RESUMEN
Tumors intricately shape a highly immunosuppressive microenvironment, hampering effective antitumor immune responses through diverse mechanisms. Consequently, achieving optimal efficacy in cancer immunotherapy necessitates the reorganization of the tumor microenvironment and restoration of immune responses. Bladder cancer, ranking as the second most prevalent malignant tumor of the urinary tract, presents a formidable challenge. Immunotherapeutic interventions including intravesical BCG and immune checkpoint inhibitors such as atezolizumab, avelumab, and pembrolizumab have been implemented. However, a substantial unmet need persists as a majority of bladder cancer patients across all stages do not respond adequately to immunotherapy. Bladder cancer establishes a microenvironment that can actively hinder an efficient anti-tumor immune response. A deeper understanding of immune evasion mechanisms in bladder cancer will aid in suppressing recurrence and identifying viable therapeutic targets. This review seeks to elucidate mechanisms of immune evasion specific to bladder cancer and explore novel pathways and molecular targets that might circumvent resistance to immunotherapy.
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Evasión Inmune , Neoplasias de la Vejiga Urinaria , Humanos , Neoplasias de la Vejiga Urinaria/patología , Inmunoterapia , Microambiente TumoralRESUMEN
Propionate is a short-chain fatty acid (SCFA) mainly produced from carbohydrates by gut microbiota. Sodium propionate (SP) has shown to suppress the invasion in G protein-coupled receptor 41 (GPR41) and GPR43-overexpressing breast cancer cells. In this study we investigated the effects of SP on the proliferation, apoptosis, autophagy, and antioxidant production of breast cancer cells. We showed that SP (5-20 mM) dose-dependently inhibited proliferation and induced apoptosis in breast cancer cell lines JIMT-1 (ER-negative and HER2-expressing) and MCF7 (ER-positive type), and this effect was not affected by PTX, thus not mediated by the GPR41 or GPR43 SCFA receptors. Meanwhile, we demonstrated that SP treatment increased autophagic and antioxidant activity in JIMT-1 and MCF7 breast cancer cells, which might be a compensatory mechanism to overcome SP-induced apoptosis, but were not sufficient to overcome SP-mediated suppression of proliferation and induction of apoptosis. We revealed that the anticancer effect of SP was mediated by inhibiting JAK2/STAT3 signaling which led to cell-cycle arrest at G0/G1 phase, and increasing levels of ROS and phosphorylation of p38 MAPK which induced apoptosis. In nude mice bearing JIMT-1 and MCF7 cells xenograft, administration of SP (20 mg/mL in drinking water) significantly suppressed tumor growth by regulating STAT3 and p38 in tumor tissues. These results suggest that SP suppresses proliferation and induces apoptosis in breast cancer cells by inhibiting STAT3, increasing the ROS level and activating p38. Therefore, SP is a candidate therapeutic agent for breast cancer.
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Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Propionatos/uso terapéutico , Animales , Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Autofagia/efectos de los fármacos , Neoplasias de la Mama/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Femenino , Puntos de Control de la Fase G1 del Ciclo Celular/efectos de los fármacos , Humanos , Ratones Desnudos , Propionatos/farmacología , Especies Reactivas de Oxígeno/metabolismo , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
The aim was to evaluate the physical properties and anti-bacterial activity of resin cement containing ursolic acid (UA) and determine the optimal concentration of UA. Five types of experimental resin cement were prepared according to UA concentration (0, 0.1, 0.5, 1.0, and 2.0 wt%). Flexural strength, film thickness and in vitro cytotoxicity were measured to confirm whether the resin was appropriate under International Organization for Standardization (ISO) criteria. Fifty extracted human molars were prepared, and indirect resin inlays were cemented with experimental resins. Acid-resistant nail varnish was applied, except for the 2-mm area around the restoration. Artificial caries were induced for 6 days through Streptococcus (S.) mutans (ATCC25175). Quantitative light-induced fluorescence (QLF) was used to evaluate the caries progression. One-way analysis of variance (ANOVA) followed by the Dunnett correction were used to statistically analyze the data. In all groups, the physical property of flexural strength, film thickness, and cytotoxicity were satisfied for ISO criteria (p > 0.05). On ∆F (-%) and ∆Q (-%â Px) values as QLF parameters, there was a tendency of being lower in groups of resin cement containing higher concentration of UA. Resin cement containing UA of greater than or equal to 0.5% significantly inhibited caries in the area around restoration (p < 0.05). There was no difference between the groups containing UA of greater than or equal to 0.5%. Resin cement containing 0.5% or more UA showed anti-carious effect in the limited range of 2% and satisfied the ISO criteria for flexural strength, film thickness and cytotoxicity.
