RESUMO
SARS-CoV-2 is an RNA virus whose success as a pathogen relies on its abilities to repurpose host RNA-binding proteins (RBPs) and to evade antiviral RBPs. To uncover the SARS-CoV-2 RNA interactome, we here develop a robust ribonucleoprotein (RNP) capture protocol and identify 109 host factors that directly bind to SARS-CoV-2 RNAs. Applying RNP capture on another coronavirus, HCoV-OC43, revealed evolutionarily conserved interactions between coronaviral RNAs and host proteins. Transcriptome analyses and knockdown experiments delineated 17 antiviral RBPs, including ZC3HAV1, TRIM25, PARP12, and SHFL, and 8 proviral RBPs, such as EIF3D and CSDE1, which are responsible for co-opting multiple steps of the mRNA life cycle. This also led to the identification of LARP1, a downstream target of the mTOR signaling pathway, as an antiviral host factor that interacts with the SARS-CoV-2 RNAs. Overall, this study provides a comprehensive list of RBPs regulating coronaviral replication and opens new avenues for therapeutic interventions.
Assuntos
Autoantígenos/genética , COVID-19/genética , RNA Viral/genética , Ribonucleoproteínas/genética , SARS-CoV-2/genética , COVID-19/virologia , Coronavirus Humano OC43/genética , Coronavirus Humano OC43/patogenicidade , Células HEK293 , Interações Hospedeiro-Patógeno/genética , Humanos , Ligação Proteica/genética , Mapas de Interação de Proteínas/genética , Proteínas de Ligação a RNA/genética , SARS-CoV-2/patogenicidade , Serina-Treonina Quinases TOR/genética , Fatores de Transcrição/genética , Transcriptoma/genética , Proteínas com Motivo Tripartido/genética , Ubiquitina-Proteína Ligases/genética , Replicação Viral/genética , Antígeno SS-BRESUMO
Cysteine-rich angiogenic inducer 61 (CYR61) is a protein from the CCN family of matricellular proteins that play diverse regulatory roles in the extracellular matrix. CYR61 is involved in cell adhesion, migration, proliferation, differentiation, apoptosis, and senescence. Here, we show that CYR61 induces chemoresistance in triple-negative breast cancer (TNBC). We observed that CYR61 is overexpressed in TNBC patients, and CYR61 expression correlates negatively with the survival of patients who receive chemotherapy. CYR61 knockdown reduced cell migration, sphere formation and the cancer stem cell (CSC) population and increased the chemosensitivity of TNBC cells. Mechanistically, CYR61 activated Wnt/ß-catenin signaling and increased survivin expression, which are associated with chemoresistance, the epithelial-mesenchymal transition, and CSC-like phenotypes. Altogether, our study demonstrates a novel function of CYR61 in chemotherapy resistance in breast cancer.
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Proteína Rica em Cisteína 61 , Resistencia a Medicamentos Antineoplásicos , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Survivina , Neoplasias de Mama Triplo Negativas , Humanos , Proteína Rica em Cisteína 61/genética , Proteína Rica em Cisteína 61/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/metabolismo , Survivina/metabolismo , Survivina/genética , Feminino , Resistencia a Medicamentos Antineoplásicos/genética , Via de Sinalização Wnt , Movimento Celular , Linhagem Celular Tumoral , Células-Tronco Neoplásicas/patologia , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/efeitos dos fármacos , Regulação para Cima , Proliferação de Células , Apoptose , Animais , CamundongosRESUMO
OBJECTIVES: This study aimed to evaluate the diagnostic performance of a deep convolutional neural network (DCNN)-based computer-assisted diagnosis (CAD) system to detect facial asymmetry on posteroanterior (PA) cephalograms and compare the results of the DCNN with those made by the orthodontist. MATERIALS AND METHODS: PA cephalograms of 1020 patients with orthodontics were used to train the DCNN-based CAD systems for autoassessment of facial asymmetry, the degree of menton deviation, and the coordinates of its regarding landmarks. Twenty-five PA cephalograms were used to test the performance of the DCNN in analyzing facial asymmetry. The diagnostic performance of the DCNN-based CAD system was assessed using independent t -tests and Bland-Altman plots. RESULTS: Comparison between the DCNN-based CAD system and conventional analysis confirmed no significant differences. Bland-Altman plots showed good agreement for all the measurements. CONCLUSIONS: The DCNN-based CAD system might offer a clinically acceptable diagnostic evaluation of facial asymmetry on PA cephalograms.
