bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra-Articular Transplantation of Atsttrin-Transduced Mesenchymal Stem Cells Ameliorate Osteoarthritis Development
Authors: Xia Qingqing , Zhu Shouan , Wu Yan , Wang Jiaqiu , Cai Youzhi , Chen Pengfei , Li Jie , Heng Boon Chin , Ouyang Hong Wei , Lu Ping 
Published: April 2015

AbstractOsteoarthritis (OA) remains an intractable clinical challenge. Few drugs are available for reversing this degenerative disease, although some promising candidates have performed well in preclinical studies. Tumor necrosis factor α (TNFα) has been identified as a crucial effector modulating OA pathogenesis. This study aimed to investigate the therapeutic effects of Atsttrin, a novel TNFα blocker, on OA treatment. We developed genetically modified mesenchymal stem cells (MSCs) that expressed recombinant Atsttrin (named as MSC-Atsttrin). Expression levels of ADAMTS-5, MMP13, and iNOS of human chondrocytes were analyzed when cocultured with MSC-GFP/Atsttrin. OA animal models were induced by anterior cruciate ligament transection, and MSC-GFP/Atsttrin were injected into the articular cavity 1 week postsurgery. The results showed that MSC-Atsttrin significantly suppressed TNFα-driven up-regulation of matrix proteases and inflammatory factors. Intra-articular injection of MSC-Atsttrin prevented the progression of degenerative changes in the surgically induced OA mouse model. Additionally, levels of detrimental matrix hydrolases were significantly diminished. Compared with nontreated OA samples at 8 weeks postsurgery, the percentages of MMP13- and ADAMTS-5-positive cells were significantly reduced from 91.33% ± 9.87% to 24.33% ± 5.7% (p &lt; .001) and from 91.33% ± 7.1% to 16.67% ± 3.1% (p &lt; .001), respectively. Our results thus indicated that suppression of TNFα activity is an effective strategy for OA treatment and that intra-articular injection of MSCs-Atsttrin could be a promising therapeutic modality.SignificanceThe main novelty of this study is the finding of Atsttrin modified mesenchymal stem cells (MSCs-Atsttrin) for blocking osteoarthritis (OA) development within an in vivo mouse surgically induced osteoarthritis model. Because MSCs have already been widely used in the treatment of patients and have demonstrated good efficacy and safety, MSC-based Atsttrin gene therapy could be a promising modality for the treatment of OA patients.
Conditioned Medium From Human Amniotic Mesenchymal Stromal Cells Limits Infarct Size and Enhances Angiogenesis
Authors: Danieli Patrizia , Malpasso Giuseppe , Ciuffreda Maria Chiara , Cervio Elisabetta , Calvillo Laura , Copes Francesco , Pisano Federica , Mura Manuela , Kleijn Lennaert , de Boer Rudolf A. , Viarengo Gianluca , Rosti Vittorio , Spinillo Arsenio , Roccio Marianna , Gnecchi Massimiliano 
Published: April 2015

Abstract

The paracrine properties of human amniotic membrane-derived mesenchymal stromal cells (hAMCs) have not been fully elucidated. The goal of the present study was to elucidate whether hAMCs can exert beneficial paracrine effects on infarcted rat hearts, in particular through cardioprotection and angiogenesis. Moreover, we aimed to identify the putative active paracrine mediators. hAMCs were isolated, expanded, and characterized. In vitro, conditioned medium from hAMC (hAMC-CM) exhibited cytoprotective and proangiogenic properties. In vivo, injection of hAMC-CM into infarcted rat hearts limited the infarct size, reduced cardiomyocyte apoptosis and ventricular remodeling, and strongly promoted capillary formation at the infarct border zone. Gene array analysis led to the identification of 32 genes encoding for the secreted factors overexpressed by hAMCs. Among these, midkine and secreted protein acidic and rich in cysteine were also upregulated at the protein level. Furthermore, high amounts of several proangiogenic factors were detected in hAMC-CM by cytokine array. Our results strongly support the concept that the administration of hAMC-CM favors the repair process after acute myocardial infarction.

