induction of TGFβ1 mediated by CMS through direct targeting of FURIN. J. Cell. Physiol. 226: 1407–1414, 2011. © 2010 Wiley‐Liss, Inc.
Analysis of dynamic tyrosine phosphoproteome in LFA‐1 triggered migrating t‐cells
Authors: Verma Navin K. , Dempsey Eugene , Freeley Michael , Botting Catherine H. , Long Aideen , Kelleher Dermot , Volkov Yuri 
Published: October 2010

AbstractThe ordered, directional migration of T‐lymphocytes is a key process during immune surveillance and response. This requires cell adhesion to the high endothelial venules or to the extracellular matrix by a series of surface receptor/ligand interactions involving adhesion molecules of the integrin family including lymphocyte function associated molecule‐1 (LFA‐1) and intercellular adhesion molecules (ICAMs). Reversible protein phosphorylation is emerging as a key player in the regulation of biological functions with tyrosine phosphorylation playing a crucial role in signal transduction. Thus, the study of this type of post‐translational modification at the proteomic level has great biological significance. In this work, phospho‐enriched cell lysates from LFA‐1‐triggered migrating human T‐cells were subjected to immunoaffinity purification of tyrosine phosphorylated proteins, mass spectrometric, and bioinformatic analysis. In addition to the identification of several well‐documented proteins, the analysis suggested involvement of a number of new and novel proteins in LFA‐1 induced T‐cell migration. This dataset expands the list of the signaling components of the LFA‐1 induced phosphotyrosine protein complexes in migrating T‐cells that will be extremely useful in the study of their specific roles within LFA‐1 associated signaling pathways. Identification of proteins previously not reported in the context of LFA‐1 stimulated signal transduction might provide new insights into understanding the LFA‐1 signaling networks and aid in the search for new potential therapeutic targets. J. Cell. Physiol. 226: 1489–1498, 2011. © 2010 Wiley‐Liss, Inc.
Control of lung development by latent TGF‐β binding proteins
Authors: Dabovic Branka , Chen Yan , Choi Jiwon , Davis Elaine C. , Sakai Lynn Y. , Todorovic Vesna , Vassallo Melinda , Zilberberg Lior , Singh Amanjot , Rifkin Daniel B. 
Published: October 2010

AbstractThe latent TGF‐β binding proteins (LTBP‐1 ‐3, and ‐4) assist in the secretion and localization of latent TGF‐β molecules. Ltbp3−/−and Ltbp4S−/− mice have distinct phenotypes and only in the lungs does deficiency of either Ltbp‐3 or Ltbp‐4 cause developmental abnormalities. To determine if these two LTBPs have additional common functions, we generated mice deficient for both Ltbp‐3 and Ltbp‐4S. The only novel defect in Ltbp3−/−;Ltbp4S−/− mice was an early lethality compared to mice with single mutations. In addition lung abnormalities were exacerbated and the terminal air sac septation defect was more severe in Ltbp3−/−;Ltbp4S−/− mice than in Ltbp4S−/− mice. Decreased cellularity of Ltbp3−/−;Ltbp4S−/− lungs was correlated with higher rate of apoptosis in newborn lungs of Ltbp3−/−;Ltbp4S−/− animals compared to WT, Ltbp3−/−, and Ltbp4S−/− mice. No differences in the maturation of the major lung cell types were discerned between the single and double mutant mice. However, the distribution of type 2 cells and myofibroblasts was abnormal, and myofibroblast segregation in some areas might be an indication of early fibrosis. We also observed differences in ECM composition between Ltbp3−/−;Ltbp4S−/− and Ltbp4S−/− lungs after birth, reflected in decreased incorporation of fibrillin‐1 and ‐2 in Ltbp3−/−;Ltbp4S−/− matrix. The function of the lungs of Ltbp3−/−;Ltbp4S−/− mice after the first week of life was potentially further compromised by macrophage infiltration, as proteases secreted from macrophages might exacerbate developmental emphysema. Together these data indicate that LTBP‐3 and ‐4 perform partially overlapping functions only in the lungs. J. Cell. Physiol. 226: 1499–1509, 2011. © 2010 Wiley‐Liss, Inc.
Regulation of PIP5K activity by Arf6 and its physiological significance
Authors: Funakoshi Yuji , Hasegawa Hiroshi , Kanaho Yasunori 
Published: October 2010