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Aprendizado Profundo , Humanos , Assimetria Facial/diagnóstico por imagem , Redes Neurais de Computação , Algoritmos , Diagnóstico por Computador/métodosRESUMO
INTRODUCTION: It is important to generate predictable statistical models by increasing the number of variables on the human skeletal and soft tissue structures on the face to increase the accuracy of human facial reconstructions. The purpose of this study was to determine mouth width 3-dimensionally based on statistical regression model. MATERIAL AND METHODS: Cone-beam computed tomography scan data from 130 individuals were used to measure the horizontal and vertical dimensions of orbital and nasal structures and intercanine width. The correlation between these hard tissue variables and the mouth width was evaluated using the statistical regression model. RESULTS: Orbital width, nasal width, and intercanine width were found to be strong predictors of the mouth width determination and were used to generate the regression formulae to find the most approximate position of the mouth. CONCLUSION: These specific variables may contribute to improving the accuracy of mouth width determination for oral and maxillofacial reconstructions.
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Face , Reconstrução Mandibular , Boca , Análise de Regressão , Boca/anatomia & histologia , Boca/diagnóstico por imagem , Face/anatomia & histologia , Face/diagnóstico por imagem , Dente/anatomia & histologia , Dente/diagnóstico por imagem , Olho/anatomia & histologia , Olho/diagnóstico por imagem , Nariz/anatomia & histologia , Nariz/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , HumanosRESUMO
OBJECTIVE: The purpose of this article was to introduce a method for the digital application of three-dimensional (3D) diagnosis and treatment with a virtual articulator and 3D data. CLINICAL CONSIDERATION: With the use of cone-beam computed tomography (CBCT) and intraoral and facial scans, we can create a virtual articulator and evaluate the mandibular position in maximum intercuspation and centric-related occlusion for the patient with an unstable occlusion and temporomandibular disorders (TMD). Based on this, we treated a case using a digital mandibular position indicator (MPI) and fabricated a stabilization splint using a 3D printer. This approach eliminates the traditional impression or model mounting process and the analog face bow transfer. Furthermore, the design of the stabilization splint is accomplished using software. CONCLUSIONS: The approach outlined in this article offers the potential for a digital diagnosis and treatment process by seamlessly integrating CBCT, intraoral scans, and facial scans with a high degree of accuracy. This may enhance precision in diagnosis and treatment planning, especially for patients with complicated TMD, in addition to facilitating effective communication with orthodontic patients who require thorough attention. CLINICAL SIGNIFICANCE: Utilizing a virtual articulator and digital MPI for the occlusal evaluation of patients with TMD and unstable occlusion makes it possible to diagnose and analyze the occlusal condition accurately. This approach also allows for precision and efficiency in treatment.
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Articuladores Dentários , Imageamento Tridimensional , Humanos , Registro da Relação Maxilomandibular/métodos , Imageamento Tridimensional/métodos , Modelos Dentários , Oclusão Dentária , Tomografia Computadorizada de Feixe Cônico/métodosRESUMO
Muscle-invasive urothelial carcinoma (MIUC) of the bladder shows highly aggressive tumor behavior, which has prompted the quest for robust biomarkers predicting invasion. To discover such biomarkers, we first employed high-throughput proteomic method and analyzed tissue biopsy cohorts from patients with bladder urothelial carcinoma (BUC), stratifying them according to their pT stage. Candidate biomarkers were selected through bioinformatic analysis, followed by validation. The latter comprised 2D and 3D invasion and migration assays, also a selection of external public datasets to evaluate mRNA expression and an in-house patient-derived tissue microarray (TMA) cohort to evaluate protein expression with immunohistochemistry (IHC). Our multilayered platform-based analysis identified tubulin beta 6 class V (TUBB6) as a promising prognostic biomarker predicting MIUC of the bladder. The in vitro 2D and 3D migration and invasion assays consistently showed that inhibition of TUBB6 mRNA significantly reduced cell migration and invasion ability in two BUC cell lines with aggressive phenotype (TUBB6 migration, P = .0509 and P < .0001; invasion, P = .0002 and P = .0044; TGFBI migration, P = .0214 and P = .0026; invasion, P < .0001 and P = .0001; T24 and J82, respectively). Validation through multiple public datasets, including The Cancer Genome Atlas (TCGA) and selected GSE (Genomic Spatial Event) databases, confirmed TUBB6 as a potential biomarker predicting MIUC. Further protein-based validation with our TMA cohort revealed concordant results, highlighting the clinical implication of TUBB6 expression in BUC patients (overall survival: P < .001). We propose TUBB6 as a novel IHC biomarker to predict invasion and poor prognosis, also select the optimal treatment in BUC patients.
Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Proteômica , Biomarcadores , Músculos , RNA Mensageiro/genética , Prognóstico , Tubulina (Proteína)/genéticaRESUMO
PURPOSE: To assess outcome and predictors of outcome after lymphatic embolization (LE) for early postoperative lymphatic leak after pelvic surgery. MATERIAL AND METHODS: Lymphangiography (LG) procedures performed between May 2015 and February 2020 for postoperative intraperitoneal lymphatic leaks after pelvic surgery were reviewed. Treatment indication was lymphatic drainage of >500 mL/d persisting for >1 week. LE was performed by injecting glue into the iliac lymph node. Fisher exact and Wilcoxon rank-sum tests were used for comparative analysis, and logistic regression was used to assess predictors of outcome. RESULTS: LG was performed in 71 patients. A leak was demonstrated in 69 patients who underwent LE. The mean drainage was 1,329 mL/d ± 773. Catheters were removed in 49 (69.0%) patients after 1 procedure and in 69 (97.2%) patients after a mean of 1.3 procedures. The mean drainage at the time of catheter removal was 157 mL/d ± 100. Failure occurred in 12 (16.9%) cases, including 2 (2.8%) cases of unsuccessful catheter removal and 10 (14.1%) cases of catheter reinsertion owing to recurrent ascites (n = 3) and lymphoceles (n = 7). Older age and drainage of >1,500 mL/d were associated with failure (P = .004). Drainage of >1,500 mL/d was associated with a post-LE catheter dwell time of longer than 1 week (P = .024). Minor adverse events were noted in 4 (5.6%) patients who presented with transient leg swelling. CONCLUSIONS: LE was effective for treating pelvic surgery-related lymphatic leaks. Reintervention may be required. Drainage of >1,500 mL/d was associated with clinical failure and a post-LE catheter dwell time of longer than 1 week.
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Embolização Terapêutica , Vasos Linfáticos , Linfocele , Humanos , Linfografia/métodos , Resultado do Tratamento , Embolização Terapêutica/efeitos adversos , Linfocele/diagnóstico por imagem , Linfocele/etiologia , Linfocele/terapia , Estudos RetrospectivosRESUMO
GroundBIRD is a ground-based telescope for measuring the polarization of cosmic microwave background radiation, and it is soon to be operational at the Teide Observatory. The GroundBIRD telescope employs Mizuguchi-Dragone dual reflectors and 161 kinetic inductance detectors coupled with single polarization antennas as photon detectors. We present the results of our optical simulation on the pointing direction, stray light response, and influence of the blackbody radiation from the baffle. We also find that the power of the baffle radiation incident on the detectors is reduced by 99.95% when corrugated feed horns are coupled to the detectors.
RESUMO
OBJECTIVE: The aim of this study was to evaluate the accuracy of 3-dimensional (3D) facial scans taken with a low-cost facial scanner compared with cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Twenty-five patients had their CBCT scan and 3D facial scan taken on the same day. Facial scans were taken with a low-cost facial scanner (Bellus3D, ARC-1 scanner) in an upright position. The facial scans were imported into Invivo5 software and were integrated with the corresponding CBCT scans. Then, 16 soft tissue landmarks were identified on the CBCT scans and the 3D-integrated facial scans. The 6 vertical, 7 horizontal, 10 oblique linear, and 11 angular anthropometric measurements were obtained and compared between the CBCT scans and 3D-integrated facial scans using paired t test and Bland-Altman plots. RESULTS: The differences between CBCT scans and 3D-integrated facial scans showed no statistical significance except for 2 vertical measurements. Bland-Altman plots showed that all anthropometric measurements were within the limit of agreement. The differences between CBCT scans and 3D-integrated facial scans were <1.5 mm or 1.5 degrees except for 2 vertical measurements. CONCLUSIONS: Three-dimensional facial scans taken with facial scanner showed a clinical acceptance when compared with CBCT scans.
