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1.
J Dent ; 146: 105061, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38729289

RESUMO

OBJECTIVES: Orthognathic surgery (OS) has evolved with technological advancements, notably through the implementation of computer-assisted orthognathic surgery (CAOS). This article aims to elucidate various types of CAOS and their efficiency and accuracy, supplemented by a thorough literature review focusing on their clinical applications in South Korea. STUDY SELECTION, DATA, AND SOURCES: A comprehensive search strategy was employed, including systematic reviews, meta-analyses, randomized controlled trials, and observational studies published until December 2023 in the PubMed, MEDLINE, and Google Scholar databases. The literature search was limited to articles written in English. RESULTS: Static CAOS demonstrated high precision, reduced operative time, and high accuracy, suggesting its potential reliability in orthognathic procedures. Dynamic CAOS presented a promising avenue for exploration, showing an accuracy comparable to that of traditional methods. The critical considerations for CAOS include accuracy, time efficiency, and cost-effectiveness. Recent studies have indicated advancements in the time efficiency of static CAOS. Static CAOS requires less equipment and is more cost-effective than dynamic CAOS. CONCLUSIONS: CAOS offers clear advantages over conventional OS in terms of surgical convenience and accuracy in implementing the surgical plan. To achieve recognition as the gold standard method for maxillofacial deformity treatment, CAOS must overcome its limitations and undergo continuous verification via well-designed studies. CLINICAL SIGNIFICANCE: The introduction of CAOS, mainly static CAOS with high precision and reduced surgical time, signifies a notable advancement in OS. However, rigorous studies are warranted to validate CAOS as the gold standard for treating maxillofacial deformities.


Assuntos
Procedimentos Cirúrgicos Ortognáticos , Cirurgia Assistida por Computador , Humanos , Cirurgia Assistida por Computador/métodos , República da Coreia , Duração da Cirurgia
2.
Bioengineering (Basel) ; 11(4)2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38671740

RESUMO

With the growing demand for orthognathic surgery and other facial treatments, the accurate identification of anatomical landmarks has become crucial. Recent advancements have shifted towards using three-dimensional radiologic analysis instead of traditional two-dimensional methods, as it allows for more precise treatment planning, primarily relying on direct identification by clinicians. However, manual tracing can be time-consuming, mainly when dealing with a large number of patients. This study compared the accuracy and reliability of identifying anatomical landmarks using artificial intelligence (AI) and manual identification. Thirty patients over 19 years old who underwent pre-orthodontic and orthognathic surgery treatment and had pre-orthodontic three-dimensional radiologic scans were selected. Thirteen anatomical indicators were identified using both AI and manual methods. The landmarks were identified by AI and four experienced clinicians, and multiple ANOVA was performed to analyze the results. The study results revealed minimal significant differences between AI and manual tracing, with a maximum deviation of less than 2.83 mm. This indicates that utilizing AI to identify anatomical landmarks can be a reliable method in planning orthognathic surgery. Our findings suggest that using AI for anatomical landmark identification can enhance treatment accuracy and reliability, ultimately benefiting clinicians and patients.

3.
Bioengineering (Basel) ; 10(9)2023 Aug 24.
Artigo em Inglês | MEDLINE | ID: mdl-37760107

RESUMO

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has shown potential in maxillofacial surgery owing to its osteoinductive properties. However, concerns about its safety and high cost have limited its widespread use. This review presents the status of rhBMP-2 use in maxillofacial surgery, focusing on its clinical application, efficacy, safety, and limitations. Studies have demonstrated rhBMP-2's potential to reduce donor site morbidity and increase bone height in sinus and ridge augmentation; however, it may not outperform autogenous bone grafts. In medication-related osteonecrosis of the jaw treatment, rhBMP-2 has been applied adjunctively with promising results, although its long-term safety requires further investigation. However, in maxillofacial trauma, its application is limited to the restoration of large defects. Safety concerns include postoperative edema and the theoretical risk of carcinogenesis. Although postoperative edema is manageable, the link between rhBMP-2 and cancer remains unclear. The limitations include the lack of an ideal carrier, the high cost of rhBMP-2, and the absence of an optimal dosing regimen. In conclusion, rhBMP-2 is a promising graft material for maxillofacial surgery. However, it has not yet become the gold standard owing to safety and cost concerns. Further research is required to establish long-term safety, optimize dosing, and develop better carriers.