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Cementos de Resina , Triterpenos , Resinas Compuestas , Resistencia Flexional , Humanos , Triterpenos/farmacología , Ácido UrsólicoRESUMEN
Patients with mutations of the THRA gene exhibit classical features of hypothyroidism, including erythroid disorders. We previously created a mutant mouse expressing a mutated TRα1 (denoted as PV; Thra1PV/+ mouse) that faithfully reproduces the classical hypothyroidism seen in patients. Using Thra1PV/+ mice, we explored how the TRα1PV mutant acted to cause abnormalities in erythropoiesis. Thra1PV/+ mice exhibited abnormal red blood cell indices similarly as reported for patients. The total bone marrow cells and erythrocytic progenitors were markedly reduced in the bone marrow of Thra1PV/+ mice. In vitro terminal differentiation assays showed a significant reduction of mature erythrocytes in Thra1PV/+ mice. In wild-type mice, the clonogenic potential of progenitors in the erythrocytic lineage was stimulated by thyroid hormone (T3), suggesting that T3 could directly accelerate the differentiation of progenitors to mature erythrocytes. Analysis of gene expression profiles showed that the key regulator of erythropoiesis, the Gata-1 gene, and its regulated genes, such as the Klf1, ß-globin, dematin genes, CAII, band3 and eALAS genes, involved in the maturation of erythrocytes, was decreased in the bone marrow cells of Thra1PV/+ mice. We further elucidated that the Gata-1 gene was a T3-directly regulated gene and that TRα1PV could impair erythropoiesis via repression of the Gata-1 gene and its regulated genes. These results provide new insights into how TRα1 mutants acted to cause erythroid abnormalities in patients with mutations of the THRA gene. Importantly, the Thra1PV/+ mouse could serve as a preclinical mouse model to identify novel molecular targets for treatment of erythroid disorders.
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Eritropoyesis/genética , Factor de Transcripción GATA1/genética , Hipotiroidismo/genética , Receptores alfa de Hormona Tiroidea/genética , Animales , Diferenciación Celular/genética , Eritrocitos , Humanos , Hipotiroidismo/fisiopatología , Factores de Transcripción de Tipo Kruppel/genética , Ratones , Ratones Transgénicos , Mutación , Transcriptoma , Triyodotironina/genética , Globinas beta/genéticaRESUMEN
Development of the eye is closely associated with neural crest cell migration and specification. Eye development is extremely complex, as it requires the working of a combination of local factors, receptors, inductors, and signaling interactions between tissues such as the optic cup and periocular mesenchyme (POM). The POM is comprised of neural crest-derived mesenchymal progenitor cells that give rise to numerous important ocular structures including those tissues that form the optic cup and anterior segment of the eye. A number of genes are involved in the migration and specification of the POM such as PITX2, PITX3, FOXC1, FOXE3, PAX6, LMX1B, GPR48, TFAP2A, and TFAP2B. In this review, we will discuss the relevance of these genes in the development of the POM and how mutations and defects result in rare ocular diseases.
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Anomalías del Ojo/genética , Oftalmopatías/genética , Cresta Neural/anomalías , Cresta Neural/metabolismo , Enfermedades Raras/genética , Segmento Anterior del Ojo/anomalías , Oftalmopatías/patología , Humanos , Mutación , Segmento Posterior del Ojo/anomalías , Enfermedades Raras/patología , Factores de TranscripciónRESUMEN
OBJECTIVES: The aim of this study is to evaluate whether the triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio is associated with periodontal disease in Korean adults. MATERIALS AND METHODS: This cross-sectional study included 12,249 individuals (4,941 men and 7,308 women) who took part in the 2012-2014 Korean National Health and Nutrition Examination Survey. We categorized the TG/HDL-C ratio into three groups. Periodontal disease was defined as a community pocket index score ≥3 with at least one affected site. Multiple logistic analyses were used to analyze the association between TG/HDL-C ratio and periodontal disease. RESULTS: In the study population, prevalence of periodontal disease was 31.6% in men and 21% in women. Compared to the lowest tertile group, OR (95% CI) of the highest tertile group for periodontal disease was 1.474 (1.220-1.780) in men and 1.259 (1.041-1.522) in women after adjusting for age, waist circumference, systolic blood pressure, fasting glucose, current smoking, alcohol drinking, physical activity, household income, oral health behavior, and use of anti-dyslipidemia medication. CONCLUSION: Our study suggests that the TG/HDL-C ratio is associated with periodontal disease in Korean adults. CLINICAL RELEVANCE: TG/HDL-C ratio is a simple and useful marker to reflect insulin resistance. And periodontal disease is also known to be related with insulin resistance. This study indicates that TG/HDL-C ratio was associated with periodontal disease in Korean adults.