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Face , Imageamento Tridimensional , Humanos , Imageamento Tridimensional/métodos , Face/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Software , AntropometriaRESUMO
Frequency-modulated continuous wave (FMCW) radar system synchronization using external clock signals can cause repeated Range-Doppler (R-D) map corruption when clock signal asynchronization problems occur between the transmitter and receiver. In this paper, we propose a signal processing method for the reconstruction of the corrupted R-D map owing to the FMCW radar's asynchronization. After calculating the image entropy for each R-D map, the corrupted ones are extracted and reconstructed using the normal R-D maps acquired before and after the individual maps. To verify the effectiveness of the proposed method, three target detection experiments were conducted: a human target detection in an indoor environment and a wide place and a moving bike-rider target detection in an outdoor environment. The corrupted R-D map sequence of observed targets in each case was reconstructed properly and showed the validity by comparing the map-by-map range and speed changes in the detected target with the ground-truth information of the target.
Assuntos
Radar , Processamento de Sinais Assistido por Computador , Humanos , Ultrassonografia DopplerRESUMO
OBJECTIVE: The aim of this study was to evaluate the changes in the upper airway following mandibular setback surgery. METHODS: The patients underwent mandibular setback surgery and cone-beam computed tomography scan data obtained at four time points: before surgery, immediately after surgery, short- and long-term follow-up. Upper airway geometries were segmented and extracted at each time point. Time-averaged airflow through the upper airway was evaluated at each time point. The measurements of airway volume and minimum cross-sectional areas were obtained at four time points. RESULTS: The airway volume and cross-sectional areas of airway significantly decreased immediately after surgery (p = 0.013 for airway volume and 0.016 for cross-sectional area). At short-term follow-up, the decreased airway volume and cross-sectional areas still showed statistically significant difference to original dimension (p = 0.017 for airway volume and 0.006 for cross-sectional area). At long-term follow-up, although there were no statistical significances (p = 0.859 for airway volume and 0.721 for cross-sectional area), the airway volume and cross-sectional areas had increased slightly compared to those at short-term follow-up. CONCLUSIONS: Although the airflow and dimensional parameters of the upper airway worsened following mandibular setback surgery, there was a tendency to gradually recover during long-term follow-up.
Assuntos
Má Oclusão Classe III de Angle , Procedimentos Cirúrgicos Ortognáticos , Prognatismo , Humanos , Faringe/diagnóstico por imagem , Prognatismo/diagnóstico por imagem , Prognatismo/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , Procedimentos Cirúrgicos Ortognáticos/métodos , Tomografia Computadorizada de Feixe Cônico/métodos , Cefalometria , SeguimentosRESUMO
INTRODUCTION: This retrospective study aimed to investigate the alveolar bone changes around mandibular incisors in patients with skeletal Class III malocclusion treated with surgery-first orthognathic approach (SFA) and conventional orthognathic surgery (COS) using cone-beam computed tomography scans. METHODS: Sixty-four patients were divided into 2 groups according to the inclusion of presurgical orthodontic treatment; the SFA group included 32 patients treated without presurgical orthodontic treatment, and the COS group included 32 patients treated with presurgical orthodontic treatment. Cone-beam computed tomography scans were obtained before treatment, after presurgical orthodontic treatment, and after treatment for the COS group and were obtained before and after treatment for the SFA group. The measurements of vertical alveolar bone height and horizontal bone thickness at 4 levels and the alveolar bone area surrounding the mandibular incisors were compared according to the treatment progress and groups. RESULTS: The vertical bone levels and horizontal bone thickness of the labial and lingual sides and the area of the alveolar bone around the mandibular incisors were reduced after treatment in both SFA and COS groups. Vertical bone loss was more prominent than horizontal bone loss after treatment in both groups, and alveolar bone loss was greater on the lingual side than on the labial side. There were no significant differences in alveolar bone changes around the mandibular incisor between the SFA and COS groups. However, the alveolar bone was reduced more in the COS group than in the SFA group. CONCLUSIONS: The results indicate that SFA and COS may trigger degeneration of the alveolar bone around the mandibular incisors after treatment in patients with mandibular prognathism. Careful consideration is needed to avoid iatrogenic degeneration of the periodontal support around the incisors, particularly during presurgical orthodontic treatment.
