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Bacterial therapy is an emerging hotspot in tumor immunotherapy, which can initiate antitumor immune activation through multiple mechanisms. Porphyromonas gingivalis (Pg), a pathogenic bacterium inhabiting the oral cavity, contains a great deal of pathogen associated molecular patterns that can activate various innate immune cells to promote antitumor immunity. Owing to the presence of protoporphyrin IX (PpIX), Pg is also an excellent photosensitizer for photodynamic therapy (PDT) via the in situ generation of reactive oxygen species. This study reports a bacterial nanomedicine (nmPg) fabricated from Pg through lysozyme degradation, ammonium chloride lysis, and nanoextrusion, which has potent PDT and immune activation performances for oral squamous cell carcinoma (OSCC) treatment. To further promote the tumoricidal efficacy, a commonly used chemotherapeutic drug doxorubicin (DOX) is efficiently encapsulated into nmPg through a simple incubation method. nmPg/DOX thus prepared exhibits significant synergistic effects on inhibiting the growth and metastasis of OSCC both in vitro and in vivo via photodynamic-immunotherapy and chemotherapy. In summary, this work develops a promising bacterial nanomedicine for enhanced treatment of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Fotoquimioterapia , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de la Boca/tratamiento farmacológico , Fotoquimioterapia/métodos , Nanomedicina , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Doxorrubicina/farmacología , Doxorrubicina/uso terapéutico , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Inmunoterapia , Línea Celular TumoralRESUMEN
BACKGROUND: MicroRNA (miRNA) is accepted as a critical regulator of cell differentiation. However, whether microRNA-223 (miR-223) could affect the osteogenic differentiation of periodontal ligament (PDL)-derived cells is still unknown. The aim of this study was to explore the mechanisms underlying the roles of miR-223 in the osteogenesis of PDL-derived cells in periodontitis. METHODS: Microarray analysis and real-time polymerase chain reaction (RT-PCR) were used to identify difference in miR-223 expression pattern between healthy and inflamed gingival tissue. The target genes of miR-223 were predicted based on Targetscan and selected for enrichment analyses based on Metascape database. The gain-and loss-of-function experiments were performed to discuss roles of miR-223 and growth factor receptor genes in osteogenic differentiation of PDL-derived cells. The target relationship between miR-223 and growth factor receptor genes was confirmed by a dual luciferase assay. Osteogenic differentiation of PDL-derived cells was assessed by Alizarin red staining, RT-PCR and western blot detection of osteogenic markers, including osteocalcin (OCN), osteopontin (OPN) and runt-related transcription factor 2 (Runx2). RESULTS: MiR-223 was significantly increased in inflamed gingival tissues and down-regulated in PDL-derived cells during osteogenesis. The expression of miR-223 in gingival tissues was positively correlated with the clinical parameters in periodontitis patients. Overexpression of miR-223 markedly inhibited PDL-derived cells osteogenesis, which was evidenced by reduced Alizarin red staining and osteogenic markers expressions. Furthermore, two growth factor receptor genes, including fibroblast growth factor receptor 2 (FGFR2) and transforming growth factor beta receptor 2 (TGFßR2), were revealed to be direct targets of miR-223 and shown to undergo up-regulation in PDL-derived cells during osteogenesis. Moreover, suppression of FGFR2 or TGFßR2 dramatically blocked PDL-derived cells osteogenic differentiation. CONCLUSIONS: Our study provides novel evidence that miR-223 can be induced by periodontitis and acts as a negative regulator of PDL-derived cells osteogenesis by targeting two growth factor receptors (TGFßR2 and FGFR2).
