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BACKGROUND: Agenesis of third molar agenesis has a higher incidence than other tooth development anomalies. Previous research identified a potential correlation between third molar agenesis and specific craniofacial morphology; however, no systematic review and meta-analysis on this topic currently exists. OBJECTIVE: The objective of this systematic review and meta-analysis was to evaluate the association between third molar agenesis and craniofacial sagittal and vertical morphology. SEARCH METHODS: An electronic search was conducted on PubMed, Embase, Web of Science, and the Cochrane Library without restrictions on publication year or language; this was supplemented by the manual retrieval of relevant literature. SELECTION CRITERIA: Cross-sectional studies that compared craniofacial morphology using angular and linear measurements obtained from lateral cephalography between patients with third molar agenesis and those without were included. DATA COLLECTION AND ANALYSIS: The quality assessment of the enrolled articles was evaluated by the Joanna Briggs Institute critical appraisal tool. Meta-analysis and sensitivity analysis were performed by Review Manager software (The Cochrane Collaborative, version 5.4, Cochrane IMS). RESULTS: A total of seven studies were included. Meta-analysis demonstrated that the ANB (mean differences (MD) = -0.75, 95% CI: -1.31 to -0.19, P < 0.01), palate length (ANS-PNS, MD = -1.68, 95% CI: -2.24 to -1.11, P < 0.01), and mandibular length (Go-Pog, MD = -0.36, 95% CI: -0.59 to -0.13, P < 0.01) were smaller in patients with third molar agenesis. With regard to vertical craniofacial morphology, the mandibular plane angle (MP-FH; MD = -1.88, 95% CI: -3.45 to -0.31, P = 0.02), gonial angle (gonial angle; MD = -1.73, 95% CI: -2.69 to -0.77, P < 0.01) and lower face height (lower face heigh angle; MD = -1.36, 95% CI: -1.94 to -0.77, P < 0.01) were smaller in patients with third molar agenesis, indicating a flatter or brachyfacial skeletal pattern. CONCLUSIONS: The results of this study suggest that third molar agenesis maybe associated with a reduced maxillary length and a flatter mandible. However, these findings need to be interpreted with caution due to inconsistencies in the certainty of evidence. CLINICAL TRIAL REGISTRATION: PROSPERO (CRD42023448226).
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Maxilar , Tercer Molar , Humanos , Tercer Molar/diagnóstico por imagen , Tercer Molar/anomalías , Estudios Transversales , Mandíbula , Hueso PaladarRESUMEN
Ultraviolet Visible (UV-Vis) spectroscopy detection technology has been widely used in quantitative analysis for its advantages of rapid and non-destructive determination. However, the difference of optical hardware severely restricts the development of spectral technology. Model transfer is one of the effective methods to establish models on different instruments. Due to the high dimension and nonlinearity of spectral data, the existing methods cannot effectively extract the hidden differences in spectra of different spectrometers. Thus, based on the necessity of spectral calibration model transfer between the traditional large spectrometer and the micro-spectrometer, a novel model transfer method based on improved deep autoencoder is proposed to realize spectral reconstruction between different spectrometers. Firstly, two autoencoders are used to train the spectral data of the master and slave instrument, respectively. Then, the hidden variable constraint is added to enhance the feature representation of the autoencoder, which makes the two hidden variables equal. Combined with a Bayesian optimization algorithm for the objective function, the transfer accuracy coefficient is proposed to characterize the model transfer performance. The experimental results show that after model transfer, the spectrum of the slave spectrometer is basically coincident with the master spectrometer and the wavelength shift is eliminated. Compared with the two commonly used direct standardization (DS) and piecewise direct standardization (PDS) algorithms, the average transfer accuracy coefficient of the proposed method is improved by 45.11% and 22.38%, respectively, when there are nonlinear differences between different spectrometers.
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Bad sitting posture is harmful to human health. Intelligent sitting posture recognition algorithm can remind people to correct their sitting posture. In this paper, a sitting pressure image acquisition system was designed. With the system, we innovatively proposed a hip positioning algorithm based on hip templates. The average deviation of the algorithm for hip positioning is 1.306 pixels (the equivalent distance is 1.50 cm), and the proportion of the maximum positioning deviation less than three pixels is 94.1%. Statistics show that the algorithm works relatively well for different subjects. At the same time, the algorithm can not only effectively locate the hip position with a small rotation angle (0°-15°), but also has certain adaptability to the sitting posture with a medium rotation angle (15°-30°) or a large rotation angle (30°-45°). Using the hip positioning algorithm, the regional pressure values of the left hip, right hip and caudal vertebrae are effectively extracted as the features, and support vector machine (SVM) with polynomial kernel is used to classify the four types of sitting postures, with a classification accuracy of up to 89.6%.