Assuntos
Má Oclusão Classe III de Angle , Cirurgia Ortognática , Prognatismo , Humanos , Incisivo/diagnóstico por imagem , Prognatismo/cirurgia , Estudos Retrospectivos , Má Oclusão Classe III de Angle/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Tomografia Computadorizada de Feixe CônicoRESUMO
Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels function as pacemaker channels in spontaneously active cells. We studied the existence of HCN channels and their functional roles in the interstitial cells of Cajal (ICC) from the mouse colon using electrophysiological, immunohistochemical and molecular techniques. HCN1 and HCN3 channels were detected in anoctamin-1 (Ca2+ -activated Cl- channel; ANO1)-positive cells within the muscular and myenteric layers in colonic tissues. The mRNA transcripts of HCN1 and HCN3 channels were expressed in ANO1-positive ICC. In the deletion of HCN1 and HCN3 channels in colonic ICC, the pacemaking potential frequency was reduced. Basal cellular adenylate cyclase activity was decreased by adenylate cyclase inhibitor in colonic ICC, whereas cAMP-specific phosphodiesterase inhibitors increased it. 8-Bromo-cyclic AMP and rolipram increased spontaneous intracellular Ca2+ oscillations. In addition, Ca2+ -dependent adenylate cyclase 1 (AC1) mRNA was detected in colonic ICC. Sulprostone, a PGE2 -EP3 agonist, increased the pacemaking potential frequency, maximum rate of rise of resting membrane in pacemaker potentials and basal cellular adenylate cyclase activity in colonic ICC. These results indicate that HCN channels exist in colonic ICC and participate in generating pacemaking potentials. Thus, HCN channels may be therapeutic targets in disturbed colonic motility disorders.
Assuntos
Células Intersticiais de Cajal , Animais , Colo , Canais Disparados por Nucleotídeos Cíclicos Ativados por Hiperpolarização/genética , Células Intersticiais de Cajal/fisiologia , CamundongosRESUMO
Heterogeneity in the etiopathology of autism spectrum disorders (ASD) limits the development of generic remedies, requires individualistic and patient-specific research. Recent progress in human-induced pluripotent stem cell (iPSC) technology provides a novel platform for modeling ASDs for studying complex neuronal phenotypes. In this study, we generated telencephalic induced neuronal (iN) cells from iPSCs derived from an ASD patient with a heterozygous point mutation in the DSCAM gene. The mRNA of DSCAM and the density of DSCAM in dendrites were significantly decreased in ASD compared to control iN cells. RNA sequencing analysis revealed that several synaptic function-related genes including NMDA receptor subunits were downregulated in ASD iN cells. Moreover, NMDA receptor (R)-mediated currents were significantly reduced in ASD compared to control iN cells. Normal NMDA-R-mediated current levels were rescued by expressing wild-type DSCAM in ASD iN cells, and reduced currents were observed by truncated DSCAM expression in control iN cells. shRNA-mediated DSCAM knockdown in control iN cells resulted in the downregulation of an NMDA-R subunit, which was rescued by the overexpression of shRNA-resistant DSCAM. Furthermore, DSCAM was co-localized with NMDA-R components in the dendritic spines of iN cells whereas their co-localizations were significantly reduced in ASD iN cells. Levels of phospho-ERK1/2 were significantly lower in ASD iN cells, suggesting a potential mechanism. A neural stem cell-specific Dscam heterozygous knockout mouse model, showing deficits in social interaction and social memory with reduced NMDA-R currents. These data suggest that DSCAM mutation causes pathological symptoms of ASD by dysregulating NMDA-R function.