4.
Bioengineering (Basel) ; 10(8)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37627799

RESUMO

Maxillofacial skeletal surgery often involves the use of patient-specific implants. However, errors in obtaining patient data and designing and manufacturing patient-specific plates and guides can occur even with accurate virtual surgery. To address these errors, bespoke Snowman plates were designed to allow movement of the mandible. This study aimed to compare the stability of bespoke four-hole miniplates with that of a bespoke Snowman plate for bilateral sagittal split ramus osteotomy (SSRO), and to present a method to investigate joint cavity changes, as well as superimpose virtual and actual surgical images of the mandible. This retrospective study included 22 patients who met the inclusion criteria and underwent orthognathic surgery at a university hospital between 2015 and 2018. Two groups were formed on the basis of the plates used: a control group with four-hole bespoke plates and a study group with bespoke Snowman plates. Stability was assessed by measuring the condyle-fossa space and superimposing three-dimensional virtual surgery images on postoperative cone-beam computed tomography (CBCT) scans. No significant differences were observed in the condyle-fossa space preoperatively and 1 year postoperatively between the control and study groups. Superimposing virtual surgery and CBCT scans revealed minimal differences in the landmark points, with no variation between groups or timepoints. The use of bespoke Snowman plates for stabilizing the mandible following SSRO exhibited clinical stability and reliability similar to those with bespoke four-hole plates. Additionally, a novel method was introduced to evaluate skeletal stability by separately analyzing the condyle-fossa gap changes and assessing the mandibular position.

5.
J Clin Med ; 10(8)2021 Apr 09.
Artigo em Inglês | MEDLINE | ID: mdl-33918920

RESUMO

OBJECTIVE: Orthognathic surgery (OGS) is a surgical intervention that corrects dentofacial deformities through the movement of maxillary and mandibular segments to achieve adequate masticatory function, joint health, and facial harmony. However, some patients present with occlusal discrepancies, condylar sag, and/or temporomandibular disorders after OGS. Various methods have been employed to solve these problems after surgery. This study aimed to evaluate the effectiveness of early screw removal in patients with occlusal discrepancies after OGS using three-dimensional cone-beam computed tomography (CBCT). METHODS: In 44 patients with dentofacial deformities, patient-customized OGSs with customized plates were performed to correct facial deformities using customized guides with computer-aided surgical simulation. Of the 44 patients, eight patients complained of occlusal discrepancies and temporomandibular disorders after OGS. These eight patients underwent screw removal under local anesthesia around four weeks. The temporomandibular joint spaces at three time points (pre-surgical, post-surgical, and after screw removal) in the sagittal and coronal planes were compared using CBCT. RESULTS: Eight patients showed an increase in joint space on CBCT images immediately after surgery (T1), but after early screw removal (T2), these spaces almost returned to their pre-surgical state, and the temporomandibular joint problem disappeared. CONCLUSIONS: The removal of screws located in the distal segment under local anesthesia between three and four weeks post-surgically may be a treatment option for patients with post-OGS occlusal discrepancies, condylar sag, and/or temporomandibular disorder.

6.
J Clin Med ; 9(9)2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32872568

RESUMO

With the great leap in the development of three-dimensional computer-assisted surgical technology, surgeons can use a variety of assistive methods to achieve better results and evaluate surgical outcomes in detail. This retrospective study aimed to evaluate the postoperative stability after bilateral sagittal split ramus osteotomy by volume rendering methods and to evaluate how postoperative stability differs depending on the type of surgical plate. Of the patients who underwent BSSRO, ten patients in each group (non-customized miniplate and customized miniplate) who met the inclusion criteria were selected. Preoperative and postoperative cone-beam computed tomography data were collected, and condylar morphological and landmark measurements were obtained using Checkpoint and OnDemand software, respectively. The postoperative condylar morphological dataset revealed no significant difference (p > 0.05) between the two groups. No significant difference (p > 0.05) was observed between the two groups in horizontal, vertical, or angular landmark measurements used to quantify operational stability. These results indicate that there is no difference in the surgical outcome between the patient-specific system and the conventional method, which will allow clinicians to take advantage of the patient-specific system for this surgical procedure, with favorable results, as with the conventional method.

