LncRNA XR_001779380 Primes Epithelial Cells for IFN-γ-Mediated Gene Transcription and Facilitates Age-Dependent Intestinal Antimicrobial Defense.

Interferon (IFN) signaling is key to mucosal immunity in the gastrointestinal tract, but cellular regulatory elements that determine interferon gamma (IFN-γ)-mediated antimicrobial defense in intestinal epithelial cells are not fully understood. We report here that a long noncoding RNA (lncRNA), GenBank accession no. XR_001779380, was increased in abundance in murine intestinal epithelial cells following infection by Cryptosporidium, an important opportunistic pathogen in AIDS patients and a common cause of diarrhea in young children. Expression of XR_001779380 in infected intestinal epithelial cells was triggered by TLR4/NF-κB/Cdc42 signaling and epithelial-specific transcription factor Elf3. XR_001779380 primed epithelial cells for IFN-γ-mediated gene transcription through facilitating Stat1/Swi/Snf-associated chromatin remodeling. Interactions between XR_001779380 and Prdm1, which is expressed in neonatal but not adult intestinal epithelium, attenuated Stat1/Swi/Snf-associated chromatin remodeling induced by IFN-γ, contributing to suppression of IFN-γ-mediated epithelial defense in neonatal intestine. Our data demonstrate that XR_001779380 is an important regulator in IFN-γ-mediated gene transcription and age-associated intestinal epithelial antimicrobial defense. IMPORTANCE Epithelial cells along the mucosal surface provide the front line of defense against luminal pathogen infection in the gastrointestinal tract. These epithelial cells represent an integral component of a highly regulated communication network that can transmit essential signals to cells in the underlying intestinal mucosa that, in turn, serve as targets of mucosal immune mediators. LncRNAs are recently identified long noncoding transcripts that can regulate gene transcription through their interactions with other effect molecules. In this study, we demonstrated that lncRNA XR_001779380 was upregulated in murine intestinal epithelial cells following infection by a mucosal protozoan parasite Cryptosporidium. Expression of XR_001779380 in infected cells primed host epithelial cells for IFN-γ-mediated gene transcription, relevant to age-dependent intestinal antimicrobial defense. Our data provide new mechanistic insights into how intestinal epithelial cells orchestrate intestinal mucosal defense against microbial infection.

m6A mRNA Methylation Regulates Epithelial Innate Antimicrobial Defense Against Cryptosporidial Infection.

Increasing evidence supports that N6-methyladenosine (m6A) mRNA modification may play an important role in regulating immune responses. Intestinal epithelial cells orchestrate gastrointestinal mucosal innate defense to microbial infection, but underlying mechanisms are still not fully understood. In this study, we present data demonstrating significant alterations in the topology of host m6A mRNA methylome in intestinal epithelial cells following infection by Cryptosporidium parvum, a coccidian parasite that infects the gastrointestinal epithelium and causes a self-limited disease in immunocompetent individuals but a life-threatening diarrheal disease in AIDS patients. Altered m6A methylation in mRNAs in intestinal epithelial cells following C. parvum infection is associated with downregulation of alpha-ketoglutarate-dependent dioxygenase alkB homolog 5 and the fat mass and obesity-associated protein with the involvement of NF-кB signaling. Functionally, m6A methylation statuses influence intestinal epithelial innate defense against C. parvum infection. Specifically, expression levels of immune-related genes, such as the immunity-related GTPase family M member 2 and interferon gamma induced GTPase, are increased in infected cells with a decreased m6A mRNA methylation. Our data support that intestinal epithelial cells display significant alterations in the topology of their m6A mRNA methylome in response to C. parvum infection with the involvement of activation of the NF-кB signaling pathway, a process that modulates expression of specific immune-related genes and contributes to fine regulation of epithelial antimicrobial defense.

A host cell long noncoding RNA NR_033736 regulates type I interferon-mediated gene transcription and modulates intestinal epithelial anti-Cryptosporidium defense.

The gastrointestinal epithelium guides the immune system to differentiate between commensal and pathogenic microbiota, which relies on intimate links with the type I IFN signal pathway. Epithelial cells along the epithelium provide the front line of host defense against pathogen infection in the gastrointestinal tract. Increasing evidence supports the regulatory potential of long noncoding RNAs (lncRNAs) in immune defense but their role in regulating intestinal epithelial antimicrobial responses is still unclear. Cryptosporidium, a protozoan parasite that infects intestinal epithelial cells, is an important opportunistic pathogen in AIDS patients and a common cause of diarrhea in young children in developing countries. Recent advances in Cryptosporidium research have revealed a strong type I IFN response in infected intestinal epithelial cells. We previously identified a panel of host cell lncRNAs that are upregulated in murine intestinal epithelial cells following microbial challenge. One of these lncRNAs, NR_033736, is upregulated in intestinal epithelial cells following Cryptosporidium infection and displays a significant suppressive effect on type I IFN-controlled gene transcription in infected host cells. NR_033736 can be assembled into the ISGF3 complex and suppresses type I IFN-mediated gene transcription. Interestingly, upregulation of NR_033736 itself is triggered by the type I IFN signaling. Moreover, NR_033736 modulates epithelial anti-Cryptosporidium defense. Our data suggest that upregulation of NR_033736 provides negative feedback regulation of type I IFN signaling through suppression of type I IFN-controlled gene transcription, and consequently, contributing to fine-tuning of epithelial innate defense against microbial infection.