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MicroARNs , Periodontitis , Antraquinonas , Diferenciación Celular/genética , Células Cultivadas , Subunidad alfa 1 del Factor de Unión al Sitio Principal/genética , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogénesis/genética , Osteopontina/metabolismo , Ligamento Periodontal , Periodontitis/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/genética , Receptor Tipo 2 de Factor de Crecimiento de Fibroblastos/metabolismo , Receptores de Factores de Crecimiento Transformadores betaRESUMEN
BACKGROUND: Periodontitis is a chronic inflammatory disease in oral cavity owing to bacterial infection. Photothermal therapy (PTT) and photodynamic therapy (PDT) have many advantages for antibacterial treatment. As an excellent photosensitizer, indocyanine green (ICG) shows prominent photothermal and photodynamic performances. However, it is difficult to pass through the negatively charged bacterial cell membrane, thus limiting its antibacterial application for periodontitis treatment. RESULTS: In this work, self-assembled nanoparticles containing ICG and polycationic brush were prepared for synergistic PTT and PDT against periodontitis. First, a star-shaped polycationic brush poly(2-(dimethylamino)ethyl methacrylate) (sPDMA) was synthesized via atom transfer radical polymerization (ATRP) of DMA monomer from bromo-substituted ß-cyclodextrin initiator (CD-Br). Next, ICG was assembled with sPDMA to prepare ICG-loaded sPDMA (sPDMA@ICG) nanoparticles (NPs) and the physicochemical properties of these NPs were characterized systematically. In vitro antibacterial effects of sPDMA@ICG NPs were investigated in porphyromonas gingivalis (Pg), one of the recognized periodontitis pathogens. A ligature-induced periodontitis model was established in Sprague-Dawley rats for in vivo evaluation of anti-periodontitis effects of sPDMA@ICG NPs. Benefiting from the unique brush-shaped architecture of sPDMA polycation, sPDMA@ICG NPs significantly promoted the adsorption and penetration of ICG into the bacterial cells and showed excellent PTT and PDT performances. Both in vitro and in vivo, sPDMA@ICG NPs exerted antibacterial and anti-periodontitis actions via synergistic PTT and PDT. CONCLUSIONS: A self-assembled nanosystem containing ICG and polycationic brush has shown promising clinical application for synergistic PTT and PDT against periodontitis.
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Nanopartículas/química , Periodontitis/metabolismo , Fotoquimioterapia/métodos , Fármacos Fotosensibilizantes , Polielectrolitos , Animales , Bacterias/efectos de los fármacos , Biopelículas/efectos de los fármacos , Femenino , Verde de Indocianina/química , Verde de Indocianina/farmacología , Periodontitis/microbiología , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Polielectrolitos/química , Polielectrolitos/farmacología , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND This study explored the clinical effects of whole-process digitalization (WD)-assisted immediate implant placement (IIP) and immediate restoration (IR) in the aesthetic zone and clarified the clinical procedures. MATERIAL AND METHODS Patients who received maxillary aesthetic region IIP and IR treatment were randomly distributed into WD-assisted and conventional groups. Postoperative assessment included implant accuracy, marginal bone loss, aesthetic evaluation, and patient satisfaction evaluation. The aesthetic evaluation included visual analog score (VAS), pink aesthetic score (PES), and white aesthetic score (WES). Numerical data, measurement data, and grade data were analyzed by χ² test, t test, and Mann-Whitney U test. RESULTS The WD-assisted group exhibited decreased implant accuracy, including coronal deviation, apical deviation, angular deviation, and depth deviation, compared with the conventional group (P<0.05). The marginal bone loss in both the mesiodistal direction and the buccolingual direction were significantly lower in the WD-assisted group than in the conventional group (P<0.05). The VAS, PES, and WES were all significantly higher in the WD-assisted group than in the conventional group at 3, 6, and 12 months after surgery (P<0.05). Patients in the WD-assisted group also reported a higher satisfaction level than those in the conventional group (P<0.05). CONCLUSIONS WD-assisted IIP and IR treatment in the aesthetic zone increased implant accuracy, decreased marginal bone loss, improved aesthetic effect, and increased patient satisfaction compared with conventional treatment. Therefore, WD-assisted IIP and IR treatment constitutes a promising approach in clinical oral implantology.
