bluuebunny/crossref_metadata_2025_split huggingface dataset:
Bone marrow‐derived stem cells contribute skin regeneration in skin and soft tissue expansion
Authors: Li Chichi , Zheng Yan , Wang Xiaoyan , Xia Wei , Gao Hongying , Li Dong , Ma Xianjie 
Published: February 2011

AbstractSkin and soft tissue expansion stimulates the proliferation of skin epidermal basal cells and increase the dermal collagen deposition and angiogenesis. To explore the contribution of bone marrow‐derived stem cells (BMSCs) to the generation of “new” skin during the expansion, we used a chimeric mouse model in which the donor C57BL mice were engrafted with the bone marrow of enhanced green fluorescent protein (EGFP) transgenic mice. BMSCs were collected from the tibia and femur of EGFP+ transgenic mice, and then injected into normal C57BL mice via the tail vein (chimeric mice). Skin was obtained at different times (days 0, 7, 14, 21, 28, and 35). Skin stromal‐derived factor‐1 (SDF‐1) expression was evaluated. The number, distribution, and phenotype changes of EGFP+ cells in the skin were also evaluated by means of fluorescent microscopy. EGFP+ cells were present stably in the normal skin. The number of EGFP+ cells of the Group A mice changed with the tension, and reached the peak on day 21(17.1 ± 6.7%), as compared with either Group B (5.5 ± 1.0%) or Group C (5.1 ± 0.9%). The SDF‐1 expression in the expanded skin was significant increased (≈11‐fold, P < 0.01) compared to non‐expanded skin on day 21. Immunofluorescence showed EGFP+ cells were converted into vascular endothelial cells, epidermal cells, and spindle‐shaped dermal fibroblasts. Strain can promote the expression of SDF‐1 and facilitate the differentiation and proliferation of BMSCs in the expanded skin. J. Cell. Physiol. 226: 2834–2840, 2011. © 2011 Wiley‐Liss, Inc.
Comparison of bone morphogenetic protein‐2 and osteoactivin for mesenchymal cell differentiation: Effects of bolus and continuous administration
Authors: Arosarena Oneida A. , Del Carpio‐Cano Fabiola E. , Dela Cadena Raul A. , Rico Mario C. , Nwodim Emeka , Safadi Fayez F. 
Published: February 2011

AbstractCurrent osteoinductive protein therapy utilizes bolus administration of large doses of bone morphogenetic proteins (BMPs), which is costly, and may not replicate normal bone healing. The limited in vivo biologic activity of BMPs requires the investigation of growth factors that may enhance this activity. In this study, we utilized the C3H10T1/2 murine mesenchymal stem cell line to test the hypotheses that osteoactivin (OA) has comparable osteoinductive effects to bone morphogenetic protein‐2 (BMP‐2), and that sustained administration of either growth factor would result in increased osteoblastic differentiation as compared to bolus administration. Sustained release biodegradable hydrogels were designed, and C3H10T1/2 cells were grown on hydrogels loaded with BMP‐2 or OA. Controls were grown on unloaded hydrogels, and positive controls were exposed to bolus growth factor administration. Cells were harvested at several time points to assess osteoblastic differentiation. Alkaline phosphatase (ALP) staining and activity, and gene expression of ALP and osteocalcin were assessed. Treatment with OA or BMP‐2 resulted in comparable effects on osteoblastic marker expression. However, cells grown on hydrogels demonstrated osteoblastic differentiation that was not as robust as cells treated with bolus administration. This study shows that OA has comparable effects to BMP‐2 on osteoblastic differentiation using both bolus administration and continuous release, and that bolus administration of OA has a more profound effect than administration using hydrogels for sustained release. This study will lead to a better understanding of appropriate delivery methods of osteogenic growth factors like OA for repair of fractures and segmental bone defects. J. Cell. Physiol. 226: 2943–2952, 2011. © 2011 Wiley‐Liss, Inc.
Negative regulation of osteoblastogenesis through downregulation of runt‐related transcription factor‐2 in osteoblastic MC3T3‐E1 cells with stable overexpression of the cystine/glutamate antiporter xCT subunit
Authors: Uno Kyosuke , Takarada Takeshi , Takarada‐Iemata Mika , Nakamura Yukari , Fujita Hiroyuki , Hinoi Eiichi , Yoneda Yukio 
Published: February 2011

