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1.
Nat Immunol ; 12(10): 984-91, 2011 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-21892175

RESUMO

Major histocompatibility complex (MHC) class I molecules present peptides on the cell surface to CD8(+) T cells, which is critical for the killing of virus-infected or transformed cells. Precursors of MHC class I-presented peptides are trimmed to mature epitopes by the aminopeptidase ERAP1. The US2-US11 genomic region of human cytomegalovirus (HCMV) is dispensable for viral replication and encodes three microRNAs (miRNAs). We show here that HCMV miR-US4-1 specifically downregulated ERAP1 expression during viral infection. Accordingly, the trimming of HCMV-derived peptides was inhibited, which led to less susceptibility of infected cells to HCMV-specific cytotoxic T lymphocytes (CTLs). Our findings identify a previously unknown viral miRNA-based CTL-evasion mechanism that targets a key step in the MHC class I antigen-processing pathway.


Assuntos
Aminopeptidases/antagonistas & inibidores , Linfócitos T CD8-Positivos/imunologia , Citomegalovirus/genética , MicroRNAs/fisiologia , Aminopeptidases/genética , Aminopeptidases/fisiologia , Apresentação de Antígeno , Linhagem Celular , Citomegalovirus/imunologia , Infecções por Citomegalovirus/imunologia , Regulação para Baixo , Humanos , Antígenos de Histocompatibilidade Menor , Ovalbumina/metabolismo
2.
J Craniofac Surg ; 34(7): e675-e678, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37582294

RESUMO

OBJECTIVES: This retrospective study aims to compare long-term stability between the mandibular setback surgery-early (MSE) approach, involving minimal orthodontics, and the mandibular setback conventional surgery (MCS) approach, involving sufficient orthodontics, in Class III patients with mandibular prognathism. METHODS: Among 210 patients who underwent orthognathic surgery, a total of 40 subjects were enrolled based on standardized inclusion criteria: only mandibular surgery, <5 mm setback difference between right and left of the mandible, orthodontics with fixed appliances, and more than 2 years of follow-up after treatment. These patients were allocated to the MSE (n = 20) and MCS groups (n = 20) according to the duration of presurgical orthodontics. Changes in cephalometric measurements were compared between the MSE and MCS groups before surgery (T0), 1 month after surgery (T1), at the end of treatment (T2), and posttreatment retention (T3). RESULTS: The MSE and MCS groups had a mean presurgical orthodontic duration of 2 and 9.5 months, respectively. From T1 to T2, the MSE group showed a significantly larger forward movement of the mandible than the MCS group (2.1 versus 0.7 mm; P < 0.001). In addition, from T2 to T3 (average 4.6 years), the MSE group presented anterior relapse of 0.6 mm in the mandible, but there were no statistically significant intergroup differences. CONCLUSION: Although the MSE group showed greater postsurgical forward mandibular relapse than the MCS group, the two groups exhibited similar skeletal and dental stability during the posttreatment retention.


Assuntos
Má Oclusão Classe III de Angle , Maxila , Humanos , Seguimentos , Estudos Retrospectivos , Resultado do Tratamento , Maxila/cirurgia , Má Oclusão Classe III de Angle/cirurgia , Mandíbula/cirurgia , Cefalometria , Recidiva
3.
BMC Oral Health ; 23(1): 308, 2023 05 22.
Artigo em Inglês | MEDLINE | ID: mdl-37217906

RESUMO

BACKGROUND: Few trials have compared the results of surgical treatment for peri-implantitis based on severity of peri-implantitis and surgical method. This study investigated the survival rate of implants based on type of surgical method used and initial severity of peri-implantitis. Classification of severity was determined based on bone loss rate relative to fixture length. METHODS: Medical records of patients who underwent peri-implantitis surgery from July 2003 to April 2021 were identified. Classification of peri-implantitis was divided into 3 groups (stage 1: bone loss < 25% (of fixture length), stage 2: 25% < bone loss < 50%, stage 3: bone loss > 50%) and performance of resective or regenerative surgery was investigated. Kaplan-Meier survival curves and Cox hazards proportional models were used to analyze the cumulative survival rate of implants. Median survival time, predicted mean survival time, hazard ratio (HR), and 95% confidence interval (CI) were calculated. RESULTS: Based on Kaplan-Meier analysis, 89 patients and 227 implants were included, and total median postoperative survival duration was 8.96 years. Cumulative survival rates for stage 1, 2, and 3 were 70.7%, 48.9%, and 21.3%, respectively. The mean survival time for implants in stage 1, 2, and 3 was 9.95 years, 7.96 years, and 5.67 years, respectively, with statistically significant difference (log-rank p-value < 0.001). HRs for stage 2 and stage 3 were 2.25 and 4.59, respectively, with stage 1 as reference. Significant difference was not found in survival time between resective and regenerative surgery groups in any peri-implantitis stage. CONCLUSIONS: The initial bone loss rate relative to the fixture length significantly correlated with the outcome after peri-implantitis surgery, demonstrating a notable difference in the long-term survival rate. Difference was not found between resective surgery and regenerative surgery in implant survival time. Bone loss rate could be utilized as a reliable diagnostic tool for evaluating prognosis after surgical treatment, regardless of surgical method used. TRIAL REGISTRATION: Retrospectively registered. (KCT0008225).


