bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physical exercise, body mass index and risk of chronic arm pain: Longitudinal data on an adult population in Norway
Authors: Mork P.J. , Holtermann A. , Nilsen T.I.L. 
Published: March 2013

AbstractAimThe aim of this study was to prospectively investigate the association between leisure time physical exercise, body mass index (BMI) and risk of chronic arm pain.MethodsThe study population comprises 14,041 women and 13,674 men in the Norwegian HUNT Study without musculoskeletal pain or physical impairment at baseline in 1984–86. Chronic arm pain was assessed at follow‐up in 1995–97. A generalized linear model was used to calculate adjusted relative risks (RRs).ResultsAt follow‐up, 2205 women and 1458 men reported chronic arm pain. Level of physical exercise was inversely associated with risk of chronic arm pain (P‐trend, ≤0.03 for both sexes). Compared with inactive persons, women and men who exercised ≥ 2 h/week had adjusted RRs of 0.84 [95% confidence interval (CI), 0.73–0.96] and 0.74 (95% CI, 0.63–0.87), respectively. BMI was positively associated with risk of chronic arm pain (P‐trend, ≤0.002 for both sexes). Compared with normal‐weight persons, women and men classified as obese (BMI ≥ 30 kg/m2) had adjusted RRs of 1.26 (95% CI, 1.11–1.44) and 1.29 (95% CI, 1.07–1.57), respectively. Combined analysis showed that obese women and men who exercised ≥ 1 h/week had a RR of 1.20 (95% CI 0.97–1.48) compared with normal‐weight women and men with a similar activity level, whereas the RR was 1.41 (95% CI 1.21–1.65) for obese women and men who were physically inactive.ConclusionRegular physical exercise reduces risk of chronic arm pain while high BMI increases the risk. Exercise can to some extent compensate for the adverse effect of obesity on risk of chronic arm pain.
The Effect of Rosiglitazone on Bone Mass and Fragility Is Reversible and Can Be Attenuated With Alendronate
Authors: Kumar Sanjay , Hoffman Sandra J , Samadfam Rana , Mansell Peter , Jolette Jacquelin , Smith Susan Y , Guldberg Robert E , Fitzpatrick Lorraine A 
Published: March 2013

ABSTRACT

Rosiglitazone (RSG) is an antidiabetic drug that has been associated with increased peripheral fractures, primarily in postmenopausal women. In this report, we investigated the underlying mechanisms of RSG-associated bone loss in ovariectomized (OVX) rats and determined whether changes in bone parameters associated with RSG administration are reversible on treatment cessation or preventable by coadministration with an antiresorptive agent. Nine-month-old Sprague-Dawley rats underwent OVX or sham operation. Sham-operated rats received oral vehicle only; OVX animals were randomized to receive vehicle, RSG, alendronate (ALN), or RSG plus ALN for 12 weeks. All treatment started the day after ovariectomy. After the 12-week treatment period, the OVX and RSG groups also underwent an 8-week treatment-free recovery period. Bone densitometry measurements, bone turnover markers, biomechanical testing, and histomorphometric analysis were conducted. Microcomputed tomography was also used to investigate changes in microarchitecture. RSG significantly increased deoxypyridinoline levels compared with OVX. Significant exacerbation of OVX-induced loss of bone mass, strength, and microarchitectural deterioration was observed in RSG-treated OVX animals compared with OVX controls. These effects were observed predominantly at sites rich in trabecular bone, with less pronounced effects in cortical bone. Coadministration of RSG and ALN prevented the bone loss associated with RSG treatment. Following cessation of RSG treatment, effects on bone mass and strength showed evidence of reversal. Thus, treatment of OVX rats with RSG results in loss of bone mass and strength, primarily at sites rich in trabecular bone, mainly due to increased bone resorption. These effects can be prevented by concomitant treatment with ALN and may be reversed following discontinuation of RSG.
Fast Trabecular Bone Strength Predictions of HR-pQCT and Individual Trabeculae Segmentation–Based Plate and Rod Finite Element Model Discriminate Postmenopausal Vertebral Fractures
Authors: Liu X Sherry , Wang Ji , Zhou Bin , Stein Emily , Shi Xiutao , Adams Mark , Shane Elizabeth , Guo X Edward 
Published: March 2013

