bluuebunny/crossref_metadata_2025_split huggingface dataset:
Monocyte Stabilin-1 Suppresses the Activation of Th1 Lymphocytes
Authors: Palani Senthil , Elima Kati , Ekholm Eeva , Jalkanen Sirpa , Salmi Marko 
Published: November 2015

Abstract
In this study, we analyzed the putative functions of stabilin-1 in blood monocytes. Microarray analysis revealed downregulation of several proinflammatory genes in the stabilin-1high monocytes when compared with stabilin-1low monocytes. When cocultured with stabilin-1high monocytes, IFN-γ synthesis by T cells was diminished in Ag-recall assays. Knockdown of stabilin-1 in monocytes increased the synthesis of several proinflammatory molecules, including TNF-α, and supported high IFN-γ and low IL-4 and IL-5 production by T cells in Ag-specific stimulation assays. Anti–stabilin-1 Ab treatment also led to increased IFN-γ synthesis in the recall assays. In clinical settings, the expression of stabilin-1 was diminished on blood monocytes and tissue macrophages under proinflammatory conditions. These data define stabilin-1 as a new immunosuppressive molecule and suggest that stabilin-1high monocytes may dampen proinflammatory reactions in vivo.
TCRVγ9 γδ T Cell Response to IL-33: A CD4 T Cell–Dependent Mechanism
Authors: Duault Caroline , Franchini Don Marc , Familliades Julien , Cayrol Corinne , Roga Stéphane , Girard Jean-Philippe , Fournié Jean-Jacques , Poupot Mary 
Published: November 2015

Abstract
The availability of specific stimuli to induce the anticancer cytotoxicity of human TCRVγ9-expressing T lymphocytes has allowed the development of γδ T cell–based cancer immunotherapies. However, the stringent dependence of such strategies on the inherently toxic IL-2 has raised safety concerns for patients, justifying a search for alternative methods for inducing γδ T cell stimulation. IL-33 is a γ-chain receptor-independent cytokine of the IL-1 superfamily that is expressed by endothelial cells from a tumor microenvironment and can sustain Th1 and Th2 immune responses. Therefore, we investigated its ability to support the stimulation of human TCRVγ9+ γδ T cells. In this study, we report that IL-33 efficiently sustained the in vitro activation of Vγ9 T lymphocytes by synthetic phosphoantigens, zoledronate, and a BTN3A1 Ab in the absence of an exogenous supply of IL-2. IL-33 was as potent as IL-2 in allowing the proliferative amplification of Vγ9 T cells isolated from PBMC following activation by the synthetic phosphoantigen bromohydrin pyrophosphate. IL-33 also induced an identical maturation into TNF-α– and IFN-γ–producing Th1 effector memory cells, and IL-33–stimulated cells showed an equivalent cytotoxicity for various tumor cells in vitro. Finally, we found that the bioactivity of IL-33 on the Vγ9 T cell was indirectly mediated through contact with CD4 T cells and IL-2 production by CD4 T cells and Vγ9 T cells themselves. These data posit IL-33 as an alternative to IL-2 for Vγ9 T cell–based cancer immunotherapies.
Priming of Qualitatively Superior Human Effector CD8+ T Cells Using TLR8 Ligand Combined with FLT3 Ligand
Authors: Lissina Anna , Briceño Olivia , Afonso Georgia , Larsen Martin , Gostick Emma , Price David A. , Mallone Roberto , Appay Victor 
Published: November 2015

Abstract
The quality of Ag-specific CD8+ T cell responses is central to immune efficacy in infectious and malignant settings. Inducing effector CD8+ T cells with potent functional properties is therefore a priority in the field of immunotherapy. However, the optimal assessment of new treatment strategies in humans is limited by currently available testing platforms. In this study, we introduce an original model of in vitro CD8+ T cell priming, based on an accelerated dendritic cell coculture system, which uses unfractionated human PBMCs as the starting material. This approach enables the rapid evaluation of adjuvant effects on the functional properties of human CD8+ T cells primed from Ag-specific naive precursors. We demonstrate that a selective TLR8 agonist, in combination with FLT3L, primes high-quality CD8+ T cell responses. TLR8L/FLT3L-primed CD8+ T cells displayed enhanced cytotoxic activity, polyfunctionality, and Ag sensitivity. The acquisition of this superior functional profile was associated with increased T-bet expression induced via an IL-12–dependent mechanism. Collectively, these data validate an expedited route to vaccine delivery or optimal T cell expansion for adoptive cell transfer.
Glucose Oxidation Is Critical for CD4+ T Cell Activation in a Mouse Model of Systemic Lupus Erythematosus
Authors: Yin Yiming , Choi Seung-Chul , Xu Zhiwei , Zeumer Leilani , Kanda Nathalie , Croker Byron P. , Morel Laurence 
Published: November 2015