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Implantación Dental/métodos , Implantación Dental/normas , Implantes Dentales , Estética Dental , Adulto , Femenino , Humanos , Imagenología Tridimensional , Masculino , Maxilar/cirugía , Satisfacción del Paciente , Radiografía , Cirugía Asistida por Computador/métodos , Cirugía Asistida por Computador/normas , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND This study aimed to compare the size and location of the traditional and conservative endodontic access cavities of the right maxillary first molar teeth, projected on the occlusal surface using cone-beam computed tomography (CBCT), to obtain an ideal access cavity. MATERIAL AND METHODS Five hundred CBCT images of the right maxillary first molars, including 198 males and 302 females, were retrospectively evaluated using KaVo eXam Vision software. First, a rectangular coordinate system was established. The coordinates of 4 pulp horns and 3 root canal orifices, which projected on the occlusal surface, were marked on it. Two different access cavities were then created by connecting these points: (1) traditional endodontic access cavity (TEC) required removal of the entire roof of the pulp chamber to establish a straight-line access to the root canal system; (2) conservative endodontic access cavity (CEC) was formed by connecting the projection of each root canal orifice on the occlusal. Data were analyzed using Kruskal-Wallis and Pearson's correlation tests at a 5% significance level. RESULTS The area of TEC was approximately 9.61 mm2 for males and 8.91 mm² for females. The area of CEC was approximately 3.4 mm² for males and 3.16 mm² for females. The projections of all pulp horns and root canal orifices were in or near the central area of nine-rectangle-grid. CONCLUSIONS Compared with the traditional access cavity, creating a conservative access cavity was less invasive. Meanwhile, the access cavity should be limited to the central or near the central area of nine-rectangle-grid.
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Tomografía Computarizada de Haz Cónico , Maxilar/diagnóstico por imagen , Diente Molar/diagnóstico por imagen , Tratamiento del Conducto Radicular/métodos , Adolescente , Adulto , Anciano , Niño , Pulpa Dental , Cavidad Pulpar/diagnóstico por imagen , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto JovenRESUMEN
INTRODUCTION: The purpose of this study was to evaluate the two-body wear resistances of natural enamel and four dental materials in vitro. METHODS: The testing machine was modified to form a type of pin-on-disk wear test apparatus. Four dental material specimens (Au-Pd alloy, Ag-Pd alloy, FiltekTMP60 and FiltekTMZ350 composite resins) and enamel were used as the pins, and a steatite ceramic grinding wheel was used as the abrasive counter face. The wear volume loss and the rigidity value was measured. The worn surface and the element analysis of the debris were analyzed. RESULT: The wear volume loss of Au-Pd alloy and its steatite antagonists were the nearest to those of the dental enamel. SEM microphotographs showed that, the main wear mechanism of the dental materials was abrasive and adhesive wear. CONCLUSIONS: Au-Pd alloy had good wear resistance and was more suitable for dental applications than other three dental materials.
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Resinas Compuestas/farmacología , Esmalte Dental/metabolismo , Alisadura de la Restauración Dental , Ensayo de Materiales/métodos , Aleaciones Dentales/farmacología , Materiales Dentales/clasificación , Materiales Dentales/farmacología , Humanos , Propiedades de SuperficieRESUMEN
BACKGROUND: The purpose of this study was to compare the shaping ability of the ProTaper Universal (PTU; Dentsply Maillefer, Ballaigues, Switzerland), WaveOne (WO; Dentsply Maillefer) and ProTaper Next (PTN; Dentsply Maillefer) in simulated L-shaped and S-shaped root canals respectively. METHODS: 30 simulated L-shaped and 30 simulated S-shaped root canals in resin blocks were employed and randomly divided into 3 groups (n = 10), respectively. The canals were prepared to a tip size 25 using PTU, WO or PTN: PTU F2 (taper 0.08 over the first 3 mm from apical tip), WO Primary (taper 0.08 over the first 3 mm from apical tip), and PTN X2 (taper 0.06 over the first 3 mm from apical tip). Photos of the simulated root canals were taken pre- and postinstrumentation. The 2 layers were superimposed after a series of image processing and 10 points were selected from apical constriction with 1 mm interval. And then the central axis transportation and straightened curvature were measured with software of image analysis. RESULTS: In simulated L-shaped root canals, PTU and PTN caused less transportation than WO at curved section (P < 0.05), and PTN caused the least transportation at apical constriction (P < 0.05). Moreover, PTN maintained the canal curvature best among the 3 groups (P < 0.05). But PTN produced more transportation at straight section compared with PTU and WO (P < 0.05). In simulated S-shaped root canals, PTN preserved the coronal curvature best (P < 0.05), but there was no significant difference in apical curvature since all the files straightened the curvature obviously. CONCLUSIONS: PTN showed a better shaping ability than PTU and WO at the curved section of root canals, and PTN maintained the best apical constriction. But all the files had a tendency to straighten the apical curvature in multi-curved canals.