ST2/IL-33 signaling promotes malignant development of experimental squamous cell carcinoma by decreasing NK cells cytotoxicity and modulating the intratumoral cell infiltrate.

Squamous cell carcinoma (SCC) is the second most common form of skin cancer and the mechanism(s) involved in the progression of this tumor are unknown. Increases in the expression of IL-33/ST2 axis components have been demonstrated to contribute to neoplastic transformation in several tumor models and interleukin-33 is correlated with poor prognosis of patients with squamous cell carcinoma of the tongue. Based on these observations, we sought to determine the role of the IL-33/ST2 pathway during the development of SCC. Our findings show that ST2-deficiency led to a marked decrease in the severity of skin lesions, suggesting that ST2 signaling contributed to tumor development. An analysis of tumor lesions in wild-type and ST2KO mice revealed that a lack of ST2 was associated with specific and significant reductions in the numbers of CD4+ T cells, CD8+ T cells, dendritic cells, and macrophages. In addition, NK cells that were isolated from ST2KO mice exhibited higher cytotoxic activity than cells isolated from wild-type mice. Notably, ST2 deficiency resulted in lower IFN-γ, TNF-α, IL-10, and IL-17 production in tumor samples. Our findings indicate that the IL-33/ST2 pathway contributes to the development of SCC by affecting leukocyte migration to tumor microenvironment and impairing NK cytotoxic activity.

Circulating monocytes from prostate cancer patients promote invasion and motility of epithelial cells.

BACKGROUND: Recruited myeloid cells are known to promote cancer initiation, malignant progression, metastasis, and resistance to therapy in the tumor niche. We tested the hypothesis that circulating blood monocytes from advanced prostate cancer (PCa) patients exhibit a protumor phenotype and directly influence the tumor microenvironment in response to tumor-derived signals. METHODS: Blood monocytes from advanced and stable PCa patients were cultured, and the conditioned media (CM) were collected and analyzed using standard invasion and wound closure assays to measure effects on invasion and motility of PCa tumor cells. We then identified the proteome profile of these monocytes using proteome array and ELISA. RESULTS: Conditioned media from circulating monocytes in patients with metastatic prostate cancer (PCa-M) increased invasion of epithelial PCa cells in vitro. Proteome Profiler Analysis revealed that monocyte-derived CM from metastatic castration-resistant (mCRPC) patients presented high levels of chitinase-3-like 1 (CHI3L1, YKL-40) when compared to patients with stable disease (PCa-N) and healthy control individuals (HC). The only described receptor for CHI3L1, interleukin-13 receptor α2 (IL-13Rα2), was significantly up-regulated in the human metastatic PCa cell line, ARCaPM . Accordingly, we observed that the activation of IL-13Rα2 from PCa-M CM increased the invasiveness of ARCaPM cells while siRNA directed against this receptor significantly reduced invasiveness of these cells in the presence of CM from PCa-M patients. CONCLUSIONS: Thus, we show that circulating monocytes from metastatic PCa patients exert a tumor-promoting role via the secretion of CHI3L1, and CHI3L1 demands further exploration as a possible therapeutic target in advanced PCa.

Autocrine Type I IFN Signaling in Dendritic Cells Stimulated with Fungal ß-Glucans or Lipopolysaccharide Promotes CD8 T Cell Activation.

Type I IFNs are key mediators of immune defense against viruses and bacteria. Type I IFNs were also previously implicated in protection against fungal infection, but their roles in antifungal immunity have not been thoroughly investigated. A recent study demonstrated that bacterial and fungal ß-glucans stimulate IFN-ß production by dendritic cells (DCs) following detection by the Dectin-1 receptor, but the effects of ß-glucan-induced type I IFNs have not been defined. We investigated whether type I IFNs regulate CD8 T cell activation by fungal ß-glucan particle-stimulated DCs. We demonstrate that ß-glucan-stimulated DCs induce CD8 T cell proliferation, activation marker (CD44 and CD69) expression, and production of IFN-γ, IL-2, and granzyme B. Moreover, we show that type I IFNs support robust CD8 T cell activation (proliferation and IFN-γ and granzyme B production) by ß-glucan-stimulated DCs in vitro and in vivo due to autocrine effects on the DCs. Specifically, type I IFNs promote Ag presentation on MHC I molecules, CD86 and CD40 expression, and the production of IL-12 p70, IL-2, IL-6, and TNF-α by ß-glucan-stimulated DCs. We also demonstrate a role for autocrine type I IFN signaling in bacterial LPS-induced DC maturation, although, in the context of LPS stimulation, this mechanism is not so critical for CD8 T cell activation (promotes IFN-γ production but not proliferation or granzyme B production). This study provides insight into the mechanisms underlying CD8 T cell activation during infection, which may be useful in the rational design of vaccines directed against pathogens and tumors.

IL17 Promotes Mammary Tumor Progression by Changing the Behavior of Tumor Cells and Eliciting Tumorigenic Neutrophils Recruitment.