Assuntos
Perda do Osso Alveolar , Implantes Dentários , Peri-Implantite , Humanos , Peri-Implantite/cirurgia , Estudos Retrospectivos , Análise de Sobrevida , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/cirurgia
4.
J Oral Implantol ; 2022 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-35881816

RESUMO

Research regarding bone density assessment using cone beam computed tomography in low bone density regions is sparse. This in vitro study aimed to evaluate the predictability of cone beam computed tomography for low bone density regions and its correlations with primary implant stability when placing tapered design implants with a stepped osteotomy. Eighteen porcine mandibular condyles were used as simulated low bone density regions. Hounsfield units (HU), obtained via multislice computed tomography, and gray values (GV), obtained via cone beam computed tomography, were measured three times at one-month intervals. The maximum implant insertion torque (MIT) and implant stability quotient (ISQ) were recorded as the taper design implants were placed using a stepped osteotomy. HU and GV were measured as 335.05-803.07 and 389.98-906.40, respectively. For repeated measurements of HU and GV, the intraclass correlation coefficients were 0.989 and 0.980; the corresponding value for mean HU and GV was 0.768. Bland-Altman plots showed a mean difference between HU and GV of -78.15. Pearson correlation coefficients revealed a strong correlation between HU and GV (r=0.91, p<0.01). The mean ± standard deviation values for MIT and ISQ were 36.44 ± 6.64 Ncm and 80.85 ± 2.03, respectively, but no statistically significant correlations were found with GV and HU. Within the study's limitations, GV showed similar bone density estimation compared to HU in soft bones. Tapered implant placement with a stepped osteotomy achieved stable primary implant stability in soft bones. However, these in vitro results need to be approved in further clinical studies.

5.
BMC Oral Health ; 22(1): 97, 2022 03 29.
Artigo em Inglês | MEDLINE | ID: mdl-35351072

RESUMO

BACKGROUND: This study was performed to evaluate the long-term clinical efficacy of the CA implants (Osstem Implant, Busan, Korea), calcium-modified surfaced treated implants on acid-etched surfaces sandblasted with alumina. METHODS: From January 2013 to December 2015, 258 implants of 120 patients placed between 2013 and 2015 were retrospectively studied. Using medical records and periapical radiographs, sex, age, location, fixture width and length of placed implants, presence or absence of bone graft, types of bone substitutes and membrane used for bone grafting, primary and secondary stability, initial and delayed complications, and marginal bone loss were investigated. The success rate and survival rate of the implants in each group were analyzed retrospectively based on the criteria suggested by Albrektsson et al. RESULTS: Between 2013 and 2015, with a follow-up longer than 5 years, 258 implants with an average diameter of 4.63 mm (3.5-5.5 mm) and an average length of 9.94 mm (7.0-13.0 mm) were placed in a total of 120 patients (61 males and 59 females) with a mean age of 63.7 years for an average of 62 months of observation period. The survival rate was 97.3%, the success rate was 94.2%, and the average final marginal bone loss was 0.074 mm. CONCLUSION: The CA implants manufactured with the improved surface treatment method exhibited a survival rate of 97.3% and a success rate of 94.2% over an average observation period of 62 months. The implants were not affected by most factors and had very high survival and success rates over a long period of observation. In particular, the stability of the implant was excellent, with no cases of failed implants in delayed placement after bone grafting and a healing period.


