RESUMO
Stress granules (SGs) are transient ribonucleoprotein (RNP) aggregates that form during cellular stress and are increasingly implicated in human neurodegeneration. To study the proteome and compositional diversity of SGs in different cell types and in the context of neurodegeneration-linked mutations, we used ascorbate peroxidase (APEX) proximity labeling, mass spectrometry, and immunofluorescence to identify â¼150 previously unknown human SG components. A highly integrated, pre-existing SG protein interaction network in unstressed cells facilitates rapid coalescence into larger SGs. Approximately 20% of SG diversity is stress or cell-type dependent, with neuronal SGs displaying a particularly complex repertoire of proteins enriched in chaperones and autophagy factors. Strengthening the link between SGs and neurodegeneration, we demonstrate aberrant dynamics, composition, and subcellular distribution of SGs in cells from amyotrophic lateral sclerosis (ALS) patients. Using three Drosophila ALS/FTD models, we identify SG-associated modifiers of neurotoxicity in vivo. Altogether, our results highlight SG proteins as central to understanding and ultimately targeting neurodegeneration.
Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Grânulos Citoplasmáticos/metabolismo , Mapas de Interação de Proteínas , Ribonucleoproteínas/metabolismo , Estresse Fisiológico , Animais , Drosophila melanogaster , Células HEK293 , Células HeLa , Humanos , Neurônios/metabolismo , Transporte ProteicoRESUMO
Despite being the frontline therapy for type 2 diabetes, the mechanisms of action of the biguanide drug metformin are still being discovered. In particular, the detailed molecular interplays between the AMPK and the mTORC1 pathway in the hepatic benefits of metformin are still ill defined. Metformin-dependent activation of AMPK classically inhibits mTORC1 via TSC/RHEB, but several lines of evidence suggest additional mechanisms at play in metformin inhibition of mTORC1. Here we investigated the role of direct AMPK-mediated serine phosphorylation of RAPTOR in a new RaptorAA mouse model, in which AMPK phospho-serine sites Ser722 and Ser792 of RAPTOR were mutated to alanine. Metformin treatment of primary hepatocytes and intact murine liver requires AMPK regulation of both RAPTOR and TSC2 to fully inhibit mTORC1, and this regulation is critical for both the translational and transcriptional response to metformin. Transcriptionally, AMPK and mTORC1 were both important for regulation of anabolic metabolism and inflammatory programs triggered by metformin treatment. The hepatic transcriptional response in mice on high-fat diet treated with metformin was largely ablated by AMPK deficiency under the conditions examined, indicating the essential role of this kinase and its targets in metformin action in vivo.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Metformina/farmacologia , Proteína Regulatória Associada a mTOR/genética , Transdução de Sinais/efeitos dos fármacos , Animais , Diabetes Mellitus Tipo 2/tratamento farmacológico , Modelos Animais de Doenças , Técnicas de Introdução de Genes , Genótipo , Hipoglicemiantes/farmacologia , Inflamação , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Metabolismo/efeitos dos fármacos , Metformina/uso terapêutico , Camundongos , Fosforilação/efeitos dos fármacos , Proteína Regulatória Associada a mTOR/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Proteína 2 do Complexo Esclerose Tuberosa/genética , Proteína 2 do Complexo Esclerose Tuberosa/metabolismoRESUMO
Advanced glycation end products (AGEs) are a diverse range of compounds that are formed when free amino groups of proteins, lipids, and nucleic acids are carbonylated by reactive carbonyl species or glycosylated by reducing sugars. Hyperglycemia in patients with diabetes can cause an overabundance of AGEs. Excess AGEs are generally acknowledged as major contributing factors to the development of diabetic complications because of their ability to break down the extracellular matrix directly and initiate intracellular signaling pathways by binding to the receptor for advanced glycation end products (RAGE). Inflammation and oxidative stress are the two most well-defined pathophysiological states induced by the AGE-RAGE interaction. In addition to oxidative stress, AGEs can also inhibit antioxidative systems and disturb iron homeostasis, all of which may induce ferroptosis. Ferroptosis is a newly identified contributor to diabetic complications. This review outlines the formation of AGEs in individuals with diabetes, explores the oxidative damage resulting from downstream reactions of the AGE-RAGE axis, and proposes a novel connection between AGEs and the ferroptosis pathway. This study introduces the concept of a vicious cycle involving AGEs, oxidative stress, and ferroptosis in the development of diabetic complications.