The aggressiveness of invasive ductal carcinoma (IDC) of the breast is associated with increased IL17 levels. Studying the role of IL17 in invasive breast tumor pathogenesis, we found that metastatic primary tumor-infiltrating T lymphocytes produced elevated levels of IL17, whereas IL17 neutralization inhibited tumor growth and prevented the migration of neutrophils and tumor cells to secondary disease sites. Tumorigenic neutrophils promote disease progression, producing CXCL1, MMP9, VEGF, and TNFα, and their depletion suppressed tumor growth. IL17A also induced IL6 and CCL20 production in metastatic tumor cells, favoring the recruitment and differentiation of Th17. In addition, IL17A changed the gene-expression profile and the behavior of nonmetastatic tumor cells, causing tumor growth in vivo, confirming the protumor role of IL17. Furthermore, high IL17 expression was associated with lower disease-free survival and worse prognosis in IDC patients. Thus, IL17 blockade represents an attractive approach for the control of invasive breast tumors.

Effects of zirconia nanoparticles addition to experimental adhesives on radiopacity and microhardness

AIM: To evaluate the radiopacity and microhardness (KHN) of experimental dental adhesives (EX). The experimental adhesive resins of the present study were formulated based on the simplified adhesive system Ambar (FGM). METHODS: Five EX with different concentrations of zirconia nanoparticles [0(EX0), 15(EX15), 25(EX25), 30(EX30) e 50%(EX50)] were incorporated in a UDMA/HEMA adhesive (control). Adper Single BondTM 2 (SB, 3M ESPE) was used as a commercial reference. For the radiopacity (n=5), KHN (n=5), adhesive specimens were fabricated using a stainless steel mold. Data were submitted to one-way ANOVA and Tukey's test (α=0.05). RESULTS: The filler addition on the EX showed radiopacity similar to enamel and higher than SB. The EX25, EX35 and EX50 showed higher KHN values when compared to the commercial SB. EX25, EX35 and EX50 showed higher KHN values when compared to the commercial SB. CONCLUSIONS: The results of the present investigation suggest that the addition of zirconia nanoparticles seems to be a good alternative to produce radiopaque adhesives with increased microhardness.

Efeito do clareamento na susceptibilidade ao manchamento de uma resina composta / Effect of bleaching on staining susceptibility of a composite resin

Objetivo: verificar o efeito do clareamento (caseiro e em consultório) na susceptibilidade ao manchamento de uma resina composta e imersão em soluções corantes. Trinta espécimes de resina composta microhíbrida sofreram avaliação de cor inicial (Vita EasyShade) e aleatoriamente divididos em 6 grupos G1: sem clareamento, com imersão em café; G2: sem clareamento, com imersão em vinho; G3: clareado com peróxido de carbamida 10% (PC 10%) e imersão em café; G4: clareado com PC 10% e imersão em vinho; G5: clareado com peróxido de hidrogênio 35% (PH 35%) e imersão café e G6: clareado com PH 35% e imersão em vinho. Em seguida, houve avaliação final de cor. Os resultados foram analisados por ANOVA 2 fatores e Pós-teste de Tukey (α=0,05). Foram avaliados valores de L (luminosidade), sendo as médias (desvio-padrão) dos valores iniciais - G1: 88,22(1,62); G2:86,76(0,86); G3:82,52(2,90); G4:84,72(1,24); G5:85,64(1,92); G6:86,30(1,13), e os valores finais: G1: 78,32(2,24); G2: 76,46(1,61); G3: 74,60(0,92); G4: 65,00(3,97); G5: 75,56(1,76); G6: 72,48(4,69). Os valores de ΔE também foram calculados (critérios do NBS). Conclusão: a resina composta, submetida ao clareamento, caseiro sofreu maior alteração de cor quando imerso em vinho tinto, comparado aos demais grupos.

Objective: to evaluate the effect of at-home and in-office bleaching on staining susceptibility of a resin composite with immersion in staining solutions. Thirty specimens of a microhybrid composite were first evaluated with a spectrophotometer (Vita Easyshade), and randomly divided into 6 groups: G1: no bleaching, immersion in coffee; G2: no bleaching, immersion in red wine; G3: bleaching with 10% carbamide peroxide (PC10%) and immersion in coffee; G4: bleaching with PC10% and immersion in wine; G5: bleaching with 35% hydrogen peroxide (PH35%) and immersion in coffee; G6: PH35% and immersion in wine. The final color was evaluated for all groups. Color change values (CIELab), by means of L values - luminosity - were evaluated and statistically analyzed by ANOVA and Tukey's post-test. Results: means(standard-deviation) for initial L values were: G1:88.22(1.62); G2:86.76(0.86); G3:82.52(2.90); G4:84.72(1.24); G5:85.64(1.92); G6:86.30(1.13), e final L values were: G1:78.32(2.24); G2:76.46(1.61); G3:74.60(0.92); G4:65.00(3.97); G5:75.56(1.76); G6:72.48(4.69). ΔE values were also calculated, according to NBS criteria. Conclusion: there was an increased staining susceptibility of the resin composite submitted to at-home bleaching when immersed in red wine, compared to the another groups, by means of luminosity.