7.
Medicine (Baltimore) ; 99(30): e21274, 2020 Jul 24.
Artigo em Inglês | MEDLINE | ID: mdl-32791707

RESUMO

We analyzed cardiopulmonary resuscitation (CPR) rates, deaths preceded by CPR, and survival trends after in-hospital CPR, using a sample of nationwide Korean claims data for the period 2003 to 2013.The Korean National Health Insurance Service-National Sample Cohort is a stratified random sample of 1,025,340 subjects selected from among approximately 46 million Koreans. We evaluated the annual incidence of CPR per 1000 admissions in various age groups, hospital deaths preceded by CPR, and survival rate following in-hospital CPR. Analyses of the relationships between survival and patient and hospital characteristics were performed using logistic regression analysis.A total of 5918 in-hospital CPR cases from 2003 to 2013 were identified among eligible patients. The cumulative incidence of in-hospital CPR was 3.71 events per 1000 admissions (95% confidence interval 3.62-3.80). The CPR rate per 1000 admissions was highest among the oldest age group, and the rate decreased throughout the study period in all groups except the youngest age group. Hospital deaths were preceded by in-hospital CPR in 18.1% of cases, and the rate decreased in the oldest age group. The survival-to-discharge rate in all study subjects was 11.7% during study period, while the 6-month and 1-year survival rates were 8.0% and 7.2%, respectively. Survival tended to increase throughout the study period; however, this was not the case in the oldest age group. Age and malignancy were associated with lower survival rates, whereas myocardial infarction and diabetes mellitus were associated with higher survival rates.Our result shows that hospital deaths were preceded by in-hospital CPR in 18.1% of case, and the survival-to-discharge rate in all study subjects was 11.7% during the study period. Survival tended to increase throughout the study period except for the oldest age group. Our results provide reliable data that can be used to inform judicious decisions on the implementation of CPR, with the ultimate goal of optimizing survival rates and resource utilization.


Assuntos
Reanimação Cardiopulmonar/mortalidade , Parada Cardíaca/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Parada Cardíaca/terapia , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Assistência Terminal/legislação & jurisprudência , Adulto Jovem
8.
J Craniofac Surg ; 30(7): e619-e622, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31157641

RESUMO

Anterior segmental osteotomy (ASO) is considered the treatment modality of choice in patients with the bimaxillary dentoalveolar protrusion. However, this meticulous surgical technique accompanies a number of possible disadvantages. The considerable time required before, during, and after the operation, limited movement of the segment, damage of the mental nerve, loss of tooth vitality, loss of a tooth or teeth, or indeed total loss of the anterior segments are those that affect the result of the surgery. Recently, the authors have devised a computer-aided surgical simulation programme and fabricated the customized osteotomy guides and the spider-shaped plates based on the programme. They were then applied to a 28-year-old patient with the complaint of a bimaxillary dentoalveolar protrusion. This approach helped to overcome several problems related to ASO reported earlier.


Assuntos
Má Oclusão/cirurgia , Osteotomia , Adulto , Feminino , Humanos , Osteotomia/instrumentação , Osteotomia/métodos , Cirurgia Assistida por Computador
9.
Nature ; 566(7743): 254-258, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30728500

RESUMO

Osteoarthritis-the most common form of age-related degenerative whole-joint disease1-is primarily characterized by cartilage destruction, as well as by synovial inflammation, osteophyte formation and subchondral bone remodelling2,3. However, the molecular mechanisms that underlie the pathogenesis of osteoarthritis are largely unknown. Although osteoarthritis is currently considered to be associated with metabolic disorders, direct evidence for this is lacking, and the role of cholesterol metabolism in the pathogenesis of osteoarthritis has not been fully investigated4-6. Various types of cholesterol hydroxylases contribute to cholesterol metabolism in extrahepatic tissues by converting cellular cholesterol to circulating oxysterols, which regulate diverse biological processes7,8. Here we show that the CH25H-CYP7B1-RORα axis of cholesterol metabolism in chondrocytes is a crucial catabolic regulator of the pathogenesis of osteoarthritis. Osteoarthritic chondrocytes had increased levels of cholesterol because of enhanced uptake, upregulation of cholesterol hydroxylases (CH25H and CYP7B1) and increased production of oxysterol metabolites. Adenoviral overexpression of CH25H or CYP7B1 in mouse joint tissues caused experimental osteoarthritis, whereas knockout or knockdown of these hydroxylases abrogated the pathogenesis of osteoarthritis. Moreover, retinoic acid-related orphan receptor alpha (RORα) was found to mediate the induction of osteoarthritis by alterations in cholesterol metabolism. These results indicate that osteoarthritis is a disease associated with metabolic disorders and suggest that targeting the CH25H-CYP7B1-RORα axis of cholesterol metabolism may provide a therapeutic avenue for treating osteoarthritis.