Assuntos
Perda do Osso Alveolar , Implantes Dentários , Perda do Osso Alveolar/diagnóstico por imagem , Perda do Osso Alveolar/etiologia , Implantação Dentária Endóssea/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
6.
BMC Oral Health ; 22(1): 8, 2022 01 16.
Artigo em Inglês | MEDLINE | ID: mdl-35034613

RESUMO

BACKGROUND: The aim of this study was to assess the accuracy of virtual planning of computer-guided surgery based on the actual outcomes of clinical dental implant placement. METHODS: This retrospective study enrolled patients among whom implant treatment was planned using computer-guided surgery with cone beam computed tomography (CBCT). The patients who received implant according to the guide with the flapless and flapped approach were classified as group 1 and 2, respectively, and the others who could not be placed according to the guide were allocated to the drop-out group. The accuracy of implant placement was evaluated with the superimposition of CBCT. RESULTS: We analyzed differences in the deviated distance of the entrance point and deviated angulation of the insertion of implant fixtures. With regard to the surgical approach, group 2 exhibited greater accuracy compared to group 1 in deviation distance (2.22 ± 0.88 and 3.18 ± 0.89 mm, respectively, P < 0.001) and angulation (4.27 ± 2.30 and 6.82 ± 2.71°, respectively, P = 0.001). The limitations of guided surgery were discussed while considering the findings from the drop-out group. CONCLUSIONS: Computer-guided surgery demonstrates greater accuracy in implant placement with the flapless approach. Further research should be conducted to enhance the availability of guides for cases with unfavorable residual bone conditions.


Assuntos
Implantes Dentários , Cirurgia Assistida por Computador , Desenho Assistido por Computador , Computadores , Tomografia Computadorizada de Feixe Cônico , Implantação Dentária Endóssea/métodos , Humanos , Imageamento Tridimensional , Planejamento de Assistência ao Paciente , Estudos Retrospectivos , Cirurgia Assistida por Computador/métodos
7.
Clin Oral Investig ; 25(8): 4861-4869, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33475827

RESUMO

OBJECTIVES: The purpose of this retrospective study was to evaluate the accuracy of intraoral scan (IOS) images in the maxillary and mandibular arches with orthodontic brackets. MATERIAL AND METHODS: From digital impressions of 140 patients who underwent orthodontic treatment, consecutive IOS images were selected based on standardized inclusion criteria: Two pre-orthodontic IOS images (IOS1 and IOS2) of permanent dentition with fully erupted second molars and IOS images obtained immediately after orthodontic bracket bonding (IOSb). Superimpositions were performed to evaluate the reproducibility of repeated IOS images. Accuracy of IOSb images was analyzed by comparing the average surface errors between IOS1c and IOS2c images, which were IOS images cut based on the same region of the interest as between IOS1 and IOSb images. RESULTS: A total of 84 IOS images was analyzed. The average surface errors between IOS1 and IOS2 images were 57 ± 8 µm and 59 ± 14 µm in the maxillary and mandibular arch, respectively, and their reliability was almost perfect. The average errors between IOSb and IOS1c images exhibited an increase, which measured 97 ± 28 µm in the maxillary arch and 95 ± 29 µm in the mandibular arch. These surface deviations between IOSb and IOS1c images were significantly larger in each region as well as entire dentition (P < 0.001) compared to those between IOS1c and IOS2c images. CONCLUSIONS: The average surface errors of the scans with brackets showed increased values compared with those without brackets. This suggests that orthodontic brackets could affect the trueness of intraoral scan images. CLINICAL RELEVANCE: It is necessary for clinicians to consider the effect of brackets on digital impression when using IOS images in orthodontic patients.


Assuntos
Braquetes Ortodônticos , Desenho Assistido por Computador , Arco Dental/diagnóstico por imagem , Técnica de Moldagem Odontológica , Humanos , Imageamento Tridimensional , Modelos Dentários , Reprodutibilidade dos Testes , Estudos Retrospectivos
8.
J Craniofac Surg ; 32(2): 612-615, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33704993

RESUMO

OBJECTIVES: To evaluate the linear, angular, and volumetric changes of soft tissue after clockwise repositioning of the maxillo-mandibular complex in skeletal class III patients using three-dimensional (3D) stereophotogrammetry and to determine the correlation between changes in the skeletal and soft tissue variables. METHODS: This study included 18 skeletal class III patients who underwent two-jaw surgery; superior impaction and clockwise rotational movement of the maxilla with the rotation center at upper incisors, and setback of the mandible. Lateral cephalograms and 3D photographs taken before and 6 months after surgery were compared. RESULTS: After maxillary impaction of anteriorly 1.7 mm and posteriorly 3.1 mm, and mandibular setback of 8.7 mm, the volume of lower lip and chin region decreased significantly by 33.6 cm3 (13% net change, P < 0.001), while paranasal and upper lip region volume increased by 3.2 cm3 (2%) and 7.2 cm3 (4%), respectively. CONCLUSION: The clockwise rotation of maxillo-mandibular complex in class III patients significantly reduced lower lip and chin volume with minimal increase in paranasal and upper lip volumes. 3D stereophotogrammetry can provide quantitative evaluation of facial soft tissue volumetric changes.