Efeito do uso de agente dessensibilizante na efetividade do clareamento e na sensibilidade dental / Assessing the effect of a desensitizing agent on dental sensitivity and effectiveness of bleaching

O objetivo deste estudo foi avaliar clinicamente o efeito de um agente dessensibilizante utilizado previamente à aplicação de um gel de peróxido de hidrogênio 200/0 contendo cálcio (PH20) na efetividade do clareamento (EC) e sensibilidade dental (SD). Foram selecionados 30 pacientes, os quais foram divididos aleatoriamente em grupo placebo (GP) e grupo experimental (GE). Um gel placebo ou dessensibilizante (Desensibilize KF 20%, FGM) foi aplicado durante 10 minutos antes do clareamento de consultório (CC) realizado com PH20% (Whiteness HP Blue, FGM), em 2 sessões com aplicação única de 50 minutos. Este protocolo foi repetido na 1ª e 2ª sessões, com intervalo de 7 dias entre as mesmas. Os pacientes utilizaram escala de 0-4 para anotarem a SD. A cor foi registrada com escala Vita antes e após cada sessão. A EC foi analisada estatisticamente pelos testes de análise de variância e Tukey (0=0,05). A porcentagem de pacientes com SD, assim como a intensidade de SD foram avaliados pelos testes exato de Fisher e Mann-Whitney, respectivamente. Ao final das 2 sessões de clareamento. 90% dos pacientes atingiram a cor A 1/B2. O CC foi efetivo para os 2 grupos avaliados com alteração de cor entre 6 e 7 unidades na escala Vita. Houve relatos de SD em 33,3% dos pacientes no GP e 20% no GE. A intensidade SD foi similar para os 2 grupos (p>0,05). Concluiu-se que o uso de agente dessensibilizante previamente ao CC com PH 20% não interferiu na EC e não reduziu a prevalência e intensidade da SD.

The aim of this clinical study was to evaluate the bleaching efficiency (BE) and tooth sensitivity (TS) of a desensitizing agent used before in-office bleaching with 20% hydrogen peroxide gel with calcium. It was selected 30 patients, which were randomized into placebo and experimental groups. A placebo or desensitizing gel (Oesensibilize KF 20%, FGM) was applied for 10 minutes before in-office bleaching with 20% hydrogen peroxide (Whiteness HP Blue, FGM), in two sessions with one application of 50 minutes This protocol was repeated on the first and second sessions, with a week of interval between sessions. The patients used a scale of O to 4 to write down their tooth sensitivity. The color was registered with a Vita scale before and after each session. The BE was analyzed by ANOVA and Tukey tests The percentage of patients with TS, as well as TS intensity were analyzed by Fisher's exact and Mann-Whitney tests At the end of two sessions of dental bleaching, 90% of patients achieved A 1/B2 color. In-office bleaching was effective for both groups with color change between 6 and 7 units in Vita scale. It was reported sensitivity in 33.3% of patients from placebo group and 20% from experimental group. The intensity ofTS was similar for both groups (p>0.05). The use of a desensitizing agent before in-office dental bleaching using 20% hydrogen peroxide had no effect on BE and did not reduce the prevalence and intensity of tooth sensitivity.

Anti-CD3ε induces splenic B220lo B-cell expansion following anti-CD20 treatment in a mouse model of allosensitization.

Antibodies targeting T cells and B cells are increasingly used for immunosuppression in clinical transplantation. However, the impact of T-cell depletion by antibodies on B-cell homeostasis is poorly understood. Using a mouse model of allosensitization with skin allograft, we investigated whether targeting T cells by anti-CD3ε alters peripheral B-cell homeostasis and alloantibody responses following B-cell depletion by anti-CD20. We found that anti-CD3ε induced a discrete B220(lo), but not a conventional B220(hi) subset, in the spleens of the allosensitized mice 14 days after anti-CD20 treatment. The splenic B220(lo) cells were refractory to anti-CD20 depletion. Flow cytometry revealed that the splenic B220(lo) cells were phenotypically similar to the B220(lo) AA4.1(+) CD23(-) sIgM(lo) sIgD(-) developing B cells (pre-B to immature B) normally presented in the bone marrow. Despite the presence of the splenic B220(lo) cells, mice treated with combined anti-CD3ε/CD20 produced limited alloantibodies in response to the primary skin allografts. Alloantibody production increased significantly in the mice following re-immunization by donor-specific splenocytes. We conclude that anti-CD3ε can induce an expansion of B220(lo) B cells in the spleens after B-cell depletion by anti-CD20. These B cells are not producing alloantibodies, but re-immunization of the mice with alloantigen leads to risk of alloantibody response.

Efeito de diferentes agentes clareadores de uso caseiro na microdureza superficial de resinas compostas: microhíbrida X nanohíbrida / Effect of different at-home bleaching agents in microhardness surface of resin composites: microhybrid X nanohybrid

Avaliou-se o efeito de agentes clareadores de uso caseiro na microdureza de resinas compostas (RC) microhíbrida e nanohíbrida. Foram confeccionados 30 corpos-de-prova (cp), divididos em seis grupos (n=5). Os grupos G1 a G3 utilizaram RC microhíbrida (Opallis), e os grupos G4 a G6, RC nanohíbrida (BrilliantNewLine). Os agentes clareadores utilizados foram: peróxido de hidrogênio 6% (PH) (White Class Cálcio) e peróxido de carbamida 16% (PC) (Whiteness Perfect). Após a confecção dos cp, o clareamento foi realizado: G1 e G4: grupo controle sem agente clareador, G2 e G5: PH - 28 dias, G3 e G6: PC - 28 dias, de acordo com as recomendações dos fabricantes. Em seguida, o teste de microdureza foi realizado. Os dados obtidos foram analisados por ANOVA e Tukey (5%). Os resultados de microdureza (HV) e desvio-padrão foram: G1-26,56 ± 3,9, G2-25,98 ± 3,3 e G3-24,94 ± 4,4; G4-27,24 ± 3,3; G5-32,02 ± 6,4 e 37,72 G6- ± 8,1. O único grupo que apresentou diferenças significativas para os outros foi o G6 (p <0,05), mas não diferiu significativamente em relação ao G5 (p = 0,0058). Concluiu-se que o uso de agentes clareadores de uso caseiro não afetou negativamente a microdureza das resinas compostas testadas.

