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1.
Odontology ; 110(1): 193-202, 2022 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-34255238

RESUMEN

This study aimed at evaluating the effectiveness of an adjuvant chlorhexidine-fluoride varnish (Cervitec F) for prevention and arrest of root caries on elderly participants using quantitative light-induced fluorescence (QLF). 23 participants with two or three non-cavitated root carious lesions were included and assigned to three groups of different varnishes (CF: Cervitec F, P: placebo, DP: Duraphate). Agents were applied once to root surface at baseline and in follow-up after 3, 6 and 9 months. The lesions were assessed clinically and with QLF. QLF-images were analyzed regarding fluorescence loss (ΔF), lesion volume (ΔQ) and bacterial activity (ΔR) before (t0), after 14 days (t1), 6- (t2) and 12-months (t3). CF showed a significant difference between t0 and t3: ∆F (- 12.51 [15.41] vs. - 7.80 [16.72], p = 0.012), ∆Q (- 2339.97 (20,898.30) vs. - 751.82 (5725.35), p < 0.001), ∆R (23.80 [41.70] vs. 7.07 [37.50], p = 0.006). Independently of the varnish application, preventive care seems positively influence the root caries progress. Although within CF group the strongest effect was observed, no superiority of a specific varnish application was confirmed over a 12-months QLF observation period. Extra topical fluoride can help remineralise dentin lesions and QLF can be used as a measurement method to determine changes in the dentin lesions.


Asunto(s)
Caries Dental , Fluorescencia Cuantitativa Inducida por la Luz , Caries Radicular , Anciano , Cariostáticos , Clorhexidina , Caries Dental/tratamiento farmacológico , Caries Dental/prevención & control , Fluoruros , Fluoruros Tópicos , Humanos , Caries Radicular/tratamiento farmacológico , Caries Radicular/prevención & control
2.
Odontology ; 109(1): 139-148, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32519114

RESUMEN

This study aimed at evaluating the marginal and internal adaptation of low-viscosity bulk-fill composites to enamel and dentin using a self-etch or an etch-and-rinse adhesive without and with artificial ageing. Hundred and twenty-eight MOD cavities in extracted molars were assigned to eight groups (n = 16), restored with the adhesives OptiBond FL (OFL) or Xeno V+ (X) and two low-viscosity bulk-fill composites SDR or x-tra base, covered with Premise. Tetric EvoCeram Bulk Fill and Premise served as a control. n = 8 per group were subjected to prolonged water storage (180 days) and thermocycling (2500×). Scanning electron microscopy was used to determine marginal gaps (MG) and interfacial adhesive defects (IAD). There were no significant differences between composite types in 44 out of 48 (MG) or 43/48 (IAD) comparisons. More MG were observed with X than with OFL (14 out of 16 comparisons, two significant), while in 16 of 16 comparisons with X more IAD were observed (14 significant). After artificial ageing, MG generally increased (9/16 significant), compared to IAD (one significant). The performance of the investigated composite types concerning the integrity of the tooth-composites interface was comparable. Compared to the 1-step self-etch system, the bond with the 3-step etch-and-rinse adhesive was raised.


Asunto(s)
Materiales Dentales , Restauración Dental Permanente , Resinas Compuestas , Esmalte Dental , Ensayo de Materiales , Cementos de Resina , Viscosidad
3.
Lasers Med Sci ; 34(5): 973-980, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30426356

RESUMEN

The aim of this study was to evaluate the ability of spectral-domain optical coherence tomography (SD-OCT) to display the roof of the pulp chamber and to estimate the residual dentin thickness (RDT) of the pulp complex. The roots of 20 extracted human molars were embedded in epoxy resin, and crowns were longitudinally sectioned in the mesial-distal direction, exposing the pulp chamber. The coronal part of the crown was removed up to an RDT to the pulp chamber roof of 2 mm. Samples were imaged by SD-OCT from coronal view and by light microscopy (LM) in the sagittal plane. Using a microtome, dentin was subsequently removed in four levels from the occlusal aspect in steps of 250 µm. At each level, RDT was documented and measured by both methods. The data were compared (Spearman's rho correlation coefficient, Wilcoxon signed-rank test). Using OCT, the roof of the pulp chamber was first displayed at a maximum RDT of 1.94 mm. The minimal RDT that could be imaged by OCT was 0.06 mm. Values from both methods were strongly correlated (r, 0.83-0.95; pi ≤ 0.05) and differed significantly for large RDTs (dentin levels 1, 2; pi < 0.05) but not for small RDTs (levels 3, 4; pi ≥ 0.226). The roof of the dental pulp chamber could be already visualized by SD-OCT with a RDT of 1.94 mm. Therefore, the method could be a useful diagnostic tool during the preparation of deep dentin cavities and might help to preserve the integrity of the pulp chamber.