ABSTRACT

Although high-resolution peripheral quantitative computed tomography (HR-pQCT) has advanced clinical assessment of trabecular bone microstructure, nonlinear microstructural finite element (µFE) prediction of yield strength using a HR-pQCT voxel model is impractical for clinical use due to its prohibitively high computational costs. The goal of this study was to develop an efficient HR-pQCT-based plate and rod (PR) modeling technique to fill the unmet clinical need for fast bone strength estimation. By using an individual trabecula segmentation (ITS) technique to segment the trabecular structure into individual plates and rods, a patient-specific PR model was implemented by modeling each trabecular plate with multiple shell elements and each rod with a beam element. To validate this modeling technique, predictions by HR-pQCT PR model were compared with those of the registered high-resolution micro–computed tomography (HR-µCT) voxel model of 19 trabecular subvolumes from human cadaveric tibia samples. Both the Young's modulus and yield strength of HR-pQCT PR models strongly correlated with those of µCT voxel models (r2 = 0.91 and 0.86). Notably, the HR-pQCT PR models achieved major reductions in element number (&gt;40-fold) and computer central processing unit (CPU) time (&gt;1200-fold). Then, we applied PR model µFE analysis to HR-pQCT images of 60 postmenopausal women with (n = 30) and without (n = 30) a history of vertebral fracture. HR-pQCT PR model revealed significantly lower Young's modulus and yield strength at the radius and tibia in fracture subjects compared to controls. Moreover, these mechanical measurements remained significantly lower in fracture subjects at both sites after adjustment for areal bone mineral density (aBMD) T-score at the ultradistal radius or total hip. In conclusion, we validated a novel HR-pQCT PR model of human trabecular bone against µCT voxel models and demonstrated its ability to discriminate vertebral fracture status in postmenopausal women. This accurate nonlinear µFE prediction of the HR-pQCT PR model, which requires only seconds of desktop computer time, has tremendous promise for clinical assessment of bone strength.
Plasminogen Plays a Crucial Role in Bone Repair
Authors: Kawao Naoyuki , Tamura Yukinori , Okumoto Katsumi , Yano Masato , Okada Kiyotaka , Matsuo Osamu , Kaji Hiroshi 
Published: March 2013

ABSTRACT

The further development in research of bone regeneration is necessary to meet the clinical demand for bone reconstruction. Plasminogen is a critical factor of the tissue fibrinolytic system, which mediates tissue repair in the skin and liver. However, the role of the fibrinolytic system in bone regeneration remains unknown. Herein, we investigated bone repair and ectopic bone formation using plasminogen-deficient (Plg–/–) mice. Bone repair of the femur is delayed in Plg–/– mice, unlike that in the wild-type (Plg+/+) mice. The deposition of cartilage matrix and osteoblast formation were both decreased in Plg–/– mice. Vessel formation, macrophage accumulation, and the levels of vascular endothelial growth factor (VEGF) and transforming growth factor-β (TGF-β) were decreased at the site of bone damage in Plg–/– mice. Conversely, heterotopic ossification was not significantly different between Plg+/+ and Plg–/– mice. Moreover, angiogenesis, macrophage accumulation, and the levels of VEGF and TGF-β were comparable between Plg+/+ and Plg–/– mice in heterotopic ossification. Our data provide novel evidence that plasminogen is essential for bone repair. The present study indicates that plasminogen contributes to angiogenesis related to macrophage accumulation, TGF-β, and VEGF, thereby leading to the enhancement of bone repair.
Noninvasive Diagnosis of Liver Fibrosis and Cirrhosis in Chronic Hepatitis C Patients
Authors: Attallah Abdelfattah M. , El‐Far Mohamed , Omran Mohamed M. , Farid Khaled , Albannan Mohamed S. , El‐Dosoky Ibrahim 
Published: March 2013