It was evaluated the effects of home bleaching agents on microhardness of microhybrid and nanohybrid composite resins. 30-of-body were made and divided into 6 groups (n=5). The groups G1 to G3 used a microhybrid CR (Opallis), while groups G4 to G6 used a nanohybrid CR (BrilliantNewLine). The bleaching agents used were: 6% hydrogen peroxide (PH) (White Class Cálcio) and 16% carbamide peroxide (PC) (Whiteness Perfect). After the specimens were prepared, the bleaching was realized as follows: G1 and G4: control group without bleaching agent, G2 and G5: PH - 28 days, G3 and G6: PC - 28 days, in accordance with the manufacturer's recommendations. After it, the microhardness test was performed. The data were statistically analyzed by ANOVA and Tukey's tests (5%). The results of microhardness (HV) and standard deviation of each group were: G1- 26.56±3.9; G2- 25.98±3.3; G3- 24.94±4.4; G4- 27.24±3.3; G5- 32.02±6.4 and G6- 37.72±8.1. The only group that showed significant differences to the anothers was the G6 (p<0.05), but did not differ significantly in relation to G5 (p=0.0058). It was concluded that the use of home bleaching agents didn't affect negatively the microhardness of the composite resins tested.

Influência do polimento após manchamento de uma resina composta submetida a diferentes bebidas / Influence of polishing after staining of a composite subjected to different drinks

Objetivo: avaliar se o polimento pode minimizar ou resolver o manchamento ocasionado porcorantes de diferentes bebidas em resina composta. Material e Métodos: Confeccionou-se 40corpos-de-prova (CP)de resina composta microhíbrida Opallis (FGM), cor B1,em matriz plástica (5mm de diâmetro e 2 mm de espessura). A fotoativação foi realizada por 30s com LEDmetron I.Aseguir os CP's foram submetidos à avaliação inicial de cor em espectrofotômetro VITA EasyshadeCompact" obtendo-se valores correspondentes da escala CIEL*a*b*. Os CP foram divididos em 4grupos (n=10): água destilada (controle), café, Coca-Colaw e vinho tinto. Realizou-se avaliaçãoinicial da cor, após imersão por 60 dias para promover o manchamento e, após o procedimentode polimento com discos de feltro e pasta diamantada. Os dados foram analisados pela ANOVA2 fatores e pós-teste de Tukey (o=O,OS).Resultados: As médias ± desvio padrão de L* mostraramque a resina composta apresentou manchamento (p>O,OOl) após 60 dias de imersão em vinho(S7,96±7,98) e no café (61,89±3,S9) quando comparado a água destilada (73,49± 1,20) e a Coca--Cola" (70,SO±1,30). O polimento não conseguiu melhoria no manchamento (p

Objective: To assesswhether the polishing can minimize or solve the staining caused by dyes ofdifferent beverages in composite resins. Methods: 40 specimens were fabricated with composite resinmicrohybrid Opallis (FGM), B1 color in the plastic matrix (S mm in diameter and 2 mm thickl Thepolymerization was carried out with 30 seconds LEDmetron I.Then the specimens underwent initialevaluation of color spectrophotometer VITA Easyshade ® Compact obtaining corresponding valuesof the scale CIEL*a*b", The specimens were divided into four groups (n = 10): distilled water (controllcoffee, Coca-Colae and red wine. The specimens were again subjected to color evaluation initial,after the immersion for 60 days to promote the staining, and after the polishing procedure (felt discwith diamond paste). Data were analyzed by two-away ANOVA and Tukev's HSD test (0= O.OS).Results:mean ± standard deviation of L* showed that the composite showed staining (p¼ 0.001) after60 days of immersion in wine (S7.96 ± 7.98) and coffee (61.89 ± 3.S9) when compared to distilledwater (73.49 ± 1.20) and Coca-Cola ® (70.S0 ± 1.30).The polishing could not improve the staining (p<0.001) caused by wine and coffee. Conclusion: the polishing didn't minimize the stains caused bywine and coffee and such changes considered clinically detectable to the human eye.

Influência de diferentes bebidas na estabilidade de cor da resina composta / Influence of different drinks on the resin composites' color stability

A maior preocupação dos pacientes na Odontologia é a estética do sorriso. Nesse sentido, os fabricantes de materiais odontológicos têm aprimorado as resinas compostas, para que apresentem excelente estética e boas propriedades mecânicas. O objetivo do presente estudo é avaliar a influência de diferentes bebidas (vinho, coca-cola e café) na estabilidade de cor da resina composta com e sem escovação com dentifrício. Foram confeccionados corpos de prova com resina composta, os quais foram submetidos à avaliação inicial da cor e divididos em grupos que foram imersos por 30 e 60 dias, nos respectivos líquidos, referentes aos grupos experimentais. Após esse período de imersão, a cor foi novamente avaliada, e os corpos de prova, submetidos à escovação, para avaliar se a escovação é um método eficaz para prevenir ou diminuir o manchamento na resina composta, ocasionado pelas bebidas em estudo. As bebidas em estudo afetaram a estabilidade de cor das resinas compostas, apresentando alterações de cores visíveis. A escovação não foi eficaz na remoção da pigmentação pelo vinho tinto, porém propiciou melhoria no manchamento ocasionado pela coca-cola.