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Postura , Sedestación , Cadera , Humanos , Receptores de Reconocimiento de Patrones , RotaciónRESUMEN
INTRODUCTION: Nonsurgical treatments that can prevent or reduce the extent of the mandibular excess at an early stage are desirable. A single botulinum toxin (BTX) injection into the unilateral and bilateral masseter can regulate mandibular contour and condylar cartilage. However, BTX injection is frequency dependent when used in facelifts. This study aimed to evaluate the effect of BTX injection into the bilateral masseter at different frequencies on the mandibular contour and condylar cartilage. METHODS: In the present study, 24 female Sprague Dawley rats (4 weeks old) were divided into 3 groups: control, single injection, and triple injection. Contour measurement of the mandible was carried out by radiographic imaging. Microcomputerized tomography was performed to determine the change in bone volume in the subchondral bone. Hematoxylin and eosin staining was used to observe the morphologic changes of condylar cartilage. Immunohistochemistry was performed to detect the expression level of biomechanically sensitive factors, including transforming growth factor-ß1, parathyroid hormone-related protein, SRY-box 9, and type II collagen. RESULTS: Bone volume and/or total volume, trabecular number, and trabecular thickness of the mineralized cartilage and subchondral bone significantly decreased in the triple injection group when compared with the single injection group. Mandibular contour also diminished after increased BTX injection frequencies. Chondrocyte proliferation ability and the expression levels of transforming growth factor-ß1, parathyroid hormone-related protein, SRY-box 9, and type II collagen significantly decreased in all BTX injection groups and more in the triple injection group. CONCLUSIONS: Morphologic changes of the mandible and condylar cartilage become more obvious after increased BTX injection frequencies, suggesting that multiple BTX injections into the masseter of patients may relieve the severity of mandibular deformity at an early stage.
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Toxinas Botulínicas , Cóndilo Mandibular/diagnóstico por imagen , Animales , Cartílago , Femenino , Humanos , Mandíbula/diagnóstico por imagen , Ratas , Ratas Sprague-DawleyRESUMEN
BACKGROUND: Hypoxia in the vicinity of bone defects triggers the osteogenic differentiation of precursor cells and promotes healing. The activation of STAT3 signaling in mesenchymal stem cells (MSCs) has similarly been reported to mediate bone regeneration. However, the interaction between hypoxia and STAT3 signaling in the osteogenic differentiation of precursor cells during bone defect healing is still unknown. METHODS: In this study, we assessed the impact of different durations of CoCl2-induced cellular hypoxia on the osteogenic differentiation of MSCs. Role of STAT3 signaling on hypoxia induced osteogenic differentiation was analyzed both in vitro and in vivo. The interaction between cellular hypoxia and STAT3 signaling in vivo was investigated in a mouse femoral bone defect model. RESULTS: The peak osteogenic differentiation and expression of vascular endothelial growth factor (VEGF) occurred after 3 days of hypoxia. Inhibiting STAT3 reversed this effect. Hypoxia enhanced the expression of hypoxia-inducible factor 1-alpha (HIF-1α) and STAT3 phosphorylation in MSCs. Histology and µ-CT results showed that CoCl2 treatment enhanced bone defect healing. Inhibiting STAT3 reduced this effect. Immunohistochemistry results showed that CoCl2 treatment enhanced Hif-1α, ALP and pSTAT3 expression in cells present in the bone defect area and that inhibiting STAT3 reduced this effect. CONCLUSIONS: The in vitro study revealed that the duration of hypoxia is crucial for osteogenic differentiation of precursor cells. The results from both the in vitro and in vivo studies show the role of STAT3 signaling in hypoxia-induced osteogenic differentiation of precursor cells and bone defect healing.