BackgroundWe aimed to derive a simple noninvasive test for liver‐fibrosis staging and then estimate its performance against four simple noninvasive tests in chronic hepatitis C (CHC) patients.MethodsCHC patients were divided into two cohorts: an estimation set (n = 324) and a validation set (n = 524). Liver fibrosis was staged according to the METAVIR scoring system. Statistical analysis was done using stepwise linear discriminant analysis and area under receiver‐operating characteristic curves (AUCs).ResultsBiotechnology Research Center (BRC) score was constructed combining several blood markers that proved useful to stage liver fibrosis. Aspartate aminotransferase /alanine aminotransferase ratio (AAR), aspartate to platelet ratio index (APRI), Fibro‐α, King, and BRC scores correlated with the histological fibrosis stages with correlation coefficient 0.26, 0.36, 0.58, 0.45, and 0.73, respectively. BRC score produced AUCs 0.87, 0.83, and 0.89 for significant (F2–F4), advanced fibrosis (F3–F4), and cirrhosis (F4), respectively. These results were reproduced in the validation study with no significant difference yielding AUCs 0.85 for F2–F4, 0.82 for F3–F4, and 0.88 for F4.ConclusionBRC score, a novel noninvasive test, is a useful and easy tool to evaluate liver fibrosis in CHC patients and seems more efficient than AAR, APRI, Fibro‐α score, and King's score in this group of Egyptian patients. J. Clin. Lab. Anal. 27:121–129, 2013. © 2013 Wiley Periodicals, Inc.
Linking membrane dynamics and trafficking to autophagy and the unfolded protein response
Authors: Chua Christelle En Lin , Tang Bor Luen 
Published: March 2013

AbstractCellular stressors typically induce two protective counter‐responses—autophagy and the unfolded protein response (UPR). It is conceivable that these two endoplasmic reticulum (ER) membrane‐based processes would intersect/interact somehow with the constitutive housekeeping process of exocytic membrane traffic from the ER. How exactly might this occur? Recent evidence indicates that a conserved Rab protein, Rab1/Ypt1p, has functional roles in UPR and autophagy. This molecular switch and its associated effectors may therefore serve to link up a network of cellular responses to stress through changes in membrane dynamics and protein turnover. The notion provides further explanations as to why elevation of Rab1/Ypt1p levels could counter the cytotoxicity of α‐synuclein, and a similar mode of protection may well be at work against other stresses. J. Cell. Physiol. 228: 1638–1640, 2013. © 2013 Wiley Periodicals, Inc.
MicroRNA transport: A new way in cell communication
Authors: Xu Ling , Yang Bao‐feng , Ai Jing 
Published: March 2013

AbstractMicroRNAs (miRNAs) can efficiently regulate gene expression by targeting mRNA to cause mRNA cleavage or translational repression. Growing evidence indicates that miRNAs exist not only in cells but also in a variety of body fluids, which stimulates substantial interest in the transport mechanism and regulating process of extracellular miRNAs. This article reviews the basic biogenesis of miRNAs in detail to explore the origin of extracellular miRNAs. Different miRNA transporters have been summarized (e.g., exosomes, microvesicles, apoptosis bodies, and RNA‐binding proteins). In addition, we discuss the regulators affecting miRNA transport (e.g., ATP and ceramide) and the selection mechanism for different miRNA transporters. Studies about miRNA transporters and the transport mechanism are new and developing. With the progress of the research, new functions of extracellular miRNAs may be uncovered in the future. J. Cell. Physiol. 228: 1713–1719, 2013. © 2013 Wiley Periodicals, Inc.
Cardiac resident nestin+ cells participate in reparative vascularisation
Authors: El‐Helou Vivianne , Chabot Andréanne , Gosselin Hugues , Villeneuve Louis , Clavet‐Lanthier Marie‐Elaine , Tanguay Jean‐Francois , Enikolopov Grigori , Fernandes Karl J.L. , Jasmin Jean‐Francois , Calderone Angelino 
Published: March 2013

AbstractThe rodent heart contains a population of nestin(+) cells derived from the embryonic neural crest and migrate to the scar after myocardial infarction (MI). The present study tested the hypothesis that intron 2 of the nestin gene drives expression and a subpopulation of nestin(+) cells participate in reparative vascularisation. The directed expression of the green fluorescent protein (GFP) by the second intron of the nestin gene identified GFP/nestin(+) cells intercalated among ventricular myocytes in the heart of normal transgenic mice. Ischemic injury led to the migration of GFP(+) cells to the scar and a subpopulation was detected in CD31/nestin(+) endothelial cells of newly formed blood vessels. The direct contribution to reparative vascularisation provided the impetus to test the hypothesis that increasing the population of nestin(+) cells in the infarcted heart will improve scar healing. Skin‐derived cells isolated from E18 Sprague–Dawley rats grew as spheres, expressed nestin, sox2, neural crest‐related transcriptional genes and a panel of peptide growth factors. Skin‐derived cells transplanted in the non‐infarcted left ventricle of 3‐day post‐MI rats migrated to the peri‐infarct/infarct region and remained engrafted for 21 days. A significantly smaller infarct, increased number of small calibre blood vessels and improved ventricular function were observed in engrafted infarcted rat hearts. Thus, the second intron of the nestin gene drives expression in the mouse heart and a subpopulation of GFP/nestin(+) cells directly participate in reparative vascularisation. Increasing the population of nestin(+) cells via the transplantation of skin‐derived cells represents a potential approach to limit ischemic damage to the heart. J. Cell. Physiol. 228: 1844–1853, 2013. © 2013 Wiley Periodicals, Inc.
Carcinoma‐associated fibroblasts: Non‐neoplastic tumour‐promoting mesenchymal cells
Authors: Polanska Urszula M. , Orimo Akira 
Published: March 2013