Assuntos
Colesterol/metabolismo , Família 7 do Citocromo P450/metabolismo , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Osteoartrite/metabolismo , Esteroide Hidroxilases/metabolismo , Animais , Transporte Biológico , Condrócitos/enzimologia , Condrócitos/metabolismo , Masculino , Camundongos , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Osteoartrite/enzimologia , Osteoartrite/patologia , Oxisteróis/metabolismo , Esteroide Hidroxilases/deficiência , Regulação para Cima
10.
BMC Oral Health ; 19(1): 18, 2019 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-30646896

RESUMO

BACKGROUND: Many reports have been published on orthognathic surgery (OGS) using computer-aided surgical simulation (CASS). The purpose of this study was to evaluate the accuracy of the maxillary repositioning and the stability of the maxilla in patients who underwent OGS using a newly developed CASS program, a customized osteotomy guide, and a customized miniplate. METHODS: Thirteen patients who underwent OGS from 2015 to 2017 were included. All patients underwent a bimaxillary operation. First, a skull-dentition hybrid 3D image was rendered by merging the cone beam computed tomography (CBCT) images with the dentition scan file. After virtual surgery (VS) using the FaceGide® program, patient-customized osteotomy guides and miniplates were then fabricated and used in the actual operation. To compare the VS with the actual surgery and postoperative skeletal changes, each reference point marked on the image was compared before the operation (T0) and three days (T1), four months (T2), and a year (T3) after the operation, and with the VS (Tv). The differences between ΔTv (Tv-T0) and ΔT1 (T1-T0) were statistically compared using tooth-based reference points. The superimposed images of Tv and T1 were also investigated at eight bone-based reference points. The differences between the reference points of the bone surface were examined to evaluate the stability of the miniplate on the maxilla over time. RESULTS: None of the patients experienced complications. There were no significant differences between the reference points based on the cusp tip between ΔTv and ΔT1 (p > 0.01). Additionally, there were no significant differences between the Tv and T1 values of the bone surface (p > 0.01). The mean difference in the bone surface between Tv and T1 was 1.01 ± 0.3 mm. Regarding the stability of the miniplate, there were no significant differences between the groups. The difference in the bone surface between T1 and T3 was - 0.37 ± 0.29 mm. CONCLUSIONS: VS was performed using the FaceGide® program, and customized materials produced based on the VS were applied in actual OGS. The maxilla was repositioned in almost the same manner as in the VSP plan, and the maxillary position remained stable for a year.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Maxila/cirurgia , Procedimentos Cirúrgicos Ortognáticos/métodos , Cirurgia Assistida por Computador/métodos , Cefalometria , Humanos , Imageamento Tridimensional , Maxila/diagnóstico por imagem , Cirurgia Ortognática
11.
Cancer Res ; 78(12): 3135-3146, 2018 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-29724720

RESUMO

Loss of the short arm of chromosome 3 (3p) occurs early in >95% of clear cell renal cell carcinoma (ccRCC). Nearly ubiquitous 3p loss in ccRCC suggests haploinsufficiency for 3p tumor suppressors as early drivers of tumorigenesis. We previously reported methyltransferase SETD2, which trimethylates H3 histones on lysine 36 (H3K36me3) and is located in the 3p deletion, to also trimethylate microtubules on lysine 40 (αTubK40me3) during mitosis, with αTubK40me3 required for genomic stability. We now show that monoallelic, Setd2-deficient cells retaining H3K36me3, but not αTubK40me3, exhibit a dramatic increase in mitotic defects and micronuclei count, with increased viability compared with biallelic loss. In SETD2-inactivated human kidney cells, rescue with a pathogenic SETD2 mutant deficient for microtubule (αTubK40me3), but not histone (H3K36me3) methylation, replicated this phenotype. Genomic instability (micronuclei) was also a hallmark of patient-derived cells from ccRCC. These data show that the SETD2 tumor suppressor displays a haploinsufficiency phenotype disproportionately impacting microtubule methylation and serves as an early driver of genomic instability.Significance: Loss of a single allele of a chromatin modifier plays a role in promoting oncogenesis, underscoring the growing relevance of tumor suppressor haploinsufficiency in tumorigenesis. Cancer Res; 78(12); 3135-46. ©2018 AACR.