Assuntos
Má Oclusão Classe III de Angle , Cefalometria , Humanos , Má Oclusão Classe III de Angle/diagnóstico por imagem , Má Oclusão Classe III de Angle/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Maxila/diagnóstico por imagem , Maxila/cirurgia , Fotogrametria , Rotação
9.
J Craniofac Surg ; 32(7): 2441-2445, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33710053

RESUMO

ABSTRACT: The authors analyzed the three-dimensional postoperative condylar position change across the plating systems. This retrospective study was conducted with the patients who underwent bilateral sagittal split ramus osteotomy with setback surgery. The condylar change was analyzed from preoperative cone-beam computed tomography to postoperative 1 month (T1) and postoperative 6 months (T2) using superimposition software, automatically merging based on the anterior cranial base. The condylar changes during T1 and T2 were analyzed across the four types of plates (4-hole sliding, heart-shaped, 3-hole sliding, and 4-hole conventional) Mean intraclass correlation coefficient values were consistently high for each measurement (>0.850). During T1, the conventional plate had a decreased condylar anterior distance when compared with the 3-hole sliding plate (P = 0.032). During T2, the conventional plate had an increased condylar posterior distance when compared with the 3-hole sliding plate (P = 0.031). Superimposition software based on the anterior cranial base could be available for measurement of condylar position with highly reproducible results. After bilateral sagittal split ramus osteotomy, the 3-hole sliding plate could effectively compensate for the anterior displacement of the condyle compared to other plates.


Assuntos
Implantes Dentários , Procedimentos Cirúrgicos Ortognáticos , Humanos , Mandíbula/diagnóstico por imagem , Mandíbula/cirurgia , Côndilo Mandibular/diagnóstico por imagem , Côndilo Mandibular/cirurgia , Osteotomia Sagital do Ramo Mandibular , Estudos Retrospectivos
10.
Int J Mol Sci ; 22(15)2021 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-34360933

RESUMO

Cisplatin is among the most widely used anticancer drugs used in the treatment of several malignancies, including oral cancer. However, cisplatin treatment often promotes chemical resistance, subsequently causing treatment failure. Several studies have shown that epidermal growth factor receptors (EGFRs) play a variety of roles in cancer progression and overcoming cisplatin resistance. Therefore, this study focused on EGFR inhibitors used in novel targeted therapies as a method to overcome this resistance. We herein aimed to determine whether the combined effects of cisplatin and cetuximab could enhance cisplatin sensitivity by inhibiting the epithelial-to-mesenchymal transition (EMT) process in cisplatin-resistant cells. In vitro analyses of three cisplatin-resistant oral squamous cell carcinoma cells, which included cell proliferation assay, combination index calculation, cell cytotoxicity assay, live/dead cell count assay, Western blot assay, propidium iodide staining assay, scratch assay, and qRT-PCR assay were then conducted. Our results showed that a cisplatin/cetuximab combination treatment inhibited cell proliferation, cell motility, and N-cadherin protein expression but induced E-cadherin and claudin-1 protein expression. Although the combination of cisplatin and cetuximab did not induce apoptosis of cisplatin-resistant cells, it may be useful in treating oral cancer patients with cisplatin resistance given that it controls cell motility and EMT-related proteins.


Assuntos
Cetuximab/farmacologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Receptores ErbB/antagonistas & inibidores , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Combinação de Medicamentos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Humanos
11.
BMC Oral Health ; 21(1): 201, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879162