Abstract
We have previously shown that CD4+ T cells from B6.Sle1Sle2.Sle3 lupus mice and patients present a high cellular metabolism, and a treatment combining 2-deoxy-d-glucose, which inhibits glucose metabolism, and metformin, which inhibits oxygen consumption, normalized lupus T cell functions in vitro and reverted disease in mice. We obtained similar results with B6.lpr mice, another model of lupus, and showed that a continuous treatment is required to maintain the beneficial effect of metabolic inhibitors. Further, we investigated the relative roles of glucose oxidation and pyruvate reduction into lactate in this process. Treatments of B6.Sle1Sle2.Sle3 mice with either 2-deoxy-d-glucose or metformin were sufficient to prevent autoimmune activation, whereas their combination was necessary to reverse the process. Treatment of B6.Sle1Sle2.Sle3 mice with dichloroacetate, an inhibitor of lactate production, failed to effectively prevent or reverse autoimmune pathology. In vitro, CD4+ T cell activation upregulated the expression of genes that favor oxidative phosphorylation. Blocking glucose oxidation inhibited both IFN-γ and IL-17 production, which could not be achieved by blocking pyruvate reduction. Overall, our data show that targeting glucose oxidation is required to prevent or reverse lupus development in mice, which cannot be achieved by simply targeting the pyruvate-lactate conversion.
The Group B Streptococcus–Secreted Protein CIP Interacts with C4, Preventing C3b Deposition via the Lectin and Classical Complement Pathways
Authors: Pietrocola Giampiero , Rindi Simonetta , Rosini Roberto , Buccato Scilla , Speziale Pietro , Margarit Immaculada 
Published: November 2015

Abstract
The group B Streptococcus (GBS) is a leading cause of neonatal invasive disease. GBS bacteria are surrounded by a thick capsular polysaccharide that is a potent inhibitor of complement deposition via the alternative pathway. Several of its surface molecules can however activate the classical and lectin complement pathways, rendering this species still vulnerable to phagocytic killing. In this study we have identified a novel secreted protein named complement interfering protein (CIP) that downregulates complement activation via the classical and lectin pathways, but not the alternative pathway. The CIP protein showed high affinity toward C4b and inhibited its interaction with C2, presumably preventing the formation of the C4bC2a convertase. Addition of recombinant CIP to GBS cip-negative bacteria resulted in decreased deposition of C3b on their surface and in diminished phagocytic killing in a whole-blood assay. Our data reveal a novel strategy exploited by GBS to counteract innate immunity and could be valuable for the development of anti-infective agents against this important pathogen.
La Variante infinitésimale de la formule des traces de Jacquet-Rallis pour les groupes
unitaires
Authors: Zydor Michał 
Published: November 2015

RésuméNous établissons une variante infinitésimale de la formule des traces de Jacquet-Rallis pour les groupes unitaires. Notre formule s’obtient par intégration d'un noyau tronqué á la Arthur. Elle posséde un côté géométrique qui est une somme de distributions Jo indexée par les classes d'éléments de l'ébre de Lie de U(n + 1) stables par U(n)-conjugaison ainsi qu'un “côté spectral” formé des transformées de Fourier des distributions précédentes. On démontre que les distributions Jo sont invariantes et ne dépendent que du choix de lamesure deHaar sur U(n)(𝔸). Pour des classes o semi-simples réguliéres, Jo est une intégrale orbitale relative de Jacquet-Rallis. Pour les classes o dites relativement semi-simples régulières, on exprime Jo en terme des intégrales orbitales relatives régularisées á l'aide des fonctions zêta.
Scaling and Root Planning decreases the Number of Melanosomes within Keratinocytes in Human Gingiva: Ultrastructural Analysis of Three Cases
Authors: Alves Claudia Maria Coelho , Imbronito Ana Vitoria , Lotufo Roberto Fraga Moreira , Arana-Chavez Victor Elias 
Published: November 2015

ABSTRACT

Aim
The aim of the present report was to evaluate the number of melanosomes within keratinocytes on pigmented gingiva, after and before scaling and root planning.