Asunto(s)
Cavidad Pulpar/anatomía & histología , Dentina/anatomía & histología , Tomografía de Coherencia Óptica/métodos , Estudios Transversales , Cavidad Pulpar/ultraestructura , Dentina/ultraestructura , Humanos , Diente Molar/anatomía & histología , Estadísticas no Paramétricas
4.
Odontology ; 107(3): 418-419, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30715631

RESUMEN

In the original publication of the article the paragraph "The four resin-based composites…" appearing below the "Materials and methods" section is incomplete. The correct paragraph is provided in this correction below.

5.
Odontology ; 107(3): 374-382, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30569286

RESUMEN

The aim of this study was to evaluate internal and marginal adaptation of high-viscosity bulk-fill composites to enamel and dentin with a self-etch (SE) and an etch-and-rinse adhesive (ER) without and with artificial aging. 128 MOD cavities in extracted human molars were prepared, randomly assigned to 8 groups (n = 16), bonded with either OptiBond FL (OFL, ER) or Xeno V+ (X, SE), and restored in 4 mm horizontal bulk layers with SonicFill (SF), Tetric EvoCeram Bulk fill (TEC), and x-tra fil (XF). Incremental layering technique with Premise (P) served as control. Half of the specimens each (n = 8) were subjected either to water storage (1 day, 37 °C) or prolonged storage (180 days) and thereafter thermocycling. Replicas were analyzed for marginal gap formation. After sectioning, interfacial adhesive defects were assessed. Results were statistical analyzed. (1) Internal adaptation: Except for TEC/OFL at enamel without artificial aging, no significant differences between bulk-fill composites and the control were observed. All groups at dentin with OFL showed less internal adhesive defects than that with X (p < 0.05). (2) Marginal adaptation: No significant differences were observed between bulk-fill composites and control except for P after artificial aging (p > 0.05). All other composites, regardless of artificial aging, formed significantly more marginal gaps at enamel with X compared to with OFL (p ≤ 0.05). Simplified restorations with high-viscosity bulk-fill composite showed comparable internal and marginal adaptation to incrementally placed fillings. A superiority of the 3-step ER approach was seen compared to the 1-step SE adhesive irrespective of the bulk-fill composite used.


Asunto(s)
Adaptación Marginal Dental , Restauración Dental Permanente , Resinas Compuestas , Materiales Dentales , Humanos , Ensayo de Materiales , Cementos de Resina , Viscosidad
6.
Biochem Biophys Res Commun ; 495(1): 1201-1207, 2018 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29180014

RESUMEN

Prompt removal of misfolded membrane proteins and misassembled membrane protein complexes is essential for membrane homeostasis. However, the elimination of these toxic proteins from the hydrophobic membrane environment has high energetic barriers. The transmembrane protein, FtsH, is the only known ATP-dependent protease responsible for this task. The mechanisms by which FtsH recognizes, unfolds, translocates, and proteolyzes its substrates remain unclear. The structure and function of the ATPase and protease domains of FtsH have been previously characterized while the role of the FtsH periplasmic domain has not clearly identified. Here, we report the 1.5-1.95 Å resolution crystal structures of the Thermotoga maritima FtsH periplasmic domain (tmPD) and describe the dynamic features of tmPD oligomerization.