The main concern of patients in dentistry is the aesthetics of the smile. In this sense, the manufacturers of dental materials have improved, like the resins that are used for restorations in anterior and posterior teeth and that have excellent aesthetics and good mechanical properties. The aim of this study is to evaluate the influence of different drinks (wine, Coke and coffee) on color stability of composite resin with and without brushing with toothpaste. Specimens were fabricated with composite resin, which underwent an initial assessment of color and divided into groups that were immersed for 30 and 60 days in their net regarding the experimental groups. After this period of immersion, the color was measured again, and the specimens were submitted to brushing, to assess whether toothbrushing is an effective method to prevent or reduce the staining in composite resin, caused by drinking in study. Drinks in the study affected the color stability of composite resins, with color changes visible. Brushing was not effective in removing the pigment in red wine, however, resulted in improved staining caused by Coke.

B cells are critical to T-cell-mediated antitumor immunity induced by a combined immune-stimulatory/conditionally cytotoxic therapy for glioblastoma.

We have demonstrated that modifying the tumor microenvironment through intratumoral administration of adenoviral vectors (Ad) encoding the conditional cytotoxic molecule, i.e., HSV1-TK and the immune-stimulatory cytokine, i.e., fms-like tyrosine kinase 3 ligand (Flt3L) leads to T-cell-dependent tumor regression in rodent models of glioblastoma. We investigated the role of B cells during immune-mediated glioblastoma multiforme regression. Although treatment with Ad-TK+Ad-Flt3L induced tumor regression in 60% of wild-type (WT) mice, it completely failed in B-cell-deficient Igh6(-/-) mice. Tumor-specific T-cell precursors were detected in Ad-TK+Ad-Flt3L-treated WT mice but not in Igh6(-/-) mice. The treatment also failed in WT mice depleted of total B cells or marginal zone B cells. Because we could not detect circulating antibodies against tumor cells and the treatment was equally efficient in WT mice and in mice with B-cell-specific deletion of Prdm 1 (encoding Blimp-1), in which B cells are present but unable to fully differentiate into antibody-secreting plasma cells, tumor regression in this model is not dependent on B cells' production of tumor antigen-specific immunoglobulins. Instead, B cells seem to play a role as antigen-presenting cells (APCs). Treatment with Ad-TK+Ad-Flt3L led to an increase in the number of B cells in the cervical lymph nodes, which stimulated the proliferation of syngeneic T cells and induced clonal expansion of antitumor T cells. Our data show that B cells act as APCs, playing a critical role in clonal expansion of tumor antigen-specific T cells and brain tumor regression.

Comparação da radiopacidade de cimentos resinosos pelos sistemas de radiografia convencional e digital / Comparison of radiopacity in luting resin cements using conventional and digital radiographic systems

Objective: To evaluate the radiopacity of three different resin composite luting cements using the histogram method (conventional radiography) and pixel counting method (digital radiography). Methods: Fifteen specimens were divided into 3 different resin composite luting cement groups: G-I) Cement-Post (Ângelus®, Londrina, Brazil), G-II) RelyX ARC (3MESPE, St. Paul, Minnesota, USA) and G-III) Variolink II (Ivoclar/Vivadent, Schaan, Liechtenstein). After 24 hours, conventional x-rays of the specimens were taken with a lead gauge, making a visual evaluation by scores, to classify the specimen?s radiopacity according to the scale shade (control); they were then scanned for the purposes of analyzing the histogram using Adobe Photoshop CS2, version 8.0. Using the same specimens, x-rays were taken using a Digital X-RAY Intra-Oral System (Gnatus DSR, Ribeirão Preto, Brazil). In this case, the capture of the digital images was performed using Cygnus Imaging® software and the digital radiopacity was measured by counting pixels, using the Image Tool® software (UTHSCSA). Results: The non-parametric Kruskal-Wallis test and Dunn?s post-test (p<0.05) showed that the means and respective standard deviation percentages of white pixels in the digital x-rays were: G-I) 48.94 ±3.16, G-II) 60.22 ±3.86 and G-III) 69.36 ±5.32. As for the conventional x-rays, the means and standard deviations of the histogram analyses that evaluated gray tones were: G-I) 71.98 ±13.02; G-II) 85.40 ±4.47; G-III) 130.51 ±5.82. Conclusion: In conclusion, regardless of the method used (conventional or digital x-rays), G-III obtained the largest radiopacity value.