Materials and methods
Inflamed gingiva biopsies were taken from three patients (group 1). Forty days after scaling and root planning, biopsies were collected from the homologous contralateral areas (group 2). Samples were fixed in 2% glutaraldehyde—2.5% formaldehyde (freshly prepared from paraformaldehyde) in 0.1 M sodium cacodylate buffer, pH 7.4 for 4 hours, and then processed for transmission electron microscopy. Eighty electron micrographs were evaluated for recording the number of granules by a cross-section grid. The granules that were on intersections were recorded as well as the points that appeared on the cytoplasm for calculating the volumetric density (Vd), i.e the volume that the melanosomes occupied into the cytoplasm of keratinocytes. The presence of melanosomes in different stages of maturation and distribution into the cells were recorded with the aid of a magnifying glass. For the statistical analysis, a student t-test was applied.

Results
Results of the present report showed that melanosomes within keratinocytes were present in a higher number in inflamed gingiva A (11.08 ± 1.47), B (3.16 ± 0.38) and C (4.92 ± 0.89) and decreased after resolving of gingival inflammation A (9.46 ± 0.88), B (1.73 ± 0.25) and C (0.76 ± 0.18).

Conclusion
There is a possibility that inflammation influences the intensity of gingival melanin pigmentation.

Clinical significance
The periodontal treatment appears to have an effect on gingival melanin pigmentation.

How to cite this article
Alves CMC, Imbronito AV, Lotufo RFM, Arana-Chavez VE. Scaling and Root Planning decreases the Number of Melanosomes within Keratinocytes in Human Gingiva: Ultrastructural Analysis of three Cases. J Contemp Dent Pract 2015;16(7):537-541.
Effect of Chlorhexidine and Ethanol Application on Longterm Push-out Bond Strength of Fiber Posts to Dentin
Authors: Basting Roberta Tarkany , Turssi Cecília Pedroso , Amaral Flavia Lucisano Botelho do , França Fabiana Mantovani Gomes , Vaneli Rafaela Crystyan , de Melo Conti Carolina 
Published: November 2015

ABSTRACT

Aim
The aim of this study was to evaluate the effect of chlorhexidine and ethanol application on the push-out bond strength and bond durability of fiber posts cemented with an etch-and-rinse adhesive system/resin cement to intraradicular dentin.

Materials and methods
Fifty-four bovine roots were shaped for the cementation of a fiberglass post and received the application of 37% phosphoric acid. They were then randomly divided into three groups, according to the type of dentin treatment (n = 18) performed: no treatment (control group), 100% ethanol, or 2% chlorhexidine. Next, the adhesive system (Adper Scotch Bond Multipurpose Plus, 3M ESPE) was applied to the dentin, according to the manufacturer's instructions. Glass fiber posts were cemented with dual resin cement (Rely X ARC, 3M ESPE). After 48 hours, the specimens were serially sectioned for push-out test analysis, providing two slices from each root third (cervical, medium and apical), one of which was tested immediately and the other stored in distilled water for 180 days. The data were analyzed with three-way analysis of variance (ANOVA) for repeated measures and Tukey's test at a 5% significance level.

Results
Intraradicular treatment with chlorhexidine yielded the highest bond strength means, followed by ethanol treatment. The control group presented the lowest bond strength means. Water storage exerted no effect on bond strength values.

Conclusion
Both chlorhexidine and ethanol improved push-out bond strength to intraradicular dentin, with the former providing the best results, regardless of the storage time.

Clinical significance
The application of 2% chlorhexidine or 100% ethanol may be an important step that can be taken to enhance bond strength of fiber posts to intraradicular dentin, when dual resin cements are used.

How to cite this article
França FMG, Vaneli RC, de Melo Conti C, Basting RT, do Amaral FLB, Turssi CP. Effect of Chlorhexidine and Ethanol Application on Long-term Pushout Bond Strength of Fiber Posts to Dentin. J Contemp Dent Pract 2015;16(7):547-553.
Color Stability and Surface Roughness of Composite submitted to Different Types and Periods of Finishing/Polishing: Physical Properties of Composites
Authors: de Morais Renata Costa , Garcia Lucas da Fonseca Roberti , Cruvinel Diogo Rodrigues , Pires-de-Souza Fernanda de Carvalho Panzeri 
Published: November 2015

ABSTRACT

Aim
The aim of this study was to evaluate the influence of accelerated artificial aging (AAA) on color stability (ΔE) and surface roughness of composite submitted to different systems and periods of finishing/polishing.

