bluuebunny/crossref_metadata_2025_split huggingface dataset:
PPAR-γ/IL-10 Axis Inhibits MyD88 Expression and Ameliorates Murine Polymicrobial Sepsis
Authors: Ferreira Ana Elisa , Sisti Flavia , Sônego Fabiane , Wang Suojuan , Filgueiras Luciano Ribeiro , Brandt Stephanie , Serezani Ana Paula Moreira , Du Hong , Cunha Fernando Q. , Alves-Filho Jose Carlos , Serezani Carlos Henrique 
Published: February 2014

Abstract
Polymicrobial sepsis induces organ failure and is accompanied by overwhelming inflammatory response and impairment of microbial killing. Peroxisome proliferator-activated receptor (PPAR)-γ is a nuclear receptor with pleiotropic effects on lipid metabolism, inflammation, and cell proliferation. The insulin-sensitizing drugs thiazolidinediones (TZDs) are specific PPAR-γ agonists. TZDs exert anti-inflammatory actions in different disease models, including polymicrobial sepsis. The TZD pioglitazone, which has been approved by the U.S. Food and Drug Administration, improves sepsis outcome; however, the molecular programs that mediate its effect have not been determined. In a murine model of sepsis, we now show that pioglitazone treatment improves microbial clearance and enhances neutrophil recruitment to the site of infection. We also observed reduced proinflammatory cytokine production and high IL-10 levels in pioglitazone-treated mice. These effects were associated with a decrease in STAT-1–dependent expression of MyD88 in vivo and in vitro. IL-10R blockage abolished PPAR-γ–mediated inhibition of MyD88 expression. These data demonstrate that the primary mechanism by which pioglitazone protects against polymicrobial sepsis is through the impairment of MyD88 responses. This appears to represent a novel regulatory program. In this regard, pioglitazone provides advantages as a therapeutic tool, because it improves different aspects of host defense during sepsis, ultimately enhancing survival.
8-Oxoguanine DNA Glycosylase-1 Augments Proinflammatory Gene Expression by Facilitating the Recruitment of Site-Specific Transcription Factors
Authors: Ba Xueqing , Bacsi Attila , Luo Jixian , Aguilera-Aguirre Leopoldo , Zeng Xianlu , Radak Zsolt , Brasier Allan R. , Boldogh Istvan 
Published: February 2014

Abstract
Among the insidious DNA base lesions, 8-oxo-7,8-dihydroguanine (8-oxoG) is one of the most abundant, a lesion that arises through the attack by reactive oxygen species on guanine, especially when located in cis-regulatory elements. 8-oxoG is repaired by the 8-oxoguanine glycosylase 1 (OGG1)–initiated DNA base excision repair pathway. In this study, we investigated whether 8-oxoG repair by OGG1 in promoter regions is compatible with a prompt gene expression and a host innate immune response. For this purpose, we used a mouse model of airway inflammation, supplemented with cell cultures, chromatin immunoprecipitation, small interfering RNA knockdown, real-time PCR, and comet and reporter transcription assays. Our data show that exposure of cells to TNF-α altered cellular redox, increased the 8-oxoG level in DNA, recruited OGG1 to promoter sequences, and transiently inhibited base excision repair of 8-oxoG. Promoter-associated OGG1 then enhanced NF-κB/RelA binding to cis-elements and facilitated recruitment of specificity protein 1, transcription initiation factor II-D, and p-RNA polymerase II, resulting in the rapid expression of chemokines/cytokines and inflammatory cell accumulation in mouse airways. Small interfering RNA depletion of OGG1 or prevention of guanine oxidation significantly decreased TNF-α–induced inflammatory responses. Taken together, these results show that nonproductive binding of OGG1 to 8-oxoG in promoter sequences could be an epigenetic mechanism to modulate gene expression for a prompt innate immune response.
Dynamics of Chemokine, Cytokine, and Growth Factor Serum Levels in BRAF-Mutant Melanoma Patients during BRAF Inhibitor Treatment
Authors: Wilmott James S. , Haydu Lauren E. , Menzies Alexander M. , Lum Trina , Hyman Jessica , Thompson John F. , Hersey Peter , Kefford Richard F. , Scolyer Richard A. , Long Georgina V. 
Published: February 2014