Assuntos
Complicações do Diabetes , Ferroptose , Produtos Finais de Glicação Avançada , Estresse Oxidativo , Espécies Reativas de Oxigênio , Receptor para Produtos Finais de Glicação Avançada , Humanos , Produtos Finais de Glicação Avançada/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Complicações do Diabetes/metabolismo , Animais , Receptor para Produtos Finais de Glicação Avançada/metabolismo , Transdução de SinaisRESUMO
The effective regeneration of large bone defects via bone tissue engineering is challenging due to the difficulty in creating an osteogenic microenvironment. Inspired by the fibrillar architecture of the natural extracellular matrix, we developed a nanoscale bioengineering strategy to produce bone fibril-like composite scaffolds with enhanced osteogenic capability. To activate the surface for biofunctionalization, self-adaptive ridge-like nanolamellae were constructed on poly(ε-caprolactone) (PCL) electrospinning scaffolds via surface-directed epitaxial crystallization. This unique nanotopography with a markedly increased specific surface area offered abundant nucleation sites for Ca2+ recruitment, leading to a 5-fold greater deposition weight of hydroxyapatite than that of the pristine PCL scaffold under stimulated physiological conditions. Bone marrow mesenchymal stem cells (BMSCs) cultured on bone fibril-like scaffolds exhibited enhanced adhesion, proliferation, and osteogenic differentiation in vitro. In a rat calvarial defect model, the bone fibril-like scaffold significantly accelerated bone regeneration, as evidenced by micro-CT, histological histological and immunofluorescence staining. This work provides the way for recapitulating the osteogenic microenvironment in tissue-engineered scaffolds for bone repair.
Assuntos
Regeneração Óssea , Células-Tronco Mesenquimais , Osteogênese , Poliésteres , Engenharia Tecidual , Alicerces Teciduais , Animais , Alicerces Teciduais/química , Ratos , Regeneração Óssea/efeitos dos fármacos , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Osteogênese/fisiologia , Engenharia Tecidual/métodos , Poliésteres/química , Diferenciação Celular , Ratos Sprague-Dawley , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Células Cultivadas , Proliferação de Células , Crânio/lesões , Crânio/patologia , Durapatita/química , Durapatita/farmacologiaRESUMO
BACKGROUND: Dento-maxillofacial deformities are common problems. Orthodontic-orthognathic surgery is the primary treatment but accurate diagnosis and careful surgical planning are essential for optimum outcomes. This study aimed to establish and verify a machine learning-based decision support system for treatment of dento-maxillofacial malformations. METHODS: Patients (n = 574) with dento-maxillofacial deformities undergoing spiral CT during January 2015 to August 2020 were enrolled to train diagnostic models based on five different machine learning algorithms; the diagnostic performances were compared with expert diagnoses. Accuracy, sensitivity, specificity, and area under the curve (AUC) were calculated. The adaptive artificial bee colony algorithm was employed to formulate the orthognathic surgical plan, and subsequently evaluated by maxillofacial surgeons in a cohort of 50 patients. The objective evaluation included the difference in bone position between the artificial intelligence (AI) generated and actual surgical plans for the patient, along with discrepancies in postoperative cephalometric analysis outcomes. RESULTS: The binary relevance extreme gradient boosting model performed best, with diagnostic success rates > 90% for six different kinds of dento-maxillofacial deformities; the exception was maxillary overdevelopment (89.27%). AUC was > 0.88 for all diagnostic types. Median score for the surgical plans was 9, and was improved after human-computer interaction. There was no statistically significant difference between the actual and AI- groups. CONCLUSIONS: Machine learning algorithms are effective for diagnosis and surgical planning of dento-maxillofacial deformities and help improve diagnostic efficiency, especially in lower medical centers.