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Regeneración Ósea/genética , Células Madre Mesenquimatosas/metabolismo , Factor de Transcripción STAT3/genética , Transducción de Señal , Cicatrización de Heridas/genética , Fosfatasa Alcalina/genética , Fosfatasa Alcalina/metabolismo , Animales , Células de la Médula Ósea/citología , Células de la Médula Ósea/efectos de los fármacos , Células de la Médula Ósea/metabolismo , Diferenciación Celular , Hipoxia de la Célula/genética , Cobalto/farmacología , Fémur/citología , Fémur/metabolismo , Regulación de la Expresión Génica , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Ratones , Ratones Endogámicos C57BL , Osteoblastos/citología , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , Osteogénesis/genética , Fosforilación , Cultivo Primario de Células , Factor de Transcripción STAT3/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
Mesenchymal stem cells (MSCs) undergo osteogenic differentiation during bone defect healing. However, the role of JAK2/STAT3 in the osteogenic differentiation of MSCs and bone defect healing is still not fully understood. In this study, we aimed to analyze the effect of AG490, a JAK2-specific inhibitor, on MSCs proliferation and osteogenic differentiation as well as in bone defect healing. We used AG490 to inhibit the JAK2/STAT3 signaling in a mice bone marrow stromal cells (BMSCs) culture. AG490 inhibited BMSCs proliferation and osteogenic differentiation markers, i.e. Col1α, Alp and Ocn expression in mRNA and protein levels. Inhibition of JAK2 reduced ALP activity and matrix mineralization in BMSCs culture. Inhibition of JAK2 reduced phosphorylation of STAT3, AKT, P38, and JNK phosphorylation. Immunohistochemistry showed high numbers of pJAK2, pSTAT3 and ALP positive cells and AG490 reduced this effect in vivo. Histology and µ-computed tomography (CT) data showed that AG490 treatment inhibits bone regeneration and bone defect healing. Our results clearly showed the inhibitory effect of AG490 on proliferation and osteogenic differentiation of BMSCs, bone regeneration and bone defect healing. Moreover, AG490 inhibited phosphorylation of STAT3, P38, JNK and AKT. This suggests the possible role of JAK2/STAT3 signaling in hypoxia-induced osteogenic differentiation of MSCs and bone defect healing.
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Curación de Fractura/efectos de los fármacos , Janus Quinasa 2/antagonistas & inhibidores , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Factor de Transcripción STAT3/antagonistas & inhibidores , Transducción de Señal/efectos de los fármacos , Animales , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Janus Quinasa 2/metabolismo , Masculino , Células Madre Mesenquimatosas/metabolismo , Ratones , Ratones Endogámicos C57BL , Factor de Transcripción STAT3/metabolismo , Tirfostinos/farmacologíaRESUMEN
Mesenchymal stem cells homing and migration is a crucial step during bone fracture healing. Hypoxic environment in fracture site induces bone marrow mesenchymal stem cells (BMSCs) migration, but its mechanism remains unclear. Our previous study and studies by other groups have reported the involvement of signal transducer and activator of transcription 3 (STAT3) pathway in cell migration. However, the role of STAT3 pathway in hypoxia-induced cell migration is still unknown. In this study, we investigated the role of STAT3 signaling in hypoxia-induced BMSCs migration and osteogenic differentiation. BMSCs isolated from C57BL/6 male mice were cultured in the presence of cobalt chloride (CoCl2 ) to simulate intracellular hypoxia. Hypoxia enhanced BMSCs migration, and upregulated cell migration related gene expression, that is, metalloproteinase (MMP) 7, MMP9, and C-X-C motif chemokine receptor 4. Hypoxia enhanced the phosphorylation of STAT3, and cell migration related proteins: c-jun n-terminal kinase (JNK), focal of adhesion kinase (FAK), extracellular regulated protein kinases, and protein kinase B 1/2 (ERK1/2). Moreover, hypoxia enhanced expression of osteogenic differentiation marker. Inhibition of STAT3 suppressed the hypoxia-induced BMSCs migration, cell migration related signaling molecules phosphorylation, and osteogenic differentiation related gene expression. In conclusion, our result indicates that hypoxia-induced BMSCs migration and osteogenic differentiation is via STAT3 phosphorylation and involves the cooperative activity of the JNK, FAK, and MMP9 signaling pathways.
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Células Madre Mesenquimatosas/efectos de los fármacos , Factor de Transcripción STAT3/efectos de los fármacos , Animales , Células de la Médula Ósea/efectos de los fármacos , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Cobalto/farmacología , Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Hipoxia/metabolismo , Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , Masculino , Metaloproteinasa 7 de la Matriz/efectos de los fármacos , Metaloproteinasa 9 de la Matriz/efectos de los fármacos , Células Madre Mesenquimatosas/citología , Ratones , Ratones Endogámicos C57BL , Osteogénesis/genética , Fosforilación , Receptores CXCR4/efectos de los fármacos , Transducción de Señal/efectos de los fármacosRESUMEN
Interleukin-34 (IL-34) has been recently identified as a novel cytokine, substituting for the function of macrophage colony-stimulating factor (M-CSF), a pivotal osteoclastogenic factor involved in bone-related diseases (e.g., osteomyelitis of the jaws). However, the molecular mechanisms are not fully understood. This study aimed to explore the potential mechanism of IL-34 in receptor activator of NF-kB ligand (RANKL)-induced osteoclast formation. We found that IL-34 alone significantly maintained the survival of bone marrow macrophages (BMMs) and enhanced the expression of the osteoclast-related genes TRAP, Ctsk, and NFATc1, as well as TRAP-positive multinucleated cells combined with RANKL, which can be reversed by AG490. Conversely, AG490 did not affect the M-CSF-mediated osteoclastogenesis in the presence of RANKL. The protein expression of p-STAT3 in BMMs was enhanced by IL-34 combined with RANKL compared with RANKL alone, and AG490 inhibited the expression of p-SATA3 at protein level in the IL-34 plus RANKL group, resulting in significantly increased Smad7 expression. This study demonstrated for the first time that IL-34 may play a crucial role in RANKL-induced osteoclastogenesis by promoting the proliferation and differentiation of BMMs, stimulating p-STAT3 expression, and inhibiting the expression of Smad7 in the absence of M-CSF.