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Lipoproteínas HDL/sangre , Enfermedades Periodontales/sangre , Enfermedades Periodontales/epidemiología , Triglicéridos/sangre , Adulto , Estudios Transversales , Femenino , Humanos , Resistencia a la Insulina , Masculino , Persona de Mediana Edad , Encuestas Nutricionales , Prevalencia , República de Corea/epidemiologíaRESUMEN
The multiplexed detection of protein biomarkers in plasma present over a range of clinically relevant concentrations continues to be difficult for surface-based bioaffinity detection platforms such as surface plasmon resonance (SPR). As well as nonspecific adsorption, challenges include quantitative comparison between targets whose concentrations differ by orders of magnitude, regenerating SPR chips after plasma exposure, and the two- or four-channel limitation of many commercial SPR instruments limiting sample throughput. In this article, we explore an approach where two protein biomarkers alpha-1 antitrypsin (AAT) and Tau 381 are detected in tandem within a single SPR channel at micromolar and femtomolar concentrations, respectively. This was achieved by creating a mixed antibody (antiAAT and antiTau) monolayer on the chip surface. After the adsorption of AAT and/or Tau, further specificity was obtained via the adsorption of a DNA aptamer specific to each target. The detection range for each target was controlled via the relative surface density ratio of each antibody type as well as each aptamer concentration. Calibration measurements were performed in both buffer and spiked plasma with the detection of native concentrations of â¼39 fM (Tau) and â¼65 µM (AAT) in a human plasma sample. Finally, tandem measurements of both targets within the same SPR signal channel were demonstrated at these very different concentrations.
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Anticuerpos/química , Resonancia por Plasmón de Superficie , alfa 1-Antitripsina/sangre , Proteínas tau/sangre , Biomarcadores/sangre , Humanos , Propiedades de SuperficieRESUMEN
We have recently identified that phosphorylation at tyrosine (Y)406 is critical for the tumor suppressor functions of the thyroid hormone receptor ß1 (TRß) in a breast cancer line. However, still unclear is whether the critical tumor suppressor role of phosphorylated Y406 of TRß is limited to only breast cancer cells or could be extended to other cell types. In the present studies, we addressed this question by stably expressing TRß, a mutated TRß oncogene (PV), or a TRß mutated at Y406 (TRßY406F) in rat PCCL3 thyroid follicular cells and evaluated their tumor characteristics in athymic mice with elevated thyroid stimulating hormone. PCCL3 cells stably expressing PV (PCCL3-PV), TRßY406F (PCCL3-TRßY406F), or vector only (PCCL3-Neo) developed tumors with sizes in the rank order of TRßY406F>PV = Neo, whereas PCCL3 cells expressing TRß (PCCL3-TRß) barely developed tumors. As evidenced by markedly elevated Ki67, cyclin D1, and p-Rb protein abundance, proliferative activity was high in PV and TRßY406F tumors, but low in TRß tumors. These results indicate that TRß acted as a tumor suppressor in PCCL3 cells, whereas TRßY406F and PV had lost tumor suppressor activity. Interestingly, TRßY406F tumors had very low necrotic areas with decreased TNFα-NFκB signaling to lower apoptotic activity. In contrast, PV tumors had prominent large necrotic areas, with no apparent changes in TNFα-NFκB signaling, indicating distinct oncogenic activities of mutant PV and TRßY406F. Thus, the present studies uncovered a novel mechanism by which TRß could function as a tumor suppressor through modulation of the TNFα-NFκB signaling. © 2016 Wiley Periodicals, Inc.