AbstractWe have previously demonstrated that glutamate (Glu) suppresses cellular proliferation toward self‐renewal through a mechanism associated with intracellular GSH depletion mediated by the bidirectional cystine/Glu antiporter in osteoblastic MC3T3‐E1 cells cultured in the absence of differentiation inducers. To further evaluate the possible role of the antiporter in osteoblastogenesis, in this study, we have established stable transfectants of the xCT subunit of the antiporter in MC3T3‐E1 cells. Stable overexpression led to a significant facilitation of cellular proliferation determined by different indices with increased GSH levels and decreased ROS generation in addition to promoted [14C]cystine incorporation, while Glu failed to significantly inhibit cellular proliferation in stable xCT transfectants. In stable transfectants cultured under differentiation conditions, drastic decreases were invariably seen in Ca2+ accumulation, alkaline phosphatase activity and several osteoblastic marker gene expressions, in addition to downregulation of mRNA and corresponding protein for runt‐related transcription factor‐2 (Runx2). Runx2 promoter activity was significantly promoted by the introduction of Runx2 expression vector in a manner sensitive to the prevention by the co‐introduction of xCT expression vector in MC3T3‐E1 cells. In both MC3T3‐E1 cells and murine calvarial osteoblasts cultured with differentiation inducers, transient transfection with xCT siRNA significantly increased Runx2 protein expression along with decreases in xCT mRNA expression and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bromide reduction. These results suggest that the cystine/Glu antiporter plays a pivotal role in cellular differentiation through a mechanism related to the regulation of transactivation of Runx2 essential for osteoblastogenesis toward maturation in osteoblastic cells. J. Cell. Physiol. 226: 2953–2964, 2011. © 2011 Wiley‐Liss, Inc.
Involvement of L‐type calcium channel and serca2a in myocardial dysfunction induced by obesity
Authors: Leopoldo André Soares , Lima‐Leopoldo Ana Paula , Sugizaki Mário Mateus , Nascimento André Ferreira do , de Campos Dijon Henrique Salomé , Luvizotto Renata de Azevedo Melo , Castardeli Edson , Alves Carlos Augusto Barnabé , Brum Patrícia Chakur , Cicogna Antonio Carlos 
Published: February 2011

AbstractObesity has been shown to impair myocardial performance. Nevertheless, the mechanisms underlying the participation of calcium (Ca2+) handling on cardiac dysfunction in obesity models remain unknown. L‐type Ca2+ channels and sarcoplasmic reticulum (SR) Ca2+‐ATPase (SERCA2a), may contribute to the cardiac dysfunction induced by obesity. The purpose of this study was to investigate whether myocardial dysfunction in obese rats is related to decreased activity and/or expression of L‐type Ca2+ channels and SERCA2a. Male 30‐day‐old Wistar rats were fed standard (C) and alternately four palatable high‐fat diets (Ob) for 15 weeks. Obesity was determined by adiposity index and comorbidities were evaluated. Myocardial function was evaluated in isolated left ventricle papillary muscles under basal conditions and after inotropic and lusitropic maneuvers. L‐type Ca2+ channels and SERCA2a activity were determined using specific blockers, while changes in the amount of channels were evaluated by Western blot analysis. Phospholamban (PLB) protein expression and the SERCA2a/PLB ratio were also determined. Compared with C rats, the Ob rats had increased body fat, adiposity index and several comorbidities. The Ob muscles developed similar baseline data, but myocardial responsiveness to post‐rest contraction stimulus and increased extracellular Ca2+ was compromised. The diltiazem promoted higher inhibition on developed tension in obese rats. In addition, there were no changes in the L‐type Ca2+ channel protein content and SERCA2a behavior (activity and expression). In conclusion, the myocardial dysfunction caused by obesity is related to L‐type Ca2+ channel activity impairment without significant changes in SERCA2a expression and function as well as L‐type Ca2+ protein levels. J. Cell. Physiol. 226: 2934–2942, 2011. © 2011 Wiley‐Liss, Inc.
Tiam1 is recruited to β1‐integrin complexes by 14‐3‐3ζ where it mediates integrin‐induced Rac1 activation and motility
Authors: O'Toole Timothy E. , Bialkowska Katarzyna , Li Xiaohong , Fox Joan E.B. 
Published: February 2011