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Osteogénesis/efectos de los fármacos , Tirfostinos/farmacología , Animales , Médula Ósea/metabolismo , Células de la Médula Ósea/metabolismo , Diferenciación Celular/efectos de los fármacos , Interleucinas/metabolismo , Macrófagos/metabolismo , Ratones , FN-kappa B/metabolismo , Osteoclastos/efectos de los fármacos , Osteoclastos/metabolismo , Ligando RANK/metabolismo , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Enhanced osteoclast formation increases bone resorption, which triggers bone remodeling. Platelet-derived growth factor BB (PDGF-BB) enhances precursor cell homing, angiogenesis, and bone healing, and thereby could also treat osteoporosis. However, the effect of PDGF-BB on osteoclast formation is not fully understood. We investigated whether exogenous recombinant PDGF-BB directly affects osteoclast formation and osteoclast precursor cell chemotaxis. The murine monocyte-macrophage cell line RAW264.7 and bone-marrow-derived macrophages were cultured with recombinant mouse PDGF-BB with or without a platelet-derived growth factor receptor ß inhibitor (AG-1295) or a Janus kinase 2 inhibitor (AG-490) to analyze the effect on osteoclastogenesis in vitro. PDGF-BB with or without AG-490 or AG-1295 was locally administrated in the mandibular fracture of 16-week-old Sprague Dawley rats (n = 18) for 1-2 weeks to analyze the effect on osteoclastogenesis in vivo. The effect of the treatments on osteoclast formation, osteoclast precursor cell migration, and expression of osteoclastogenic signaling molecules was analyzed. PDGF-BB enhanced osteoclast formation both in vitro and in vivo, but AG-490 and AG-1295 inhibited this effect. PDGF-BB enhanced phosphorylation of extracellular-signal-regulated kinase 1/2 (ERK1/2), Akt, and signal transducer and activator of transcription 3 (STAT3) in RAW264.7 cells. AG-490 inhibited PDGF-BB-induced STAT3 phosphorylation. PDGF-BB enhanced RAW264.7 cell migration and gene expression of osteoclastogenic signaling molecules (i.e., nuclear factor of activated T cells 1, dendrocyte-expressed seven transmembrane protein, and B-cell lymphoma 2), and treatment with AG-1295, AG-490, or S3I-201 (a STAT3 inhibitor) reduced this effect. PDGF-BB enhanced osteoclast formation, osteoclast precursor cell chemotaxis, and phosphorylation of STAT3, Akt, and ERK1/2. but AG-1295 and AG-490 reduced this effect. These findings reflect the complexity of PDGF-BB in bone biology.
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Quimiotaxis/efectos de los fármacos , Osteoclastos/metabolismo , Proteínas Proto-Oncogénicas c-sis/farmacología , Ácidos Aminosalicílicos/farmacología , Animales , Becaplermina , Bencenosulfonatos/farmacología , Células Cultivadas , Quimiotaxis/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Macrófagos/citología , Macrófagos/efectos de los fármacos , Macrófagos/metabolismo , Masculino , Ratones , Osteoclastos/efectos de los fármacos , Osteogénesis/efectos de los fármacos , Osteogénesis/genética , Fosforilación/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Células RAW 264.7 , Ratas Sprague-Dawley , Factor de Transcripción STAT3/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Tirfostinos/farmacologíaRESUMEN
PURPOSE: The purpose of this study was to describe the application of computer-assisted navigation for the retrieval of accidentally displaced mandibular third molars. PATIENTS AND METHODS: All patients identified as having an accidentally displaced mandibular third molar or root fragment and presented to the authors' department from April 2013 through June 2015 were included in this prospective study. Retrieval of the displaced molar was performed in these patients under the guidance of computer-assisted navigation, in which a registered forceps was used to clamp and retrieve the molar. Postoperative complications were assessed for all patients. RESULTS: Twelve patients were included in this case series. Using computer-assisted navigation, the operation proceeded successfully in all patients. These patients displayed uneventful healing without postoperative complications. CONCLUSION: Computer-assisted navigation is a safe, straightforward, and minimally invasive treatment method that can be applied for the retrieval of accidentally displaced third molars. It is recommended as an intraoperative tool for the retrieval of teeth or tooth fragments displaced into areas that are difficult to access.