Assuntos
Anormalidades Maxilofaciais , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Humanos , Inteligência Artificial , Aprendizado de Máquina , Anormalidades Maxilofaciais/cirurgia , AlgoritmosRESUMO
Integrating a biomimetic extracellular matrix to improve the microenvironment of 3D printing scaffolds is an emerging strategy for bone substitute design. Here, a "soft-hard" bone implant (BM-g-DPCL) consisting of a bioactive matrix chemically integrated on a polydopamine (PDA)-coated porous gradient scaffold by polyphenol groups is constructed. The PDA-coated "hard" scaffolds promoted Ca2+ chelation and mineral deposition; the "soft" bioactive matrix is beneficial to the migration, proliferation, and osteogenic differentiation of stem cells in vitro, accelerated endogenous stem cell recruitment, and initiated rapid angiogenesis in vivo. The results of the rabbit cranial defect model (Φ = 10 mm) confirmed that BM-g-DPCL promoted the integration between bone tissue and implant and induced the deposition of bone matrix. Proteomics confirmed that cytokine adhesion, biomineralization, rapid vascularization, and extracellular matrix formation are major factors that accelerate bone defect healing. This strategy of highly chemically bonded soft-hard components guided the construction of the bioactive regenerative scaffold.
Assuntos
Osteogênese , Alicerces Teciduais , Animais , Coelhos , Porosidade , Biomimética , Remodelação ÓsseaRESUMO
Antibiotic multiresistance (AMR) has emerged as a major threat to human health as millions of people die from AMR-related problems every year. As has been witnessed during the global COVID-19 pandemic, the significantly increased demand for antibiotics has aggravated the issue of AMR. Therefore, there is an urgent need to find ways to alleviate it. Tetrahedral framework nucleic acids (tFNAs) are novel nanomaterials that are often used as drug delivery platforms because of their structural diversity. This study formed a tFNAs-antibiotic compound (TAC) which has a strong growth inhibitory effect on Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA) in vitro owing to the increased absorption of antibiotics by bacteria and improved drug movement across cell membranes. We established a mouse model of systemic peritonitis and local wound infections. The TAC exhibited good biosafety and improved the survival rate of severely infected mice, promoting the healing of local infections. In addition to the better transport of antibiotics to the target, the TAC may also enhance immunity by regulating the differentiation of M1 and M2 macrophages, providing a new option for the treatment of infections.
Assuntos
COVID-19 , Staphylococcus aureus Resistente à Meticilina , Ácidos Nucleicos , Infecções Estafilocócicas , Humanos , Camundongos , Animais , Preparações Farmacêuticas , Ácidos Nucleicos/uso terapêutico , Pandemias , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologiaRESUMO
INTRODUCTION: Osteoporosis invariably manifests as loss of bone, which is replaced by adipose tissue; this can easily lead to fractures, accompanied by delayed and poor healing. Adiponectin (APN) balances osteogenesis and adipogenesis in bone marrow mesenchymal stem cells (BMSCs). Therefore, this study explored whether adiponectin promotes bone fracture healing by regulating the balance between osteogenesis and adipogenesis. MATERIALS AND METHODS: We used adenovirus overexpression vectors carrying APN (Ad-APN-GFP) to treat ovariectomized (OVX) mouse BMSCs and osteoporotic bone fractures to investigate the role of APN in bone microenvironment metabolism in osteoporotic fractures. We subsequently established an OVX mice and bone fracture model using Ad-APN-GFP treatment to investigate whether APN could promote bone fracture healing in osteoporotic mice. RESULTS: The experimental results showed that APN is a critical molecule in diverse differentiation directions in OVX mouse BMSCs, with pro-osteogenesis and anti-adipogenesis properties. Importantly, our study revealed that Ad-APN-GFP treatment facilitates bone generation and healing around the osteoporotic fracture ends. Moreover, we identified that Sirt1 and Wnt signaling were closely related to the pro-osteogenesis and anti-adipogenesis commitment of APN in OVX mouse BMSCs and femoral tissues. CONCLUSION: We demonstrated that APN overexpression facilitates bone fracture healing in osteoporosis. Furthermore, APN overexpression promoted bone formation in OVX mouse BMSCs and bone fracture ends by regulating the balance between osteogenesis and adipogenesis both in vitro and in vivo.