Asunto(s)
Proteasas ATP-Dependientes/química , Proteasas ATP-Dependientes/ultraestructura , Péptido Hidrolasas/química , Péptido Hidrolasas/ultraestructura , Multimerización de Proteína , Thermotoga maritima/enzimología , Sitios de Unión , Simulación por Computador , Activación Enzimática , Modelos Químicos , Modelos Moleculares , Unión Proteica , Conformación Proteica , Dominios Proteicos , Relación Estructura-Actividad
7.
Lasers Med Sci ; 33(7): 1573-1579, 2018 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-29725944

RESUMEN

Evaluation of variance in the extent of carious lesions in depth at smooth surfaces within the same ICDAS code group using optical coherence tomography (OCT) in vitro and in vivo. (1) Verification/validation of OCT to assess non-cavitated caries: 13 human molars with ICDAS code 2 at smooth surfaces were imaged using OCT and light microscopy. Regions of interest (ROI) were categorized according to the depth of carious lesions. Agreement between histology and OCT was determined by unweighted Cohen's Kappa and Wilcoxon test. (2) Assessment of 133 smooth surfaces using ICDAS and OCT in vitro, 49 surfaces in vivo. ROI were categorized according to the caries extent (ICDAS: codes 0-4, OCT: scoring based on lesion depth). A frequency distribution of the OCT scores for each ICDAS code was determined. (1) Histology and OCT agreed moderately (κ = 0.54, p ≤ 0.001) with no significant difference between both methods (p = 0.25). The lesions (76.9% (10 of 13)) _were equally scored. (2) In vitro, OCT revealed caries in 42% of ROI clinically assessed as sound. OCT detected dentin-caries in 40% of ROIs visually assessed as enamel-caries. In vivo, large differences between ICDAS and OCT were observed. Carious lesions of ICDAS codes 1 and 2 vary largely in their extent in depth.


Asunto(s)
Caries Dental/diagnóstico por imagen , Caries Dental/diagnóstico , Tomografía de Coherencia Óptica/métodos , Caries Dental/patología , Humanos , Diente Molar/diagnóstico por imagen , Diente Molar/patología , Reproducibilidad de los Resultados , Propiedades de Superficie
8.
Opt Express ; 25(12): 13822-13833, 2017 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-28788924

RESUMEN

We systematically analyzed the magnetodielectric resonances of Se colloids for the first time in an attempt to utilize them as building blocks for all-dielectric optical metafluids. By taking advantages of the synergistic properties of Se colloids, including their (i) high-refractive-index at optical frequencies, (ii) unprecedented structural uniformity, and (iii) ready availability, we were able to observe Kerker-type directional light scattering, resulting from the efficient coupling between strong electric and magnetic resonances, directly from Se colloidal suspensions. Thus, the use of Se colloids as a generic magnetodielectric building block suggests the opportunity for the production of fluidic low-loss optical antennas, which can be processed via spin-coating and painting.

10.
J Clin Lab Anal ; 30(6): 1061-1070, 2016 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-27132877

RESUMEN

BACKGROUND: Despite recent advances in the investigation of myeloproliferative neoplasms (MPN), the impact of genetic heterogeneity on its molecular pathogenesis has not been fully elucidated. Thus, in this study, we aim to characterize the genetic complexity in Korean patients with polycythemia vera (PV) and essential thrombocythemia (ET). METHODS: We conducted association studies using 84 single-nucleotide polymorphisms (SNPs) in 229 patients (96 with PV and 133 with ET) and 170 controls. Further, whole-genome sequencing was performed in six patients (two with JAK2 V617F and four with wild-type JAK2), and putative somatic mutations were validated in a further 69 ET patients. Clinical and laboratory characteristics were also analyzed. RESULTS: Several germline SNPs and the 46 haplotype were significantly associated with PV and ET. Three somatic mutations in MPDZ, IQCH, and CALR genes were selected and validated. The frequency of the CALR mutation was 58.0% (40/69) in ET patients, who did not carry JAK2/MPL mutations. Moreover, compared with JAK2 V617F-positive patients, those with CALR mutations showed lower hemoglobin and hematocrit levels (P = 0.004 and P = 0.002, respectively), higher platelet counts (P =0.008), and a lower frequency of cytoreductive therapy (P = 0.014). CONCLUSION: This study was the first comprehensive investigation of the genetic characteristics of Korean patients with PV and ET. We found that somatic mutations and the 46 haplotype contribute to PV and ET pathogenesis in Korean patients.