Abstract
The purpose of this study is to profile the changes in the serum levels of a range of chemokines, cytokines, and growth and angiogenic factors in MAPK inhibitor–treated metastatic melanoma patients and to correlate these changes with clinical outcome and changes in melanoma tissue biopsies taken from the same patients. Forty-two chemokine, cytokine, angiogenic, and growth factors were measured in the sera of 20 BRAF inhibitor–treated and four combination BRAF and MEK inhibitor–treated metastatic melanoma patients using a multiplex chemokine assay. The changes were correlated with Ki-67 and CD8+ tumor-infiltrating lymphocytes in the tumor biopsies taken at the same time points, as well as clinical outcome, including response rate, progression-free survival, and overall survival. Serum levels of IFN-γ, CCL4, and TNF-α were significantly increased, whereas CXCL8 significantly decreased from pretreatment (PRE) to early during treatment (EDT) serum samples. The decrease in serum CXCL8 levels from PRE to EDT significantly correlated with decreases in markers of melanoma proliferation (Ki-67) and increases in cytotoxic tumor-infiltrating T cells in corresponding tumor biopsies. In addition, a greater fold reduction in CXCL8 serum levels from PRE to EDT serum samples was associated with decreased overall survival. These results suggest that BRAF inhibition causes decreased CXCL8 secretion from melanoma cells and induce an immune response against the tumor associated with increased IFN-γ, CCL4, and TNF-α. Further studies are needed to determine if CXCL8 is predictive of response and to confirm the functions of these chemokine and cytokine in BRAF-mutant melanoma under BRAF inhibition.
Inhibition of the Membrane Attack Complex of the Complement System Reduces Secondary Neuroaxonal Loss and Promotes Neurologic Recovery after Traumatic Brain Injury in Mice
Authors: Fluiter Kees , Opperhuizen Anne Loes , Morgan B. Paul , Baas Frank , Ramaglia Valeria 
Published: February 2014

Abstract
Traumatic brain injury (TBI) is the leading cause of disability and death in young adults. The secondary neuroinflammation and neuronal damage that follows the primary mechanical injury is an important cause of disability in affected people. The membrane attack complex (MAC) of the complement system is detected in the traumatized brain early after TBI; however, its role in the pathology and neurologic outcome of TBI has not yet been investigated. We generated a C6 antisense oligonucleotide that blocks MAC formation by inhibiting C6, and we compared its therapeutic effect to that of Ornithodoros moubata complement inhibitor (OmCI), a known inhibitor of C5 activation that blocks generation of the anaphylatoxin C5a and C5b, an essential component of MAC. Severe closed head injury in mice induced abundant MAC deposition in the brain. Treatment with C6 antisense reduced C6 synthesis (85%) and serum levels (90%), and inhibited MAC deposition in the injured brain (91–96%). Treatment also reduced accumulation of microglia/macrophages (50–88%), neuronal apoptosis, axonal loss and weight loss (54–93%), and enhanced neurologic performance (84–92%) compared with placebo-treated controls after injury. These data provide the first evidence, to our knowledge, that inhibition of MAC formation in otherwise complement-sufficient animals reduces neuropathology and promotes neurologic recovery after TBI. Given the importance of maintaining a functional complement opsonization system to fight infections, a critical complication in TBI patients, inhibition of the MAC should be considered to reduce posttraumatic neurologic damage. This work identifies a novel therapeutic target for TBI and will guide the development of new therapy for patients.
IDO2 Is a Critical Mediator of Autoantibody Production and Inflammatory Pathogenesis in a Mouse Model of Autoimmune Arthritis
Authors: Merlo Lauren M. F. , Pigott Elizabeth , DuHadaway James B. , Grabler Samantha , Metz Richard , Prendergast George C. , Mandik-Nayak Laura 
Published: February 2014

Abstract
Rheumatoid arthritis and other autoimmune disorders are associated with altered activity of the immunomodulatory enzyme IDO. However, the precise contributions of IDO function to autoimmunity remain unclear. In this article, we examine the effect of two different IDO enzymes, IDO1 and IDO2, on the development of autoimmune arthritis in the KRN preclinical model of rheumatoid arthritis. We find that IDO2, not IDO1, is critical for arthritis development, providing direct evidence of separate in vivo functions for IDO1 and IDO2. Mice null for Ido2 display decreased joint inflammation relative to wild-type mice owing to a reduction in pathogenic autoantibodies and Ab-secreting cells. Notably, IDO2 appears to specifically mediate autoreactive responses, but not normal B cell responses, as total serum Ig levels are not altered and IDO2 knockout mice are able to mount productive Ab responses to model Ags in vitro and in vivo. Reciprocal adoptive transfer studies confirm that autoantibody production and arthritis are modulated by IDO2 expression in a cell type extrinsic to the T cell. Taken together, our results, provide important insights into IDO2 function by defining its pathogenic contributions to autoantibody-mediated autoimmunity.
Human γδ Thymocytes Are Functionally Immature and Differentiate into Cytotoxic Type 1 Effector T Cells upon IL-2/IL-15 Signaling
Authors: Ribot Julie C. , Ribeiro Sérgio T. , Correia Daniel V. , Sousa Ana E. , Silva-Santos Bruno 
Published: February 2014