RESUMO

BACKGROUND: We previously reported similar efficacies of alveolar ridge preservation (ARP) on single extraction socket with two different E. coli derived recombinant human bone morphogenetic protein-2 (rhBMP-2) delivery systems (Cowell BMP, Cowell medi Co, Busan, Korea; ß-tricalcium phosphate and hydroxyapatite particle & O-BMP, Osstem Implant Co, Busan, Korea; absorbable collagen sponge). After the trial, we completed implant therapy and observed over an average of 3 years. This follow-up study was performed retrospectively to compare result of implant treatment at the preserved alveolar ridge site. METHODS: Patients who underwent extraction of single tooth and received ARP with one of two rhBMP-2 delivery systems from October 2015 to October 2016 were enrolled. Twenty-eight patients (Group 1: Cowell BMP 14; Group 2: O-BMP 14) who underwent implant therapy and prosthetic treatment were included in study. Stability and marginal bone loss (MBL) of each implant were collected from medical charts and radiographs, and analyzed. The survival and success rates of implants were calculated. RESULTS: The primary implant stability represented by implant stability quotient (ISQ) for Groups 1 and 2 was 69.71 and 72.86, respectively. The secondary implant stability for Groups 1 and 2 was 78.86 and 81.64, respectively. Primary and secondary stabilities were not statistically different (P = 0.316 and 0.185, respectively). MBL at the latest follow-up was 0.014 mm in Group 1 over 33.76 ± 14.31 months and 0.021 mm in Group 2 over 40.20 ± 9.64 months, with no significant difference (P = 0.670). In addition, the success rate of implants was 100% (14/14) in Group 1 and 92.9% (13/14) in Group 2, with survival rate of 100% (14/14) in Group 1 and 92.9% (13/14) in Group 2. CONCLUSIONS: We confirmed good prognosis in both groups as a result of implant therapy after ARP with each of two rhBMP-2 carriers.


Assuntos
Aumento do Rebordo Alveolar , Implantes Dentários para Um Único Dente , Implantes Dentários , Processo Alveolar/diagnóstico por imagem , Processo Alveolar/cirurgia , Proteína Morfogenética Óssea 2 , Escherichia coli , Seguimentos , Humanos , Prognóstico , Proteínas Recombinantes , República da Coreia , Estudos Retrospectivos , Extração Dentária , Alvéolo Dental/cirurgia , Fator de Crescimento Transformador beta
12.
BMC Oral Health ; 21(1): 182, 2021 04 09.
Artigo em Inglês | MEDLINE | ID: mdl-33836733

RESUMO

BACKGROUND: Occlusal stress from oral parafunctional habits is one of the causes of temporomandibular disorders (TMD) and mandibular torus (MT). Although some studies have investigated the correlation between TMD and MT, understanding of the relationships between types of TMD and MT is insufficient. Therefore, we conducted this study to investigate the associations between presence of MT and TMD types. METHODS: This study included 77 patients diagnosed with TMD who first visited our clinic for TMD between March 2019 and July 2020. Among them, 30 (38.9%) had MT, and 54 (70.1%) had oral parafunction. Parafunctional activity during sleep was confirmed using a temporary splint for checking bruxism (TSCB). RESULTS: The relationship between prevalence of MT and oral parafunction in TMD patients was not statistically significant (P = 0.131), but the odds ratio was relatively high at 2.267. An analysis of TMD type revealed that Type I, which is classified as myalgia of the masticatory muscles, and MT had a significant association (P = 0.011). We fabricated a TSCB for 27 patients to wear during sleep and confirmed that 23 (85.2%) had nocturnal bruxism. The TSCB results and presence of MT showed a significant relationship (P = 0.047). CONCLUSION: Through the results of this study, clinicians may consider the hyperactivity of masticatory muscles in the presence of MT when treating TMD patients. In addition, TSCB has a great diagnostic value as it can be easily manufactured and be useful for discovering pre-existing oral parafunctions that patients are not aware of.


Assuntos
Bruxismo , Transtornos da Articulação Temporomandibular , Bruxismo/complicações , Humanos , Músculos da Mastigação , Fatores de Risco , Contenções
13.
Circ Res ; 123(4): 443-450, 2018 08 03.
Artigo em Inglês | MEDLINE | ID: mdl-29986945