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Mutación Puntual , Glándula Tiroides/patología , Receptores beta de Hormona Tiroidea/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/patología , Animales , Línea Celular , Línea Celular Tumoral , Proliferación Celular , Femenino , Genes Supresores de Tumor , Humanos , Ratones , Ratones Desnudos , Fosforilación , Ratas , Glándula Tiroides/metabolismo , Receptores beta de Hormona Tiroidea/química , Tirosina/análisis , Tirosina/genéticaRESUMEN
STATEMENT OF PROBLEM: The marginal and internal discrepancies of computer-aided design and computer-aided manufacturing (CAD-CAM) endocrowns are unknown. PURPOSE: The purpose of this in vitro study was to evaluate the marginal and internal discrepancies of endocrowns with different cavity depths by measuring them with microcomputed tomography (µCT). MATERIAL AND METHODS: Endocrowns (n=48) of 2 different cavity depths (2 mm and 4 mm) were fabricated in 2 different chairside CAD-CAM systems (CEREC AC and E4D). A µCT scan was made before and after cementation. For analysis of the marginal and internal discrepancies, reference points were selected in 2-dimensional views of 3 buccolingual cross-sections and 3 mesiodistal cross-sections. To calculate the total discrepancy volume, the µCT sections were reconstructed 3-dimensional views, and changes in volume and surface area were examined. Statistical analysis was performed using 2-way ANOVA with Bonferroni correction (α=.05). RESULTS: An endocrown with a 4-mm cavity showed a larger marginal and internal volume than one with a 2-mm cavity. Cementation did not show significant differences in total discrepancy thickness. Discrepancies on the pulpal floor were largest in other sites. Both chairside CAD-CAM systems showed similar discrepancy in the endocrowns. CONCLUSIONS: Based on the present study, marginal and internal discrepancies increased depending on cavity depth. Cementation did not increase the dimension of the discrepancy between the restoration and the cavity wall. The discrepancy on the pulpal floor appeared to affect these results.
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Diseño Asistido por Computadora , Coronas , Preparación de la Cavidad Dental/métodos , Diseño de Prótesis Dental/métodos , Cementación , Adaptación Marginal Dental/normas , Humanos , Técnicas In Vitro , Radiografía Dental/métodos , Microtomografía por Rayos XRESUMEN
STATEMENT OF PROBLEM: Post space size and cement thickness can differ because of variations in root canal morphology, such as an oval shape, and because the entire canal space cannot be included in the post space preparation. As a result, increased cement thickness around the post may affect the bond strength between the post and the dentin. PURPOSE: The purpose of this in vitro study was to evaluate the push-out bond strength of fiber-reinforced composite resin posts to root dentin with cement layers of varying thickness. MATERIAL AND METHODS: Thirty human premolars were endodontically treated and restored with fiber-reinforced composite resin posts. Post space was prepared using a drill with a 1.5-mm diameter and diameters of 1.25 mm (small [S] group), 1.375 mm (medium [M] group), and 1.5 mm (large [L] group) were cemented. The specimens were sectioned horizontally into 1-mm-thick slices, and the push-out bond strengths of the apical and coronal fragments were evaluated. Bond strength was compared using analysis of variance and 2-sample t tests (α=.05). RESULTS: No significant differences were found in the debonding force and push-out bond strength among fiber-reinforced composite posts of different sizes (P>.05). The mean debonding force and standard deviation of the posts were 25.05 ±9.52 N for the S group, 28.17 ±11.38 N for the M group, and 33.78 ±12.47 N for the L group. The corresponding push-out bond strength values were 3.11 ±1.54 MPa, 3.39 ±1.4 MPa, and 4.15 ±1.75 MPa. The differences in debonding force between the apical (26.43 ±10.72 N) and coronal (31.57 ±12.03 N) areas were not significant (P>.05). However, the differences in push-out bond strength between the apical (4.27 ±1.73 MPa) and coronal areas (2.83 ±1.08 MPa) were significant (P<.05). CONCLUSIONS: The widening of post spaces and, consequently, the increased cement thickness do not significantly affect the bond strength of fiber-reinforced composite resin posts to root dentin.
