RESUMO
Extramedullary infiltration (EMI) is a concomitant manifestation that may indicate poor outcome of acute myeloid leukemia (AML). The underlying mechanism remains poorly understood and therapeutic options are limited. Here, we employed single-cell RNA sequencing on bone marrow (BM) and EMI samples from a patient with AML presenting pervasive leukemia cutis. A complement C1Q+ macrophage-like leukemia subset, which was enriched within cutis and existed in BM before EMI manifestations, was identified and further verified in multiple patients with AML. Genomic and transcriptional profiling disclosed mutation and gene expression signatures of patients with EMI that expressed high levels of C1Q. RNA sequencing and quantitative proteomic analysis revealed expression dynamics of C1Q from primary to relapse. Univariate and multivariate analysis demonstrated adverse prognosis significance of C1Q expression. Mechanistically, C1Q expression, which was modulated by transcription factor MAF BZIP transcription factor B, endowed leukemia cells with tissue infiltration ability, which could establish prominent cutaneous or gastrointestinal EMI nodules in patient-derived xenograft and cell line-derived xenograft models. Fibroblasts attracted migration of the C1Q+ leukemia cells through C1Q-globular C1Q receptor recognition and subsequent stimulation of transforming growth factor ß1. This cell-to-cell communication also contributed to survival of C1Q+ leukemia cells under chemotherapy stress. Thus, C1Q served as a marker for AML with adverse prognosis, orchestrating cancer infiltration pathways through communicating with fibroblasts and represents a compelling therapeutic target for EMI.
Assuntos
Complemento C1q , Leucemia Mieloide Aguda , Humanos , Proteômica , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Medula Óssea/metabolismo , Prognóstico , Doença Crônica , RecidivaRESUMO
OBJECTIVE: The fabrication of bioactive coatings on metallic implants to enhance osseointegration has become a topic of general interest in orthopedics and dentistry. Hydroxyapatite (HA) coating has been shown to induce bone formation and promote bone-implant integration. Unfortunately, poor mechanical performance has hindered this from becoming a favorable coating material. The majority of present studies have focused in incorporating different elements into HA coatings to improve mechanical properties. In recent years, tantalum (Ta) has received increasing attention due to its excellent biocompatibility and corrosion resistance. The aim of on the present study was to investigate the fabrication and biological performance of Ta-incorporated HA coatings. METHODS: Ta-incorporated HA coatings were fabricated using the plasma spray technique on a titanium substrate, and the surface characteristics and mechanical properties were examined. In addition, the effects of Ta-incorporated HA coatings on the biological behavior of mesenchymal stem cells (BMSCs) were investigated. RESULTS: Ta-incorporated HA coatings with microporous structure had higher roughness and wettability. In addition, the bonding strength of Ta/HA coatings with the substrate was substantially superior to HA coatings. Furthermore, Ta-incorporated HA coatings not only facilitated initial cell adhesion and faster proliferation, but also promoted the osteogenic differentiation of BMSCs. CONCLUSION: These results indicate that the incorporation of Ta could improve mechanical performance and increase the osteogenic activity of HA coatings. The Ta-incorporated HA coating fabricated by plasma spraying is expected to be a promising bio-coating material for metallic implants.