AbstractCancerous stroma coevolves alongside tumour progression, thereby promoting the malignant conversion of epithelial carcinoma cells. To date, an abundance of data have supported crucial roles of the tumour microenvironment (TME) in providing cancer cells with proliferative, migratory, survival and invasive propensities favouring the processes of tumourigenesis. The cancerous reactive stroma is frequently populated by a large number of myofibroblasts (MFs), which are activated, non‐transformed fibroblasts expressing α‐smooth muscle actin (α‐SMA). MFs together with non‐MF cells present in the tumour‐associated stroma are collectively referred to as carcinoma‐associated fibroblasts (CAFs), one of the major stromal cell types recognised in various human carcinomas. Recruitment of fibroblasts and/or their progenitors to a tumour mass and their subsequent transdifferentiation into MFs, as well as ongoing maintenance of their activated state, are believed to be essential processes facilitating tumour progression. However, the complex networks of signalling pathways mediating the phenotypic conversion into CAFs, as well as those underlying their tumour‐promoting interactions with other tumour‐constituting cells, have yet to be fully explored. Histopathological confirmation of the presence of large numbers of CAF MFs within TME and their altered gene expression profiles are known to be associated with disease progression and to serve as independent negative prognostic factors for a wide range of tumour types. In this review, we examine the current evidence shedding light on the emerging roles of tumour‐promoting CAFs, cells that are pivotal for epithelial cancer development and progression, and discuss the therapeutic potential of targeting these cells. J. Cell. Physiol. 228: 1651–1657, 2013. © 2013 Wiley Periodicals, Inc.
Adenosine, Adenosine Receptors and Their Role in Glucose Homeostasis and Lipid Metabolism
Authors: Koupenova Milka , Ravid Katya 
Published: March 2013

AbstractAdenosine is an endogenous metabolite that is released from all tissues and cells including liver, pancreas, muscle, and fat, particularly under stress, intense exercise, or during cell damage. The role of adenosine in glucose homeostasis has been attributed to its ability to regulate, through its membrane receptors, processes such as insulin secretion, glucose release and clearance, glycogenolysis, and glycogenesis. Additionally, adenosine and its multiple receptors have been connected to lipid metabolism by augmenting insulin‐mediated inhibition of lipolysis, and the subsequent increase in free fatty acids and glycerol levels. Furthermore, adenosine was reported to control liver cholesterol synthesis, consequently affecting plasma levels of cholesterol and triglycerides, and the amount of adipose tissue. Alterations in the balance of glucose and lipid homeostasis have implications in both cardiovascular disease and diabetes. The ability of different adenosine receptors to activate and inhibit the same signaling cascades has made it challenging to study the influence of adenosine, adenosine analogs and their receptors on health and disease. This review focuses on the role and significance of different adenosine receptors in mediating the effect of adenosine on glucose and lipid homeostasis. J. Cell. Physiol. 228: 1703–1712, 2013. © 2013 Wiley Periodicals, Inc.
Inactivation of p27kip1 promotes chemical hepatocarcinogenesis through enhancing inflammatory cytokine secretion and STAT3 signaling activation
Authors: Guo Jian , Ma Qingyong , Zhou Xiaojie , Fan Ping , Shan Tao , Miao Dengshun 
Published: March 2013