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Resinas Compuestas/química , Técnica de Perno Muñón , Cementos de Resina/química , Análisis del Estrés Dental , Humanos , Tratamiento del Conducto RadicularRESUMEN
Mutations of the thyroid hormone receptor α gene (THRA) cause hypothyroidism in patients with growth and developmental retardation, and skeletal dysplasia. Genetic evidence indicates that the dominant negative activity of TRα1 mutants underlies pathological manifestations. Using a mouse model of hypothyroidism caused by a dominant negative TRα1PV mutant and its derived mouse model harboring a mutated nuclear receptor corepressor (NCOR1ΔID) (Thra1(PV/+)Ncor1(ΔID/ΔID) mice), we recently showed that aberrant release of TRα1 mutants from the NCOR1 repressor complex mediates dominant negative actions of TRα1 mutants in vivo. We tested the hypothesis that deacetylation of nucleosomal histones associated with aberrant recruitment of corepressors by TRα1 mutants underlies pathological phenotypic expression. We treated Thra1(PV/+)and Thra1(PV/+)Ncor1(ΔID/ΔID) mice with a histone deacetylase (HDAC) inhibitor, suberoylanilide hydroxyamic acid (SAHA). SAHA significantly ameliorated the impaired growth, bone development and adipogenesis of Thra1(PV/+) mice. In Thra1(PV/+)Ncor1(ΔID/ΔID) mice, SAHA improved these abnormalities even further. We focused our molecular analyses on how SAHA improved the impaired adipogenesis leading to the lean phenotype. We found that SAHA reverted the impaired adipogenesis by de-repressing the expression of the two master regulators of adipogenesis, C/ebpα and Pparγ, as well as other adipogenic genes at both the mRNA and protein levels. Chromatin immunoprecipitation analyses indicated SAHA increased the extent of acetylation of nucleosomal H4K5 and H3 to re-activate adipogenic genes to reverting adipogenesis. Thus, HDAC confers in vivo aberrant actions of TRα1 mutants. Importantly, for the first time, the present studies show that HDAC inhibitors are clearly beneficial for hypothyroidism and could be therapeutics for treatment.
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Inhibidores de Histona Desacetilasas/uso terapéutico , Ácidos Hidroxámicos/uso terapéutico , Hipotiroidismo/tratamiento farmacológico , Receptores alfa de Hormona Tiroidea/genética , Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Animales , Proteínas Potenciadoras de Unión a CCAAT/genética , Proteínas Potenciadoras de Unión a CCAAT/metabolismo , Evaluación Preclínica de Medicamentos , Epigénesis Genética/efectos de los fármacos , Expresión Génica , Inhibidores de Histona Desacetilasas/farmacología , Histona Desacetilasas/metabolismo , Ácidos Hidroxámicos/farmacología , Hipotiroidismo/sangre , Hipotiroidismo/genética , Grasa Intraabdominal/efectos de los fármacos , Grasa Intraabdominal/patología , Masculino , Ratones Transgénicos , PPAR gamma/genética , PPAR gamma/metabolismo , Regiones Promotoras Genéticas , Unión Proteica , Hormonas Tiroideas/sangre , Vorinostat , Aumento de Peso/efectos de los fármacosRESUMEN
Genetic evidence from patients with mutations of the thyroid hormone receptor α gene (THRA) indicates that the dominant negative activity of mutants underlies the pathological manifestations. However, the molecular mechanisms by which TRα1 mutants exert dominant negative activity in vivo are not clear. We tested the hypothesis that the severe hypothyroidism in patients with THRA mutations is due to an inability of TRα1 mutants to properly release the nuclear corepressors (NCORs), thereby inhibiting thyroid hormone-mediated transcription activity. We crossed Thra1(PV) mice, expressing a dominant negative TRα1 mutant (TRα1PV), with mice expressing a mutant Ncor1 allele (Ncor1(ΔID) mice) that cannot recruit the TR or PV mutant. TRα1PV shares the same C-terminal mutated sequences as those of patients with frameshift mutations of the THRA gene. Remarkably, NCOR1ΔID ameliorated abnormalities in the thyroid-pituitary axis of Thra1(PV/+) mice. The severe retarded growth, infertility, and delayed bone development were partially reverted in Thra1(PV/+) mice expressing NCOR1ΔID. The impaired adipogenesis was partially corrected by de-repression of peroxisome-proliferator activated receptor γ and CCAAT/enhancer-binding protein α gene, due to the inability of TRα1PV to recruit NCOR1ΔID to form a repressor complex. Thus, the aberrant recruitment of NCOR1 by TRα1 mutants could lead to clinical hypothyroidism in humans. Therefore, therapies aimed at the TRα1-NCOR1 interaction or its downstream actions could be tested as potential targets in treating TRα1 mutant-mediated hypothyroidism in patients.