Assuntos
Fraturas Ósseas , Osteoporose , Camundongos , Animais , Osteogênese , Adiponectina/genética , Consolidação da Fratura , Diferenciação Celular , Osteoporose/metabolismoRESUMO
The long noncoding RNA (lncR) ANRIL in the human genome is an established genetic risk factor for atherosclerosis, periodontitis, diabetes, and cancer. However, the regulatory role of lncR-ANRIL in bone and adipose tissue metabolism remains unclear. To elucidate the function of lncRNA ANRIL in a mouse model, we investigated its ortholog, AK148321 (referred to as lncR-APDC), located on chr4 of the mouse genome, which is hypothesized to have similar biological functions to ANRIL. We initially revealed that lncR-APDC in mouse bone marrow cells (BMSCs) and lncR-ANRIL in human osteoblasts (hFOBs) are both increased during early osteogenesis. Subsequently, we examined the osteogenesis, adipogenesis, osteoclastogenesis function with lncR-APDC deletion/overexpression cell models. In vivo, we compared the phenotypic differences in bone and adipose tissue between APDC-KO and wild-type mice. Our findings demonstrated that lncR-APDC deficiency impaired osteogenesis while promoting adipogenesis and osteoclastogenesis. Conversely, the overexpression of lncR-APDC stimulated osteogenesis, but impaired adipogenesis and osteoclastogenesis. Furthermore, KDM6B was downregulated with lncR-APDC deficiency and upregulated with overexpression. Through binding-site analysis, we identified miR-99a as a potential target of lncR-APDC. The results suggest that lncR-APDC exerts its osteogenic function via miR-99a/KDM6B/Hox pathways. Additionally, osteoclasto-osteogenic imbalance was mediated by lncR-APDC through MAPK/p38 and TLR4/MyD88 activation. These findings highlight the pivotal role of lncR-APDC as a key regulator in bone and fat tissue metabolism. It shows potential therapeutic for addressing imbalances in osteogenesis, adipogenesis, and osteoclastogenesis.
Assuntos
MicroRNAs , RNA Longo não Codificante , Humanos , Camundongos , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Osso e Ossos/metabolismo , Osteogênese/genética , Tecido Adiposo/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Histona Desmetilases com o Domínio JumonjiRESUMO
BACKGROUND: Digital splints are indispensable in orthognathic surgery. However, the present design process of splints is time-consuming and has low reproducibility. To solve these problems, an algorithm for artificial intelligent splints has been developed in this study, making the automatic design of splints accessible. METHODS: Firstly, the algorithm and program of the artificial intelligence splint were created. Then a total of 54 patients with skeletal class III malocclusion were included in this study from 2018 to 2020. Pre and postoperative radiographic examinations were performed. The cephalometric measurements were recorded and the difference between virtual simulation and postoperative images was measured. The time cost and differences between artificial intelligent splints and digital splints were analyzed through both model surgery and radiographic images. RESULTS: The results showed that the efficiency of designing splints is significantly improved. And the mean difference between artificial intelligent splints and digital splints was <0.15 mm in model surgery. Meanwhile, there was no significant difference between the artificial intelligent splints and digital splints in radiological image analysis. CONCLUSIONS: In conclusion, compared with digital splints, artificial intelligent splints could save time for preoperative design while ensuring accuracy. The authors believed that it is conducive to the presurgical design of orthognathic surgery.