Asunto(s)
Predisposición Genética a la Enfermedad/genética , Janus Quinasa 2/genética , Policitemia Vera/genética , Polimorfismo de Nucleótido Simple/genética , Receptores de Trombopoyetina/genética , Trombocitemia Esencial/genética , Adulto , Anciano , Anciano de 80 o más Años , Proteínas Portadoras/genética , Análisis Mutacional de ADN , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Genotipo , Humanos , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , Policitemia Vera/epidemiología , República de Corea/epidemiología , Estadísticas no Paramétricas , Trombocitemia Esencial/epidemiología , Adulto Joven
11.
Langmuir ; 31(51): 13773-82, 2015 Dec 29.
Artículo en Inglés | MEDLINE | ID: mdl-26638691

RESUMEN

The stability of gold nanoparticles (AuNPs) in biological samples is very important for their biomedical applications. Although various molecules such as polystyrenesulfonate (PSS), phosphine, DNA, and polyethylene glycol (PEG) have been used to stabilize AuNPs, it is still very difficult to stabilize large AuNPs. As a result, biomedical applications of large (30-100 nm) AuNPs are limited, even though they possess more favorable optical properties and are easier to be taken up by cells than smaller AuNPs. To overcome this limitation, we herein report a novel method of preparing large (30-100 nm) AuNPs with a high colloidal stability and facile chemical or biological functionality, via surface passivation with an amphiphilic polymer polyvinylpyrrolidone (PVP). This PVP passivation results in an extraordinary colloidal stability for 13, 30, 50, 70, and 100 nm AuNPs to be stabilized in PBS for at least 3 months. More importantly, the PVP capped AuNPs (AuNP-PVP) were also resistant to protein adsorption in the presence of serum containing media and exhibit a negligible cytotoxicity. The AuNP-PVPs functionalized with a DNA aptamer AS1411 remain biologically active, resulting in significant increase in the uptake of the AuNPs (∼12,200 AuNPs per cell) in comparison with AuNPs capped by a control DNA of the same length. The novel method developed in this study to stabilize large AuNPs with high colloidal stability and biological activity will allow much wider applications of these large AuNPs for biomedical applications, such as cellular imaging, molecular diagnosis, and targeted therapy.


Asunto(s)
ADN/química , Oro/química , Nanopartículas del Metal/química , Línea Celular Tumoral , Supervivencia Celular , Células Cultivadas , Estabilidad de Medicamentos , Humanos , Modelos Biológicos , Estructura Molecular , Polietilenglicoles/química
12.
Dent Mater ; 40(2): 359-369, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38143188

RESUMEN

OBJECTIVES: To evaluate the effect of an additional layer of universal adhesive on the interfacial enamel/dentin-composite gap formation in relation to application mode and aging, via spectral domain optical coherence tomography (SD-OCT) and scanning electron microscopy (SEM). METHODS: In vitro class V cavities in 114 caries-free premolars were restored by applying one or two layers of a universal adhesive (Scotchbond Universal, SBU) in self-etch (se) and etch-and-rinse (er) mode or the reference adhesive OptiBond FL (OFL-er). The restorations were imaged by SD-OCT (six groups, n = 8) and SEM (n = 3) directly after filling (t1), water storage (t2, 24 h), embedding (t3), and thermo-mechanical loading (t4, TCML). The interfacial gaps were quantified using 26 parameters and analyzed using principal component analysis and linear mixed effect models. RESULTS: Gap formation at enamel and dentin was significantly influenced by the adhesive, the application mode and number of layers (p < 0.001). This was due to the influence of the SBU-er mode (p < 1e-05), which showed significantly more gap formation and a greater range of variation with double application when compared to SBU-se and OFL. The fewest interfacial gaps occurred with one or two applications of OFL-er and one layer of SBU-er. SIGNIFICANCE: Adhesive application mode and the number of adhesive layers are relevant factors in the tooth-composite bond failure. Double application worsened the adaptation of SBU to freshly prepared dentin conditioned with phosphoric acid.