RESUMO

RATIONALE: Human-induced pluripotent stem cell-derived endothelial cells (iPSC-ECs) have risen as a useful tool in cardiovascular research, offering a wide gamut of translational and clinical applications. However, inefficiency of the currently available iPSC-EC differentiation protocol and underlying heterogeneity of derived iPSC-ECs remain as major limitations of iPSC-EC technology. OBJECTIVE: Here, we performed droplet-based single-cell RNA sequencing (scRNA-seq) of the human iPSCs after iPSC-EC differentiation. Droplet-based scRNA-seq enables analysis of thousands of cells in parallel, allowing comprehensive analysis of transcriptional heterogeneity. METHODS AND RESULTS: Bona fide iPSC-EC cluster was identified by scRNA-seq, which expressed high levels of endothelial-specific genes. iPSC-ECs, sorted by CD144 antibody-conjugated magnetic sorting, exhibited standard endothelial morphology and function including tube formation, response to inflammatory signals, and production of NO. Nonendothelial cell populations resulting from the differentiation protocol were identified, which included immature cardiomyocytes, hepatic-like cells, and vascular smooth muscle cells. Furthermore, scRNA-seq analysis of purified iPSC-ECs revealed transcriptional heterogeneity with 4 major subpopulations, marked by robust enrichment of CLDN5, APLNR, GJA5, and ESM1 genes, respectively. CONCLUSIONS: Massively parallel, droplet-based scRNA-seq allowed meticulous analysis of thousands of human iPSCs subjected to iPSC-EC differentiation. Results showed inefficiency of the differentiation technique, which can be improved with further studies based on identification of molecular signatures that inhibit expansion of nonendothelial cell types. Subtypes of bona fide human iPSC-ECs were also identified, allowing us to sort for iPSC-ECs with specific biological function and identity.


Assuntos
Células Endoteliais/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Transcriptoma , Receptores de Apelina/genética , Receptores de Apelina/metabolismo , Diferenciação Celular , Células Cultivadas , Claudina-5/genética , Claudina-5/metabolismo , Conexinas/genética , Conexinas/metabolismo , Células Endoteliais/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Proteoglicanas/genética , Proteoglicanas/metabolismo , Análise de Célula Única , Proteína alfa-5 de Junções Comunicantes
14.
Proc Natl Acad Sci U S A ; 114(52): E11111-E11120, 2017 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-29203658

RESUMO

Patient-specific pluripotent stem cells (PSCs) can be generated via nuclear reprogramming by transcription factors (i.e., induced pluripotent stem cells, iPSCs) or by somatic cell nuclear transfer (SCNT). However, abnormalities and preclinical application of differentiated cells generated by different reprogramming mechanisms have yet to be evaluated. Here we investigated the molecular and functional features, and drug response of cardiomyocytes (PSC-CMs) and endothelial cells (PSC-ECs) derived from genetically relevant sets of human iPSCs, SCNT-derived embryonic stem cells (nt-ESCs), as well as in vitro fertilization embryo-derived ESCs (IVF-ESCs). We found that differentiated cells derived from isogenic iPSCs and nt-ESCs showed comparable lineage gene expression, cellular heterogeneity, physiological properties, and metabolic functions. Genome-wide transcriptome and DNA methylome analysis indicated that iPSC derivatives (iPSC-CMs and iPSC-ECs) were more similar to isogenic nt-ESC counterparts than those derived from IVF-ESCs. Although iPSCs and nt-ESCs shared the same nuclear DNA and yet carried different sources of mitochondrial DNA, CMs derived from iPSC and nt-ESCs could both recapitulate doxorubicin-induced cardiotoxicity and exhibited insignificant differences on reactive oxygen species generation in response to stress condition. We conclude that molecular and functional characteristics of differentiated cells from human PSCs are primarily attributed to the genetic compositions rather than the reprogramming mechanisms (SCNT vs. iPSCs). Therefore, human iPSCs can replace nt-ESCs as alternatives for generating patient-specific differentiated cells for disease modeling and preclinical drug testing.


Assuntos
Diferenciação Celular , Metilação de DNA , Células Endoteliais/metabolismo , Regulação da Expressão Gênica , Células-Tronco Embrionárias Humanas/metabolismo , Células-Tronco Pluripotentes Induzidas/metabolismo , Miócitos Cardíacos/metabolismo , Técnicas de Transferência Nuclear , Células Endoteliais/citologia , Estudo de Associação Genômica Ampla , Células-Tronco Embrionárias Humanas/citologia , Humanos , Células-Tronco Pluripotentes Induzidas/citologia , Miócitos Cardíacos/citologia
15.
Int J Mol Sci ; 21(23)2020 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-33255409

RESUMO

Cisplatin and paclitaxel are commonly used to treat oral cancer, but their use is often limited because of acquired drug resistance. Here, we tested the effects of combined cisplatin and paclitaxel on three parental (YD-8, YD-9, and YD-38) and three cisplatin-resistant (YD-8/CIS, YD-9/CIS, and YD-38/CIS) oral squamous cell carcinoma (OSCC) cell lines using cell proliferation assays and combination index analysis. We detected forkhead box protein M1 (FOXM1) mRNA and protein expression via real-time qPCR and Western blot assays. Cell death of the cisplatin-resistant cell lines in response to these drugs with or without a FOXM1 inhibitor (forkhead domain inhibitory compound 6) was then measured by propidium iodide staining and TdT dUTP nick end labeling (TUNEL) assays. In all six OSCC cell lines, cell growth was more inhibited by paclitaxel alone than combination therapy. Cisplatin-induced overexpression of FOXM1 showed the same trend only in cisplatin-resistant cell lines, indicating that it was associated with inhibition of paclitaxel-related apoptosis. In summary, these results suggest that, in three cisplatin-resistant cell lines, the combination of cisplatin and paclitaxel had an antagonistic effect, likely because cisplatin blocks paclitaxel-induced apoptosis. Cisplatin-induced FOXM1 overexpression may explain the failure of this combination.