Significance
The demonstration that stem cells repair infarcted hearts mainly through paracrine mechanisms represents a potential breakthrough. Characterization of therapeutic paracrine mediators could lead to the possibility of treating acute myocardial infarction (AMI) with a single stem cell-derived molecule or a mixture. Compared with cell therapy, this approach would be technically easier to translate to the bedside. An even more straightforward strategy consists of the administration of the entire stem cell secretome (i.e., conditioned medium [CM]). Despite these potential advantages, this approach has not been thoroughly investigated using human cells. This study shows that CM of fetal stromal cells (human amniotic membrane-derived mesenchymal stromal cell [hAMC]-CM), derived from an ethically acceptable source such as the placenta, can repair infarcted hearts without the need for any manipulation. The use of hAMC-CM might be readily translated to the clinical arena in the setting of AMI upon demonstration of its effectiveness in a large animal model.
Human Umbilical Cord Mesenchymal Stem Cell Exosomes Enhance Angiogenesis Through the Wnt4/β-Catenin Pathway
Authors: Zhang Bin , Wu Xiaodan , Zhang Xu , Sun Yaoxiang , Yan Yongmin , Shi Hui , Zhu Yanhua , Wu Lijun , Pan Zhaoji , Zhu Wei , Qian Hui , Xu Wenrong 
Published: April 2015

Abstract

Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, we isolated and characterized the exosomes from hucMSCs (hucMSC-Ex) and demonstrated that hucMSC-Ex promoted the proliferation, migration, and tube formation of endothelial cells in a dose-dependent manner. Furthermore, we demonstrated that hucMSC-Ex promoted wound healing and angiogenesis in vivo by using a rat skin burn model. We discovered that hucMSC-Ex promoted β-catenin nuclear translocation and induced the increased expression of proliferating cell nuclear antigen, cyclin D3, N-cadherin, and β-catenin and the decreased expression of E-cadherin. The activation of Wnt/β-catenin is critical in the induction of angiogenesis by hucMSC-Ex, which could be reversed by β-catenin inhibitor ICG-001. Wnt4 was delivered by hucMSC-Ex, and the knockdown of Wnt4 in hucMSC-Ex abrogated β-catenin nuclear translocation in endothelial cells. The in vivo proangiogenic effects were also inhibited by interference of Wnt4 expression in hucMSC-Ex. Taken together, these results suggest that hucMSC-Ex-mediated Wnt4 induces β-catenin activation in endothelial cells and exerts proangiogenic effects, which could be an important mechanism for cutaneous wound healing.

Significance
Human umbilical cord mesenchymal stem cells (hucMSCs) and their exosomes have been considered as potential therapeutic tools for tissue regeneration; however, the underlying mechanisms are still not well understood. In this study, it is reported that hucMSC-Ex-mediated Wnt4 induces β-catenin activation in endothelial cells and exerts proangiogenic effects, which could be one of the important mechanisms responsible for cutaneous wound healing.
La construcción de la identidad nacional española a través de los cuadernos escolares (1957-1959)
Authors: Sanchidrián Blanco Carmen , Arias Gómez Bárbara 
Published: April 2015

El proceso de construcción de la identidad nacional que se llevó a cabo en las escuelas durante el nacional-catolicismo, quedó reflejado en los cuadernos escolares que los alumnos elaboraron en el desarrollo de su actividad diaria. Los cuadernos son un medio en el que han permanecido todos los elementos de integración que permitieron producir, desde la escuela, el concepto de identidad nacional pretendido. En ellos se observa, cómo se trata de un hecho cognitivo y emocional que la escuela debía promover y que se creó partiendo de la interacción de los alumnos en un contexto en el que predominaban por un lado, aspectos como la autoestima individual y colectiva asociadas a la idea de España, y por otro, los sentimientos y emociones que el franquismo pudo despertar en los jóvenes.<p> </p><div><div><p> </p></div></div>
Anisotropic tomography of Hokkaido reveals delamination‐induced flow above a subducting slab
Authors: Koulakov Ivan , Kukarina Ekaterina , Fathi Ismail Husain , El Khrepy Sami , Al‐Arifi Nassir 
Published: April 2015