Assuntos
Carcinoma de Células Renais/genética , Cromossomos Humanos Par 3/genética , Histona-Lisina N-Metiltransferase/genética , Neoplasias Renais/genética , Microtúbulos/metabolismo , Animais , Carcinogênese/genética , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Fibroblastos , Técnicas de Silenciamento de Genes , Instabilidade Genômica , Haploinsuficiência , Histona-Lisina N-Metiltransferase/metabolismo , Histonas/metabolismo , Humanos , Neoplasias Renais/patologia , Túbulos Renais Proximais/citologia , Túbulos Renais Proximais/patologia , Lisina/metabolismo , Metilação , Camundongos , Micronúcleos com Defeito Cromossômico
12.
Exp Mol Med ; 50(1): e421, 2018 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-29303508

RESUMO

The gene encoding ß-catenin is frequently mutated in hepatocellular carcinoma cells. While the oncogenicity of ß-catenin has been extensively studied, ß-catenin's role in hepatocellular carcinoma tumor metabolism is currently less well understood. In this study, we found that ß-catenin regulates the expression of glutamine synthetase and triggers a series of metabolic changes leading to induction of autophagy in hepatocellular carcinoma cells. ß-Catenin-active Hep3B and HepG2 cells exhibited higher basal levels of autophagic activity than did ß-catenin wild-type cells. We also found that autophagy in ß-catenin-active cells was mediated by glutamine synthetase, as silencing of glutamine synthetase significantly reduced autophagic activity. We also showed that ß-catenin-active hepatocellular carcinoma cells were more sensitive to sorafenib than were ß-catenin wild-type cells. Our results demonstrated that glutamine synthetase-mediated autophagy explains the high sensitivity of ß-catenin-active hepatocellular carcinoma cells to sorafenib. Our results highlight the importance of glutamine metabolism in the regulation of autophagy in hepatocellular carcinoma cells. More importantly, our study unravels the molecular mechanisms leading to sorafenib sensitivity in hepatocellular carcinoma.


Assuntos
Carcinoma Hepatocelular/tratamento farmacológico , Glutamato-Amônia Ligase/metabolismo , Neoplasias Hepáticas/tratamento farmacológico , Sorafenibe/farmacologia , beta Catenina/metabolismo , Antineoplásicos/farmacologia , Autofagia/efeitos dos fármacos , Autofagia/fisiologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Glutamato-Amônia Ligase/genética , Humanos , Neoplasias Hepáticas/metabolismo
13.
Cancer Res ; 77(19): 5313-5326, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-28807937

RESUMO

Chromophobe renal cell carcinoma (ChRCC) is characterized by major changes in chromosomal copy number (CN). No model is available to precisely elucidate the molecular drivers of this tumor type. HNF1B is a master regulator of gene expression. Here, we report that the transcription factor HNF1B is downregulated in the majority of ChRCC and that the magnitude of HNF1B loss is unique to ChRCC. We also observed a strong correlation between reduced HNF1B expression and aneuploidy in ChRCC patients. In murine embryonic fibroblasts or ACHN cells, HNF1B deficiency reduced expression of the spindle checkpoint proteins MAD2L1 and BUB1B, and the cell-cycle checkpoint proteins RB1 and p27. Furthermore, it altered the chromatin accessibility of Mad2l1, Bub1b, and Rb1 genes and triggered aneuploidy development. Analysis of The Cancer Genome Atlas database revealed TP53 mutations in 33% of ChRCC where HNF1B expression was repressed. In clinical specimens, combining HNF1B loss with TP53 mutation produced an association with poor patient prognosis. In cells, combining HNF1B loss and TP53 mutation increased cell proliferation and aneuploidy. Our results show how HNF1B loss leads to abnormal mitotic protein regulation and induction of aneuploidy. We propose that coordinate loss of HNF1B and TP53 may enhance cellular survival and confer an aggressive phenotype in ChRCC. Cancer Res; 77(19); 5313-26. ©2017 AACR.