Materials and methods
A Teflon matrix was used to fabricate 60 specimens that were separated into four groups, according to the finishing/polishing system: G1: no polishing; G2: abrasive papers; G3: rubber polishing disks; and G4: G2 + G3. Polishing was performed at three different time intervals (n = 6): immediately (Im), 24 hours (24 hours) and 7 days (7 day) after specimen fabrication. Initial color and surface roughness readouts were taken. Afterwards, specimens were submitted to AAA (480 hours) and new readouts were taken.

Results
Results demonstrated that G2 (7 day) presented lower ΔE, statistically different from G1 and G4 (7 days) (two-way analysis of variance (ANOVA), Bonferroni, p < 0.05).

Conclusion
Regarding roughness, there was no difference among groups and periods. Polishing performed with abrasive papers, 7 days after performing the restoration, promoted less color alteration.

Clinical significance
Most of composite restorations are replaced within a period shorter than 5 years due to esthetic failure, and correct finishing and polishing procedures are fundamental to avoid these problems.

How to cite this article
de Morais RC, da Fonseca Roberti Garcia L, Cruvinel DR, Pires-de-Souza FCP. Color Stability and Surface Roughness of Composite submitted to Different Types and Periods of Finishing/Polishing: Physical Properties of Composites. J Contemp Dent Pract 2015;16(7):565-570.
Human Periodontal Stem Cells Release Specialized Proresolving Mediators and Carry Immunomodulatory and Prohealing Properties Regulated by Lipoxins
Authors: Cianci Eleonora , Recchiuti Antonio , Trubiani Oriana , Diomede Francesca , Marchisio Marco , Miscia Sebastiano , Colas Romain A. , Dalli Jesmond , Serhan Charles N. , Romano Mario 
Published: November 2015

Abstract

Unresolved inflammation and tissue destruction are underlying mechanisms of periodontitis, which is linked to dysregulated polymorphonuclear neutrophil (PMN) functions. Lipoxin A4 (LXA4) is a specialized proresolving lipid mediator (SPM) that dampens excessive inflammation, promotes resolution, and protects from leukocyte-mediated tissue damage. Human periodontal ligament stem cells (hPDLSCs) represent key players during tissue regeneration and may contribute to resolution of inflammation; thus, they may represent a promising tool in regenerative dentistry. In the present study, we investigated the actions of hPDLSCs on PMN apoptosis and antimicrobial functions, and determined the impact of LXA4 on hPDLSCs. hPDLSCs significantly reduced apoptosis and stimulated microbicidal activity of human PMNs, via both cell-cell interactions and paracrine mechanisms. Lipid mediator metabololipidomics analysis demonstrated that hPDLSCs biosynthesize SPMs, including resolvin D1, D2, D5, and D6; protectin D1; maresins; and LXB4; as well as prostaglandins D2, E2, and F2α. LXA4 significantly enhanced proliferation, migration, and wound healing capacity of hPDLSCs through the activation of its cognate receptor ALX/FPR2, expressed on hPDLSCs. Together, these results demonstrate that hPDLSCs modulate PMN functions, and provide the first evidence that stem cells generate SPM and that the LXA4-ALX/FPR2 axis regulates regenerative functions of hPDLSCs by a novel receptor-mediated mechanism.

Significance
These findings uncovered unappreciated features of stem cells from the periodontal ligament, supporting the notion that these cells may act as master regulators of pathophysiological events through the release of mediators that promote the resolution of inflammation and bacterial killing. The study also demonstrated that it is possible to modulate important functions of periodontal stem cells using lipoxin A4, a potent endogenous stop signal of inflammation. Thus, this study revealed an unappreciated anti-inflammatory proregenerative circuit that may be exploited to combat periodontal pathologies using resident stem cells. Moreover, the data may represent a more general template to explain the immunomodulatory functions of stem cells.
Challenging Regeneration to Transform Medicine
Authors: Tsukamoto Ann , Abbot Stewart E. , Kadyk Lisa C. , DeWitt Natalie D. , Schaffer David V. , Wertheim Jason A. , Whittlesey Kevin J. , Werner Michael J. 
Published: November 2015