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Cirugía Asistida por Computador/métodos , Extracción Dental/métodos , Adolescente , Adulto , Femenino , Humanos , Masculino , Tercer Molar/diagnóstico por imagen , Tercer Molar/cirugía , Extracción Dental/efectos adversos , Raíz del Diente/diagnóstico por imagen , Raíz del Diente/cirugía , Adulto JovenRESUMEN
BACKGROUND: It has traditionally been difficult to create full-thickness defects in the mandibles of rodent animals because of dissimilar anatomic structures with humans, interference from teeth of jaws, and limited surgical access. To better mimic the cellular situation and the unique masticatory stresses in maxillofacial regions of humans, we developed an animal model of mandibular defects, in which rabbits were implanted with the beta-tricalcium phosphate/chitosan (ß-TCP/CS) scaffolds after a dental extraction and the creation of a full-thickness bone defect. METHODS: Seventy-two New Zealand rabbits underwent unilateral mandibular defect surgery in the premolar region and were randomly divided into three groups as follows: (1) The full-thickness bicortical defect with tooth extraction of the mandibular first premolar and implantation of bone marrow stromal cells/ß-TCP/CS scaffold graft (group G + E); (2) the bicortical defect, not treated with tooth extraction and implanted with the bone marrow stromal cells/ß-TCP/CS grafts (group G); and (3) the bicortical defects created in the same location in the negative control group, not treated with tooth extraction and graft implantation (group C). The defects in all groups were examined at 4 and 12 wk using mechanical tests, x-ray, and histology observation to determine the biomechanical stability, quantity, and quality of the newly formed bone. RESULTS: Group G + E displayed the largest amount of new bone formation, with high mechanical forces in compression and three-point bending tests, filled in the mandibular defects at 4 wk, and complete reconstruction of bony contours and bridging by 12 wk after implantation. Although similar mechanical forces and new bone formation were demonstrated by the normal healing specimens, the abnormal cases with periapical diseases of group G demonstrated less amount of new bone formation and smaller mechanical forces when compared with those of group G + E at 4 and 12 wk. In contrast, the defect without graft implantation in the negative control group (group C) failed to bridge itself and displayed fibrous tissue filled in the defects with the lowest mechanical forces at both 4 and 12 wk of implantation. CONCLUSIONS: A 10-mm diameter, full-thickness mandibular defect treated with tooth extraction of the first mandibular premolar can mimic the segmental jawbone defects and fulfill the requirements of a critical-size mandibular defect in rabbits. Furthermore, the new bone regeneration and biomechanical stability of the mandible can be promoted by extraction of the teeth located in the defect side, which demonstrated the potential of this model as a test bed for tissue-engineering grafts used in jawbone defects.
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Modelos Animales de Enfermedad , Traumatismos Mandibulares , Animales , Peso Corporal , Remodelación Ósea , Fuerza Compresiva , Ingestión de Alimentos , Masculino , Mandíbula/diagnóstico por imagen , Mandíbula/patología , Conejos , Radiografía , Distribución Aleatoria , Andamios del Tejido , Extracción DentalRESUMEN
Zinc is a crucial strategic metal resource. The concentration of cobalt ions in zinc refining solution significantly impacts the efficiency of zinc electrolysis production. The traditional method of detecting cobalt ions in zinc solution is time-consuming, labor-intensive and ineffective. However, optical detection offers the advantage of high efficiency and low cost, making it a potential replacement for the traditional method. In this study, the spectral curve of cobalt ions in zinc solution is detected by ultraviolet-visible (UV-Vis) spectrophotometry. Additionally, we propose a model for the concentration-absorbance relationship of cobalt ions in zinc solution based on discrete wavelet transform and extreme gradient boosting (DWT-XGBoost) algorithms. First, the spectral curve's information region is denoised by using Savitzky-Golay (S-G) smoothing. Then, the denoised spectra is utilized to extract features through discrete wavelet transform and principal component analysis. These features are used as inputs to the XGBoost model to establish prediction models for low and high cobalt ions in zinc solution. Bayesian optimization is implemented to adjust the model's hyperparameters, including learning rate, feature sampling ratio, to enhance the prediction performance. Finally, applying the model to zinc solution samples from a zinc smelter and compared with other state-of-the-art algorithms, the DWT-XGBoost algorithm exhibits the lowest RMSE, MAE and MAPE, with values of 0.034 mg/L, 0.025 mg/L, 6.983 % for low cobalt and with values of 0.231 mg/L, 0.067 mg/L and 0.472 % for high cobalt. The experimental results demonstrate that the DWT-XGBoost model exhibits significantly superior prediction performance.