Abstract14‐3‐3 is an adaptor protein that localizes to the leading edge of spreading cells, returning to the cytoplasm as spreading ceases. Previously, we showed that integrin‐induced Rac1 activation and spreading were inhibited by sequestration of 14‐3‐3ζ and restored by its overexpression. Here, we determined whether 14‐3‐3 mediates integrin signaling by localizing a guanine nucleotide exchange factor (GEF) to Rac1‐activating integrin complexes. We showed that GST‐14‐3‐3ζ recruited the Rac1‐GEF, Tiam1, from cell lysates through Tiam1 residues 1–182 (N1–182 Tiam1). The physiological relevance of this interaction was examined in serum‐starved Hela cells plated on fibronectin. Both Tiam1 and N1–182 Tiam1 were recruited to 14‐3‐3‐containing β1‐integrin complexes, as shown by co‐localization and co‐immunoprecipitation. Integrin‐induced Rac1 activation was inhibited when Tiam1 was depleted with siRNA or by overexpression of catalytically inactive N1–182 Tiam1, which was incorporated into 14‐3‐3/β1‐integrin complexes and inhibited spreading in a manner that was overcome by constitutively active Rac1. Integrin‐induced Rac1 activation, spreading, and migration were also inhibited by overexpression of 14‐3‐3ζ S58D, which was unable to recruit Tiam1 from lysates, co‐immunoprecipitate with Tiam1, or mediate its incorporation into β1‐integrin complexes. Taken together, these findings suggest a previously unrecognized mechanism of integrin‐induced Rac1 activation in which 14‐3‐3 dimers localize Tiam1 to integrin complexes, where it mediates integrin‐dependent Rac1 activation, thus initiating motility‐inducing pathways. Moreover, since Tiam1 is recruited to other sites of localized Rac1 activation through its PH‐CC‐EX domain, the present findings show that a mechanism involving its N‐terminal 182 residues is utilized to recruit Tiam1 to motility‐inducing integrin complexes. J. Cell. Physiol. 226: 2965–2978, 2011. © 2011 Wiley‐Liss, Inc.
Interplay between steroid receptors and neoplastic progression in sarcoma tumors
Authors: Fiorelli A. , Ricciardi C. , Pannone G. , Santoro A. , Bufo P. , Santini M. , Serpico R. , Rullo R. , Pierantoni G.M. , Di Domenico M. 
Published: February 2011

AbstractSteroid hormones are expressed at low levels in mesenchymal cells and are highly expressed in soft tissue sarcoma. In human soft tissue fibrosarcoma cell line (HT‐1080), the epidermal growth factor (EGF) stimulates the express of matrix metal (MMPs) expression through a Src‐dependent mechanism. In human fibrosarcomas, increased expression of MMPs correlates with the metastatic progression. Our recent data in human breast cancer cell line MCF‐7, demonstrates that EGF stimulates estradiol receptor (ER) phosphorylation on tyrosine at position 537 thereby promoting the association of a complex among EGF receptor (EGFR), androgen receptor (AR), ER, and Src that activates EGF‐dependent signaling pathway. In the present study, we demonstrate that, in HT‐1080 cells, the Src kinase activity is involved in EGFR phosphorylation and this activity is regulated by an interplay between Src, steroid receptors, and EGFR. In these cells, estradiol (E2)/ER and synthetic androgen (R1881)/AR trans‐activate EGFR leading to the downstream signaling and to ERK activation. Indeed, the association between ER/AR and EGFR enhances metastatic progression of fibrosarcoma tumors. A population pilot study performed on 16 patients with soft tissue neoplasias highlights that MMPs expression correlates with progression of anaplastic sarcoma as well as overexpression of EGFR. These findings suggest that there is a crosstalk among AR, ER, and EGFR that lead to src activation also in fibrosarcoma cells. J. Cell. Physiol. 226: 2997–3003, 2011. © 2011 Wiley‐Liss, Inc.
TGFβ‐ and bleomycin‐induced extracellular matrix synthesis is mediated through Akt and mammalian target of rapamycin (mTOR)
Authors: Goc Anna , Choudhary Mrunal , Byzova Tatiana V. , Somanath Payaningal R. 
Published: February 2011