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Cavidad Pulpar/anatomía & histología , Preparación del Conducto Radicular/instrumentación , Colorantes , Aleaciones Dentales/química , Diseño de Equipo , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Ensayo de Materiales , Modelos Anatómicos , Níquel/química , Fotograbar/métodos , Distribución Aleatoria , Rotación , Titanio/química , Ápice del Diente/anatomía & histología , TorqueRESUMEN
Anodic oxidation was applied to produce nanostructures on the surface of titanium (Ti) implants. The bioactivity of the Ti implants was evaluated by simulated body fluid soaking test. The biocompatibility was investigated by in vitro cell culture test. The results showed that bone-like apatite was formed on the anodized Ti surface, but not on the as-polished Ti surface after immersion in simulated body fluid for 2 weeks. Cells cultured on the anodized Ti surface showed enhanced cell adhesion and proliferation, compared to those cultured on the as-polished Ti surface. Based on these results, it can be concluded that anodic oxidation improved the bioactivity and biocompatibility of Ti surface, which was attributed to the formation of nanostructures as well as the nanostructure induced high surface roughness and hydrophilicity.
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Materiales Biocompatibles Revestidos/química , Nanoestructuras/química , Prótesis e Implantes , Titanio/química , Células 3T3 , Animales , Adhesión Celular , Proliferación Celular , Células Cultivadas , Fluoruros/química , Interacciones Hidrofóbicas e Hidrofílicas , Ensayo de Materiales , Ratones , Nanoporos/ultraestructura , Nanoestructuras/ultraestructura , Oseointegración , Oxidación-Reducción , Propiedades de SuperficieRESUMEN
Condylar-base-associated multiple mandibular fractures are more prevalent than single ones. Direct trauma to mandibular symphysis, body or angle are prone to induce indirect condylar fracture. However, little is known about the effects of various rigid internal fixation modalities in condylar base for relevant multiple mandibular fractures, especially when we are confused in the selection of operative approach. Within the finite element analysis, straight-titanium-plate implanting positions in condylar base contained posterolateral zone (I), anterolateral zone (II), and intermediate zone (III). Von Mises stress (SS) in devices and bone and mandibular displacement (DT) were solved, while maximum values (SSmax and DTmax) were documented. For rigid internal fixation in condylar-base-and-symphysis fractures, I + II modality exhibited least SSmax in screws and cortical bone and least DTmax, I + III modality exhibited least SSmax in plates. For rigid internal fixation in condylar-base-and-contralateral-body fractures, I + III modality exhibited least SSmax in screws and cortical bone, I + II modality exhibited least SSmax in plates and least DTmax. For rigid internal fixation in condylar-base-and-contralateral-angle fractures, I + III modality exhibited least DTmax. The findings suggest that either I + II or I + III modality is a valid guaranty for rigid internal fixation of condylar base fractures concomitant with symphysis, contralateral body or angle fractures.