Assuntos
Materiais Biocompatíveis/química , Durapatita/química , Osteogênese , Tantálio/química , Titânio/química , Animais , Adesão Celular , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células , Células Cultivadas , Materiais Revestidos Biocompatíveis/química , Corrosão , Teste de Materiais , Células-Tronco Mesenquimais/citologia , Metais , Osseointegração , Porosidade , Pós , Próteses e Implantes , Desenho de Prótese , Ratos , Ratos Sprague-Dawley , Estresse Mecânico , Propriedades de SuperfícieRESUMO
BACKGROUND AND AIM: To compare blood and salivary levels of lipofuscin in healthy adults and to analyze the relationship between the lipofuscin level and the healthy adults' age. METHODS: One hundred and twenty-two healthy volunteers were recruited and divided into three groups according to their age: young (n = 42, 20-44 years old), middle-aged (n = 51, 45-59 years old), and elderly (n = 29, 60-74 years old). One ml saliva and 5 ml whole blood were collected from each person. An ELISA kit was used to measure both the plasma and salivary lipofuscin levels. The differences between the groups were compared with independent-sample t test, and the relationship between the salivary lipofuscin level and the age was assessed with linear regression analysis. RESULTS: The mean ± SD of the lipofuscin level in the saliva and plasma of 122 subjects was 68.93 ± 1.32 and 78.05 ± 1.75 µmol/l, respectively. No gender-dependent differences were observed in either the salivary or the plasma lipofuscin level (saliva: p = 0.443, plasma: p = 0.459). The salivary and plasma lipofuscin levels of the elderly subjects were significantly higher than those of the young (saliva: 80.72 ± 13.53 mmol/l versus 59.12 ± 1.92 mmol/l, p = 0.0003; plasma: 93.31 ± 3.14 mmol/l versus 67.43 ± 2.54 mmol/l, p = 0.0002) and middle-aged (saliva: 80.72 ± 13.53 mmol/l versus 70.31 ± 11.17 mmol/l, p = 0.0004; plasma: 93.31 ± 3.14 mmol/l versus 78.12 ± 2.40 mmol/l, p = 0.0002) subjects. Similarly, the salivary and plasma lipofuscin levels of the middle-aged subjects were significantly higher than those of the young subjects (saliva: 70.31 ± 11.17 mmol/l versus 59.12 ± 1.92 mmol/l, p < 0.0001; plasma: 78.12 ± 2.40 mmol/l versus 67.43 ± 2.54 mmol/l, p = 0.0019). The lipofuscin levels in the saliva and plasma were significantly positively correlated with the subject age (r = 0.551, p = 0.0001; r = 0.528, p < 0.0001). Furthermore, the salivary lipofuscin level and plasma lipofuscin level also were found to have a positive correlation (r = 0.621, p < 0.0001). CONCLUSION: No gender-dependent differences were observed in either the salivary or plasma lipofuscin levels. The salivary and plasma lipofuscin levels were positively correlated, and the age is positively correlated with lipofuscin content in saliva.
Assuntos
Envelhecimento/metabolismo , Lipofuscina , Saliva/metabolismo , Adulto , Idoso , Feminino , Voluntários Saudáveis , Humanos , Modelos Lineares , Lipofuscina/sangue , Lipofuscina/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores Sexuais , Estatística como AssuntoRESUMO
OBJECTIVE: To explore the effect of high glucose on proliferation of bone marrow stromal stem cells through Wnt/Β-catenin pathway. METHODS: Bone marrow stormal cells were obtained from the mandible of Wistar rats and stimulated with different concentrations of glucose (5.5 and 16.5 mmol/L). Cell proliferation was evaluated with methyl thiazolyl tetrazolium assay (1, 3, 5, and 7 d)and cell cycle analysis by flow cytometry (5 d). Β-catenin and cyclin D1 protein levels were determined by Western blot. The mRNA expression of lymphoid enhancer binding factor-1 (LEF-1) and cyclin D1 were tested by real-time polymerase chain reaction. RESULTS: The results of methyl thiazolyl tetrazolium assay indicated that the optical density values of two different concentrations of the glucose had no statistical difference on day 1 (P=0.700). On days 3, 5, and 7, the optical density values of the 16.5 mmol/L group were significantly lower than those in the 5.5 mmol/L group (P=0.006, P=0.002, and P=0.003). Cell cycle analysis indicated that high glucose concentration could reduced the progression from phase G1 to S, and the proliferation index values of the 16.5 mmol/L group were significantly lower than those of the 5.5 mmol/L group (P=0.014). The Β-catenin and cyclin D1 levels were lower in the 16.5 mmol/L group when compared with the 5.5 mmol/L group. High glucose condition also reduced the mRNA expressions of LEF-1 and cyclin D1. CONCLUSION: High glucose can inhibit the proliferation of bone marrow stormal cells by suppressing the expressions of Β-catenin, LEF-1, and cyclin D1 in the Wnt/Β-catenin pathway.