AbstractA number of pro‐fibrogenic stimuli, such as growth factors, cytokines, and extracellular matrix (ECM) proteins, involve Akt and its downstream substrates in mediating their effects. We previously reported that absence of Akt1, which is the predominant isoform of the three gene Akt family in vascular cells, resulted in impaired ECM remodeling in skin and vasculature. In the current study, we investigated the importance of Akt1 in TGFβ‐ and bleomycin‐induced synthesis and secretion of ECM proteins by fibroblasts. We observed that both TGFβ and bleomycin stimulated the synthesis of ECM proteins in a dose‐ and time‐dependent manner. Treatment with TGFβ and bleomycin also resulted in increased phosphorylation of Akt, mammalian target of rapamycin (mTOR) and their downstream signaling partners, p70S6 Kinase, Ribosomal S6 protein and 4E‐BP1, resulting in the activation of this pathway. The effects of TGFβ and bleomycin on ECM synthesis were blunted by pre‐treatment with an mTOR inhibitor rapamycin. Whereas mTOR is responsible for the transcriptional regulation of a number of ECM proteins, adhesion molecules and matrix metalloproteases (MMPs), synthesis of major ECM proteins such as fibronectin and collagens (types I, II and V) by fibroblasts in response to TGFβ and bleomycin is regulated by mTOR at the translational level. These findings indicate the importance of the Akt‐mTOR signaling pathway in TGF‐mediated fibrogenic events in vivo. J. Cell. Physiol. 226: 3004–3013, 2011. © 2011 Wiley‐Liss, Inc.
Neuregulin induces HaCaT keratinocyte migration via Rac1‐mediated NADPH‐oxidase activation
Authors: Kim Jun‐Sub , Bak Eun‐Jung , Lee Boung‐Chul , Kim Yong‐Sun , Park Jae‐Bong , Choi Ihn‐Geun 
Published: February 2011

AbstractNeuregulin (NRG), a member of the epidermal growth factor family, plays important roles in the development of the nervous system and heart, and in cancer progression. Recent reports have suggested that NRG is involved in wound healing in keratinocytes, although the cellular mechanisms remain unclear. Here, we showed that NRG treatment increased slingshot‐1L (SSH‐1L)‐mediated cofilin dephosphorylation and activation in HaCaT keratinocytes. Additionally, Rac1 activation and NADPH‐oxidase (Nox)‐dependent reactive oxygen species (ROS) generation, both known to be upstream regulators of the SSH‐cofilin pathway, were increased in NRG‐stimulated HaCaT cells. Inhibition of Rac1 or Nox activity blocked NRG‐induced cofilin activation and cell migration by HaCaT cells. Moreover, the effects of Rac1 on cofilin activation were dependent on Nox activity. These findings indicate that NRG‐induced HaCaT cell migration via the ROS‐SSH‐1L‐cofilin pathway is activated as a consequence of Rac1 and Nox activation. J. Cell. Physiol. 226: 3014–3021, 2011. © 2011 Wiley‐Liss, Inc.
New players in ovarian cancer
Authors: Bovicelli Alessandro , D'Andrilli Giuseppina , Giordano Antonio 
Published: February 2011