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Background: To explore the association between the number of missing teeth and the prevalence of hyperlipidemia in a Chinese adult population. Methods: 13,932 adults were investigated in the TCLSIH cohort study. The number of missing teeth was determined at baseline through a self-reported questionnaire, and then classified into three categories: 0, 1-2, and ≥3. We defined hyperlipidemia as total cholesterol (TC) ≥ 5.17 mmol/L or triglycerides (TG) ≥ 1.7 mmol/L or low-density lipoprotein (LDL) cholesterol ≥ 3.37 mmol/L or a self-report of physician-diagnosed hyperlipidemia during follow-up visits. Cox proportional-hazards regression models were employed to assess the relationship between the number of missing teeth and incident hyperlipidemia. Results: A total of 6756 first-incident cases of hyperlipidemia occurred during 42,048 person-years of follow-up (median follow-up, 4.2 years). After adjusted confounders, multivariable HRs and 95% CI for incident of hyperlipidemia across the categories of missing teeth were as follows: in male participants, 1.00 (reference), 1.10 (0.98, 1.22), and 1.03 (0.91, 1.16) (P for trend = 0.30); in female participants, 1.00 (reference), 1.09 (0.99, 1.19), and 1.18 (1.04, 1.33) (P for trend < 0.01). Conclusion: The number of missing teeth is associated with an increased risk of hyperlipidemia in female participants but not in male participants. Systemic chronic inflammation may potentially mediate this association.
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Photothermal therapy (PTT) and photodynamic therapy (PDT) are emerging alternative antibacterial approaches. However, due to the lack of selectivity of photosensitizers for pathogenic bacteria, these methods often show more or less different degrees of in vivo toxicity. Moreover, it is difficult for PDT to exert effective antibacterial effects against anaerobic infections due to the oxygen deficiency. As one of the major anaerobic pathogens in oral infections, Porphyromonas gingivalis (P. gingivalis) acquires iron and porphyrin mainly from hemoglobin in the host. Hence, we developed a nanophotosensitizer named as oxyHb@IR820 through stable complexation between oxyhemoglobin and IR820, which is a photosensitizer possessing both PTT and PDT performance, for fighting P. gingivalis oral infection specifically and efficiently. Owing to hydrophobic interaction, oxyHb@IR820 had much stronger photoabsorption at 808 nm than free IR820, and thus exhibited significantly enhanced photothermal conversion efficiency. As an oxygen donor, oxyHb played an important role in enhancing the photodynamic efficiency of oxyHb@IR820. More importantly, oxyHb@IR820 showed efficient and specific uptake in P. gingivalis and exerted synergistic PTT/PDT performance against P. gingivalis and oral infection in golden hamsters. In summary, this study provides an efficient strategy for delivering photosensitizers specifically to P. gingivalis and augmenting antibacterial PDT against anaerobic infections.
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Fotoquimioterapia , Fármacos Fotosensibilizantes , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Fármacos Fotosensibilizantes/química , Fotoquimioterapia/métodos , Porphyromonas gingivalis , Oxihemoglobinas , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
Bacteria eradication and subsequent periodontal tissue reconstruction is the primary task for periodontitis treatment. Commonly used antibiotic therapy suffers from antibiotic resistance. Meanwhile, promoting fibroblast activity is crucial for re-establishing a damaged periodontal structure. In addition to the fibroblast activation property of Mg2+, photobiomodulation (PBM) has recently attracted increasing attention in wound healing. Using the same 635 nm laser resource, PBM could simultaneously work with antibacterial photodynamic therapy (aPDT) to achieve antibacterial function and fibroblast activation effect. Herein, multifunctional microspheres were designed by employing poly (lactic-co-glycolic acid) (PLGA) microspheres to load tetrakis (4-carboxyphenyl) porphyrin (TCPP) and magnesium oxide (MgO) nanoparticles, named as PMT, with sustained Mg2+ release for 20 days. PMT achieved excellent antibacterial photodynamic effect for periodontal pathogens F. nucleatum and P. gingivalis by generating reactive oxygen species, which increases cell membrane permeability and destroys bacteria integrity to cause bacteria death. Meanwhile, PMT itself exhibited improved fibroblast viability and adhesion, with the PMT + light group revealing further activation of fibroblast cells, suggesting the coordinated action of Mg2+ and PBM effects. The underlying molecular mechanism might be the elevated gene expressions of Fibronectin 1, Col1a1, and Vinculin. In addition, the in vivo rat periodontitis model proved the superior therapeutic effects of PMT with laser illumination using micro-computed tomography analysis and histological staining, which presented decreased inflammatory cells, increased collagen production, and higher alveolar bone level in the PMT group. Our study sheds light on a promising strategy to fight periodontitis using versatile microspheres, which combine aPDT and PBM-assisted fibroblast activation functions.