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BACKGROUND: Chronic periodontitis triggers an increase in osteoclastogenesis, with glycolysis playing a crucial role in this process. Pyruvate kinase M2 (PKM2) is a critical enzyme involved in glycolysis and pyruvate metabolism. Yet, the precise function of PKM2 in osteoclasts and their formation remains unclear and requires further investigation. METHODS: Bioinformatics was used to investigate critical biological processes in osteoclastogenesis. In vitro, osteoclastogenesis was analyzed using tartrate-resistant acid phosphatase (TRAP) staining, phalloidin staining, quantitative realtime PCR (RT-qPCR), and Western blotting. Small interfering RNA (siRNA) of PKM2 and Shikonin, a specific inhibitor of PKM2, were used to verify the role of PKM2 in osteoclastogenesis. The mouse model of periodontitis was used to assess the effect of shikonin on bone loss. Analyses included micro computed tomography, immunohistochemistry, flow cytometry, TRAP staining and HE staining. RESULTS: Bioinformatic analysis revealed a significant impact of glycolysis and pyruvate metabolism on osteoclastogenesis. Inhibition of PKM2 leads to a significant reduction in osteoclastogenesis. In vitro, co-culture of the heat-killed Porphyromonas gingivalis significantly promoted osteoclastogenesis, concomitant with an increased PKM2 expression in osteoclasts. Shikonin weakened the promoting effect of porphyromonas gingivalis on osteoclastogenesis. In vivo experiments demonstrated that inhibition of PKM2 by shikonin alleviated bone loss induced by periodontitis, suppressed excessive osteoclastogenesis in alveolar bone, and reduced tissue inflammation to some extent. CONCLUSION: PKM2 inhibition by shikonin, a specific inhibitor of this enzyme, attenuated osteoclastogenesis and bone resorption in periodontitis. Shikonin appears to be a promising therapeutic agent for treating periodontitis.
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Naftoquinonas , Osteogénesis , Periodontitis , Ratones , Animales , Microtomografía por Rayos X , Osteoclastos , Periodontitis/tratamiento farmacológico , Periodontitis/metabolismo , Piruvatos/farmacologíaRESUMEN
In the last decade, the risk evaluation and the investment decision are among the most prominent issues of efficient project management. Especially, the innovative financial sources could have some specific risk appetite due to the increasing return of investment. Hence, it is important to uncover the risk factors of fintech investments and investigate the possible impacts with an integrated approach to the strategic priorities of fintech lending. Accordingly, this study aims to analyze a unique risk set and the strategic priorities of fintech lending for clean energy projects. The most important contributions to the literature can be listed as to construct an impact-direction map of risk-based strategic priorities for fintech lending in clean energy projects and to measure the possible influences by using a hybrid decision making system with golden cut and bipolar q-rung orthopair fuzzy sets. The extension of multi stepwise weight assessment ratio analysis (M-SWARA) is applied for weighting the risk factors of fintech lending. The extension of elimination and choice translating reality (ELECTRE) is employed for constructing and ranking the risk-based strategic priorities for clean energy projects. In this process, data is obtained with the evaluation of three different decision makers. The main superiority of the proposed model by comparing with the previous models in the literature is that significant improvements are made to the classical SWARA method so that a new technique is created with the name of M-SWARA. Hence, the causality analysis between the criteria can also be performed in this proposed model. The findings demonstrate that security is the most critical risk factor for fintech lending system. Moreover, volume is found as the most critical risk-based strategy for fintech lending. In this context, fintech companies need to take some precautions to effectively manage the security risk. For this purpose, the main risks to information technologies need to be clearly identified. Next, control steps should be put for these risks to be managed properly. Furthermore, it has been determined that the most appropriate strategy to increase the success of the fintech lending system is to increase the number of financiers integrated into the system. Within this framework, the platform should be secure and profitable to persuade financiers.
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This study examines the effect of the lateral bone cut end (LBCE) on the pattern of lingual split during bilateral sagittal split osteotomy (BSSO) in patients with skeletal class III malocclusion. A case-control study according to the pattern of the sagittal split osteotomy (SSO) lingual split line was conducted in patients who underwent BSSO. The primary predictor variable was the ratio of the LBCE. The primary outcome variable was the type of lingual fracture line classified according to the lingual split scale (LSS). Other variables included patients' weight, sex, age, left and right sides of the mandible, and experience of the surgeon. Logistic regression analysis or the chi-squared test was performed to determine the effect of these variables on various types of lingual fracture line. The significance level was 95% (p < 0.05). There were 271 patients enrolled in this study. The SSO lingual split lines were divided into LSS1 (329/542), LSS2 (82/542), LSS3 (93/542), and LSS4 (38/542) splits. Logistic regression analysis showed that the LSS3 split was more likely to appear when the LBCE was closer to the lingual side (p = 0.0017). The age of patients significantly affected the possibilities of LSS2 (p = 0.0008) and LSS3 (p = 0.0023) splits. A LBCE close to the lingual side was an inducer for the formation of a LSS3 split in patients with skeletal class III malocclusion during BSSO. The age of the patient also affected the possibility of LSS2 and LSS3 splits.