Abstract
Cytotoxicity and IFN-γ production by human γδ T cells underlie their potent antitumor functions. However, it remains unclear where and how human γδ T cells acquire these key effector properties. Given the recent disclosure of a major contribution of the thymus to murine γδ T cell functional differentiation, in this study we have analyzed a series of human pediatric thymuses. We found that ex vivo–isolated γδ thymocytes produced negligible IFN-γ and lacked cytolytic activity against leukemia cells. However, these properties were selectively acquired upon stimulation with IL-2 or IL-15, but not IL-4 or IL-7. Unexpectedly, TCR activation was dispensable for these stages of functional differentiation. The effects of IL-2/IL-15 depended on MAPK/ERK signaling and induced de novo expression of the transcription factors T-bet and eomesodermin, as well as the cytolytic enzyme perforin, required for the cytotoxic type 1 program. These findings have implications for the manipulation of γδ T cells in cancer immunotherapy.
Microleakage at enamel and dentin margins with a bulk fills flowable resin
Authors: Scotti Nicola , Comba Allegra , Gambino Alberto , Paolino Davide Salvatore , Alovisi Mario , Pasqualini Damiano , Berutti Elio 
Published: February 2014

ABSTRACT
Objective: The aim of this in vitro study was to evaluate the marginal sealing ability of a bulk fill flowable resin composite on both enamel and dentin substrates. Materials and Methods: 48 non-carious molars were selected and four Class-V cavities were prepared at the CEJ of each sample. Cavities were filled with Venus Diamond (Heraeus Kulzer); Venus Diamond Flow (Heraeus Kulzer) and Surefil SDR (Dentsply). Samples were divided into two groups: First group samples were immersed in a methylene blue solution for 30 min at 25°C. Second group samples were artificially aged and then treated with methylene blue. Samples were sectioned in the center of the restoration and observed with a 40x stereomicroscope, and the percentage of cavity infiltration was calculated. Results: Results were analyzed statistically by ANOVA (P < 0.05). The amount of infiltration was significantly lower for the enamel substrate compared with dentin (P = 0.0001) and in samples immediately immersed in methylene blue compared with those that were artificially aged (P = 0.011). The interaction between the composite material and the marginal substrate significantly affected dye penetration (P = 0.006). Conclusions: Bulk fill flowable resins provided significantly better marginal seal in dentin, both before and after artificial ageing. Nanohybrid resin composites and bulk fill flowable resins showed similar microleakage values at enamel margins. Bulk fills flowable resins provided significantly better marginal seal in dentin, both before and after artificial ageing. Nanohybrid resin composites and bulk fill flowable resins showed similar microleakage values at enamel margins.
Influence of softening test and light-activation protocols on resin composite polymer structure
Authors: Giorgi Maria Cecília Caldas , Lima Débora Alves Nunes Leite , Marchi Giselle Maria , Ambrosano Gláucia Maria , Aguiar Flávio Henrique Baggio 
Published: February 2014

ABSTRACT
Objective: This study analyzed the influences of the light-activation protocol and softening test on the degree of conversion (DC) and Knoop Hardness (KHN) of a microhybrid resin composite. Materials and Methods: Filtek Z250 (3M ESPE) was light-activated with a third-generation light-emitting diode (Valo Ultradent) by three protocols – standard, high power, and plasma emulation – or with a quartz-tungsten halogen XL 3000 (3M ESPE) in conventional mode. All modes were set to deliver 19 J/cm2. The DC (N = 20) was determined by Fourier transform infrared spectrometry on the top (T) and bottom (B) surfaces. For the KHN test, samples were subdivided in four groups (n = 5 each) according to the storage media: absolute ethanol, 75% ethanol, distilled water, and air (control group). The KHN values were evaluated on T and B before and 24 h after immersion in the storage media. Data were analyzed by split-plot analysis of variance (ANOVA; for DC) or repeated-measures split-plot ANOVA (for KHN), followed by Tukey's test (α = 0.05). Results: For the DC, the light-activation protocol did not influence the results and there was no difference between T and B. For the KHN test, the light-activation protocol did not influence the results and T showed higher microhardness values than B for all experimental conditions. There were significant differences in KHN depending on the storage media. Samples immersed in absolute ethanol generally presented lower KHN values, with no differences compared to samples in 75% ethanol. Conclusion: The storage media affected the outcomes of the softening test.
Effect of different adhesive strategies on the post-operative sensitivity of class I composite restorations
Authors: Sancakli Hande Sar , Yildiz Esra , Bayrak Isil , Ozel Sevda 
Published: February 2014