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Periodontitis , Fotoquimioterapia , Ratas , Animales , Óxido de Magnesio , Microesferas , Microtomografía por Rayos X , Fotoquimioterapia/métodos , Periodontitis/tratamiento farmacológico , Periodontitis/microbiología , Antibacterianos/farmacologíaRESUMEN
OBJECTIVE: This study aims to investigate the effects of microRNA-126 (miR-126) on the macrophage polarization in vitro and alveolar bone resorption in vivo. DESIGN: The relationship between miR-126 and MEK/ERK kinase 2 (MEKK2) was confirmed by dual-luciferase reporter assay. Real-time quantitative polymerase chain reaction, enzyme-linked immunosorbent assay or Western blot was used to detect the changes of miR-126, inducible nitric oxide synthase (iNOS), arginase-1 (Arg-1), tumor necrosis factor (TNF)-α, interleukin (IL)-10, MEKK2 and MEKK2-related pathways: mitogen-activated protein kinase (MAPK) and nuclear factor kappa-B (NF-κB) in RAW264.7 macrophages challenged with Porphyromonas gingivalis (P. gingivalis) lipopolysaccharide (LPS) and/or high glucose and/or miR-126 mimic. In mice with diabetic periodontitis, the expressions of iNOS and Arg-1 in gingiva, and alveolar bone level were detected after miR-126 mimic injection. RESULTS: MiR-126 could directly bind with MEKK2 3'-untranslated region (UTR). MEKK2, phosphorylation of NF-κB and MAPK signaling proteins, TNF-α and iNOS increased (P < 0.05), while miR-126, Arg-1 and IL-10 were inhibited (P < 0.05) in macrophage challenged with high glucose and/or P. gingivalis LPS, however, miR-126 mimic reversed these effects (P < 0.05). The expressions of iNOS in gingiva and alveolar bone resorption were elevated (P < 0.05), the expression of Arg-1 in gingiva decreased (P < 0.05) in mice with diabetic periodontitis, which could be inhibited by miR-126 mimic. CONCLUSIONS: miR-126 might prevent alveolar bone resorption in diabetic periodontitis and inhibit macrophage M1 polarization via regulating MEKK2 signaling pathway.
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Pérdida de Hueso Alveolar , Diabetes Mellitus , MicroARNs , Periodontitis , Ratones , Animales , FN-kappa B/metabolismo , MicroARNs/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/metabolismo , Periodontitis/prevención & control , Periodontitis/metabolismo , Macrófagos/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Pérdida de Hueso Alveolar/prevención & control , Pérdida de Hueso Alveolar/patología , GlucosaRESUMEN
After periodontal tissue injury, reconstruct soft tissue sealing around the tooth surface is of fundamental importance to treat periodontitis. Among multiple cell types, fibroblast plays a central role in reestablishing functional periodontium. To enhance fibroblast activity, a novel metal-organic framework-based nanoplatform is fabricated using mesoporous Prussian blue (MPB) nanoparticles to load baicalein (BA), named MPB-BA. Drug release test displayed sustained BA release of MPB-BA. Cell proliferation, transwell migration and wound healing tests revealed accelerated fibroblast proliferation and migration for the established MPB-BA nanoplatform. Moreover, vinculin immunofluorescence staining, western blot and quantitative real-time PCR analysis showed up-regulated vinculin protein and integrin α5 and integrin ß1 gene expressions for MPB-BA, suggesting improved cell adhesion. In addition, hematoxylin and eosin (H&E) and Masson trichromatic staining suggested superior anti-inflammatory and collagen fiber reconstruction effects for MPB-BA in a rat experimental periodontitis model in vivo. Our study may provide a promising strategy for the treatment of periodontitis.