AbstractAlthough the expression of p27 has been regarded as a prognostic parameter in human liver cancer since the implication of decreased p27 expression levels in the genesis and progression of hepatocellular carcinoma (HCC), the molecular mechanism linking p27 deficiency and HCC development is still unclear. Here, we report an increase in tumorigenesis and progression as well as an enhanced inflammatory response in p27 deficient mice (p27−/−) and hypothesize the possible mechanism. We show that p27−/− mice display increased proliferation and decreased apoptosis of tumor cells, accompanied by an increase in the serum inflammatory cytokines IL‐6 and TNF‐α. Furthermore, our data indicated that the increased number and signal transducers and activator of transcription 3 (STAT3) phosphorylation status of infiltrated inflammatory cells was accompanied by increased IL‐6 and TNF‐α mRNA levels in tumor and normal liver tissue in the p27−/− mice. Moreover, using tumor cell and splenocytes co‐culture and tumor homologous transplantation, we validated our hypothesis in vitro and in vivo. Collectively, these data demonstrate that the loss of p27 promotes carcinogens‐induced HCC genesis and progression via the elevation of inflammatory cytokines and the augmented activation of STAT3 signaling in tumor cells and infiltrated inflammatory cells. Altogether, the loss of the cyclin kinase inhibitor p27, traditionally regarded as a consequence of DNA damage, can in turn promote HCC progression through enhancing the inflammatory response, potentially representing a promising therapeutic target in the prevention of HCC genesis and progression. J. Cell. Physiol. 228: 1967–1976, 2013. © 2013 Wiley Periodicals, Inc.
Transcriptional profiling of endometriosis tissues identifies genes related to organogenesis defects
Authors: Crispi Stefania , Piccolo Maria Teresa , D'avino Alfredo , Donizetti Aldo , Viceconte Rosa , Spyrou Maria , Calogero Raffaele A. , Baldi Alfonso , Signorile Pietro G. 
Published: March 2013

AbstractEndometriosis is a common benign pathology, characterised by the presence of endometrial tissue outside the endometrial cavity with a prevalence of 10–15% in reproductive‐aged women. The pathogenesis is not completely understood, and several theories have been proposed to explain the aetiology. Our group has recently described the presence of ectopic endometrium in a consistent number of human female foetuses analysed by autopsy, reinforcing the hypothesis that endometriosis may be generated by defects during the organogenesis of the female reproductive trait. Herein, in order to identify, at molecular level, changes involved in the disease, we compared the transcriptional profiling of ectopic endometrium with the corresponding eutopic one. Statistical analyses lead us to identify some genes specifically deregulated in the ectopic endometrium, that are involved in gonad developmental process or in wound healing process. Among them, we identified BMP4 and GREM1. BMP4 was never associated before to endometriosis and is involved in the mesoderm‐Müllerian duct differentiation. GREM1 is needed for the initial step of the ureter growth and perhaps could possibly be involved in Müller ducts differentiation. These molecules might be related to the endometriosis aetiology since we showed that their expression is not related to the menstrual cycle phase both at RNA and at protein levels. These data support the theory that embryological defects could be responsible of the endometriosis generation. J. Cell. Physiol. 228: 1927–1934, 2013. © 2013 Wiley Periodicals, Inc.
CONDITIONED REINFORCEMENT IN CHAIN SCHEDULES WHEN TIME TO REINFORCEMENT IS HELD CONSTANT
Authors: Bell Matthew C. , Williams Ben A. 
Published: March 2013

AbstractTwo alternative approaches describe determinants of responding to a stimulus temporally distant from primary reinforcement. One emphasizes the temporal relation of each stimulus to the primary reinforcer, with relative proximity of the stimulus determining response rate. A contrasting view emphasizes immediate consequences of responding to the stimulus, the key factor being the conditioned reinforcement value of those immediate consequences. To contrast these approaches, 4 pigeons were exposed to a two‐component multiple schedule with three‐link chain schedules in each component. Only middle‐link stimuli differed between chains. Baseline reinforcement probabilities were 0.50 for both chains; during discrimination phases it was 1.0 for one chain and 0.0 for the other. During discrimination phases pigeons responded more to the reinforcement‐correlated middle link than to the extinction‐correlated middle link, demonstrating that responding was affected by the probability change. Terminal link responding was also higher in the reinforced chain, even though the terminal link stimulus was identical in both chains. Of greatest interest is initial link responding, which was temporally most distant from reinforcement. Initial link responding, necessarily equal in the two chains, was significantly higher during the 1.0/0.0 discrimination phases, even though overall reinforcement probability remained constant. For 3 of 4 birds, in fact, initial‐link response rates were higher than terminal‐link response rates, an outcome that can be ascribed only to the potent conditioned reinforcement properties of the middle‐link stimulus during the discrimination phases. Results are incompatible with any account of chain behavior based solely on relative time to reinforcement.