Assuntos
Ciclina D1/metabolismo , Glucose/farmacologia , Fator 1 de Ligação ao Facilitador Linfoide/metabolismo , Células-Tronco Mesenquimais/citologia , Via de Sinalização Wnt , beta Catenina/metabolismo , Animais , Células da Medula Óssea/citologia , Proliferação de Células/efeitos dos fármacos , Masculino , Mandíbula/citologia , Ratos , Ratos WistarRESUMO
Osimertinib is a third-generation covalent EGFR inhibitor that is used in treating non-small cell lung cancer. First-generation EGFR inhibitors were found to elicit pro-differentiation effect on acute myeloid leukemia (AML) cells in preclinical studies, but clinical trials yielded mostly negative results. Here, we report that osimertinib selectively induced apoptosis of CD34+ leukemia stem/progenitor cells but not CD34- cells in EGFR-negative AML and chronic myeloid leukemia (CML). Covalent binding of osimertinib to CD34 at cysteines 199 and 177 and suppression of Src family kinases (SFK) and downstream STAT3 activation contributed to osimertinib-induced cell death. SFK and STAT3 inhibition induced synthetic lethality with osimertinib in primary CD34+ cells. CD34 expression was elevated in AML cells compared with their normal counterparts. Genomic, transcriptomic, and proteomic profiling identified mutation and gene expression signatures of patients with AML with high CD34 expression, and univariate and multivariate analyses indicated the adverse prognostic significance of high expression of CD34. Osimertinib treatment induced responses in AML patient-derived xenograft models that correlated with CD34 expression while sparing normal CD34+ cells. Clinical responses were observed in two patients with CD34high AML who were treated with osimertinib on a compassionate-use basis. These findings reveal the therapeutic potential of osimertinib for treating CD34high AML and CML and describe an EGFR-independent mechanism of osimertinib-induced cell death in myeloid leukemia. SIGNIFICANCE: Osimertinib binds CD34 and selectively kills CD34+ leukemia cells to induce remission in preclinical models and patients with AML with a high percentage of CD34+ blasts, providing therapeutic options for myeloid leukemia patients.
Assuntos
Acrilamidas , Compostos de Anilina , Carcinoma Pulmonar de Células não Pequenas , Indóis , Leucemia Mieloide Aguda , Neoplasias Pulmonares , Pirimidinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteômica , Proliferação de Células , Neoplasias Pulmonares/metabolismo , Leucemia Mieloide Aguda/genética , Células Progenitoras Mieloides , Receptores ErbB/metabolismo , Antígenos CD34/metabolismo , Células-Tronco Neoplásicas/metabolismoRESUMO
The effects of Tip-Edge plus appliance in the treatment of Angle II(1) malocclusion and the mechanism were investigated. Fifty-two Angle II(1) children, aged from 12.3-14.2 years, with mandibular retrusion in permanent dentition were selected and treated with Tip-Edge plus appliance. Lateral cephalometric films taken before and after treatment were analyzed. The arithmetic mean and standard deviation were calculated for each variable. Paired t-test was performed to evaluate the significant treatment change. Results showed that the average treatment time was 16 months. Normal overjet and overbite were established with retroclination of upper incisors and proclination of lower incisors. U1-NA was decreased by 15.4° (P<0.01). ANB and Y axial angle were decreased significantly (P<0.05). Soft tissue measurements showed that FCA and UL-E were decreased dramatically (P<0.05), and LL-E was increased significantly (P<0.05). Remarkable soft tissue change was noted after the treatment and convex facial profile changed to the straight profile. In conclusion, Tip-Edge plus technique can quickly and efficiently correct anterior bite and lateral outlook.
Assuntos
Má Oclusão Classe II de Angle/terapia , Aparelhos Ortodônticos , Adolescente , Criança , Feminino , Humanos , MasculinoRESUMO
The purpose of this study was to investigate the cortical bone thickness of the inter-dental area of both jaws for orthodontic miniscrew placement. The cone-beam computerized tomography images of 32 non-orthodontic adults with normal occlusion were taken to measure the cortical bone thickness in both jaws. One-way analysis of variance (ANOVA) was used to analyze the differences in cortical bone thickness. Buccal cortical bone in the mandible was thicker than that in the maxilla. In the maxilla, cortical bone thickness was thicker in the buccal side than in the palatal side. Buccal cortical bone thickness in the mandible was thickest at the site distal to the first molar, and in the maxilla it was thickest at the site mesial to the first molar, while in the palatal side of maxilla it was thickest at the site mesial to the second premolar. The changing pattern of cortical bone thickness varies at different sites. In the buccal side of maxilla, the thinnest cortical bone thickness was found to be at 4 mm level from the alveolar crest, while the thickest was at 10 mm level (except for the site mesial to the first premolar). The buccal cortical bone thickness at the sites mesial or distal to the first molar in the mandible and palatal cortical bone thickness of maxilla tended to increase with increasing distance from the alveolar bone.