AbstractWe present a new 3‐D anisotropic seismic model for the crust and upper mantle beneath Hokkaido (Japan) based on tomographic inversion of P and S arrival times from a regional seismic database. The P model is parameterized with three parameters at each point that describe the azimuthal anisotropy; the S model is represented isotropically. The isotropic P and S velocity anomalies match nearly perfectly. In the crust, they show a prominent linear anomaly in central Hokkaido along the Kamuikotan and Hidaka Belts, which represents the area of eastward underthrusting of the Japan Block underneath the Kuril fore arc. We interpret the high‐velocity anomaly beneath the Hidaka zone as being delaminated mafic crust and entrained mantle lithosphere, which developed due to crustal shortening in the collision zone. One of our vertical sections shows a very unusual configuration for a subduction zone: a low‐velocity slab is overlain by a high‐velocity body in the mantle wedge. We propose that the high‐velocity delaminated material sinking along the slab surface prevents the escape of fluids and melts from the upper part of the slab, where they are generated due to phase transitions. As a result, a large portion of the fluids is entrained downward and lowers the seismic velocities in the slab. The azimuthal anisotropy in the crust clearly corresponds to the major tectonic units and delineates the major suture zones. In the mantle, the anisotropy has a fan‐shaped configuration and most likely represents the deviating of flows starting in southern Hokkaido and splitting into three directions. The western and eastern flows proceed toward the two volcanic groups on Hokkaido, and they may carry with them additional material to trigger the characteristic caldera‐forming eruptions in these groups.
Effectiveness of Nonpharmacologic Interventions in Systemic Sclerosis: A Systematic Review
Authors: Willems Linda M. , Vriezekolk Johanna E. , Schouffoer Anne A. , Poole Janet L. , Stamm Tanja A. , Boström Carina , Kwakkenbos Linda , Vliet Vlieland Theodora P. M. , van den Ende Cornelia H. M. 
Published: April 2015

ObjectiveTo systematically and comprehensively document the effectiveness of nonpharmacologic interventions on physical functioning and psychological well‐being in patients with systemic sclerosis (SSc).MethodsMultiple electronic databases were searched for studies on the effectiveness of nonpharmacologic interventions in SSc. Randomized clinical trials (RCTs), controlled clinical trials (CCTs), and observational designs (ODs) with ≥10 participants were included. Two reviewers independently assessed methodologic quality using the Downs and Black checklist.ResultsTwenty‐three studies (9 RCTs, 4 CCTs, and 10 ODs) were included. Studies assessing comparable interventions were grouped, resulting in data for 16 different interventions. The total number of patients included per study ranged from 10 to 53. Seventeen different outcome domains were assessed, with hand function, limitations in activities, and quality of life being assessed most frequently. Three studies, all RCTs, were rated as high quality. These RCTs reported that 1) a multifaceted oral health intervention improves mouth hygiene, and additional orofacial exercises did not improve mouth opening, 2) a multidisciplinary team‐care program improves limitations in activities, mouth opening, and hand grip strength, and 3) manual lymph drainage improves hand function, limitations in activities, and quality of life.ConclusionThe body of knowledge regarding nonpharmacologic care in SSc is very limited due to the wide variety in studied interventions and outcomes in the relatively uncommon but highly disabling disease. To structure and focus future research, an international consensus should be established to prioritize primary targets for nonpharmacologic treatment and the content of interventions and to agree on a core set of outcome measures.
Dehydroepiandrosterone and multiple measures of functional immunity in young adults
Authors: Prall Sean P. , Muehlenbein Michael P. 
Published: April 2015

ObjectivesHuman immune function is strongly influenced by variation in hormone concentrations. The adrenal androgens dehydroepiandrosterone (DHEA) and dehydroepiandrosterone‐sulfate (DHEA‐S) are thought to be beneficial to immune function and disease resistance, but physiologically interact with testosterone and cortisol. We predict that DHEA and DHEA‐S will interact with these other hormones in determining immunological outcomes. Understanding the interactive effects of these hormones will aid in understanding variability in immunocompetence and clarify discrepancies in human studies of androgen–immune interactions.MethodsThirty‐eight participants collected morning saliva over three days, from which concentrations of DHEA, DHEA‐S, testosterone, and cortisol were measured, as well as salivary bacteria killing ability to measure innate immune function. From blood collection, serum was collected to measure innate immune function via a hemolytic complement assay, and whole blood collected and processed to measure proliferative responses of lymphocytes in the presence of mitogens.ResultsDHEA was negatively correlated with T cell proliferation, and positively correlated with salivary bacteria killing in male participants. Additionally, using regression models, DHEA‐S was negatively associated with hemolytic complement activity, but interaction variables did not yield statistically significant relationships for any other outcome measure.ConclusionsWhile interactions with other hormones did not significantly relate with immune function measures in this sample, DHEA and DHEA‐S did differentially impact multiple branches of the immune system. Generally characterized as immunosupportive in action, DHEA is shown to inhibit certain facets of innate and cell‐mediated immunity, suggesting a more complex role in regulating immunocompetence. Am. J. Hum. Biol. 27:877–880, 2015. © 2015 Wiley Periodicals, Inc.
Distance Measurement on an Endogenous Membrane Transporter in E. coli Cells and Native Membranes Using EPR Spectroscopy
Authors: Joseph Benesh , Sikora Arthur , Bordignon Enrica , Jeschke Gunnar , Cafiso David S. , Prisner Thomas F. 
Published: April 2015