Assuntos
Carcinoma de Células Renais/patologia , Proteínas de Ciclo Celular/metabolismo , Fator 1-beta Nuclear de Hepatócito/metabolismo , Neoplasias Renais/patologia , Proteínas Mad2/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Aneuploidia , Animais , Apoptose , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/metabolismo , Ciclo Celular , Proteínas de Ciclo Celular/genética , Proliferação de Células , Células Cultivadas , Instabilidade Cromossômica , Embrião de Mamíferos/citologia , Embrião de Mamíferos/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Fator 1-beta Nuclear de Hepatócito/genética , Humanos , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteínas Mad2/genética , Camundongos , Proteínas Serina-Treonina Quinases/genética
14.
Cell Physiol Biochem ; 41(1): 252-264, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28214840

RESUMO

BACKGROUND: The protein transduction domain (PTD) enables therapeutic proteins to directly penetrate the membranes of cells and tissues, and has been increasingly utilized. Glutaredoxin-1 (GRX-1) is an endogenous antioxidant enzyme involved in the cellular redox homeostasis system. In this study, we investigated whether PEP-1-GRX-1, a fusion protein of GRX-1 and PEP-1 peptide, a PTD, could suppress catabolic responses in primary human articular chondrocytes and a mouse carrageenan-induced paw edema model. METHODS: Human articular chondrocytes were isolated enzymatically from articular cartilage and cultured in a monolayer. The transduction efficiency of PEP-1-GRX-1 into articular chondrocytes was measured by western blot and immunohistochemistry. The effects of PEP-1-GRX-1 on matrix metalloproteinases (MMPs) and catabolic factor expression in interleukin (IL)-1ß- and lipopolysaccharide (LPS)-treated chondrocytes were analyzed by real-time quantitative reverse transcription-polymerase chain reaction and western blot. The effect of PEP-1-GRX1 on the mitogen-activated protein kinase (MAPK) and nuclear factor kappa-light chain-enhancer of activated B cells (NF-κB) signaling pathway were also analyzed by western blot. Finally, the inhibitory effect of PEP-1-GRX-1 on MMP-13 production was measured in vivo in a mouse carrageenan-induced paw edema model. RESULTS: PEP-1-GRX-1 significantly penetrated into human chondrocytes and mouse cartilage, whereas GRX-1 did not. PEP-1-GRX-1 significantly suppressed MMP-13 expression and nitric oxide (NO) production in LPS-stimulated chondrocytes, and NO production in IL-1ß-stimulated chondrocytes, compared with GRX-1. In addition, PEP-1-GRX-1 decreased IL-1ß- and LPS-induced activation of MAPK and NF-κB. In the mouse model of carrageenan-induced paw edema, PEP-1-GRX-1 significantly suppressed carrageenan-induced MMP-13 production as well as paw edema. CONCLUSION: These results demonstrate that PEP-1-GRX-1 can be transduced efficiently in vitro and in vivo into human chondrocytes and mouse cartilage tissue and downregulate catabolic responses in chondrocytes by inhibiting the MAPK and NF-κB pathway. PEP-1-GRX-1 thus has the potential to reduce catabolic responses in chondrocytes and cartilage.


Assuntos
Cartilagem Articular/metabolismo , Metaloproteinase 13 da Matriz/metabolismo , Óxido Nítrico/metabolismo , Animais , Carragenina/toxicidade , Cartilagem Articular/citologia , Cartilagem Articular/efeitos dos fármacos , Células Cultivadas , Cisteamina/análogos & derivados , Cisteamina/metabolismo , Modelos Animais de Doenças , Regulação para Baixo/efeitos dos fármacos , Edema/induzido quimicamente , Edema/metabolismo , Edema/patologia , Glutarredoxinas/genética , Glutarredoxinas/metabolismo , Humanos , Imuno-Histoquímica , Interleucina-1beta/farmacologia , Lipopolissacarídeos/toxicidade , Masculino , Metaloproteinase 13 da Matriz/genética , Camundongos , Camundongos Endogâmicos C57BL , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Peptídeos/genética , Peptídeos/metabolismo , Proteínas Recombinantes de Fusão/biossíntese , Proteínas Recombinantes de Fusão/isolamento & purificação , Proteínas Recombinantes de Fusão/farmacologia , Transdução de Sinais/efeitos dos fármacos
15.
Cell ; 166(4): 950-962, 2016 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-27518565