Assuntos
Parafusos Ósseos , Tomografia Computadorizada de Feixe Cônico/métodos , Implantação Dentária Endo-Óssea Endodôntica/instrumentação , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Maxila/diagnóstico por imagem , Maxila/cirurgia , Adulto , Implantação Dentária Endo-Óssea Endodôntica/métodos , Feminino , Humanos , Masculino , Radiografia Dentária/métodos , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Cirurgia Assistida por Computador/métodos , Adulto JovemRESUMO
PURPOSE: The epidermal growth factor receptor (EGFR) is one of the four human epidermal receptors. The efficacy and safety of EGFR-targeted therapies for treating non-small-cell lung cancer (NSCLC) remained controversial. The aim of this study was to systematically evaluate EGFR-targeted therapies plus chemotherapy for advanced NSCLC. METHODS: Cochrane Central Register of Controlled Trials, PubMed, and Embase were searched for relevant studies. Quantitative analysis was carried out to evaluate survival, response, and toxicity of EGFR-targeted therapies. RESULTS: Ten randomized controlled trials (RCTs) involving 5,936 patients were identified out of 107 studies. There was no statistical difference in overall (OS) and 1-year (OYS) survival rate when small-molecule tyrosine kinase inhibitors (TKIs) plus platinum-based doublet chemotherapy (PBDC) were compared with PBDC alone. However, progression-free survival [hazard ratio (HR)=0.87, 95% confidence interval (CI) 0.76-0.99] and overall response rate (ORR) were marginally improved. Prolonged OS (HR=0.87, 95% CI 0.78-0.96) and increased ORR and OYS were found when cetuximab plus PBDC was compared with PBDC alone. Adverse events in the combination arms were similar in incidence to those of the chemotherapy-alone arms, with the exception of an increased incidence of rash and diarrhea. CONCLUSIONS: Cetuximab adds benefits to NSCLC patients compared with PBDC alone. Small-molecule TKIs plus PBDC lead to a slightly additive efficacy compared with PBDC alone.
Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/fisiopatologia , Cetuximab , Intervalo Livre de Doença , Sistemas de Liberação de Medicamentos , Receptores ErbB/antagonistas & inibidores , Humanos , Neoplasias Pulmonares/fisiopatologia , Inibidores de Proteínas Quinases/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Dental stem/progenitor cells are a promising cell sources for alveolar bone (AB) regeneration because of their same embryonic origin and superior osteogenic potential. However, their molecular processes during osteogenic differentiation remain unclear. The objective of this study was to identify the responsiveness of dental follicle cells (DFCs) and AB marrow-derived mesenchymal stem cells (ABM-MSCs) to recombinant human bone morphogenetic protein-2 (rhBMP-2). These cells expressed vimentin and MSC markers and did not express cytokeratin and hematopoietic stem cell markers and showed multilineage differentiation potential under specific culture conditions. DFCs exhibited higher proliferation and colony-forming unit-fibroblast efficiency than ABM-MSCs; rhBMP-2 induced DFCs to differentiate toward a cementoblast/osteoblast phenotype and ABM-MSCs to differentiate only toward a osteoblast phenotype; and rhBMP-2-induced DFCs exhibited higher osteogenic differentiation potential than ABM-MSCs. These cells adhered, grew, and produced extracellular matrix on nanohydroxyapatite/collagen/poly(l-lactide) (nHAC/PLA). During a 14-day culture on nHAC/PLA, the extracellular alkaline phosphatase (ALP) activity of DFCs decreased gradually and that of ABM-MSCs increased gradually; rhBMP-2 enhanced their extracellular ALP activity, intracellular osteocalcin (OCN), and osteopontin (OPN) protein expression; and DFCs exhibited higher extracellular ALP activity and intracellular OCN protein expression than ABM-MSCs. When implanted subcutaneously in severe combined immunodeficient mice for 3 months, DFCs+nHAC/PLA+rhBMP-2 obtained higher percentage of bone formation area, OCN, and cementum attachment protein expression and lower OPN expression than ABM-MSCs+nHAC/PLA+rhBMP-2. These results showed that DFCs possessed superior proliferation and osteogenic differentiation potential in vitro, and formed higher quantity and quality bones in vivo. It suggested that DFCs might exhibit a more sensitive responsiveness to rhBMP-2, so that DFCs enter a relatively mature stage of osteogenic differentiation earlier than ABM-MSCs after rhBMP-2 induction. The findings imply that these dental stem/progenitor cells are alternative sources for AB engineering in regenerative medicine, and developing dental tissue may provide better source for stem/progenitor cells.