Assuntos
Má Oclusão Classe III de Angle , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Cirurgia Assistida por Computador , Humanos , Contenções , Procedimentos Cirúrgicos Ortognáticos/métodos , Inteligência Artificial , Reprodutibilidade dos Testes , Má Oclusão Classe III de Angle/cirurgia , Cirurgia Assistida por Computador/métodosRESUMO
BACKGROUND: Reduction malarplasty is one of the most common aesthetic procedures to improve a wide bizygomatic width and a prominent zygomatic body. Although there are various kinds of modifications, any method is imperfect, while some complications may occur. The purpose of this review was to compare kinds of complications of reduction malarplasty to provide certain suggestions for clinical application. METHODS: A comprehensive computerized search of scientific literature was performed via the PubMed, Web of Science, and Library of Congress databases, involved in articles from January 1st, 1983 to February 28th, 2022. The outcomes were extracted and analyzed by 3 independent authors, including patient demographics, diagnoses, surgical techniques, postoperative outcomes, and complications. RESULTS: A total of 29 studies covering 6611 patients were included according to the inclusion and exclusion criteria. The L-shaped osteotomy may obtain a better effect when someone has both zygomatic body and arch protrusion. In the view of complications, our conclusion suggested that L-shaped osteotomy without bony resection reduced the zygomatic complex effectively with the lowest incidence of postoperative complications (0.02%). But the amount of bone resection is limited. If increasing bone resection is necessary, L-shaped osteotomy with long arm bony resection and L-shaped osteotomy with short arm bony resection are both preferable choices with lowest incidence of structural and functional complications, respectively. CONCLUSION: L-shaped osteotomy may obtain a better effect when a patient has both zygomatic body and arch protrusion. L-shaped osteotomy without bony resection reduced the zygomatic complex effectively with the lowest incidence of postoperative complications. LEVEL OF EVIDENCE III: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Procedimentos de Cirurgia Plástica , Zigoma , Humanos , Zigoma/cirurgia , Procedimentos de Cirurgia Plástica/efeitos adversos , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/cirurgia , Osteotomia/efeitos adversos , Osteotomia/métodos , Estética , Resultado do TratamentoRESUMO
PURPOSE: The surgical condylar displacement often resulted in relapse and serious symptoms of temporomandibular joint disorders (TMD) after orthognathic surgery. To minimize the displacement, numerous techniques have been proposed. To verify their accuracy in positioning and effectiveness in preventing post-operative TMD and relapse, we reviewed the literature related to intraoperative condylar positioning techniques on the mandible in this study. METHODS: The literature on condylar positioning techniques was reviewed with two charts, including the non-computer-assisted and the computer-assisted positioning methods. The pre- and post-operative alterations of condyles, the post-operative temporomandibular joint (TMJ) function and surgical relapse were analysed regarding the techniques. The clinical usage and characteristics were reviewed as well. RESULTS: A total of 22 articles, including 907 patients, have been reported since 2001. Nearly all methods reach a considerable positioning accuracy within the range of 1-2 mm and 1-2° from the pre-operative position. We ranked the accuracy of the methods from high to low: CAD/CAM CPDs > CAD/CAM titanium plate positioning > manual positioning > computer-assisted navigation systems > imaging positioning systems. Most skeletal class II and class III patients achieved great occlusion and had no TMJ dysfunction or relapse after condylar positioning. CONCLUSIONS: Both the non-computer-assisted and computer-assisted condylar positioning techniques reach considerable accuracy in locating the pre-operative condyle position and preventing TMJ dysfunction and surgical relapse. Different levels of surgeons and cases can benefit from multiple suggested positioning methods. Further research with large samples and long-term follow-up is worth looking forward to upgrading the current methods, improving the clinical utility and developing new positioning techniques.