Asunto(s)
Recubrimiento Dental Adhesivo , Cementos Dentales , Recubrimientos Dentinarios/química , Resinas Compuestas/química , Ensayo de Materiales , Cementos de Resina/química , Dentina
13.
J Biol Chem ; 287(5): 3313-25, 2012 Jan 27.
Artículo en Inglés | MEDLINE | ID: mdl-22158615

RESUMEN

Stimulation of the proapoptotic tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) receptors, death receptors 4 (DR4) and 5 (DR5), conventionally induces caspase-dependent apoptosis in tumor cells. Here we report that stimulation of DR4 and/or DR5 by the agonistic protein KD548-Fc, an Fc-fused DR4/DR5 dual-specific Kringle domain variant, activates plasma membrane-associated Nox1 NADPH oxidase to generate superoxide anion and subsequently accumulates intracellular reactive oxygen species (ROS), leading to sustained c-Jun N-terminal kinase activation and eventual apoptotic cell death in human HeLa and Jurkat tumor cells. KD548-Fc treatment induces the formation of a DR4/DR5 signaling complex containing riboflavin kinase (RFK), Nox1, the Nox1 subunits (Rac1, Noxo1, and Noxa1), TNF receptor-associated death domain (TRADD), and TNF receptor-associated factor 2 (TRAF2). Depletion of RFK, but not the Nox1 subunits, TRADD and TRAF2, failed to recruit Nox1 and Rac1 to DR4 and DR5, demonstrating that RFK plays an essential role in linking DR4/DR5 with Nox1. Knockdown studies also reveal that RFK, TRADD, and TRAF2 play critical, intermediate, and negligible roles, respectively, in the KD548-Fc-mediated ROS accumulation and downstream signaling. Binding assays using recombinantly expressed proteins suggest that DR4/DR5 directly interact with cytosolic RFK through RFK-binding regions within the intracellular death domains, and TRADD stabilizes the DR4/DR5-RFK complex. Our results suggest that DR4 and DR5 have a capability to activate Nox1 by recruiting RFK, resulting in ROS-mediated apoptotic cell death in tumor cells.


Asunto(s)
Apoptosis/fisiología , NADPH Oxidasas/metabolismo , Fosfotransferasas (Aceptor de Grupo Alcohol)/metabolismo , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/metabolismo , Superóxidos/metabolismo , Técnicas de Silenciamiento del Gen , Células HeLa , Humanos , Proteínas Quinasas JNK Activadas por Mitógenos/genética , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , NADPH Oxidasa 1 , NADPH Oxidasas/genética , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/genética , Proteína de Dominio de Muerte Asociada a Receptor de TNF/genética , Proteína de Dominio de Muerte Asociada a Receptor de TNF/metabolismo , Factor 2 Asociado a Receptor de TNF/genética , Factor 2 Asociado a Receptor de TNF/metabolismo , Proteína de Unión al GTP rac1/genética , Proteína de Unión al GTP rac1/metabolismo
14.
Exp Cell Res ; 318(13): 1564-76, 2012 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-22513214

RESUMEN

Head and neck squamous cell carcinoma (HNSCC) is often resistant to conventional chemotherapy and thus requires novel treatment regimens. Here, we investigated the effects of the proteasome inhibitor MG132 in combination with tumor necrosis factor-related apoptosis inducing ligand (TRAIL) or agonistic TRAIL receptor 1 (DR4)-specific monoclonal antibody, AY4, on sensitization of TRAIL- and AY4-resistant human HNSCC cell lines. Combination treatment of HNSCC cells synergistically induced apoptotic cell death accompanied by caspase-8, caspase-9, and caspase-3 activation and Bid cleavage into truncated Bid (tBid). Generation and accumulation of tBid through the cooperative action of MG132 with TRAIL or AY4 and Bik accumulation through MG132-mediated proteasome inhibition are critical to the synergistic apoptosis. In HNSCC cells, Bak was constrained by Mcl-1 and Bcl-X(L), but not by Bcl-2. Conversely, Bax did not interact with Mcl-1, Bcl-X(L), or Bcl-2. Importantly, tBid plays a major role in Bax activation, and Bik indirectly activates Bak by displacing it from Mcl-1 and Bcl-X(L), pointing to the synergistic mechanism of the combination treatment. In addition, knockdown of both Mcl-1 and Bcl-X(L) significantly sensitized HNSCC cells to TRAIL and AY4 as a single agent, suggesting that Bak constraint by Mcl-1 and Bcl-X(L) is an important resistance mechanism of TRAIL receptor-mediated apoptotic cell death. Our results provide a novel molecular mechanism for the potent synergy between MG132 proteasome inhibitor and TRAIL receptor agonists in HNSCC cells, suggesting that the combination of these agents may offer a new therapeutic strategy for HNSCC treatment.