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Transtorno do Espectro Autista , Moléculas de Adesão Celular/genética , Receptores de N-Metil-D-Aspartato , Animais , Transtorno do Espectro Autista/metabolismo , Humanos , Camundongos , Camundongos Knockout , Mutação/genética , Neurônios/metabolismo , Receptores de N-Metil-D-Aspartato/genética , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
ABSTRACT: The purpose of this report is to introduce a digital approach to evaluating three-dimensional root position without radiation using virtual tooth model which is composed of intraoral-scanned crown and cone-beam computed tomography (CBCT)-scanned root. Successful treatment depends not only on the formulation of a proper initial diagnosis, but also on an accurate assessment of treatment progress, which should include the monitoring and evaluation of tooth and root movements. Although CBCT allows the visualization of the true root position and angulation in three-dimensions, the obtaining of serial CBCT scans for this purpose is associated with concerns regarding radiation exposure. This report introduces a method for monitoring three-dimensional root position following tooth movement during treatment that does not require repeated CBCT scans. This method uses an individual virtual tooth model composed of intraoral-scanned crowns and CBCT-scanned roots. When an evaluation of root positions is needed during treatment, only additional intraoral scan is needed and is integrated into the tooth model; this allows root positions to be estimated without the need for another CBCT scan. The use of a virtual tooth model can potentially allow clinicians to accurately monitor tooth position in routine clinical practice, without the hazards of increased radiation exposure.
Assuntos
Raiz Dentária , Dente , Tomografia Computadorizada de Feixe Cônico/métodos , Humanos , Modelos Dentários , Coroa do Dente , Raiz Dentária/diagnóstico por imagemRESUMO
This case-report described the 3-dimensional (3D) evaluation of airway changes using 3D printing technology in a patient with mandibular prognathism, treated via mandibular setback surgery with maxillary posterior impaction. The airway dimensions, following orthognathic surgery, were printed using 3D printing technology and the sequential airway changes were visualized. The patient underwent orthognathic surgery for the correction of mandibular prognathism. Five years later, the airway changes were visualized and evaluated using rapid prototyping. The 3D visualization of the airway changes following surgery alerted clinicians of patients with mandibular prognathism and facilitated effective communication with their patients. This case-report documented the long-term evaluation and visualization of the postoperative airway changes in patients with mandibular prognathism using cone-beam computed tomography and 3D printing technology.
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Má Oclusão Classe III de Angle , Procedimentos Cirúrgicos Ortognáticos , Prognatismo , Humanos , Prognatismo/diagnóstico por imagem , Prognatismo/cirurgia , Seguimentos , Imageamento Tridimensional/métodos , Cefalometria/métodos , Mandíbula/cirurgia , Faringe/diagnóstico por imagem , Faringe/cirurgia , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , Procedimentos Cirúrgicos Ortognáticos/métodos , Impressão Tridimensional , TecnologiaRESUMO
ABSTRACT: The purpose of this paper was to introduce a method for creating a digital virtual patient by combining cone-beam computed tomography (CBCT), intraoral scan, and facial scan with a high accuracy of integration. CBCT scan, facial scan, and intraoral scan were obtained from initial visit. The virtual patient was created using the integration of these imaging modalities. Once the virtual patient was generated, digital workflow could be applied to initial patient consultation, diagnosis, treatment planning, virtual tooth setup, virtual treatment simulation, and post-treatment evaluation. integration of digital technology allows clinicians to improve diagnosis and treatment outcome. in addition, it allows for favorable patient communication. This technique eliminates the traditional impression process and complicated laboratory procedures for evaluating patient's occlusion during smile and habitual resting position. Based on this protocol, it is possible to create a digital virtual patient using CBCT, intraoral scan, and facial scan with a high accuracy of integration. it would be helpful for precision diagnosis and accurate treatment as well as favorable communication with patient.