Assuntos
Proteína Morfogenética Óssea 2/farmacologia , Diferenciação Celular/efeitos dos fármacos , Saco Dentário/citologia , Células-Tronco Mesenquimais/citologia , Osteogênese/efeitos dos fármacos , Células-Tronco/citologia , Fator de Crescimento Transformador beta/farmacologia , Animais , Diferenciação Celular/genética , Células Cultivadas , Colágeno/metabolismo , Durapatita/metabolismo , Expressão Gênica/efeitos dos fármacos , Humanos , Imuno-Histoquímica , Células-Tronco Mesenquimais/metabolismo , Células-Tronco Mesenquimais/ultraestrutura , Microscopia Eletrônica de Varredura , Osteocalcina/genética , Osteocalcina/metabolismo , Osteogênese/genética , Osteopontina/genética , Osteopontina/metabolismo , Poliésteres/metabolismo , Ratos Sprague-Dawley , Proteínas Recombinantes/farmacologia , Células-Tronco/metabolismo , Células-Tronco/ultraestruturaRESUMO
OBJECTIVE: To investigate the transforming growth factor beta induced (TGFBI; BIGH3) gene mutation and founder effect of two large Chinese families clinically diagnosed as Thiel-Behnke corneal dystrophy. METHODS: Fifteen members including 13 affected and 2 healthy in family A, 14 members including 6 affected and 8 healthy in family B, as well as 20 other unrelated healthy individuals were tested for TGFBI gene mutation. Haplotype analysis and clinical examination were also carried out in the two families. RESULTS: In exon 12 of the TGFBI gene, 1664G to A change was detected in all the patients, which leads to an amino acid replacement of arginine with glutamine (p.Arg555Gln). Members of the two families share some similar haplotypes. CONCLUSION: Genetic analysis is helpful in the diagnosis of corneal dystrophy. The two families may come from a same ancestor.
Assuntos
Proteínas da Matriz Extracelular/genética , Efeito Fundador , Fator de Crescimento Transformador beta/genética , Adolescente , Adulto , Idoso , Povo Asiático/genética , Sequência de Bases , Criança , Distrofias Hereditárias da Córnea/diagnóstico , Distrofias Hereditárias da Córnea/genética , Éxons , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dados de Sequência Molecular , Linhagem , Mutação Puntual , Adulto JovemRESUMO
Human umbilical cord mesenchymal stem cells (hUC-MSCs) are a promising alternative source of mesenchymal stem cells (MSCs) that are enormously attractive for clinical use. This study was designed to investigate the effect of recombinant human bone morphogenetic protein-7 (rhBMP-7) and/or osteogenic media (OMD) on bone regeneration of hUC-MSCs seeded on nanohydroxyapatite/collagen/poly(l-lactide) (nHAC/PLA) in a rabbit model. The characteristics of stem cells were analyzed by plastic adherence, cell phenotype, and multilineage differentiation potential. Cell proliferation was examined using cell counting kit-8 assay. Osteogenic differentiation was evaluated by quantitative Ca2+ concentration, PO43- concentration, alkaline phosphatase (ALP) activity, osteocalcin (OCN) secretion, and mineralized matrix formation. Bone regeneration was investigated in jaw bone defect repair in rabbit by microcomputed tomography, fluorescent labeling, and hematoxylin and eosin staining. Except for initial stress response, OMD and OMD + rhBMP-7 inhibited the proliferation of hUC-MSCs seeded on nHAC/PLA; rhBMP-7 inhibited cell proliferation in the nonlogarithmic phase and attenuated the inhibitory effect of OMD on cell proliferation. The inhibitory effects of OMD, rhBMP-7, and OMD + rhBMP-7 on cell proliferation were ranked as OMD > OMD + rhBMP-7 > rhBMP-7. OMD, rhBMP-7, and OMD + rhBMP-7 promoted Ca2+ concentration, PO43- concentration, ALP activity, OCN secretion, and mineralized matrix formation of hUC-MSCs seeded on nHAC/PLA. The promoting effects of OMD, rhBMP-7, and OMD+rhBMP-7 on Ca2+ concentration, PO43- concentration, ALP activity, OCN secretion, and mineralized matrix formation were ranked as rhBMP-7 > OMD > OMD + rhBMP-7, OMD > OMD + rhBMP-7 > rhBMP-7, OMD > rhBMP-7 > OMD + rhBMP-7, rhBMP-7 > OMD + rhBMP-7 > OMD, and OMD > rhBMP-7 > OMD + rhBMP-7, respectively. In rabbit jaw bone defect repair, OMD, rhBMP-7, and OMD + rhBMP-7 enhanced bone regeneration of hUC-MSCs seeded on nHAC/PLA, but the largest bone mineral apposition rate and bone formation were presented in cultures with rhBMP-7. These findings suggested that the combined use of rhBMP-7 and OMD may have no ideal synergistic effect on bone regeneration of hUC-MSCs seeded on nHAC/PLA in rabbit jaw bone defect.