AbstractMembrane proteins may be influenced by the environment, and they may be unstable in detergents or fail to crystallize. As a result, approaches to characterize structures in a native environment are highly desirable. Here, we report a novel general strategy for precise distance measurements on outer membrane proteins in whole Escherichia coli cells and isolated outer membranes. The cobalamin transporter BtuB was overexpressed and spin‐labeled in whole cells and outer membranes and interspin distances were measured to a spin‐labeled cobalamin using pulse EPR spectroscopy. A comparative analysis of the data reveals a similar interspin distance between whole cells, outer membranes, and synthetic vesicles. This approach provides an elegant way to study conformational changes or protein–protein/ligand interactions at surface‐exposed sites of membrane protein complexes in whole cells and native membranes, and provides a method to validate outer membrane protein structures in their native environment.
Red, Green, and Blue Luminescence by Carbon Dots: Full‐Color Emission Tuning and Multicolor Cellular Imaging
Authors: Jiang Kai , Sun Shan , Zhang Ling , Lu Yue , Wu Aiguo , Cai Congzhong , Lin Hengwei 
Published: April 2015

AbstractA facile approach for preparation of photoluminescent (PL) carbon dots (CDs) is reported. The three resulting CDs emit bright and stable red, green and blue (RGB) colors of luminescence, under a single ultraviolet‐light excitation. Alterations of PL emission of these CDs are tentatively proposed to result from the difference in their particle size and nitrogen content. Interestingly, up‐conversion (UC)PL of these CDs is also observed. Moreover, flexible full‐color emissive PVA films can be achieved through mixing two or three CDs in the appropriate ratios. These CDs also show low cytotoxicity and excellent cellular imaging capability. The facile preparation and unique optical features make these CDs potentially useful in numerous applications such as light‐emitting diodes, full‐color displays, and multiplexed (UC)PL bioimaging.
Proton‐conductive membranes based on vanadium substituted heteropoly acids with Keggin structure and polymers
Authors: Tian Naiqin , Wu Xuefei , Yang Baihe , Wu Qingyin , Cao Fahe , Yan Wenfu , Yaroslavtsev Andrei B. 
Published: April 2015

ABSTRACTIn this article, novel proton‐conducting composite membranes SPEEK/PW11V and PVA/SiW11V were synthesized from vanadium substituted heteropoly acids (H4PW11VO40·8H2O and H5SiW11VO40·15H2O, abbreviated as PW11V and SiW11V) and polymers (SPEEK or PVA) at the weight ratio 70 : 30. The membranes were characterized by the infrared spectroscopy, X‐ray powder diffraction, and scanning electron microscopy, which confirmed the maintenance of the Keggin framework and dispersion homogeneously in the polymer matrix without long‐range ordering. Their proton‐conducting properties were investigated with electrochemical impedance spectroscopy. The results show that the respective proton conductivities of SPEEK/PW11V and PVA/SiW11V membranes were in the order of 10−2 and 10−4 S cm−1 at ambient temperature. The temperature dependence of the two composite membrane electrolytes exhibit Arrhenius behavior, and the observed activation energies to be 15.82 kJ mol−1 for SPEEK/PW11V and 14.40 kJ mol−1 for PVA/SiW11V, which indicates that the proton conduction complies with the Grotthuss mechanism. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42204.
Irbesartan‐loaded electrospun nanofibers‐based PVP K90 for the drug dissolution improvement: Fabrication, in vitro performance assessment, and in vivo evaluation
Authors: Adeli Ehsan 
Published: April 2015

ABSTRACTIrbesartan with a low bioavailability is known as a poorly water‐soluble drug. The purpose of this investigation is the improvement of physicochemical properties (such as solubility and dissolution rate) of Irbesartan using electrospun nanofibers‐based solid dispersion preparation. Nanofibers were prepared using certain weight ratios of the drug and polyvinylpyrrolidone K90 (PVP K90). Then, dissolution studies were carried out. Moreover, selected samples were examined by many different tests such as Fourier transform infra red (FTIR), differential scanning calorimetry (DSC), X‐ray diffraction (XRD), high‐performance liquid chromatography (HPLC), and scanning electron microscopy (SEM). Though solubility and dissolution rate of all Irbesartan‐PVP nanofibers improved, but the best result was obtained through of ENSD5 (3% (w/v) : 7% (w/v)). In sink condition approximately 97% of this sample was released during 60 min. The drug content was among the different batches from 40.55 ± 1.01 to 245.32 ± 1.77 μg/mL. The maximum saturation solubility was belonged to this sample. According to the results of the thermal analysis and FTIR spectroscopy, there is no chemical reaction between drug and carrier, also samples has not changed during the process. Amorphous structure for nanofibers was confirmed by DSC thermograms and XRD diffractograms and morphological structure of samples were observed by SEM images. Ultimately, in vivo studies were performed in healthy grey rabbits and the results were satisfactory. The drug–polymer nanofibers showed an increase in relative bioavailability than the plain Irbesartan suspension. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015, 132, 42212.
Reversal of Arthritis by Human Monomeric IgA Through the Receptor‐Mediated SH2 Domain–Containing Phosphatase 1 Inhibitory Pathway
Authors: Rossato Elisabetta , Ben Mkaddem Sanae , Kanamaru Yutaka , Hurtado‐Nedelec Margarita , Hayem Gilles , Descatoire Véronique , Vonarburg Cédric , Miescher Sylvia , Zuercher Adrian W. , Monteiro Renato C. 
Published: April 2015