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Estructuras Metalorgánicas , Periodontitis , Ratas , Animales , Vinculina/farmacología , Estructuras Metalorgánicas/farmacología , Cicatrización de Heridas , Fibroblastos , Periodontitis/tratamiento farmacológicoRESUMEN
As one of the most common malignancies, oral squamous cell carcinoma (OSCC) with high rates of invasiveness and metastasis threatens people's health worldwide, while traditional therapeutic approaches have not met the requirement of its cure. Phototherapies including photothermal therapy (PTT) and photodynamic therapy (PDT) have shown great potential for OSCC treatment due to their noninvasiveness or minimal invasiveness, high selectivity and little tolerance. However, PTT or PDT alone makes it difficult to eradicate OSCC and prevent its metastasis and recurrence. Here, double-layered membrane vesicles (DMVs) were extracted from attenuated Porphyromonas gingivalis, one of the most common pathogens inside the oral region, and served as an immune adjuvant to develop a biomimetic phototherapeutic nanoagent named PBAE/IR780@DMV for OSCC treatment via combining dual PTT/PDT and robust antitumor immunity. To obtain PBAE/IR780@DMV, poly(ß-amino) ester (PBAE) was used as a carrier material to prepare the nanoparticles for loading IR780, a widely known photosensitizer possessing both PTT and PDT capabilities, followed by surface wrapping with DMVs. Upon 808 nm laser irradiation, PBAE/IR780@DMV exerted strong antitumor effects against OSCC both in vitro and in vivo, via combining PTT/PDT and specific immune responses triggered by tumor-associated antigens and DMVs. Altogether, this study provides a promising biomimetic phototherapeutic nanoagent for comprehensive treatment of OSCC.
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Carcinoma de Células Escamosas , Neoplasias de Cabeza y Cuello , Neoplasias de la Boca , Fotoquimioterapia , Humanos , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas de Cabeza y Cuello , Biomimética , Neoplasias de la Boca/tratamiento farmacológicoRESUMEN
Peri-implantitis, an infectious disease originating from dental biofilm that forms around dental implants, which causes the loss of both osseointegration and bone tissue. KN-17, a truncated cecropin B peptide, demonstrated efficacy against certain bacterial strains associated with peri-implantitis. This study aimed to assess the antibacterial and anti-inflammatory properties and mechanisms of KN-17. The effects of KN-17 on oral pathogenic bacteria were assessed by measuring its minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Moreover, the cytotoxicity and anti-inflammatory effects of KN-17 were evaluated. KN-17 inhibited the growth of Streptococcus gordonii and Fusobacterium nucleatum during in vitro biofilm formation and possessed low toxicity to hBMSCs cells. KN-17 also caused RAW264.7 macrophages to transform from M1 to M2 by downregulating pro-inflammatory and upregulating anti-inflammatory factors. It inhibited the NF-κB signaling pathway by reducing IκBα and P65 protein phosphorylation while promoting IκBα degradation and nuclear P65 translocation. KN-17 might be an efficacious prophylaxis against peri-implant inflammation.
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Plasminogen activator inhibitor-1 (PAI-1), a serine protease inhibitor, is constitutively produced by endothelial cells and plays a vital role in maintaining vascular homeostasis. Chronic periodontitis is an inflammatory disease characterized by bleeding of periodontal tissues that support the tooth. In this study, we aimed to determine the role of PAI-1 produced by endothelial cells in response to infections caused by the primary periodontal pathogen Porphyromonas gingivalis. We demonstrated that P. gingivalis infection resulted in significantly reduced PAI-1 levels in human endothelial cells. This reduction in PAI-1 levels could be attributed to the proteolysis of PAI-1 by P. gingivalis proteinases, especially lysine-specific gingipain-K (Kgp). We demonstrated the roles of these degradative enzymes in the endothelial cells using a Kgp-specific inhibitor and P. gingivalis gingipain-null mutants, in which the lack of the proteinases resulted in the absence of PAI-1 degradation. The degradation of PAI-1 by P. gingivalis induced a delayed wound healing response in endothelial cell layers via the low-density lipoprotein receptor-related protein. Our results collectively suggested that the proteolysis of PAI-1 in endothelial cells by gingipains of P. gingivalis might lead to the deregulation of endothelial homeostasis, thereby contributing to the permeabilization and dysfunction of the vascular endothelial barrier.