Abstract

Summary
The aging population in the U.S. and other developed countries has led to a large increase in the number of patients suffering from degenerative diseases. Transplantation surgery has been a successful therapeutic option for certain patients; however, the availability of suitable donor organs and tissues significantly limits the number of patients who can benefit from this approach. Regenerative medicine has witnessed numerous recent and spectacular advances, making the repair or replacement of dysfunctional organs and tissues an achievable goal. Public-private partnerships and government policies and incentives would further catalyze the development of universally available donor tissues, resulting in broad medical and economic benefits. This article describes a Regenerative Medicine Grand Challenge that the Alliance for Regenerative Medicine recently shared with the White House's Office of Science and Technology Policy in response to a White House call to action in scientific disciplines suggesting that the development of “universal donor tissues” should be designated as a Regenerative Medicine Grand Challenge. Such a designation would raise national awareness of the potential of regenerative medicine to address the unmet needs of many diseases and would stimulate the scientific partnerships and investments in technology needed to expedite this goal. Here we outline key policy changes and technological challenges that must be addressed to achieve the promise of a major breakthrough in the treatment of degenerative disease. A nationalized effort and commitment to develop universal donor tissues could realize this goal within 10 years and along the way result in significant innovation in manufacturing technologies.

Significance
Regenerative therapies, in which dysfunctional or degenerating cells, tissues, or organs are repaired or replaced, have the potential to cure chronic degenerative diseases. Such treatments are limited by a shortage of donor organs and tissues and the need for immune suppression to prevent rejection. This article proposes a 21st Century Grand Challenge that would address this significant medical need by coordinating a national effort to convene the multidisciplinary expertise needed to manufacture functional and engraftable cells, tissues, or organs that could be made available to any patient without significant risk of rejection—so-called universal donor tissues.
P53 Codon 72 and Endometrium Cancer
Authors: F. Gloria-Bottini  , M. Nicotra  , C. Spina  , P.L. Benedetti-Panici  , P. Saccucci  , A. Neri  , A. Magrini  , E. Bottini  
Published: November 2015

Background: The possible role p53 codon 72 in endometrium cancer has been investigated in several human populations: a positive association with the Pro variant has been observed in Asiatic but not in Caucasian populations. We reasoned that polymorphisms associated with endometrium cancer may interact with p53 codon 72 influencing the degree of association between this polymorphism and cancer. Methods: Sixty nine women admitted to the hospital for endometrium cancer and 473 healthy subjects were studied in the White population of Rome. Verbal consent was obtained from these subjects to participate to the study that was approved by the Department. P53 codon 72, ADA1, ADA6 and PTPN22 genotypes were determined by DNA analysis Statistical analysis were performed by using commercial software (SPSS). Results: The joint genotype carrying the *Pro allele of p53 codon 72and the ADA1*2 allele, the joint genotype carrying the *Pro allele and ADA6 *1 allele and the joint genotype carrying the *Pro allele and *C/*C genotype of PTPN22 show a proportion greater in cancer than in controls. The proportion of *Pro allele carriers in endometrium cancer shows a positive correlation (p=0.019) with the number of genetic factors considered i.e. ADA1,ADA6, PTPN22. Conclusion: Our data suggest that the strength of association between the disease and p53 codon 72 depends on other genetic factors. Thus the different patterns of association between p53 codon 72 and endometrium cancer observed among human populations could be at least in part related to differences in allelic frequencies of these genetic factors.
Isoreserpine Reverses Multidrug Resistance Mediated by ABCB1
Authors: Yang-Hui Huang  , Sung-Han Hsiao  , Chung-Pu Wu  
Published: November 2015

One of the major obstacles to successful cancer chemotherapy is the development of multidrug resistance (MDR) that is associated with the overexpression of ATP-binding cassette (ABC) drug transporter ABCB1 (P-glycoprotein/ MDR1). Currently, the most efficient way to overcome ABCB1-mediated MDR in cancer is by direct inhibition of ABCB1 function. Many drugs with known biological activities have been discovered to inhibit the function of ABCB1 and reverse ABCB1-mediated MDR in cancers. However, clinical trial results suggested that many of these clinically active drugs should not be used as ABCB1 modulators due to direct toxicity or undesirable side effects. In this study, we demonstrated that isoreserpine, an indole alkaloid with relatively low toxicity, can significantly inhibit ABCB1-mediated efflux of calcein-AM, a known substrate of ABCB1, in a dose-dependent manner. Moreover, we showed that at non-toxic concentrations, isoreserpine potently reversed ABCB1-mediated resistance to doxorubicin and colchicine in ABCB1-overexpressing human KB-V-1 epidermal cancer cells. Collectively, our findings revealed thatby inhibiting the transport function of ABCB1, isoreserpine can restore drug sensitivity of ABCB1-overexpressing cells to conventional chemotherapeutic drugs. In conclusion, isoreserpine should be further developed into a promising reversal agent for the treatment of MDR in ABCB1-overexpressing cancers.