Assuntos
Proteína Morfogenética Óssea 7/farmacologia , Regeneração Óssea/efeitos dos fármacos , Colágeno/farmacologia , Durapatita/farmacologia , Células-Tronco Mesenquimais/citologia , Osteogênese , Poliésteres/farmacologia , Proteínas Recombinantes/farmacologia , Cordão Umbilical/citologia , Fosfatase Alcalina/metabolismo , Animais , Calcificação Fisiológica/efeitos dos fármacos , Cálcio/análise , Adesão Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Meios de Cultura , Feminino , Humanos , Arcada Osseodentária/efeitos dos fármacos , Arcada Osseodentária/patologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/ultraestrutura , Osteocalcina/metabolismo , Fosfatos/análise , CoelhosRESUMO
The present study aimed to evaluate the stem cell markers, characteristics and biological functions of cancer stemlike side population (SP) cells in human oral cancer. SP cells were isolated from the human oral squamous cell carcinoma Tca8113 cell line by Hoechst 33342 fluorescence dye and flow cytometry. The colony forming and proliferative capability of SP and nonSP cells were detected using a livecell analysis system in vitro. The number of cells expressing stem cell markers was compared between SP cells and nonSP cells by flow cytometry. Reverse transcriptionquantitative polymerase chain reaction and western blotting were used to detect the mRNA and protein expression levels of stem cell genes, respectively. Differential expression of microRNAs (miRNAs) in SP and nonSP cells was determined by microarray hybridization and an miRNA regulation network was produced. With regard to the proliferation capability, SP cells reached 60.0% confluence after 40 h of growth compared with 35.1% confluence for nonSP cells (P<0.05). The number of colonies in SP cells was 43.1±9.2 compared with 33.0±8.2 of nonSP cells (P<0.05). The aldehyde dehydrogenase1 (ALDH1)positive cell number in the SP cells was increased by 10 times compared with the nonSP cells (P<0.01). The mRNA and protein expression levels of ALDH1, SRYbox 2, POU class 5 homeobox 1 and Nanog homeobox in SP cells were significantly higher compared with nonSP cells (P<0.05). Microarray hybridization demonstrated that 21 miRNAs were upregulated and 13 miRNAs were downregulated in SP cells compared with nonSP cells. SP cells in Tca8113 demonstrated greater capability of proliferation and colony formation compared with nonSP cells in vitro. Stem cell markers were overexpressed in SP cells compared with nonSP cells.
Assuntos
Neoplasias de Cabeça e Pescoço/genética , MicroRNAs/genética , Células da Side Population/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Transcriptoma , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Células da Side Population/patologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Partially sintered 3 mol % yttria-stabilized tetragonal zirconium dioxide (ZrO(2), zirconia) polycrystal (3Y-TZP) ceramics are used in dental posterior restorations with computer-aided design-computer-aided manufacturing (CAD/CAM) techniques. High strength is acquired after sintering, but shape distortion of preshaped compacts during their sintering is inevitable. The aim of this study is to fabricate new machinable ceramic composites with strong mechanical properties that are fit for all-ceramic dental restorations. Aluminum oxide (Al(2)O(3))-coated 3Y-TZP powders were first prepared by the heterogeneous precipitation method starting with 3Y-TZP, Al(NO(3))(3) . 9H(2)O, and ammonia, then amorphous boron nitride (BN) was produced and the as-received composite powders were coated via in situ reaction with boric acid and urea. Transmission electron microscopy (TEM) and X-ray diffraction (XRD) were used to analyze the status of Al(2)O(3)-BN on the surface of the 3Y-TZP particles. TEM micrographs show an abundance of Al(2)O(3) particles and amorphous BN appearing uniformly on the surface of the 3Y-TZP particles after the coating process. The size of the Al(2)O(3) particles is about 20 nm. The XRD pattern shows clearly the peak of amorphous BN among the peaks of ZrO(2).