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Mutación , Co-Represor 1 de Receptor Nuclear/fisiología , Receptores alfa de Hormona Tiroidea/metabolismo , Alelos , Animales , Desarrollo Óseo , Cruzamientos Genéticos , Femenino , Mutación del Sistema de Lectura , Hipotiroidismo/metabolismo , Hipotiroidismo/fisiopatología , Infertilidad/patología , Metabolismo de los Lípidos , Masculino , Ratones , Hipófisis/metabolismo , Hipófisis/patología , Dominios y Motivos de Interacción de Proteínas , Glándula Tiroides/metabolismo , Glándula Tiroides/patología , Tiroxina/metabolismo , Triyodotironina/metabolismoRESUMEN
Mineral trioxide aggregate (MTA) is considered a pulp-capping agent of choice, but has the drawback of a long setting time. This study aimed to assess two different types of calcium-silicate cements as pulp-capping agents, by investigating their in vitro cytotoxicity and angiogenic effects in human pulp cells. ProRoot MTA, Endocem Zr, and Retro MTA were prepared as set or freshly mixed pellets. Human pulp-derived cells were grown in direct contact with these three cements, Dycal, or no cement, for 7 days. Initial cell attachment, viability, calcium release, and the levels of vascular endothelial growth factor (VEGF), angiogenin, and basic fibroblast growth factor (FGF-2) were evaluated statistically using a linear mixed model (P < 0.05). The biocompatibility of Retro MTA was similar to those of the control and ProRoot MTA. Endocem Zr groups showed fewer and more rounded cells after a 3-day culture; however, the initial cytotoxicity appeared transient. All test materials showed significant increases in calcium concentration compared with the control group (P < 0.05). VEGF and angiogenin levels in ProRoot MTA and Retro MTA groups were significantly higher than those in the Endocem Zr group (P < 0.05). FGF-2 levels were not significantly different between groups (P > 0.05). We demonstrate that Retro MTA, which has a short setting time, has similar biocompatibility and angiogenic effects on human pulp cells, and can therefore potentially be as effective in pulp capping as ProRoot MTA. Endocem Zr showed intermittent cytotoxicity and elicited lower levels of VEGF and angiogenin expression.
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Inductores de la Angiogénesis/farmacología , Pulpa Dental/citología , Cemento de Silicato/farmacología , Calcio/metabolismo , Calcio/farmacología , Supervivencia Celular , Células Cultivadas , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Humanos , Ensayo de Materiales , Ribonucleasa Pancreática/metabolismo , Silicatos/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Cancer gender disparity has been observed for a variety of human malignancies. Thyroid cancer is one such cancer with a higher incidence in women, but more aggressive disease in men. There is scant evidence on the role of sex hormones on cancer initiation/progression. Using a transgenic mouse model of follicular thyroid cancer (FTC), we found castration led to lower rates of cancer in females and less advanced cancer in males. Mechanistically, less advanced cancer in castrated males was due to increased expression of tumor suppressor (Glipr1, Sfrp1) and immune-regulatory genes and higher tumor infiltration with M1 macrophages and CD8 cells. Functional study showed that GLIPR1 reduced cell growth and increased chemokine secretion (Ccl5) that activates immune cells. Our data demonstrate that testosterone regulates thyroid cancer progression by reducing tumor suppressor gene expression and tumor immunity.
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Adenocarcinoma Folicular/patología , Genes Supresores de Tumor , Proteínas de Neoplasias/genética , Proteínas del Tejido Nervioso/genética , Testosterona/metabolismo , Neoplasias de la Tiroides/patología , Adenocarcinoma Folicular/genética , Adenocarcinoma Folicular/inmunología , Animales , Linfocitos T CD8-positivos/inmunología , Castración , Línea Celular , Proliferación Celular , Quimiocina CCL5/metabolismo , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Células HEK293 , Humanos , Péptidos y Proteínas de Señalización Intercelular/biosíntesis , Macrófagos/inmunología , Masculino , Proteínas de la Membrana/biosíntesis , Ratones , Ratones Transgénicos , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/metabolismo , Proteínas del Tejido Nervioso/biosíntesis , Proteínas del Tejido Nervioso/metabolismo , Interferencia de ARN , ARN Interferente Pequeño , Distribución por Sexo , Receptores beta de Hormona Tiroidea/genética , Neoplasias de la Tiroides/genética , Neoplasias de la Tiroides/inmunologíaRESUMEN
Mutations in the ligand-binding domain of the thyroid hormone receptor ß (TRß) lead to resistance to thyroid hormone (RTH). These TRß mutants function in a dominant-negative fashion to interfere with the transcription activity of wild-type thyroid hormone receptors (TRs), leading to dysregulation of the pituitary-thyroid axis and resistance in peripheral tissues. The molecular mechanism by which TRß mutants cause RTH has been postulated to be an inability of the mutants to properly release the nuclear corepressors (NCORs), thereby inhibiting thyroid hormone (TH)-mediated transcription activity. To test this hypothesis in vivo, we crossed Thrb(PV) mice (a model of RTH) expressing a human TRß mutant (PV) with mice expressing a mutant Ncor1 allele (Ncor1(ΔID) mice) that cannot recruit a TR or a PV mutant. Remarkably, in the presence of NCOR1ΔID, the abnormally elevated thyroid-stimulating hormone and TH levels found in Thrb(PV) mice were modestly but significantly corrected. Furthermore, thyroid hyperplasia, weight loss, and other hallmarks of RTH were also partially reverted in mice expressing NCOR1ΔID. Taken together, these data suggest that the aberrant recruitment of NCOR1 by RTH TRß mutants leads to clinical RTH in humans. The present study suggests that therapies aimed at the TR-NCOR1 interaction or its downstream actions could be tested as potential targets in treating RTH.