Asunto(s)
Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Leupeptinas/administración & dosificación , Inhibidores de Proteasoma , Receptores del Ligando Inductor de Apoptosis Relacionado con TNF/agonistas , Anticuerpos Monoclonales/administración & dosificación , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/antagonistas & inhibidores , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/antagonistas & inhibidores , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/genética , Proteína Proapoptótica que Interacciona Mediante Dominios BH3/metabolismo , Secuencia de Bases , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Línea Celular Tumoral , Sinergismo Farmacológico , Técnicas de Silenciamiento del Gen , Neoplasias de Cabeza y Cuello/metabolismo , Neoplasias de Cabeza y Cuello/patología , Humanos , Proteínas de la Membrana/antagonistas & inhibidores , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas Mitocondriales , Proteína 1 de la Secuencia de Leucemia de Células Mieloides , Estabilidad Proteica/efectos de los fármacos , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/genética , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/genética , Ligando Inductor de Apoptosis Relacionado con TNF/administración & dosificación , Proteína Destructora del Antagonista Homólogo bcl-2/metabolismo , Proteína X Asociada a bcl-2/metabolismo , Proteína bcl-X/antagonistas & inhibidores , Proteína bcl-X/genética , Proteína bcl-X/metabolismo
15.
Proc Natl Acad Sci U S A ; 107(21): 9567-71, 2010 May 25.
Artículo en Inglés | MEDLINE | ID: mdl-20460308

RESUMEN

Here, we report the development of target-specific binding proteins based on the kringle domain (KD) ( approximately 80 residues), a ubiquitous modular structural unit occurring across eukaryotic species. By exploiting the highly conserved backbone folding by core residues, but using extensive sequence variations in the seven loop regions of naturally occurring human KDs, we generated a synthetic KD library on the yeast cell surface by randomizing 45 residues in the loops of a human KD template. We isolated KD variants that specifically bind to anticancer target proteins, such as human death receptor 4 (DR4) and/or DR5, and that function as agonists to induce apoptotic cell death in several cancer cell lines in vitro and inhibit tumor progression in mouse models. Combined treatments with KD variants possessing different recognition sites on the same target protein exerted synergisitic tumoricidal activities, compared to treatment with individual variants. In addition to the agonists, we isolated an antagonistic KD variant that binds human tumor necrosis factor-alpha (TNFalpha) and efficiently neutralizes TNFalpha-induced cytotoxicity in vitro and in vivo. The KD scaffold with seven flexible loops protruding from the central core was strongly sequence-tolerant to mutations in the loop regions, offering a potential advantage of distinct binding sites for target recognition on the single domain. Our results suggest that the KD scaffold can be used to develop target-specific binding proteins that function as agonists or antagonists toward given target molecules, indicative of their potential use as biotherapeutics.


Asunto(s)
Kringles , Dominios y Motivos de Interacción de Proteínas , Proteínas/química , Secuencia de Aminoácidos , Animales , Línea Celular Tumoral , Femenino , Humanos , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Modelos Moleculares , Datos de Secuencia Molecular , Biblioteca de Péptidos , Unión Proteica , Ingeniería de Proteínas , Pliegue de Proteína , Estructura Terciaria de Proteína , Proteínas/genética , Proteínas/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Alineación de Secuencia , Ensayos Antitumor por Modelo de Xenoinjerto
16.
Front Physiol ; 14: 1199771, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37304827