Assuntos
Cisplatino/farmacologia , Proteína Forkhead Box M1/genética , Paclitaxel/farmacologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Cisplatino/efeitos adversos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia
16.
Mol Biol Rep ; 46(1): 617-625, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30478746

RESUMO

The purpose of this study was to evaluate the synergistic apoptotic effect of CKD-602 in combination with cisplatin on different p53 statuses of oral squamous cell carcinoma (OSCC) cell lines, YD-8, YD-9, and YD-38. MTT assays were used to evaluate the inhibitory effect of the treatments modality on cell growth. The combination index was calculated using CompuSyn software. Detection of cell death was carried out using the propidium iodide (PI)/RNase staining assay, Annexin V/PI double staining assay, and Western blotting. Combination treatment using CKD-602 and cisplatin inhibited proliferation and increased the apoptotic effect on the three OSCC cell lines. Apoptotic cell death was detected in the cell lines, and significant synergistic effects of CKD-602 in combination with cisplatin were observed despite the differences in p53 status. From these results, it was suggested that the combination of CKD-602 with cisplatin might be a potential therapeutic strategy for OSCC. In particular, cell line-specific therapy is necessary because of the differences in treatment response based on p53 status.


Assuntos
Camptotecina/análogos & derivados , Cisplatino/farmacologia , Proteína Supressora de Tumor p53/fisiologia , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Camptotecina/farmacologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Sinergismo Farmacológico , Células Epiteliais/metabolismo , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
17.
Clin Oral Implants Res ; 30(5): 396-409, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30883942

RESUMO

OBJECTIVES: This 12-week clinical trial evaluated efficacy and adverse events for two recombinant human bone morphogenetic protein-2 (rhBMP-2) delivery systems in alveolar ridge preservation. MATERIALS AND METHODS: Sixty-four patients had a single tooth that required replacement with an implant, surrounded by > 50% alveolar bone height. Two cohorts (n = 32 patients each) were randomized to receive a rhBMP-2-soaked absorbable collagen sponge (test group), or ß-tricalcium phosphate and hydroxyapatite particles (control group) immersed in rhBMP-2, at the implant site. Bone height and width changes at 25%, 50%, and 75% of extraction socket level (ESL) were compared. Adverse events were assessed in the same period. In addition to the randomized controlled clinical trial, histological analysis of 21 patients (test group [n = 12], control group [n = 9]) was conducted, 4 months after alveolar ridge preservation. A non-inferiority test was used to analyze changes in alveolar bone height between groups (p = 0.05). A Wilcoxon rank-sum test was used to analyze changes in alveolar bone width and histomorphometric results between groups (p = 0.05). RESULTS: All patients showed good healing without severe adverse events. The lower limit of the one-sided 97.5% confidence interval in the difference between the two groups was 0.0033 (non-inferiority margin: -0.185); thus, the test group showed non-inferiority to the control group. Wilcoxon rank-sum test analysis did not show statistically significant differences between groups with regard to changes in alveolar bone width and histomorphometric analysis. CONCLUSIONS: The delivery systems showed similar efficacy for alveolar ridge preservation without severe adverse events.


Assuntos
Perda do Osso Alveolar , Aumento do Rebordo Alveolar , Processo Alveolar , Proteína Morfogenética Óssea 2 , Humanos , Proteínas Recombinantes , Extração Dentária , Alvéolo Dental , Fator de Crescimento Transformador beta
18.
J Nanosci Nanotechnol ; 19(7): 4015-4019, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-30764963

RESUMO

This study investigated the room-temperature compressive property and deformation behavior of microporous STS 316L stainless steel tube for catalyst manufactured with powder sintering after two-way compression molding. The microporous tube was manufactured using STS 316L powder stocks with an outer diameter of 30 mm, inner diameter of 25 mm and length of 120 mm. In initial microstructure observed from different directions and locations, the porosity was measured as 32%, and the relative density obtained using micro-computed tomography was 0.54. Phase analysis did not identify phases other than γ-Fe. In a room temperature compression test, compressive yield strength measured 32 MPa. Observation of fractpgraphy after compression test revealed that dimples were formed at the powder-powder interface during the process where necks were disconnected. Based on the above findings, this study attempted to identify the deformation behavior of microporous STS 316L material manufactured with powder sintering after two-way compression molding and powder sintering process.