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Co-Represor 1 de Receptor Nuclear/fisiología , Síndrome de Resistencia a Hormonas Tiroideas/genética , Síndrome de Resistencia a Hormonas Tiroideas/fisiopatología , Animales , Modelos Animales de Enfermedad , Genes erbA , Humanos , Masculino , Ratones , Ratones Mutantes , Ratones Transgénicos , Mutación , Co-Represor 1 de Receptor Nuclear/química , Co-Represor 1 de Receptor Nuclear/genética , Estructura Terciaria de Proteína , Eliminación de Secuencia , Receptores beta de Hormona Tiroidea/genética , Receptores beta de Hormona Tiroidea/fisiología , Síndrome de Resistencia a Hormonas Tiroideas/patología , Hormonas Tiroideas/sangre , Hormonas Tiroideas/fisiologíaRESUMEN
Although there is consensus among dentists that visual aids not only improve vision but also help improve posture, evidence is scarce. This study aimed to evaluate the effect of visual aids (loupe and microscope) on the muscle workload of dentists during crown preparation on dentiform first molars in each quadrant of a phantom head, considering dentists' muscles, patients' tooth positions and surfaces. Six right-handed dentists from a single tertiary hospital participated. Surface electromyography device recorded the muscle workload of the bilateral upper trapezius, sternocleidomastoid, cervical erector spinae, and anterior deltoid during crown preparation. The results showed significantly lower workload in all examined muscles when using a microscope compared to the naked eye (p < 0.05), whereas the loupe showed reduced workload in some specific muscles. The muscle with the highest workload for all visual aids was the cervical erector spinae, followed by the upper trapezius. When analyzed by tooth surface, while the loupe did not significantly reduce overall workload compared to the naked eye for each surface, the microscope significantly reduced workload for most surfaces (p < 0.05). Therefore, during crown preparation, the workload of the studied muscles can successfully be reduced with the use of a loupe or microscope.
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Odontólogos , Hombro , Humanos , Masculino , Adulto , Femenino , Hombro/fisiología , Electromiografía , Microscopía/métodos , Coronas , Músculos del Cuello/fisiología , Carga de Trabajo , Músculo Esquelético/fisiologíaRESUMEN
Innate lymphoid cells (ILCs) play an important role in maintaining tissue homeostasis and various inflammatory responses. ILCs are typically classified into three subsets, as is the case for T-cells. Recent studies have reported that IL-10-producing type 2 ILCs (ILC210s) have an immunoregulatory function dependent on IL-10. However, the surface markers of ILC210s and the role of ILC210s in contact hypersensitivity (CHS) are largely unknown. Our study revealed that splenic ILC210s are extensively included in PD-L1highSca-1+ ILCs and that IL-27 amplifies the development of PD-L1highSca-1+ ILCs and ILC210s. Adoptive transfer of PD-L1highSca-1+ ILCs suppressed oxazolone-induced CHS in an IL-10-dependent manner Taken together, our results demonstrate that ILC210s are critical for the control of CHS and suggest that ILC210s can be used as target cells for the treatment of CHS.