RESUMEN

Introduction: The aim of this study was to characterize the hemodynamics of Fontan patients using both four-dimensional flow magnetic resonance imaging (4D Flow MRI) and computational fluid dynamics (CFD). Methods: Twenty-nine patients (3.5 ± 0.5 years) who had undergone the Fontan procedure were enrolled, and the superior vena cava (SVC), left pulmonary artery (LPA), right pulmonary artery (RPA), and conduit were segmented based on 4D Flow MRI images. Velocity fields from 4D Flow MRI were used as boundary conditions for CFD simulations. Hemodynamic parameters such as peak velocity (Vmax), pulmonary flow distribution (PFD), kinetic energy (KE), and viscous dissipation (VD) were estimated and compared between the two modalities. Results and discussion: The Vmax, KE, VD, PFDTotal to LPA, and PFDTotal to RPA of the Fontan circulation were 0.61 ± 0.18 m/s, 0.15 ± 0.04 mJ, 0.14 ± 0.04 mW, 41.3 ± 15.7%, and 58.7 ± 15.7% from 4D Flow MRI; and 0.42 ± 0.20 m/s, 0.12 ± 0.05 mJ, 0.59 ± 0.30 mW, 40.2 ± 16.4%, and 59.8 ± 16.4% from CFD, respectively. The overall velocity field, KE, and PFD from the SVC were in agreement between modalities. However, PFD from the conduit and VD showed a large discrepancy between 4D Flow MRI and CFD, most likely due to spatial resolution and data noise. This study highlights the necessity for careful consideration when analyzing hemodynamic data from different modalities in Fontan patients.

18.
Photodiagnosis Photodyn Ther ; 37: 102675, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-34906738

RESUMEN

BACKGROUND: This in vitro study aimed to assess carious lesions on root surfaces using quantitative light-induced fluorescence (QLF) and to compare the readings with axial lesion depth on µCT. METHODS: The root surfaces of 107 extracted human teeth were included after visual-tactile inspection. For further analysis, the following parameters were assessed: clinical findings (non-cavitated: leathery or hard, cavitated), QLF- (QLF-D Biluminator 2+), and µCT-images (Bruker Skyscan 1172). The shape of the undamaged tooth surface of the cavitated lesions was virtually re-constructed during µCT analysis. Clinical surface texture,% fluorescence loss, and lesion depth (µCT) were determined. STATISTICAL ANALYSIS: chi²-test, Spearman-Rho test, regression analysis. RESULTS: ∆F was significantly lower in non-cavitated leathery (-50.37 ± 15.10) and cavitated (-61.23 ± 9.92) compared to non-cavitated surfaces with a hard texture (-17.04 ± 16.10, p < 0.01). For non-cavitated surfaces, a negative correlation was observed between ∆F and lesion depth in µCT images regardless of texture (-0.748, p < 0.01). Regression analysis revealed that ∆F predicted lesion depth in µCT for non-cavitated surfaces (ß: 0.703, CI95: 0.67--0.43, p < 0.01). CONCLUSION: The percentage of fluorescence loss (∆F) in QLF predicted lesion depth of non-cavitated demineralized root surfaces. Therefore, QLF can be recommended for estimating the lesion depth of carious root lesions and seems to expand the possibilities of follow-up and lesion monitoring, especially for non-cavitated surfaces.


Asunto(s)
Caries Dental , Fotoquimioterapia , Fluorescencia Cuantitativa Inducida por la Luz , Caries Radicular , Caries Dental/diagnóstico por imagen , Fluorescencia , Humanos , Luz , Fotoquimioterapia/métodos , Proyectos de Investigación , Caries Radicular/diagnóstico por imagen , Caries Radicular/tratamiento farmacológico
19.
J Adhes Dent ; 24(1): 165-174, 2022 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-35416444