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Simulação por Computador , Tecnologia Digital , Realidade Virtual , Tomografia Computadorizada de Feixe Cônico , Oclusão Dentária , Face/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Boca/diagnóstico por imagemRESUMO
Chemoresistance is a daunting obstacle to the effective treatment of breast cancer patients receiving chemotherapy. Although the mechanism of chemotherapy drug resistance has been explored broadly, the precise mechanism at the proteome level remains unclear. Especially, comparative studies between widely used anticancer drugs in breast cancer are very limited. In this study, we employed proteomics and bioinformatics approaches on chemoresistant breast cancer cell lines to understand the underlying resistance mechanisms that resulted from doxorubicin (DR), paclitaxel (PR), and tamoxifen (TAR). In total, 10,385 proteins were identified and quantified from three TMT 6-plex and one TMT 10-plex experiments. Bioinformatics analysis showed that Notch signaling, immune response, and protein re-localization processes were uniquely associated with DR, PR, and TAR resistance, respectively. In addition, proteomic signatures related to drug resistance were identified as potential targets of many FDA-approved drugs. Furthermore, we identified potential prognostic proteins with significant effects on overall survival. Representatively, PLXNB2 expression was associated with a highly significant increase in risk, and downregulation of ACOX3 was correlated with a worse overall survival rate. Consequently, our study provides new insights into the proteomic aspects of the distinct mechanisms underlying chemoresistance in breast cancer.
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Neoplasias da Mama , Proteômica , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Biologia Computacional , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , HumanosRESUMO
CD44 is a transmembrane glycoprotein that can regulate the oncogenic process. This is known to be a marker of the claudin-low subtype of breast cancer, as well as a cancer stem cell marker. However, its functional regulatory roles are poorly understood in claudin-low breast cancer. To gain comprehensive insight into the function of CD44, we performed an in-depth tandem mass tag-based proteomic analysis of two claudin-low breast cancer cell lines (MDA-MB-231 and Hs 578T) transfected with CD44 siRNA. As a result, we observed that 2736 proteins were upregulated and 2172 proteins were downregulated in CD44-knockdown MDA-MB-231 cells. For Hs 578T CD44-knockdown cells, 412 proteins were upregulated and 443 were downregulated. Gene ontology and network analyses demonstrated that the suppression of this marker mediates significant functional alterations related to oncogenic cellular processes, including proliferation, metabolism, adhesion, and gene expression regulation. A functional study confirmed that CD44 knockdown inhibited proliferation by regulating the expression of genes related to cell cycle, translation, and transcription. Moreover, this promoted the expression of multiple cell adhesion-associated proteins and attenuated cancer cell migration. Finally, our proteomic study defines the landscape of the CD44-regulated proteome of claudin-low breast cancer cells, revealing changes that mediate cell proliferation and migration. Our proteomics data set has been deposited to the ProteomeXchange Consortium via the PRIDE repository with the data set identifier PXD015171.
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Neoplasias da Mama , Neoplasias da Mama/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Claudinas/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Receptores de Hialuronatos/genética , Células MCF-7 , ProteômicaRESUMO
PURPOSE: This study aimed to evaluate the sequential changes in the pharyngeal airway dimensions after mandibular setback surgery and to verify its correlation with postsurgical mandibular stability in patients with mandibular prognathism. PATIENTS AND METHODS: This retrospective study included 28 patients with mandibular prognathism who underwent surgical orthodontic treatment and isolated mandibular setback surgery. Patients who had cone-beam computed tomography before surgery, immediately after surgery, at short-term follow-up (11.8 ± 5.1 months), and long-term follow-up (43.0 ± 13.1 months) were included. Airway dimensions, including distance, minimum cross-sectional area, and airway volume, were measured to evaluate the changes following mandibular setback surgery. With the measurements of postsurgical mandibular relapse, the relationship between sequential changes in airway dimensions and the mandible was verified using correlation analysis. RESULTS: Airway dimensions decreased immediately after mandibular setback surgery. The decreased airway dimensions recovered during short-term follow-up and maintained to the long-term follow-up. The mandible was set back 7.7 ± 5.1 mm at pogonion immediately after surgery. Postsurgical skeletal relapse was 1.1 mm at pogonion during short-term follow-up. During long-term follow-up, the mandible moved 0.4 mm anteriorly, which was about 50% of the changes during short-term follow-up. Statistically significant correlations were found between the sequential changes in airway dimensions and the postsurgical skeletal relapse. CONCLUSION: The decreased airway dimensions following mandibular setback surgery recovered during short-term follow-up and maintained to the long-term follow-up. Dimensional recovery of the pharyngeal airway was correlated with postsurgical skeletal relapse during the 1-year follow-up period.