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Fracturas Óseas , Maloclusión de Angle Clase III , Enfermedades de la Lengua , Humanos , Estudios de Casos y Controles , Osteotomía Sagital de Rama Mandibular , Maloclusión de Angle Clase III/cirugía , Mandíbula/cirugía , LenguaRESUMEN
OBJECTIVE: The preoperative inclination angle of mandibular incisors was crucial for surgical and postoperative stability while the effect of proclined mandibular incisors on skeletal stability has not been investigated. This study aimed to evaluate the effects of differences in presurgical mandibular incisor inclination on skeletal stability after orthognathic surgery in patients with skeletal Class III malocclusion. METHODS: A retrospective cohort study of 80 consecutive patients with skeletal Class III malocclusion who underwent bimaxillary orthognathic surgery was conducted. According to incisor mandibular plane angle (IMPA), patients were divided into 3 groups: retroclined inclination (IMPA < 87°), normal inclination (87° ≤ IMPA < 93°) and proclined inclination (IMPA ≥ 93°). Preoperative characteristics, surgical changes and postoperative stability were compared based on lateral cephalograms obtained 1 week before surgery (T0), 1 week after surgery (T1), and at 6 to 12 months postoperatively (T2). RESULTS: The mandible demonstrated a forward and upward relapse in all three groups. No significant differences in skeletal relapse were observed in the 3 groups of patients. However, the proclined inclination group showed a negative overbite tendency postoperatively compared with the other two groups and a clinically significant mandibular relapse pattern. Proclined IMPA both pre- and postoperatively was correlated with mandibular relapse. CONCLUSION: Sufficient presurgical mandibular incisor decompensation was of crucial importance for the maintenance of skeletal stability in patients with skeletal Class III malocclusion who subsequently underwent orthognathic surgery.
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Endochondral ossification is a complex process involving chondrogenesis and osteogenesis regulated by many hormones and growth factors. Parathyroid hormone (PTH), one of the key hormones regulating bone metabolism, promotes osteoblast differentiation and osteogenesis by intermittent administration, whereas continuous PTH administration inhibits bone formation. However, the effects of PTH on chondrocyte proliferation and differentiation are still unclear. In this study, intermittent PTH administration presented enhanced effects on condylar chondrocyte differentiation and bone formation, as demonstrated by increased mineral nodule formation and alkaline phosphatase (ALP) activity, up-regulated runt-related transcription factor 2 (RUNX2), ALP, collagen type X (COL10a1), collagen type I (COL1a1), osteocalcin (OCN), bone sialoprotein (BSP), bone morphogenetic protein 2 (BMP2) and osterix (OSX) mRNA and/or protein expression. On the contrary, continuous PTH administration promoted condylar chondrocyte proliferation and suppressed its differentiation, as demonstrated by up-regulated collagen type II (COL2a1) mRNA expression, reduced mineral nodule formation and down-regulated expression of the mRNAs and/or proteins mentioned above. Our data suggest that PTH can regulate condylar chondrocyte proliferation and differentiation, depending on the type of PTH administration. These results provide new insight into the effects of PTH on condylar chondrocytes and new evidence for using local PTH administration to cure mandibular asymmetry.
Asunto(s)
Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Condrocitos/efectos de los fármacos , Cóndilo Mandibular/citología , Cóndilo Mandibular/crecimiento & desarrollo , Osteogénesis/efectos de los fármacos , Hormona Paratiroidea/administración & dosificación , Animales , Proteína Morfogenética Ósea 2/metabolismo , Condrocitos/citología , Colágeno Tipo II/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Femenino , Cóndilo Mandibular/metabolismo , Osteopontina/metabolismo , Ratas , Ratas Sprague-DawleyRESUMEN
One of the most prominent characteristics of bisphosphonate-related osteonecrosis of the jaw(BRONJ) is its site-specificity. Osteonecrosis tends to occur specifically in maxillofacial bones, in spite of a systemic administration of the medicine. Previous studies suggested rich blood supply and fast bone turnover might be reasons for BRONJ. Yet, a sound scientific basis explaining its occurrence is still lacking. The present study aimed to explore the role of Porphyromonas gingivalis (P. gingivalis), an important oral pathogen, on the site-specificity of bisphosphonate-induced osteonecrosis and to elucidate its underlying mechanism. Mice were intraperitoneally injected with zoledronic acid (ZA) or saline for 3 weeks. In the third week, the right mandibular first molars were extracted and circular bone defects with a diameter of 1 mm were created in right femurs. After the operation, drug administration was continued, and P. gingivalis suspension was applied to the oral cavities and femur defects. The mice were killed after four or eight weeks postoperatively. The right mandibles and femurs were harvested for micro-CT and histological analyses. A poor healing of bone defects of both jaws and femurs was noted in mice injected with both ZA and P. gingivalis. Micro-CT analysis showed a decreased bone volume, and histological staining showed an increased number of empty osteocyte lacunae, a decreased collagen regeneration, an increased inflammatory infiltration and a decreased number of osteoclasts. In addition, the left femurs were collected for isolation of osteoclast precursors (OCPs). The osteoclastogenesis potential of OCPs was analyzed in vitro. OCPs extracted from mice of ZA-treated groups were shown to have a lower osteoclast differentiation potential and the expression level of related genes and proteins was declined. In conclusion, we established a mouse model of bisphosphonate-related osteonecrosis of both the jaw and femur. P. gingivalis could inhibit the healing of femur defects under the administration of ZA. These findings suggest that P. gingivalis in the oral cavity might be one of the steering compounds for BRONJ to occur.