AbstractOvarian cancer is the leading cause of gynecologic cancer mortality worldwide. The aim of this review is to highlight the most recent studies regarding ovarian cancer pathogenesis and the new therapeutic approaches against this insidious disease. We focus on the relevance of some cell cycle genes, transcription factors, and microRNAs in the carcinogenesis of ovarian cancer as well as on a new hypothesis for therapy using histone deacetylase inhibitors. We also report recent studies regarding some mechanisms of chemoresistance, a major obstacle in the treatment of ovarian cancer. Together these studies can improve our knowledge of ovarian cancer tumorigenesis and diagnosis providing new tools to hopefully defeat this deadly disease. J. Cell. Physiol. 226: 2500–2504, 2011. © 2011 Wiley‐Liss, Inc.
Regulation of non‐classical FGF1 release and FGF‐dependent cell transformation by CBF1‐mediated notch signaling
Authors: Kacer Doreen , McIntire Christian , Kirov Alek , Kany Erin , Roth Jennifer , Liaw Lucy , Small Deena , Friesel Robert , Basilico Claudio , Tarantini Francesca , Verdi Joseph , Prudovsky Igor 
Published: February 2011

AbstractFGF1, a widely expressed proangiogenic factor involved in tissue repair and carcinogenesis, is released from cells through a non‐classical pathway independent of endoplasmic reticulum and Golgi. Although several proteins participating in FGF1 export were identified, genetic mechanisms regulating this process remained obscure. We found that FGF1 export and expression are regulated through Notch signaling mediated by transcription factor CBF1 and its partner MAML. The expression of a dominant negative (dn) form of CBF1 in 3T3 cells induces transcription of FGF1 and sphingosine kinase 1 (SphK1), which is a component of FGF1 export pathway. dnCBF1 expression stimulates the stress‐independent release of transduced FGF1 from NIH 3T3 cells and endogenous FGF1 from A375 melanoma cells. NIH 3T3 cells transfected with dnCBF1 form colonies in soft agar and produce rapidly growing highly angiogenic tumors in nude mice. The transformed phenotype of dnCBF1 transfected cells is efficiently blocked by dn forms of FGF receptor 1 and S100A13, which is a component of FGF1 export pathway. FGF1 export and acceleration of cell growth induced by dnCBF1 depend on SphK1. Similar to dnCBF1, dnMAML transfection induces FGF1 expression and release, and accelerates cell proliferation. The latter effect is strongly decreased in FGF1 null cells. We suggest that the regulation of FGF1 expression and release by CBF1‐mediated Notch signaling can play an important role in tumor formation. J. Cell. Physiol. 226: 3064–3075, 2011. © 2011 Wiley‐Liss, Inc.
Vertices of degree k in random unlabeled trees
Authors: Panagiotou Konstantinos , Sinha Makrand 
Published: February 2011

AbstractLet ℋ︁n be the class of unlabeled trees with n vertices, and denote by Hn a tree that is drawn uniformly at random from this set. The asymptotic behavior of the random variable degk(Hn) that counts vertices of degree k in Hn was studied, among others, by Drmota and Gittenberger in [J Graph Theory 31(3) (1999), 227–253], who showed that this quantity satisfies a central limit theorem. This result provides a very precise characterization of the “central region” of the distribution, but does not give any non‐trivial information about its tails. In this work, we study further the number of vertices of degree k in Hn. In particular, for k = 𝒪((logn/(loglogn))1/2) we show exponential‐type bounds for the probability that degk(Hn) deviates from its expectation. On the technical side, our proofs are based on the analysis of a randomized algorithm that generates unlabeled trees in the so‐called Boltzmann model. The analysis of such algorithms is quite well‐understood for classes of labeled graphs, see e.g. the work [Bernasconi et al., SODA '08: Proceedings of the 19th Annual ACM‐SIAM Symposium on Discrete Algorithms, Society for Industrial and Applied Mathematics, Philadelphia, PA, 2008, pp. 132–141; Bernasconi et al., Proceedings of the 11th International Workshop, APPROX 2008, and 12th International Workshop, RANDOM 2008 on Approximation, Randomization and Combinatorial Optimization, Springer, Berlin, 2008, pp. 303–316] by Bernasconi, the first author, and Steger. Comparable algorithms for unlabeled classes are unfortunately much more complex. We demonstrate in this work that they can be analyzed very precisely for classes of unlabeled graphs as well. © 2011 Wiley Periodicals, Inc. J Graph Theory. 69:114‐130, 2012
Hamiltonian cycles in bipartite quadrangulations on the torus
Authors: Nakamoto Atsuhiro , Ozeki Kenta 
Published: February 2011