AbstractThe phospholipid kinase phosphatidylinositol 4‐phosphate 5‐kinase (PIP5K) catalyzes the phosphorylation of the membrane phospholipid phosphatidylinositol 4‐phosphate to generate the pleiotropic phospholipid phosphatidylinositol 4,5‐bisphosphate [PI(4,5)P2]. To date, three mammalian PIP5K isozymes, α, β, and γ, and several splicing variants of the γ isozyme have been identified. These PIP5K isozymes and PIP5Kγ variants play critical roles in various cellular functions through their product PI(4,5)P2. The small GTPase Arf6 is one of the key activators of PIP5K. Increasing evidence suggests that PIP5K functions as a downstream effector of Arf6 to regulate a wide variety of cellular functions, such as exocytosis, endocytosis, endosomal recycling, membrane ruffle formation, immune response, and bacterial invasion. In this review, we place our focus on the recent advances in Arf6/PIP5K signaling and its linkage to cellular functions. J. Cell. Physiol. 226: 888–895, 2011. © 2010 Wiley‐Liss, Inc.
Human embryonic stem cell proliferation and differentiation as parameters to evaluate developmental toxicity
Authors: Pal Rajarshi , Mamidi Murali Krishna , Kumar Das Anjan , Bhonde Ramesh 
Published: October 2010

AbstractIn vitro models based on embryonic stem cells (ESC) are highly promising for improvement of predictive toxicology screening in humans. After the successful validation of embryonic stem cell test (EST) in 2001; concerns have been raised on the usage of mouse ESC and also the morphological evaluation of beating cell clusters. This requires specialized skill‐sets and is highly prone to misjudgement and false positive results. To overcome these limitations, we undertook the present study incorporating improvisations over the conventional EST. Here, we explored the potential of a human ESC (hESC)‐based assay to evaluate the potential toxicity of penicillin‐G, caffeine, and hydroxyurea. Drug treatment inhibited hESC adhesion and substantially altered the morphology and viability (∼50%) of embryoid bodies (EBs). Flow cytometry analysis not only showed a significant increase of apoptotic cells in the highest doses but also induced a diverse pattern in DNA content and cell cycle distribution relative to control. Both semi‐quantitative and quantitative RT‐PCR studies revealed a selective down regulation of markers associated with stemness (Nanog, Rex1, SOX‐2, and hTERT); cardiac mesoderm (Cripto1, MEF‐2C, and Brachyury); hepatic endoderm (AFP, HNF‐3β, HNF‐4α, GATA‐4, and SOX‐17); and neuroectoderm (Nestin, SOX‐1, NURR1, NEFH, Synaptophysin, TH, and Olig2) in a drug as well as dose dependent manner indicating abnormal differentiation. Furthermore, a decrease in the expression of AFP and GFAP proteins followed by a dose‐dependent reduction in the levels of hCG‐β, progesterone‐II, and estradiol hormones was demonstrated by immunocytochemistry and ECLIA, respectively. This new and unique approach comprising of DNA cell cycle analysis, germ layer‐specific marker expression and hormone levels as endpoints might offer a clinically relevant and commercially viable alternative for predicting in vivo developmental toxicity. J. Cell. Physiol. 226: 1583–1595, 2011. © 2010 Wiley‐Liss, Inc.
Divalent metal transporter 1 is a hypoxia‐inducible gene
Authors: Qian Zhong‐Ming , Mei Wu Xiao , Fan Ming , Yang Lin , Du Fang , Yung Wing‐Ho , Ke Ya 
Published: October 2010