ObjectiveRheumatoid arthritis (RA), one of the most frequent chronic inflammatory rheumatic disorders, is characterized by the presence of autoantibodies and joint infiltration by activated immune cells, leading to cartilage and bone destruction. IgA occurs predominantly as monomers (mIgA) in plasma and regulates many cell responses through interaction with the Fcα receptor type I (FcαRI). FcαRI targeting by anti‐FcαRI Fab inhibits activating receptors by inducing an inhibitory immunoreceptor tyrosine–based activation motif (ITAMi) configuration through SH2 domain–containing phosphatase 1 (SHP‐1) recruitment. The aim of this study was to investigate the potential utility of mIgA for the treatment of arthritis by acting as an inducer of ITAMi signaling.MethodsThe effect of plasma‐derived human mIgA on inhibition of multiple heterologous receptors was evaluated on FcαRI+ cell transfectants, blood phagocytes from healthy individuals, and synovial cells from RA patients. FcαRI‐transgenic mice and wild‐type mice treated with mIgA were studied in models of collagen antibody–induced arthritis (CAIA) and collagen‐induced arthritis (CIA). The mice were assessed for development of arthritis using an arthritis score, and joint tissue samples were evaluated for the extent of leukocyte infiltration and expression of phosphatase.ResultsTreatment with mIgA impaired cell activation in an FcαRI–FcRγ‐dependent manner, involving ITAMi signaling. Human mIgA or anti‐FcαRI Fab were strongly effective in either preventing or attenuating CAIA or CIA in FcαRI‐transgenic mice. Administration of mIgA markedly inhibited the recruitment of leukocytes to the inflamed joints of mice, which was associated with induction of SHP‐1 phosphorylation in joint tissue cells. Moreover, mIgA reversed the state of inflammation in the synovial fluid of RA patients by inducing an ITAMi configuration.ConclusionThese results demonstrate a therapeutic potential of human mIgA in experimental arthritis. The findings support future clinical exploration of mIgA for the treatment of RA.
Conformation Diversity of a Fused‐Ring Pyrazine Derivative on Au(111) and Highly Ordered Pyrolytic Graphite
Authors: Yan Hui‐Juan , Sändig Nadja , Wang Haifeng , Wang Dong , Zerbetto Francesco , Zhan Xiaowei , Wan Li‐Jun 
Published: April 2015

AbstractHeterocyclic aromatic compounds have attracted considerable attention because of their high carrier mobility that can be exploited in organic field‐effect transistors. This contribution presents a comparative study of the packing structure of 3,6‐didodecyl‐12‐(3,6‐didodecylphenanthro[9,10‐b]phenazin‐13‐yl)phenanthro[9,10‐b]phenazine (DP), an N‐heterocyclic aromatic compound, on Au(111) and highly ordered pyrolytic graphite (HOPG). High‐resolution scanning tunneling microscopy (STM) combined with atomistic simulations provide a picture of the interface of this organic semiconductor on an electrode that can have an impact on the field‐effect transistor (FET) performance. DP molecules adsorb with different conformational isomers (R/S: trans isomers; C: cis isomer) on HOPG and Au(111) substrates. All three isomers are found in the long‐range disordered lamella domains on Au(111). In contrast, only the R/S trans isomers self‐assemble into stable chiral domains on the HOPG surface. The substrate‐dependent adsorption configuration selectivity is supported by theoretical calculations. The van der Waals interaction between the molecules and the substrate dominates the adsorption binding energy of the DP molecules on the solid surface. The results provide molecular evidence of the interface structures of organic semiconductors on electrode surfaces.