ABSTRACT
Objective: To evaluate the post-operative sensitivity of occlusal restorations using different dentin adhesives performed by an undergraduate and a post-doctorate dentist. Materials and Methods: One hundred and eighty-eight molar occlusal restorations were placed in 39 patients (ages between 18 and 30) using 3 different kind of adhesive systems; Optibond FL (OBF), Clearfil Protect Bond (CPB), and iBond (IB) by a post-doctorate dentist or a fifth-year dental student according to the manufacturers’ instructions. Post-operative sensitivity to cold and air was evaluated using a Visual Analog Scale (VAS) after 24 hours, 30, 90, and 180 days. Data were analyzed using the Mann-Whitney U and Friedman tests (P < 0.05). Results: Post-operative sensitivity scores for OBF and CPB were higher for the dental student (P < 0.05), while IB scores did not differ statistical significantly according to the operator (P > 0.05). Conclusion: Operator skill and experience appears to play a role in determining the outcome of post-operative sensitivity of multi-step adhesive systems although the post-operative sensitivity was low. It is suggested that the less experienced clinicians (rather than experienced clinicians) should better use the self-etching dentin bonding systems with reduced application steps to minimize the potential risk of post-operative sensitivity of dental adhesives.
A comparative in-vivo evaluation of the alignment efficiency of 5 ligation methods: A prospective randomized clinical trial
Authors: Reddy Vijaya Bhaskara , Kumar Talapaneni Ashok , Prasad Mandava , Nuvvula Sivakumar , Patil Rajedra Goud , Reddy Praveen Kumar 
Published: February 2014

ABSTRACT
Objectives: To conduct a prospective randomized study comparing the efficiency of 5 different ligation systems (ELL; elastomeric ligature, SSL; stainless steel ligature, LL; leone slide ligature, PSL; passive self-ligation and ASL; active self-ligation) over the duration of mandibular crowding alleviation. Materials and Methods: Fifty consecutive patients (54.2% male, 45.8% female; mean age: 16.69 years) satisfying the inclusion criteria were randomly allocated to 5 ligation groups with an equal sample size of 10 per group. The 5 groups received treatment with 0.022-inch MBT pre-adjusted edge-wise technique (ELL: Gemini 3M Unitek, SSL: Gemini 3M Unitek, LL: Gemini 3M Unitek, PSL: SmartClip 3M Unitek and ASL: In-Ovation R Euro GAC International). The models and cephalograms were evaluated for anterior arch alignment, extraction space closure, and lower incisal inclinations at pre-treatment T1 and at the end of initial alignment T2. Analysis of variance (ANOVA) and Post-hoc tests were used for data analysis. Results: Forty-eight participants completed the study, and SL systems showed a significant difference over CL groups in time to alignment, passive space closure, and incisal inclination. Multiple regression showed a reduction of 5.28 days in time to alignment by changing the ligation group in the order of ELL to ASL group and 1 mm increase in initial irregularity index increases time to alignment by 11.68 days. Conclusion: Self-ligation brackets were more efficient than conventional ligation brackets during initial leveling and alignment.
Comparative analysis of three different filling techniques and the effects of experimental internal resorptive cavities on apical microleakage
Authors: Keles Ali , Ahmetoglu Fuat , Ocak Mevlut S. , Dayi Burak , Bozkurt Alperen , Orucoglu Hasan 
Published: February 2014