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Dermatitis por Contacto , Interleucina-27 , Antígeno B7-H1 , Inmunidad Innata , Interleucina-10 , LinfocitosRESUMEN
Our research efforts have been devoted to development of nanobead multilayer-based sensitive immunoassays on cyclic olefin copolymer (COC) plastic surfaces. To facilitate nanobead attachment and impart antibiofouling properties to a COC substrate, we used an amphiphilic copolymer comprising benzyl, polyethylene glycol, and reactive ester moieties to coat the hydrophobic COC surface in an aqueous environment. Subsequently, NH2-modified polystyrene nanobeads were reacted with the polymer-coated COC surface and further assembled into multilayers that increased the overall surface area available for attaching capture antibodies. After treatment of the nanobead multilayers with an amine-reactive homobifunctional crosslinker, a model capture antibody (anti-rabbit IgG) was covalently immobilized onto the activated surface of nanobeads. Finally, a sandwich immunoassay was carried out using rabbit IgG as a target analyte and rhodamine-labeled anti-rabbit IgG as a probe. Compared with a nanobead-free, polymer-coated COC surface, the nanobead multilayer-based immunoassay exhibited ~4-fold higher fluorescence intensity. In addition, our nanobead-based assay system exhibited a wide dynamic range of detection (0.1 to 1,000 ng/mL) and high specificity for rabbit IgG. Furthermore, much better detection sensitivity for rabbit IgG was attained in the nanobead multilayer-based immunoassay than with a conventional ELISA system (0.1 ng/mL versus 10 ng/mL), indicating the potential value of the proposed immunoassay system in plastic-based portable biochip applications.
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Anticuerpos Inmovilizados/química , Cicloparafinas/química , Inmunoensayo/instrumentación , Microesferas , Nanotecnología/instrumentación , Plásticos/química , Animales , Anticuerpos Inmovilizados/inmunología , Incrustaciones Biológicas/prevención & control , Propiedades de SuperficieRESUMEN
This case report describes the successful treatment of an adult with a skeletal Class II Division 2 posttraumatic dentition with consequential restorations. The extracted maxillary premolar was autotransplanted to replace the hopeless mandibular first molar. The endodontically treated maxillary right canine was extracted instead of the premolar. A multidisciplinary approach including autotransplantation and orthodontic treatment provided a satisfactory outcome.
Asunto(s)
Diente Premolar/trasplante , Maloclusión Clase II de Angle/terapia , Enfermedades Periodontales/cirugía , Técnicas de Movimiento Dental/métodos , Adulto , Cefalometría/métodos , Diente Canino/cirugía , Femenino , Defectos de Furcación/cirugía , Humanos , Diente Molar/cirugía , Planificación de Atención al Paciente , Enfermedades Periapicales/cirugía , Absceso Periodontal/cirugía , Bolsa Periodontal/cirugía , Caries Radicular/cirugía , Extracción Dental , Fracturas de los Dientes/cirugía , Técnicas de Movimiento Dental/instrumentación , Raíz del Diente/lesiones , Diente no Vital/cirugía , Trasplante Autólogo , Resultado del TratamientoRESUMEN
INTRODUCTION: This study evaluated the microtensile bond strength of calcium silicate-based sealers and epoxy resin-based sealer, depending on the use of phosphoric acid (PA) etching before immediate resin restoration. METHODS: Exposed dentin surfaces of extracted human third molars were randomly assigned to 3 groups depending on sealer type (AH Plus [Dentsply DeTrey], CeraSeal [Meta Biomed Co.], and EndoSeal MTA [Maruchi]). Half of the samples were treated with PA for 30 seconds, and the other half were cleaned with water. Completely untreated specimens were used as controls. Self-etching adhesive (Clearfil SE Bond, Kuraray) was applied and composite resin (Tetric N-Ceram, Ivoclar Vivadent) was used to create build-ups. After 24 hours, the microtensile bond strength was measured (EZ Test, Shimadzu Co.). The failure mode was determined by light microscopy and scanning electron microscopy. One-way analysis of variance with the Bonferroni correction was used to analyze the data (P < .05). RESULTS: The bond strength of the water-washed dentin surfaces in the calcium silicate-based sealer groups did not differ significantly from those of the control surfaces but the PA-pretreated surfaces exhibited relatively low-bond strength. The AH Plus-treated group had lower bond strength than the control group when no PA treatment was applied, but PA treatment restored the bond strength. The adhesive failure mode was most frequently found in the AH Plus group without PA etching. CONCLUSIONS: When a water-soluble calcium silicate-based sealer is used, sufficient bond strength can be obtained by washing with water alone, with no need for PA use.