19.
J Oral Maxillofac Surg ; 77(5): 1072.e1-1072.e9, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30707985

RESUMO

PURPOSE: The aims of this study were to compare the presurgical conditions, surgical changes, and postsurgical changes in patients with skeletal Class III malocclusion with different degrees of horizontal relapse after mandibular setback surgery (MS) with minimal presurgical orthodontics (MPO) and to identify the factors contributing to this relapse. MATERIALS AND METHODS: For this retrospective study, 33 consecutive patients who underwent MS-MPO were selected. Lateral cephalograms were taken preoperatively (T0), 1 month after surgery (T1), and at orthodontic debonding (T2). Patients were divided into low relapse (LR; n = 18; relapse, <1 mm) and high relapse (HR; n = 15; relapse, >2 mm) groups based on the cephalometric distance of mandibular horizontal relapse. Paired t test, independent t test, and Pearson correlation analysis were used to evaluate surgical (T0 to T1) and postsurgical (T1 to T2) changes in the skeletodental variables and to explore the relation between surgical changes and horizontal relapse. RESULTS: Compared with the LR group, the HR group exhibited more upward movement with counterclockwise rotation of the mandible from T1 to T2. The HR group presented at T0 with a more prognathic mandible, greater vertical facial height, and a positive overbite. In addition, the HR group presented more posterior movement with clockwise rotation of the mandible, increased overjet, and decreased overbite from T0 to T1. Horizontal relapse of the mandible was positively correlated with the amount of setback and clockwise rotation of the mandible and the change in overjet and was negatively correlated with the change in overbite. CONCLUSIONS: Mandibular instability was related to the extent of setback and clockwise rotation of the mandible, decreased overbite, and increased overjet during MS-MPO.


Assuntos
Ortodontia , Procedimentos Cirúrgicos Ortognáticos , Cefalometria , Seguimentos , Humanos , Má Oclusão Classe III de Angle , Mandíbula/cirurgia , Maxila , Recidiva , Estudos Retrospectivos
20.
Implant Dent ; 28(1): 39-45, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30570584

RESUMO

PURPOSE: The purpose of this study was to evaluate the clinical, histological and radiographic outcomes of the calcium phosphate double-coated anorganic bovine bone (InduCera; Oscotec Inc., Seongnam, Gyeonggi, Republic of Korea) compared with that of anorganic bovine bone (Bio-Oss; Geistlich Biomaterials, Wolhusen, Switzerland) in maxillary sinus augmentation, prospectively. PATIENTS AND METHODS: Twenty-eight sinuses in 25 patients (3 bilateral) with vertical alveolar bone height from 2 to 5 mm were included in this study. The maxillary sinus was augmented with InduCera or Bio-Oss, followed by a healing period of 6 months. Trephine cores were obtained for histomorphometric evaluation with the implant placement. Cone-beam computed tomography (CBCT) scans were taken at 1 week and 6 months after sinus augmentation. RESULTS: The graft sites were healed without any notable complications in both groups. In histomorphometric analysis, the area of the newly formed bone was measured as 21.37 ± 8.87% for InduCera and 23.02 ± 5.88% for Bio-Oss, with no significant differences. Radiographically, no statistically significant differences were calculated between the groups in bone height at baseline, the height of bone augmentation, the final alveolar bone height (alveolar bone height + augmented height) after 6 months in panoramic radiograph. There were also no significant differences in the shrinkage rate of the grafted area volume in CBCT. CONCLUSION: Although calcium phosphate double-coated anorganic bovine bone showed no additional effect compared with anorganic bovine bone from a histological and radiographical point of view, it could be used as the bone graft material in maxillary sinus augmentation.


Assuntos
Substitutos Ósseos/uso terapêutico , Seio Maxilar/cirurgia , Levantamento do Assoalho do Seio Maxilar/métodos , Animais , Fosfatos de Cálcio , Bovinos , Materiais Revestidos Biocompatíveis , Tomografia Computadorizada de Feixe Cônico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Minerais , Estudos Prospectivos , Radiografia Panorâmica , República da Coreia
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