Assuntos
Óxido de Alumínio/química , Compostos de Boro/química , Cerâmica/química , Desenho Assistido por Computador , Implantes Dentários , Nanopartículas Metálicas/química , Ítrio/química , Zircônio/química , Materiais Biocompatíveis/química , Microscopia Eletrônica de Transmissão , Pós , Difração de Raios XRESUMO
OBJECTIVE: To observe the characteristics of brain activation during unilateral premolar occlusion. METHODS: Functional magnetic resonance imaging was collected from 10 healthy volunteers during occlusion of the left first premolar (L1), left second premolar (L2), and right first premolar (R1). The brain activation patterns were analyzed, and the primary sensorimotor cortex, supplementary motor area, insula, thalamus, and prefrontal cortex were chosen as regions of interest. RESULTS: Single premolar occlusion activated the precentral gyrus, postcentral gyrus, cerebellum, thalamus, frontal lobe, hippocampus, cingulate gyrus, and parietal lobe. The brain areas showing activation during single premolar occlusion were similar to those activated by chewing. The activation pattern of L1 was more similar to that of L2 than R1. No significant left and right hemisphere differences in signal intensity were detected within the regions of interest. CONCLUSION: Brain activation patterns from two ipsilateral premolars were more similar than the pattern from a contralateral premolar.
Assuntos
Dente Pré-Molar/fisiologia , Encéfalo/fisiologia , Oclusão Dentária , Adulto , Dente Pré-Molar/diagnóstico por imagem , Córtex Cerebral/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Mastigação/fisiologia , Córtex Motor/fisiologia , Córtex Pré-Frontal/fisiologia , Córtex Sensório-Motor/fisiologia , Tálamo/fisiologia , Adulto JovemRESUMO
Tooth preparation is the primary and core operation technique for dental esthetic restoration treatment, due to its effect of providing restoration space, bonding interfaces and marginal lines for dental rehabilitation after tooth tissue reduction. The concept of microscopic minimal invasive dentistry put forward the issue of conducting high-quality tooth preparation, conserve tooth-structure, protect vital pulp and periodontal tissue simultaneously. This study reviewed the concepts, physiology background, design and minimal invasive microscopic tooth preparation, and in the meantime, individualized strategies and the two core elements of tooth preparation (quantity and shape) are listed.
Assuntos
Porcelana Dentária , Estética Dentária , Preparo do Dente , Restauração Dentária PermanenteRESUMO
OBJECTIVE: To investigate the feasibility of using natural poritos as scaffolds in bone tissue engineering (TE) and repair of caprine mandibular segmental defect with titanium reticulum reinforced. METHODS: Natural poritos with a pore of 190-230 microm in size and porosity of about 50percent-65percent was molded into the shape of granules 5 mm x 5 mm x 5 mm in size. Expanded autologous caprine marrow mesenchymal stem cells were induced by recombinant human morphogenetic protein-2 (rhBMP2) to improve osteoblastic phenotype. Then marrow derived osteoblasts were seeded into poritos in density of 4 x 10(7)/ml and incubated in vitro for 48 hours prior to implantation. Then osteoblastic cells/poritos complexes were implanted into mandibular defect and the defect was reinforced by titanium reticulum. Implantation of poritos alone acted as the control. Bone regeneration was assessed 4, 8, 16 weeks after implantation using roentgenographic analysis and histological observation was done after 16 weeks. RESULTS: New bone could be observed histologically on the surface and in the pores of natural coral in all specimens in the cell-seeding group, whereas in the control group there was no evidence of osteogenesis process in the center of the construction. The results showed that new bone grafts were successfully restored 16 weeks after implantation. CONCLUSIONS: This study suggests the feasibility of using porous coral as scaffold material transplanted with marrow derived osteoblasts by TE method. By means of titanium reticulum reinforcement, mandibular defect could be successfully restored. It shows the potentiality of using this method for the reconstruction of bone defect in clinic.