Assuntos
Cirurgia Ortognática , Transtornos da Articulação Temporomandibular , Humanos , Mandíbula/cirurgia , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/cirurgia , Recidiva , Articulação Temporomandibular/cirurgia , Transtornos da Articulação Temporomandibular/cirurgia , TitânioRESUMO
PURPOSE: To investigate current Computer-Aided Design and Computer-Aided Manufacturing (CAD/CAM) technologies applied in the treatment of dentofacial deformities secondary to condylar osteochondroma and introduce a modified method with additional pre-bent titanium miniplates to improve the accuracy of operation. METHODS: Literature review about the application of CAD/CAM in the treatment of condylar osteochondroma and secondary dentofacial deformities was conducted. And 8 patients with condylar osteochondroma and secondary dentofacial deformities were treated by the CAD/CAM cutting and drilling surgical guides as well as pre-bent titanium miniplates. Pre- and post-operative 3D-cephalometric measurement were recorded and the difference between virtual simulation and postoperative modeling images was measured. Follow-up and radiographic examinations were performed. RESULTS: A total of 17 studies (including 216 patients) about the application of CAD/CAM in the treatment of dentofacial deformities secondary to condylar osteochondroma have been reported since 2010, including the 8 present patients. In our study, all patients were satisfied with the surgical outcome, without obvious relapse or evidence of temporomandibular joint disorder or other complications during follow-up; all patients avoided condylar reconstruction and sagittal split of ramus osteotomy on the ipsilateral mandible side. Comparison between simulated plans and actual postoperative outcomes showed surgical simulation plan was accurately transferred to the actual surgery. CONCLUSIONS: The application of CAD/CAM cutting and drilling guides as well as pre-bent titanium plates could achieve more accurate and favorable outcomes, improving the clinical planning and surgical execution for patients with condylar osteochondroma and secondary dentofacial deformities.
Assuntos
Deformidades Dentofaciais , Osteocondroma , Cirurgia Assistida por Computador , Desenho Assistido por Computador , Deformidades Dentofaciais/cirurgia , Humanos , Mandíbula , Recidiva Local de Neoplasia/complicações , Osteocondroma/complicações , Osteocondroma/diagnóstico por imagem , Osteocondroma/cirurgia , Cirurgia Assistida por Computador/métodos , TitânioRESUMO
ABSTRACT: This study summarized the literature regarding the application of pre-bent titanium miniplates in orthognathic surgery and evaluated the extra deformation of the manually pre-bent titanium miniplates via finite element analysis for acquiring higher surgical accuracy. The literature was reviewed with a chart. Three models of titanium miniplates with different thicknesses (1.0âmm, 0.8âmm, 0.6âmm) were created using COMSOL Multiphysics software for biomechanical behavior analysis. The 3 models were virtually bent into 5 angles (15 degree, 30 degree, 45 degree, 60 degree, 80 degree). respectively to simulate the preoperative virtual bending, then to simulate the practical manual bending via finite element analysis. The stresses and displacements of these models were recorded. The models from virtual bending simulation and manual bending simulation were registered to analyze the deviations. The results showed that the maximum stress and the displacement deviations between the virtual bending models and the manual bending models increased with the thickness and bending angle of the pre-bent miniplate models. To improve the surgical accuracy, measures should be applied to the manually pre-bent titanium miniplates to reduce the extra deformation when the plate being thicker and the bending angle being larger.
Assuntos
Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Placas Ósseas , Análise de Elementos Finitos , Fixação Interna de Fraturas , Humanos , Estresse Mecânico , TitânioRESUMO
BACKGROUND: MicroRNAs (miRNAs) are considered as promising cancer biomarkers. The aim of the present study is to investigate the prognostic significance of miR-200c in patients with oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: Quantitative real-time PCR (qRT-PCR) was used to determine the expression levels of miR-200c in 204 pairs of OSCC and adjacent noncancerous. Correlations between miR-200c expression levels and clinicopathological characteristics were investigated. Survival analysis was performed using the Kaplan-Meier method and log-rank test. Multivariate analysis of the prognostic factors was performed with a Cox proportional hazards regression model. RESULTS: The expression of miR-200c was significantly down-regulated in OSCC tissues compared with adjacent non-tumor tissues (p < 0.0001). Low expression of miR-200c in tumor tissues was significantly correlated with the positive N classification (p = 0.013), advanced TNM stage (p = 0.007) and poor differentiation grade (p = 0.026). Lower miR-200c expression in patients was significantly associated with poor recurrence-free survival (RFS, p = 0.0003) and overall survival (OS, p = 0.0026). Multivariate analysis confirmed that low miR-200c expression was an independent predictor for poor RFS (hazard ratio (HR) 1.705, 95% CI 1.136-2.56, p = 0.01) and OS (HR 1.669, 95% CI 1.03-2.703, p = 0.037) in patients with OSCC. CONCLUSION: Our results suggest that the miR-200c might be a potential prognostic biomarker for OSCC.