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Células Endoteliales , Porphyromonas gingivalis , Adhesinas Bacterianas/metabolismo , Cisteína Endopeptidasas/metabolismo , Cisteína Endopeptidasas/farmacología , Cisteína-Endopeptidasas Gingipaínas , Humanos , Inhibidor 1 de Activador Plasminogénico , Porphyromonas gingivalis/fisiología , Cicatrización de HeridasRESUMEN
Periodontitis is the most important oral disease causing human tooth loss. Although supragingival and subgingival scaling is the main strategy of periodontitis clinical treatments, drug treatment has an indispensable auxiliary role to some degree. Periodontitis medical treatment is divided into systemically administered treatments and local periodontally administered treatments. Compared with systemic administration, local administration can increase local drug concentrations, reduce dosages, and prolong action times while also improving patient compliance and avoiding possible adverse effects due to systemic administration responses. However, some studies show that minocycline ointment, a clinical local drug commonly used in periodontal pockets, has an unstable release rate; 80% of the drug is usually released within 2-3 days after pocket placement. This release is not conducive to controlling periodontal infection and may hinder the periodontal tissue repair and regeneration. Therefore, choosing a suitable carrier for minocycline hydrochloride is necessary to control its local release in periodontal tissue. Phase transition lysozyme (PTL) has been widely used in many studies and the development of macromolecular carrier material, and we selected PTL as the carrier for minocycline hydrochloride drugs because of its good biocompatibility, good drug-carrying capacity, and stable release. Due to its release characteristics and simple preparation, PTL is a promising carrier material.
Asunto(s)
Periodontitis Crónica , Fármacos Dermatológicos , Antibacterianos/uso terapéutico , Periodontitis Crónica/tratamiento farmacológico , Fármacos Dermatológicos/uso terapéutico , Humanos , Minociclina/uso terapéutico , Muramidasa/uso terapéutico , Bolsa Periodontal/tratamiento farmacológicoRESUMEN
In esthetic rehabilitation, methods used to enhance the margin quality have always been the focus and difficulty of improving the level of diagnosis and treatment, prevention and treatment of complications, and collaboration between clinicians and technicians. However, it is impeded by the ambiguous definition and classification of margin, unstandardized tooth preparation, manufacturing process of restoration, and lack of reliable means of checking the quantitative requirements of preparation or restoration. The digital technologies that are increasingly applied, such as intra-oral scanner, impression scanner, and computerized numerical control cutting machine, have strict requirements about margin quality. Failure of recognizing margins by these scanners will hinder the digital process of diagnosis and treatment. Even if these sharp and narrow margins are successfully scanned, they cannot be milled accurately. To overcome these problems, this article demonstrated the clear and complete definition of preparation margin and restoration margin, as well as their subclassifications, by analyzing the target restoration space from a geometric perspective. Practical approaches to measuring the margin width and inspecting the margin quality were proposed. The new and full understanding and proposal about preparation margin and restoration margin characterized by measurements will effectively support the thoroughly digitalized process of esthetic rehabilitation using porcelain in fixed prosthodontics, which is based on the guidance of values.
RESUMEN
Innate lymphoid cells (ILCs) are emerging as important players in inflammatory diseases. The oral mucosal barrier harbors all ILC subsets, but how these cells regulate the immune responses in periodontal ligament tissue during periodontitis remains undefined. Here, we show that total ILCs are markedly increased in periodontal ligament of periodontitis patients compared with healthy controls. Among them, ILC1s and ILC3s, particularly NKp44+ILC3 subset, are the predominant subsets accumulated in the periodontal ligament. Remarkably, ILC1s and ILC3s from periodontitis patients produce more IL-17A and IFN-γ than that from healthy controls. Collectively, our results highlight the role of ILCs in regulating oral immunity and periodontal ligament inflammation and provide insights into targeting ILCs for the treatment of periodontitis.