Objetivo: Avaliar a radiopacidade de cimentos resinosos pelo método do histograma (radiografia convencional) e da contagem de pixels (radiografia digital). Métodos: Foram utilizados 15 corpos-de-prova divididos em três grupos de cimentos resinosos: Grupo I) Cement-Post (Ângelus®, Londrina, Brasil), Grupo II) RelyX ARC (3MESPE, St. Paul, USA) e Grupo III) Variolink II (Ivoclar/Vivadent, Schaan, Liechtenstein). Após 24 horas, foram realizadas radiografias convencionais dos corpos-de-prova juntamente com uma escala de chumbo, realizando assim uma avaliação visual por escores para classificar a radiopacidade dos corpos-de-prova de acordo com a tonalidade da escala (controle); e em seguida, foram escaneadas para análise do histograma no software Adobe Photoshop CS2 versão 8.0. Com os mesmos corpos-de-prova, realizaram-se tomadas radiográficas empregando-se o Sistema Intra-oral de Raio-X Digital (Gnatus, Ribeirão Preto, Brasil), sendo a captura das imagens digitais realizadas com o software Cygnus Imaging® e a radiopacidade digital mensurada pela contagem de pixels com o software Image Tool® (UTHSCSA). Resultados: O teste não-paramétrico de Kruskal-Wallis e Dunn (p<0,05) mostrou que as médias das porcentagens de pixels brancos das radiografias digitais e os seus respectivos desvios-padrão foram: Grupo I) 48,94 ±3,16; Grupo II) 60,22 ±3,86 e Grupo III) 69,36 ±5,32. Já nas radiografias convencionais, as médias e os desvios-padrão das análises do histograma avaliando tons de cinza foram: Grupo I) 71,98 ±13,02; Grupo II) 85,40 ±4,47 e Grupo III) 13,51 ±5,82. Conclusão: Pode-se concluir que utilizando tanto o sistema de radiografia convencional quanto o sistema digital, o Grupo III obteve uma maior radiopacidade.

Efeito de diferentes dentifrícios contendo evidenciador de placa e clorexidina na estabilidade de cor e rugosidade superficial de uma resina composta / Effect of different dentifrices containing plaque disclosing and chlorhexidine in color stability and surface roughness of a composite resin

O presente estudo analisou a alteração de cor e rugosidade superficial de um compósito utilizando quatro dentifrícios, desenvolvidos para estimular pacientes em sua higiene bucal. Utilizou-se um compósito microhíbrido,cor B1, e foram confeccionados 40 corpos de prova (cp). A seguir, os cp foram submetidos à avaliação inicial de cor em espectrofotômetro e de rugosidade inicial em rugosímetro digital. Os cp foram divididos em oito grupos (n = 5) para se realizar a escovação: G1e G5, dentifrício com flúor; G2 e G6, dentifrício com flúor + clorexidina; G3 e G7, dentifrício com flúor + evidenciador de placa + clorexidina; G4 e G8, dentifrício com flúor + evidenciador de placa. Esse teste foi realizado na máquina de escovação. Posteriormente, G1a G4 foram novamente submetidos à avaliação de cor e G5 a G8, de rugosidade final. ANOVA e pós-teste de Tukey (a = 0,05) demonstraram que as maiores médias (± desvio padrão) de variação de cor foram para G3 = 10,1(±6,4) e G4 = 8,6(±4,4), e as menores, para G1 = 0,8(±1,4) e G2 = 0,8(±0,8), com diferença significativa entre G1-G2 e G3-G4 (p < 0,0035). Para a rugosidade,ANOVA 2 fatores e pós-teste de Bonferroni (a = 0,05) mostraram diferença significativa (p < 0,0001) entre os valores de rugosidade (média ± desvio padrão) em mm antes (G5 = 0,7 ± 0,2; G6 = 0,8 ± 0,5; G7 = 0,6 ± 0,1; G8 = 0,5 ± 0,2) e após escovação (G5:1,4 ± 0,3; G6 = 1,4 ± 0,4; G7 = 1,5 ± 0,3; G8 = 1,2 ± 0,2) em todos os grupos. Concluiu-se que o evidenciador de placa demonstrou a maior alteração de cor no compósito e houve aumento significativo da rugosidade superficial após a escovação em todos os grupos.

This study evaluated the color stability and the surface roughness of a composite resin using four toothpastes developed to stimulate oral hygiene in persons. Methods: A hybrid composite resin, color B1, was used, and forty specimens were made. Subsequently, the specimens? colors were at first evaluated in a spectrophotomer and the initial roughness in a roughness meter. The specimens were then divided into 8 groups (n = 5): G1 and G5 toothpaste with fluoride; G2 and G6 toothpaste with chlorhexidine; G3 and G7 toothpaste with fluoride + plaquedisclosing (erythrosine) + chlorhexidine; G4 and G8 toothpaste with fluoride + plaque disclosing (erythrosine). This test was conducted in a mechanical toothbrushing machine. The specimens (G1 to G4) were again subjected to color evaluation and final roughness (G5 to G8). ANOVA and Tukey's test (a = 0.05) showed that the highest values mean (±standard-deviation) went to G3 = 10.1 (±6.4) and G4 = 8.6 (±4.4) and the lowest to G1 = 0.8(±1.4) and G2 = 0.8(±0.8), with a significant difference between groups G1-G2 and G3-G4 (p < 0.0035). For surface roughness, 2-way ANOVA and Bonferroni?s test (a = 0.05) showed significant differences (p < 0.0001) between roughness values (mean ± standard- deviation) in mm before (G5 = 0.7 ± 0.2; G6 = 0.8 ± 0.5; G7 = 0.6 ± 0.1; G8 = 0.5 ± 0.2) and after (G5:1.4 ± 0.3; G6 = 1.4 ± 0.4; G7 = 1.5 ± 0.3; G8 = 1.2 ± 0.2) brushing for all groups. Conclusion: plaque disclosing showed the highest change of color in the composite resin and significant increase of superficial roughness happens after brushing in all the experimental groups.