Assuntos
Carcinoma de Células Escamosas/patologia , MicroRNAs/metabolismo , Neoplasias Bucais/patologia , Adulto , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Regulação para Baixo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/mortalidade , Prognóstico , Análise de SobrevidaRESUMO
Computer-aided surgery has been widely used in treatment of hemifacial microsomia and matured in recent decades. These techniques include the computer-aided design, virtual surgical planning, modeling surgery, rapid prototyping techniques, intraoperative navigation and so on. The purpose of this article is to summarize the current application of computer-aided design/computer-aided manufacturing technology in the treatment for hemifacial microsomia during the last 5 years, as well as the views and discussions on some topics, and finally introduce a method of our team. Our effort is that using the holes predrilled in cutting guides, the pre-bent titanium plates are easily placed. Avoiding potential bone autorotation caused by unfitness between conventional titanium plates and bone surface, which keeps the bone fixation precisely in line with the preoperative virtual plan and reduce the movement of bone segments due to the undesirable stress of the plates.
Assuntos
Síndrome de Goldenhar/cirurgia , Cirurgia Assistida por Computador , Desenho Assistido por Computador , Humanos , Imageamento Tridimensional , TitânioRESUMO
The aim of this study is to evaluate the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones in ovariectomized (OVX) animal models. The literature on the osteogenesis around titanium implant and in bone defect or fracture in jaw bones and long bones was reviewed with charts. Fourty-eight rats were randomly divided into OVX group with ovariectomy and SHAM (sham-surgery) group with sham surgery. Titanium implants were inserted in the right mandibles and tibiae; bone defects were created in the left mandibles and tibiae. Two-week postoperatively, mandibles and tibiae of 8 rats were harvested and examined by hematoxylin and eosin staining and histological analysis; 4-week postoperatively, all mandibles and tibiae were harvested and examined by Micro-CT and histological analysis. A total of 52 articles were included in this literature review. Tibial osteogenesis around titanium implant and in bone defect in OVX group were significantly decreased compared with SHAM group. However, osteogenesis differences in the mandible both around titanium implant and in bone defect between groups were not statistically significant. OVX-induced osteoporosis suppresses osteogenesis around titanium implant and in the bone defect or fracture in long bones significantly while has less effect on that in the jaw bones.
Assuntos
Implantes Experimentais/efeitos adversos , Arcada Osseodentária/efeitos dos fármacos , Tíbia/efeitos dos fármacos , Titânio/farmacologia , Animais , Feminino , Procedimentos Cirúrgicos Ortognáticos , Osteogênese/efeitos dos fármacos , Osteoporose/induzido quimicamente , Osteoporose/patologia , Ovariectomia , Ratos , Tíbia/cirurgiaRESUMO
BACKGROUND: Adiponectin (APN) has been reported to promote bone formation. However, it is difficult to utilize a conventional method that administers sufficient APN to the implant site. The present study investigated the efficacy of an APN transgene to accelerate the implant osseointegration in ovariectomized (OVX) rats. METHODS: In vitro, bone marrow stromal cells were transduced with reconstructed adenovirus (Ad-APN-EGFP) and osteoclast precursor RAW264.7 cells were co-cultured with the conditioned medium secreted by transduced bone marrow stromal cells. Tartrate-resistant acid phosphatase staining and bone slice resorption assay were performed to evaluate the activity of osteoclastogenesis. In vivo, Ad-APN-EGFP was administered into the bone defect prior to implant placement in OVX rats. At 7 and 28 days post implantation, the femurs were harvested and prepared for a real-time reverse transcriptase-polymerase chain reaction, hemotoxylin and eosin staining, immunohistochemical staining, micro-computed tomography analysis and biomechanical testing. RESULTS: The results showed the formation and function of osteoclasts were significantly suppressed in vitro. Successful transgene expression was confirmed, and a significant increase of OCN, Runx2 and ALP expression was detected in the Ad-APN-EGFP group in vivo. Interestingly, we also found that the overexpression of APN decreased the expression level of potent adipogenic transcription factors such as PPARγ2 and C/EBP-α. At 28 days after implantation, the Ad-APN-EGFP group revealed a significantly increased osseointegration and implant stability in OVX rats compared to the control groups (Ad-EGFP and PBS groups). CONCLUSIONS: APN via direct adenovirus-mediated gene transfer could ameliorate osseointegration surrounding titanium implants in OVX-related osteoporosis rats. Furthermore, it may be an effective strategy for promoting bone regeneration under osteoporotic conditions.