RESUMEN

PURPOSE: To compare a self-etch and a two-step etch-and-rinse adhesive in terms of internal and marginal composite-tooth bond failure separately on enamel and dentin/cement at 36-48 months after restoration placement using optical coherence tomography (OCT). MATERIALS AND METHODS: Twenty-seven patients with two or three class V composite restorations of noncarious cervical lesions 36-48 months after placement were included. The one-step self-etch adhesive Futurabond M ([Voco] group SE, n = 25) and the two-step etch-and-rinse adhesive Solobond M ([Voco] group ER, n = 20) combined with the nanohybrid composite Amaris (Voco) were evaluated. The four-step etch-and-rinse adhesive Syntac classic combined with Tetric EvoCeram (Ivoclar Vivadent) served as the control (n = 18). Spectral-domain OCT (SD-OCT, 1310-nm center wavelength) was applied. Marginal gaps and internal interfacial adhesive defects were quantified in cross-sectional OCT images. Groups were statistically compared using the Friedman/Wilcoxon test (α = 0.05). RESULTS: In enamel, nonsignificantly different percentages of marginal gap formation and internal interfacial adhesive defects were found between the groups (pi ≥ 0.258). In dentin/cement, SE showed significantly less marginal gap formation compared to ER (p < 0.001) and control (p = 0.001), and at the internal dentin-composite interface less adhesive defects were found compared to ER (p < 0.001) and control (p = 0.003). CONCLUSION: The self-etch adhesive used in the current study appears recommendable for restoration of noncarious cervical lesions with composite.


Asunto(s)
Restauración Dental Permanente , Tomografía de Coherencia Óptica , Resinas Compuestas/química , Estudios Transversales , Cementos Dentales , Esmalte Dental , Adaptación Marginal Dental , Recubrimientos Dentinarios/química , Humanos , Cementos de Resina/química
20.
J Dent ; 119: 104068, 2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35192908

RESUMEN

OBJECTIVES: To evaluate a universal adhesive clinically using FDI criteria and by optical coherence tomography (OCT). METHODS: In 50 patients, three or four non-carious cervical lesions (NCCL) were restored with composite (Venus® Diamond Flow, Kulzer) using iBond® Universal (iBU, Kulzer) applied in self-etch (iBU-SE, n = 50), selective-enamel-etch (iBU-SEE, n = 29) or etch-and-rinse mode (iBU-ER, n = 50) and the reference OptiBond™ FL (OFL, Kerr, n = 50). Restorations were imaged by SD-OCT. The weighted mean length of interfacial adhesive defects (AD, %) was quantified per restoration immediately after placement (t0), simultaneously with clinical assessment (FDI criteria) after 14 days (t1), 6 (t2) and 12 months (t3). Data were statistically analyzed (McNemar-/Wilcoxon-/Mann-Whitney-U test (α = 0.05), Kaplan-Meier survival curves). RESULTS: After 12 months, cumulative failure rates were lower with iBU-SE (0.0%; p = 0.016), iBU-SEE (0.0%; p = 0.125), and iBU-ER (2.1%; p = 0.070; loss t3) compared to OFL (16.7%; losses t2, t3). Generally, marginal adaptation decreased (pi < 0.001) and marginal staining increased (pi ≤ 0.031), without significant group differences (pi > 0.064). AD increased in all groups (pi < 0.001). At enamel, AD appeared more extended with iBU-SE vs. iBU-SEE (t2-t3; pi ≤ 0.005), iBU-ER (t1-t3; pi ≤ 0.051) and OFL (t0-t3; pi ≤ 0.018). At dentin/cement iBU generally caused fewer defects than OFL (t1-t3; pi ≤ 0.010) and with SE vs. ER (t2-t3; pi = 0.010). CONCLUSIONS: In NCCLs, iBU generally provides a more durable bond than OFL. Recommended mode is SEE. Clinic and OCT provided comparable results. OCT has higher statistical power, shows group differences earlier and specifically for the different hard tooth tissues. CLINICAL SIGNIFICANCE: The universal adhesive iBU was superior against the reference OFL in NCCLs. It can be recommended with SEE. Evaluation of interfacial adhesive defects by OCT seems to allow early prediction of adhesives' clinical performance.


Asunto(s)
Recubrimientos Dentinarios , Tomografía de Coherencia Óptica , Resinas Compuestas/química , Resinas Compuestas/uso terapéutico , Cementos Dentales/uso terapéutico , Adaptación Marginal Dental , Restauración Dental Permanente/métodos , Recubrimientos Dentinarios/química , Humanos , Cementos de Resina/química
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