ABSTRACT
Objectives: The aim of this study was to evaluate the sealing abilities of three different gutta-percha techniques in experimentally defective roots (EDR) and non-defective roots (NR). Materials and Methods: Sixty canine teeth were divided into six groups of ten; Group 1, NR + cold lateral condensation (CLC); Group 2, EDR + LC; Group 3, NR + BeeFill; Group 4, EDR + BeeFill; Group 5, NR + Thermafil; and Group 6, EDR + Thermafil. Apical leakage was measured using a computerized fluid filtration meter with a laser system. Results: Statistical analysis revealed that the CLC demonstrated more microleakage in the EDR than in the NR (P < 0.01). Thermafil demonstrated more microleakage in the NR than in the EDR (P < 0.01). No statistically significant differences were found between the BeeFill groups (P > 0.05). Conclusions: The results of this study indicate that internal resorptive cavities can affect the apical sealing properties of different root canal filling techniques, with Thermafil ensuring the lowest apical microleakage.
Evaluation of dental maturation in children according to sagittal jaw relationship
Authors: Esenlik Elcin , Atak Aslihan , Altun Ceyhan 
Published: February 2014

ABSTRACT
Objective: The aims of this retrospective study were to determine compliance with dental and chronological ages and to analyze the relationships between dental age and orthodontic sagittal anomalies. Materials and Methods: A total of 221 subjects between the ages of 7 and 15.9 years (165 girls and 156 boys) were included in the study. The dental age of seven left mandibular teeth was assessed according to the Demirjian method. The maxillary protrusion, mandibular protrusion, maxillo-mandibular and vertical plane angles were measured from cephalometric films. Results: The mean difference between the chronological age and dental age in female patients was 0.94 years and 0.33 years in male patients (P < 0.01). No differences between the sagittal classification groups were found. There was no relationship between dental age and the SNA° or the GoGn-SN°. A statistically significant negative relationship was found between dental age and the SNB° and there was a significant linear relationship between dental age and the ANB°. Conclusion: Dental age in girls and boys has been estimated to be more advanced than chronological age in all classes and dental maturation advanced in cases with a tendency to develop Class II malocclusions.
Effectiveness of different irrigation systems on smear layer removal: A scanning electron microscopic study
Authors: Ahmetoglu Fuat , Keles Ali , Yalcin Muhammet , Simsek Neslihan 
Published: February 2014

ABSTRACT
Objectives: To evaluate effectiveness of the apical negative pressure irrigation (EndoVac), passive ultrasonic irrigation (PUI), and conventional needle irrigation (CI) systems on smear layer (SR) removal. Materials and Methods: Sixty single-rooted canines were prepared using NiTi rotary files and subjected to different irrigation regimens: EndoVac with NaOCl (Group 1) or NaOCl/EDTA (Group 2); PUI with NaOCl (Group 3) or NaOCl/EDTA (Group 4); CI with NaOCl (Group 5) or NaOCl/EDTA (Group 6). The roots were split longitudinally. SEM images were taken to evaluate the amount of residual SR. Results: In Groups 1, 3, and 5, there was no removal of SR (P > 0.05). The coronal thirds within Groups 2, 4, and 6 were cleaned completely, but the middle and the apical thirds was achieved partially or completely (P > 0.05). Conclusion: Regardless of which irrigation system was used, the use of NaOCl alone failed to remove the SR. In NaOCl/EDTA combination groups, the SR was removed partially or completely and no statistical significance. This study demonstrated that in order to remove the SR should be used EDTA solution for final irrigation in the root canal, regardless of the technique in each of the three.
Effect of Er:YAG laser on debonding strength of laminate veneers
Authors: Iseri Ufuk , Oztoprak Mehmet Oguz , Ozkurt Zeynep , Kazazoglu Ender , Arun Tulin 
Published: February 2014

ABSTRACT
Objective: The purpose of this study was to evaluate the debonding strength of laminate veneers after using erbium-doped: yttrium aluminium garnet (Er:YAG) laser. Materials and Methods: A total of 60 bovine mandibular incisor teeth were divided into two groups (n = 30). Cylindrical specimens (0.7 mm × 5 mm) were fabricated from Empress II ceramic. Then, they were cemented to incisors using dual-cured resin cement (Variolink II). In the first group, no laser application was performed. The Er:YAG laser was applied on each laminate veneer at the test group for 9 s by using the scanning method. Shear force to remove the laminate veneers were applied with universal testing machine at a crosshead speed of 1 mm/min. Results: Results of this study exhibited significant differences between the control (27.28 ± 2.24 MPa) and test group (3.44 ± 0.69 MPa) (P < 0.05). Conclusion: This study shows that application of Er:YAG laser decreased the bond strength of laminate veneers.