Assuntos
Adiponectina/metabolismo , Fêmur/metabolismo , Terapia Genética/métodos , Osteogênese , Implantação de Prótese/métodos , Titânio/química , Adenoviridae/genética , Adiponectina/genética , Animais , Células Cultivadas , Fêmur/diagnóstico por imagem , Fêmur/fisiopatologia , Proteínas de Fluorescência Verde/genética , Proteínas de Fluorescência Verde/metabolismo , Humanos , Camundongos , Osseointegração/genética , Osteoclastos/citologia , Osteoclastos/metabolismo , Osteoporose/genética , Osteoporose/terapia , Ovariectomia , Próteses e Implantes , Ratos Sprague-Dawley , Transgenes/genética , Microtomografia por Raio-XRESUMO
OBJECTIVE: Temporomandibular joint (TMJ) dislocation means the condyle moves out of the normal position. There are several treatments for TMJ dislocation, including conservative treatment, injection treatment, minimally invasive treatment, and open surgical treatment. In this study, we tried to review the literature related to the augmentation of the articular eminence and proposed a modified eminoplasty technique of TMJ dislocation by computer-aided design and computer-aided manufacturing (CAD/CAM) cutting guides. METHODS: The literature on eminoplasty for TMJ was reviewed with 3 charts. Besides, 2 (67 and 69 years old) patients with chronic recurrent dislocation were treated by the CAD/CAM-guided surgical technique in our study, and postoperative measures were recorded to verify the safety and effectiveness regarding this technique. RESULTS: A total of 28 studies (including 268 patients) of the augmentation of the articular eminence have been reported since 1967, including the 2 present patients. According to the analysis of the recurrence and complications in the review, we found the modified technique had an obvious advantage. The technique with cutting guides was also found having higher accuracy. CONCLUSION: The modified technique was a reliable method when treating the TMJ dislocation, and the combination of CAD/CAM cutting guides was useful for more accuracy, even reduced the operation difficulty.
Assuntos
Desenho Assistido por Computador , Luxações Articulares/cirurgia , Procedimentos Cirúrgicos Bucais/métodos , Osteotomia/métodos , Articulação Temporomandibular/lesões , Idoso , Humanos , Modelos Anatômicos , Recidiva , Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/cirurgia , Zigoma/diagnóstico por imagem , Zigoma/cirurgiaRESUMO
Facial asymmetry is a common maxillofacial deformity which requires surgery to recover the 3-dimensional relationship of bones. The computer-aided design and computer-aided manufacturing (CAD/CAM) has been developed and applied to improve orthognathic analysis and surgery design. How to accurately realize the preoperative design of orthognathic surgery with CAD/CAM occlusal splints during operation remains a big problem. In this study, 24 consecutive patients with facial asymmetry were recruited and assigned to 2 groups. For Group A, CAD/CAM was applied to designing and producing not only the occlusal splints, but also the drilling guiding templates and pre-bent titanium plates, and for Group B CAD/CAM was applied for occlusal splints only. Postoperative clinical examinations, symmetry evaluation through 3D cephalometric analysis, accuracy comparison using color distance maps and quantitative accuracy analysis were performed. Symmetry evaluation showed that patients of both groups achieved improved facial symmetry after surgery. The color distance maps and quantitative accuracy analysis together demonstrated significantly less difference found between virtual simulated surgery and postoperative CT scan data in Group A than in Group B. In conclusion, by navigation with the drilling guiding templates and pre-bent titanium plates, the facial symmetry for patients with facial asymmetry was successfully restored after orthognathic surgery, same as applying CAD/CAM occlusal splints only. However, the drilling guiding templates and pre-bent titanium plates would provide a more accurate performance according to preoperative simulation, especially for proximal mandibular segments.