Asunto(s)
Osteonecrosis de los Maxilares Asociada a Difosfonatos , Animales , Osteonecrosis de los Maxilares Asociada a Difosfonatos/tratamiento farmacológico , Osteonecrosis de los Maxilares Asociada a Difosfonatos/patología , Difosfonatos/efectos adversos , Fémur/patología , Imidazoles/farmacología , Ratones , Porphyromonas gingivalis , Ácido Zoledrónico/uso terapéuticoRESUMEN
PURPOSE: To evaluate and compare the influence of different types of mandibular reconstruction on health-related quality of life (HR-QoL) of nonrecurrence patients. PATIENTS AND METHODS: We recruited 252 patients who underwent mandibular reconstruction between 1994 and 2007 for this cross-sectional study. They were classified into groups based on reconstruction technique: free bone graft (FBG) group, particulate bone cancellous marrow graft (PBCMG) group, reconstruction plate (RP) group, and microvascular free flap group. The University of Washington Head and Neck Quality of Life Questionnaire and 5 supplemental domains regarding the donor sites were used to evaluate and compare HR-QoL among the groups. RESULTS: The outcomes of the University of Washington Head and Neck Quality of Life Questionnaire differed significantly among the groups (P < .0001). The results of the additional donor site domains also differed greatly among the groups (P < .0001). Appearance, chewing, activity, appearance-donor site, and function-donor site were the domains that were most frequently chosen by the patients as the most important issues. Most of the patients rated their HR-QoL as somewhat better compared with their experience the month before they underwent reconstruction. The HR-QoL and overall quality of life (QoL) during the past 7 days were rated as very good in the FBG group and PBCMG group and good in the RP group and microvascular free flap group. CONCLUSIONS: HR-QoL of patients in the FBG and PBCMG groups did not differ significantly with regard to any of the domains, and these 2 groups consistently had the highest mean scores. Both groups differed significantly from the RP group, which tended to report the lowest mean scores for the domains.
Asunto(s)
Mandíbula/cirugía , Neoplasias Mandibulares/cirugía , Procedimientos de Cirugía Plástica/psicología , Calidad de Vida , Adolescente , Adulto , Anciano , Trasplante Óseo , Niño , Femenino , Colgajos Tisulares Libres , Estado de Salud , Humanos , Masculino , Enfermedades Mandibulares/cirugía , Persona de Mediana Edad , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Recent study established the role of integrins in keratinocyte growth factor (KGF)-induced oral epithelial adhesion and rete peg elongation. However, how extracellular matrix (ECM) remodeling cooperates with the increased epithelial adhesion during rete peg elongation has yet to be determined. Podosomes are cell-matrix contact structures that combine several abilities, including adhesion and matrix degradation. In the present study, we identified podosome formation at the ventral side of human immortalized oral epithelial cells (HIOECs) upon KGF treatment. Moreover, podosomal components including integrin α6ï¼ß4ï¼α3ï¼ß1 and MMP14 colocalized with the F-actin-cortactin complex and matrix degradation assays demonstrated the ability of the F-actin-cortactin complex to degrade matrix. Inhibition both of integrin subunits ß4 and ß1 with specific blocking antibodies and inhibition of Erk1/2 abrogated the KGF-induced podosome formation. Notably, knockdown of integrin subunits ß4 and ß1 with specific small interfering RNA (siRNA) downregulated the phosphorylation levels of Erk1/2. In contrast, inhibition of both Erk1/2 could upregulate the expression of integrin subunits ß4 and ß1. These results demonstrate that KGF induces podosome formation via integrin-Erk1/2 signaling in HIOECs, suggesting a novel mechanism by which integrins enhance oral epithelial adhesion and rete peg elongation.