Avaliação clínica do uso de um dessensibilizante antes do clareamento de consultório / Clinical evaluation of a desensitizing agent used before in-office bleeching

Objetivo: avaliar clinicamente o efeito de um agente dessensibilizante utilizado previamente. ià aplicação de um gel de peróxido de hidrogênio 3S% (PH3S) na eficiência do clareamento (EC) ."e sensibilidade dental (50). Material e Métodos: Foram selecionados 30 pacientes divididos em grupo placebo (GP; n=lS) e grupo experimental (GE; n=lS). Um gel placebo ou dessensibilizante (Oesensibilize KF 2%) foi aplicado sobre as superfícies vestibulares dos dentes durante 10 minantes do clareamento com PH3S (Whiteness HP Blue 3S%). Este protocolo foi repetido na l' . e 2' sessões. Os pacientes utilizaram uma escala de O a 4 para anotarem a sensibilidade. A corfoi registrada no início e após a l' e 2' sessões de clareamento usando a escala Vita ordenada por valor. A EC foi analisada estatisticamente pelos testes de análise de variância e de Tukey. A porcentagem de pacientes com 50, assim como a intensidade foram avaliados pelos testes exato de Fisher e Mann-Whitney (a=O,OS), respectivamente. Resultados: O uso de um agente dessensibilizante não afetou a EC (cor B1/A 1 após duas semanas para 90% dos pacientes). 40% e 6,7% dos participantes do GP e GE, respectivamente apresentaram 50 (p < O,OS). A intensidade da 50 foi similar para os grupos (p > O,OS). Conclusão: O uso de um agente dessensibilizante antes do clareamento de consultório reduziu a prevalência de 50.

Objective: To evaluate the bleaching efficiency (BE) and tooth sensitivity (T5) of a desen¬sitizing agent used before in-office bleaching with 3S% hydrogen peroxide gel. Methods: We selected 30 patients for this study, which were divided into placebo and experimental groups. A placebo or desensitizing gel (Oesensibilize KF 2%) was applied on the buccal surfaces of ali teeth for 10 min (n = lS). This protocol was repeated one week later. Patients used a scale of O to 4 to write down their tooth sensitivity. The color was registered before and after the 1 st and 2nd sessions of bleaching using a value-oriented Vita Classical scale. The BE was analyzed by ANOVA and Tukey tests. The % of patients with T5 as well as T5 intensity was analyzed by the Fisher's exact and Mann-Whitney tests (a=O.OS). Results: The use of a desensitizing gel didn 't affect the BE (B 1 /A 1 color after two weeks for 90% of patients). 40% and 6.7% of the participants from the placebo and experimental groups presented T5 (pO.OS). Conclusion: The use of desensitizing gel before in-office bleaching reduced the prevalence of this side effect.

Constitutive TL1A (TNFSF15) expression on lymphoid or myeloid cells leads to mild intestinal inflammation and fibrosis.

TL1A is a member of the TNF superfamily and its expression is increased in the mucosa of inflammatory bowel disease patients. Moreover, a subset of Crohn's disease (CD) patients with the risk TL1A haplotype is associated with elevated TL1A expression and a more severe disease course. To investigate the in vivo role of elevated TL1A expression, we generated two transgenic (Tg) murine models with constitutive Tl1a expression in either lymphoid or myeloid cells. Compared to wildtype (WT) mice, constitutive expression of Tl1a in either lymphoid or myeloid cells showed mild patchy inflammation in the small intestine, which was more prominent in the ileum. In addition, mice with constitutive Tl1a expression exhibited enhanced intestinal and colonic fibrosis compared to WT littermates. The percentage of T cells expressing the gut homing chemokine receptors CCR9 and CCR10 was higher in the Tl1a Tg mice compared to WT littermates. Sustained expression of Tl1A in T cells also lead to increased Foxp3+ Treg cells. T cells or antigen presenting cells (APC) with constitutive expression of Tl1a were found to have a more activated phenotype and mucosal mononuclear cells exhibit enhanced Th1 cytokine activity. These results indicated an important role of TL1A in mucosal T cells and APC function and showed that up-regulation of TL1A expression can promote mucosal inflammation and gut fibrosis.

Relato de duas técnicas de microabrasão do esmalte para remoção de manchas: discussão de casos clínicos / Report of two microabrasion techniques of enamel to remove stains and discussion

O objetivo deste trabalho foi relatar e discutir por meio da apresentação de casos clínicos a utilização de duas diferentes técnicas de microabrasão do esmalte na remoção de manchas. No primeiro caso clínico, utilizou-se uma mistura de pedra-pomes e ácido fosfórico 37%. No segundo caso clínico, foi utilizado ácido clorídrico 6% e carbeto de silício. Independentemente da técnica selecionada, o sucesso na remoção das manchas está relacionado a corretos diagnósticos. Pode-se concluir que as duas técnicas de microabrasão do esmalte foram capazes de remover as manchas intrínsecas do esmalte, mostrando sua eficácia e, assim, restabelecendo a estética dos elementos dentários envolvidos.

The aim of this study was to report and discuss, through the presentation of clinical cases, the use of two different enamel microabrasion techniques to remove stains. Two techniques were compared between themselves. In the first clinical case used a mixture of pumice and 37% phosphoric acid. In the second case was used 6% cloridric acid and siliceous carbide. Regardless of the technique selected the successful of spots removal is related to a correct diagnosis. It can be concluded that two enamel microabrasion techniques were able to remove intrinsic stains from enamel, demonstrating its effectiveness and thus restoring the esthetics of the teeth involved.