AbstractOur recent study revealed a high correlation between the expression of hypoxia‐inducible factor‐1 (HIF‐1) alpha and divalent metal transporter 1 (DMT1) in HepG2 cells treated with chemical or physical hypoxia. We therefore speculated that DMT1 might be one of the target genes of HIF‐1. Here, we characterized the DMT1 exon1B promoter region and identified a functional hypoxia response element (HRE, 5′‐TCAGTACCTAACGTGGCGCCACGGC‐3′) harboring a binding site for HIF‐1. We demonstrated that hypoxia‐dependent activation of a luciferase reporter gene in transfected HepG2 cells is mediated by a fragment of human DMT1 exon1B promoter containing the putative HRE sequence. We also showed that the HIF‐1 binding site (HBS) is in DMT1 exon1B promoter with the core sequence of HRE (5′‐ACGTG‐3′) at −327 to −323 relative to the transcription start site of the human DMT1 exon1B gene. The mutation of this sequence prevented stimulation of luciferase activity. Electrophoretic mobility shift assays revealed that the HRE sequence found in the DMT1 gene promoter was bound by HIF‐1. In addition, we provide evidence that hypoxia could significantly increase ferrous uptake, while the silencing of total DMT1 by RNA interference down‐regulates DMT1 expression and ferrous uptake in HepG2 cells. We conclude that DMT1 is a hypoxia‐inducible gene. J. Cell. Physiol. 226: 1596–1603, 2011. © 2010 Wiley‐Liss, Inc.
Exhaustive exercise increases inflammatory response via toll like receptor‐4 and NF‐κBp65 pathway in rat adipose tissue
Authors: Rosa José C. , Lira Fábio S. , Eguchi Ricardo , Pimentel Gustavo D. , Venâncio Daniel P. , Cunha Cláudio A. , Oyama Lila M. , De Mello Marco T. , Seelaender Marília , Oller do Nascimento Cláudia M. 
Published: October 2010

AbstractCytokines (IL‐6, IL‐10, and TNF‐α) are increased after exhaustive exercise in the retroperitoneal adipose tissue (RPAT) and mesenteric adipose tissue (MEAT). An exhaustive acute exercise protocol induces inflammation in adipose tissue that lasts 6 h after the exercise has ended. It is well‐established that this protocol increases circulating plasma levels of non‐esterified fatty acids (NEFAs) and lipopolysaccharides (LPS), compounds that are important in stimulating signaling via toll like receptor‐4 (TLR‐4) in different type cells. In the present study, we investigated the regulation of TLR‐4 and DNA‐binding of nuclear factor‐κBp65 (NF‐κBp65) in different depots of adipose tissue in rats after exhaustive exercise. Rats were killed by decapitation immediately (E0 group, n = 6), 2 (E2 group, n = 6), and 6 h (E6 group, n = 6) after the exhaustive exercise, which consisted of running on a treadmill (approximately 70% VO2max) for 50 min and then running at an elevated rate that increased at 1 m/min, until exhaustion. The control group (C group, n = 6) was not subjected to exercise. In RPAT, TLR‐4, MYD‐88, and IkBα increased in the E2 group after exercise. MYD‐88 and TRAF6 remained increased in the E6 group in comparison with the control group. DNA‐binding of NF‐κBp65 was not altered. In MEAT, TLR‐4, MYD‐88, TRAF6, and DNA‐binding of NF‐κBp65 were increased only in the E6 group. In conclusion, we have shown that increases in pro‐inflammatory cytokines in adipose tissue pads after exhaustive exercise may be mediated via TLR‐4 signaling, leading to increases in NF‐κBp65 binding to DNA in MEAT. J. Cell. Physiol. 226: 1604–1607, 2011. © 2010 Wiley‐Liss, Inc.
Recurrent readmissions in medical patients: A prospective study
Authors: Mudge Alison M , Kasper Karen , Clair Anne , Redfern Helen , Bell Jack J , Barras Michael A , Dip Grad , Pachana Nancy A 
Published: October 2010