AbstractIn this article, we shall prove that every bipartite quadrangulation G on the torus admits a simple closed curve visiting each face and each vertex of G exactly once but crossing no edge. As an application, we conclude that the radial graph of any bipartite quadrangulation on the torus has a hamiltonian cycle. Copyright © 2011 Wiley Periodicals, Inc. J Graph Theory 69:143‐151, 2012
Claw‐free graphs and 2‐factors that separate independent vertices
Authors: Faudree Ralph J. , Magnant Colton , Ozeki Kenta , Yoshimoto Kiyoshi 
Published: February 2011

AbstractIn this article, we prove that a line graph with minimum degree δ≥7 has a spanning subgraph in which every component is a clique of order at least three. This implies that if G is a line graph with δ≥7, then for any independent set S there is a 2‐factor of G such that each cycle contains at most one vertex of S. This supports the conjecture that δ≥5 is sufficient to imply the existence of such a 2‐factor in the larger class of claw‐free graphs.It is also shown that if G is a claw‐free graph of order n and independence number α with δ≥2n/α−2 and n≥3α3/2, then for any maximum independent set S, G has a 2‐factor with α cycles such that each cycle contains one vertex of S. This is in support of a conjecture that δ≥n/α≥5 is sufficient to imply the existence of a 2‐factor with α cycles, each containing one vertex of a maximum independent set. © 2011 Wiley Periodicals, Inc. J Graph Theory 69: 251–263, 2012
Catch‐up and targeted growth following variable duration protein restriction: Effects on bone and body mass
Authors: Jones Donna Carlson , Bernstein Marica , German Rebecca Z. 
Published: February 2011

AbstractProtein malnutrition leads to growth retardation that can be reversed through catch‐up growth, once normative nutrition is restored. Because growth is a dynamic process, catch‐up capacity is likely influenced by the maturity of the animal and/or the duration of the insult, in addition to the type of insult experienced. We compared length of malnutrition, sexual dimorphism, body mass, and skeletal growth. Eighty Rattus norvegicus were divided into 10 treatment groups (five diets; male and female) and followed for more than 1 year. At weaning, animals were placed on either a control or low‐protein isocaloric diet. Three experimental groups were switched to the control diet at 40, 60, or 90 days. Beginning with 21 days of age, animals were weighed daily and radiographed throughout the study. To determine the presence of catch‐up growth, growth rates (GRs) were calculated (linear regression) for 20‐day time spans before and after diet changes and compared among treatment groups. Targeted growth was measured as final size or as the coefficient of variation with age. These results show that 1) protein‐restricted animals experience catch‐up growth with dietary rehabilitation; 2) for females, catch‐up GRs are proportional to GRs in control animals at the same age as the timing of dietary rehabilitation but not for males; and 3) targeted growth was observed in some, but not all, aspects of anatomy. The length of the tibia and humerus was indistinguishable from controls, regardless of length of malnutrition or gender, whereas the ulna and male body mass exceeded control sizes. Although most measures decreased in variation with ontogeny, the tibia failed to do so. These results support a complex biological regulation of catch‐up and targeted growth. The implications for selection are that flexible and responsive developmental trajectories may have an advantage over those programed into a single size. J. Morphol., 2011. © 2011 Wiley‐Liss, Inc.