Assuntos
Antozoários , Mandíbula/cirurgia , Osteoblastos/transplante , Osteogênese , Procedimentos de Cirurgia Plástica , Engenharia Tecidual , Titânio , Animais , Células da Medula Óssea , Proteínas Morfogenéticas Ósseas , Técnicas de Cultura de Células , Condrogênese , Cabras , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Camundongos , Porosidade , Radiografia , StentsRESUMO
In this study, the complete mitochondrial genome sequence of bearded pig, Sus barbatus, with the total length of 16,480 bp, is determined for the first time. This mitogenome harbors 13 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes, and one control region (D-loop). The overall base composition is A (34.80%), C (26.07%), G (13.12%), and T (26.01%), so the slight A-T bias (60.81%) was detected. Most of the genes are distributed on the H-strand, except for the ND6 subunit gene and eight tRNA genes. To obtain the phylogenetic relationship of the Cetartiodactyla, 11 mitochondrial genomes were used for phylogenetic analysis. The mitochondrial genome of S. barbatus presented here will contribute to a better understanding of the population genetics.
Assuntos
Genoma Mitocondrial , Genômica , Suínos/classificação , Suínos/genética , Animais , Composição de Bases , Genes Mitocondriais , Tamanho do Genoma , Genômica/métodos , Fases de Leitura Aberta , Filogenia , Análise de Sequência de DNA , Sequenciamento Completo do GenomaRESUMO
PURPOSE: To investigate bilateral temporomandibular joint of patients with unilateral multiple symptoms in cone-beam computed tomography (CBCT) and explore the reference planes that may be different,providing reference for the diagnosis of temporomandibular disorders and comparative study. METHODS: 50 cases with unilateral multiple symptomsï¼except for cases with unilateral single symptomï¼were examined by CBCT and the following indexes were observed and analyzed,including horizontal angles of the cross-sectional condyle after the reconstruction in the same patient, joint space, macroaxis diameter of condyle and vertical angles of condyle, which were commonly used at oblique position parallelled to the long axis of condyle, the gradient of articular tubercle and the joint space,which could be obtained at sagittal and oblique position vertical to the long axis of condyle.The data obtained was analyzed by paired t test with SPSS13.0 software package. RESULTS: There was significant difference between the bilateral measured value of joint space when the angle was 60° in sagittal plane (P<0.05).The difference was more significant when the angle was 120° in parallel plane and 90° in sagittal plane (P<0.01). The other measured parameters were not significant different. CONCLUSIONS: For patients with TMD, it is more easily to observe differences between the bilateral measured value of joint space in the sagittal or vertical plane,where the increase of the front joint space can be seen and construction was more significant.
Assuntos
Tomografia Computadorizada de Feixe Cônico , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Articulação Temporomandibular/diagnóstico por imagem , Estudos Transversais , Humanos , Côndilo MandibularRESUMO
The present study aimed to investigate the distribution and photodynamic therapeutic effect of chlorin e6 (Ce6) in the human tongue squamous cell carcinoma Tca8113 cell line in vitro. The distribution of Ce6 in the Tca8113 cells was observed in situ combined with mitochondrial and lysosomal fluorescent probes. Next, 630-nm semiconductor laser irradiation was performed. The MTS colorimetric method was used to determine cell survival. Annexin V fluorescein isothiocyanate/propidium iodide (PI) double staining was used to detect early apoptosis following photodynamic therapy (PDT). The flow cytometer was used to analyze the DNA content subsequent to PI-staining. It was observed that Ce6 could combine with the cellular membrane following 30 min of incubation with the Tca8113 cells. As the length of incubation increased, Ce6 gradually entered the cells in a particular distribution and reached saturation by 3 h. Co-localization analysis demonstrated that Ce6 was more likely to be present in the mitochondria than in the lysosomes. The cells incubated with 5 µg/ml Ce6 for 24 h exhibited a low toxicity of 5%, however, following light irradiation, Ce6-PDT was able to kill the Tca8113 cells in vitro. The cell toxicity was positively correlated with Ce6 concentration and light dose, therefore, the effect of Ce6 was concentration/dose-dependent (P<0.01). The lower Ce6 concentrations and light doses could significantly induce apoptosis in the Tca8113 cells, while higher doses increased necrosis/percentage of dead cells. In summary, Ce6 saturated the Tca8113 cells following 3 h of incubation. Furthermore, Ce6-PDT effectively killed the cultured Tca8113 cells in vitro at a safe concentration. At a low concentration and light dose, Ce6 is more likely to induce cell apoptosis via the mitochondria than the lysosomes.