AbstractBACKGROUND:Hospital readmissions are common and costly. A recent previous hospitalization preceding the index admission is a marker of increased risk of future readmission.OBJECTIVES:To identify factors associated with an increased risk of recurrent readmission in medical patients with 2 or more hospitalizations in the past 6 months.DESIGN:Prospective cohort study.SETTING:Australian teaching hospital acute medical wards, February 2006‐February 2007.PARTICIPANTS:142 inpatients aged ≥50 years with a previous hospitalization ≤6 months preceding the index admission. Patients from residential care, with terminal illness, or with serious cognitive or language difficulties were excluded.VARIABLES OF INTEREST:Demographics, previous hospitalizations, diagnosis, comorbidities and nutritional status were recorded in hospital. Participants were assessed at home within 2 weeks of hospital discharge using validated questionnaires for cognition, literacy, activities of daily living (ADL)/instrumental activities of daily living (IADL) function, depression, anxiety, alcohol use, medication adherence, social support, and financial status.MAIN OUTCOME MEASURE:Unplanned readmission to the study hospital within 6 months.RESULTS:A total of 55 participants (38.7%) had a further unplanned hospital admission within 6 months. In multivariate analysis, chronic disease (adjusted odds ratio [OR] 3.4; 95% confidence interval [CI], 1.3‐9.3, P = 0.002), depressive symptoms (adjusted OR, 3.0; 95% CI, 1.3‐6.8, P = 0.01), and underweight (adjusted OR, 12.7; 95% CI, 2.3‐70.7, P = 0.004) were significant predictors of readmission after adjusting for age, length of stay and functional status.CONCLUSIONS:In this high‐risk patient group, multiple chronic conditions are common and predict increased risk of readmission. Post‐hospital interventions should consider targeting nutritional and mood status in this population. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.
A comparison study of continuous insulin infusion protocols in the medical intensive care unit: Computer‐guided vs. standard column‐based algorithms
Authors: Newton Christopher A. , Smiley Dawn , Bode Bruce W. , Kitabchi Abbas E. , Davidson Paul C. , Jacobs Sol , Steed R. Dennis , Stentz Frankie , Peng Limin , Mulligan Patrick , Freire Amado X. , Temponi Angel , Umpierrez Guillermo E. 
Published: October 2010

AbstractPURPOSE:To compare the safety and efficacy of continuous insulin infusion (CII) via a computer‐guided and a standard paper form protocol in a medical intensive care unit (ICU).METHODS:Multicenter randomized trial of 153 ICU patients randomized to CII using the Glucommander (n = 77) or a standard paper protocol (n = 76). Both protocols used glulisine insulin and targeted blood glucose (BG) between 80 mg/dL and 120 mg/dL.RESULTS:The Glucommander resulted in a lower mean BG value (103 ± 8.8 mg/dL vs. 117 ± 16.5 mg/dL, P < 0.001) and in a shorter time to reach BG target (4.8 ± 2.8 vs.7.8 hours ± 9.1 hours, P < 0.01), and once at target resulted in a higher percentage of BG readings within target (71.0 ± 17.0% vs. 51.3 ± 19.7%, P < 0.001) than the standard protocol. Mean insulin infusion rate in the Glucommander was similar to the standard protocol (P = 0.12). The percentages of patients with ≥1 episode of BG <40 mg/dL and <60 mg/dL were 3.9% and 42.9% in the Glucommander and 5.6% and 31.9% in the standard, respectively [P = not significant (NS)]. Repeated measures analyses show that the probabilities of BG reading <40 mg/dL or <60 mg/dL were not significantly different between groups (P = 0.969, P = 0.084) after accounting for within‐patient correlations with or without adjusting for time effect. There were no differences between groups in the length of hospital stay (P = 0.704), ICU stay (P = 0.145), or inhospital mortality (P = 0.561).CONCLUSION:Both treatment algorithms resulted in significant improvement in glycemic control in critically ill patients in the medical ICU. The computer‐based algorithm resulted in tighter glycemic control without an increased risk of hypoglycemic events compared to the standard paper protocol. Journal of Hospital Medicine 2010. © 2010 Society of Hospital Medicine.