RESUMO

Posttranslational modifications (PTMs) of tubulin specify microtubules for specialized cellular functions and comprise what is termed a "tubulin code." PTMs of histones comprise an analogous "histone code," although the "readers, writers, and erasers" of the cytoskeleton and epigenome have heretofore been distinct. We show that methylation is a PTM of dynamic microtubules and that the histone methyltransferase SET-domain-containing 2 (SETD2), which is responsible for H3 lysine 36 trimethylation (H3K36me3) of histones, also methylates α-tubulin at lysine 40, the same lysine that is marked by acetylation on microtubules. Methylation of microtubules occurs during mitosis and cytokinesis and can be ablated by SETD2 deletion, which causes mitotic spindle and cytokinesis defects, micronuclei, and polyploidy. These data now identify SETD2 as a dual-function methyltransferase for both chromatin and the cytoskeleton and show a requirement for methylation in maintenance of genomic stability and the integrity of both the tubulin and histone codes.


Assuntos
Montagem e Desmontagem da Cromatina , Citoesqueleto/metabolismo , Código das Histonas , Histona-Lisina N-Metiltransferase/metabolismo , Linhagem Celular Tumoral , Citocinese , Instabilidade Genômica , Histona-Lisina N-Metiltransferase/genética , Histonas/metabolismo , Humanos , Lisina/metabolismo , Metilação , Microtúbulos/metabolismo , Mitose , Processamento de Proteína Pós-Traducional , Tubulina (Proteína)/metabolismo
16.
Korean J Gastroenterol ; 65(5): 321-5, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25998980

RESUMO

Up-to-date imaging modalities such as three-dimensional dynamic contrast-enhanced CT (3D CT) and MRI may contribute to detection of hypervascular nodules in the liver. Nevertheless, distinguishing a malignancy such as hepatocellular carcinoma from benign hypervascular hyperplastic nodules (HHN) based on the radiological findings is sometimes difficult. Multiple incidental liver masses were detected via abdominal ultrasonography (US) in a 65-year-old male patient. He had no history of alcohol intake and no remarkable past medical history or relevant family history, and his physical examination results and laboratory findings were normal. 3D CT and MRI showed numerous enhanced nodules with hypervascularity during the arterial phase. After US guided liver biopsy, the pathological diagnosis was HHN. To date, several cases of HHN have been reported in patients with chronic alcoholic liver disease or cirrhosis. Herein, we report on a case of HHN in a patient with no history of alcoholic liver disease or cirrhosis.


Assuntos
Hiperplasia Nodular Focal do Fígado/diagnóstico , Fígado/patologia , Abdome/diagnóstico por imagem , Idoso , Alcoolismo/patologia , Doença Crônica , Diagnóstico Diferencial , Humanos , Imageamento Tridimensional , Fígado/diagnóstico por imagem , Hepatopatias/patologia , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada por Raios X , Ultrassonografia
17.
BMB Rep ; 48(7): 407-12, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25887750

RESUMO

The 12 kDa FK506-binding protein (FK506BP12), an immunosuppressor, modulates T cell activation via calcineurin inhibition. In this study, we investigated the ability of PEP-1-FK506BP12, consisting of FK506BP12 fused to the protein transduction domain PEP-1 peptide, to suppress catabolic responses in primary human chondrocytes and in a mouse carrageenan-induced paw arthritis model. Western blotting and immunofluorescence analysis showed that PEP-1-FK506BP12 efficiently penetrated chondrocytes and cartilage explants. In interleukin-1ß (IL-1ß)-treated chondrocytes, PEP-1-FK506BP12 significantly suppressed the expression of catabolic enzymes, including matrix metalloproteinases (MMPs)-1, -3, and -13 in addition to cyclooxygenase-2, at both the mRNA and protein levels, whereas FK506BP12 alone did not. In addition, PEP-1-FK506BP12 decreased IL-1ß-induced phosphorylation of the mitogen-activated protein kinase (MAPK) complex (p38, JNK, and ERK) and the inhibitor kappa B alpha. In the mouse model of carrageenan-induced paw arthritis, PEP-1-FK506BP12 suppressed both carrageenan-induced MMP-13 production and paw inflammation. PEP-1-FK506BP12 may have therapeutic potential in the alleviation of OA progression.


Assuntos
Artrite/enzimologia , Artrite/patologia , Cartilagem Articular/patologia , Condrócitos/enzimologia , Cisteamina/análogos & derivados , Metaloproteinase 13 da Matriz/metabolismo , Peptídeos/farmacologia , Proteína 1A de Ligação a Tacrolimo/metabolismo , Animais , Artrite/induzido quimicamente , Artrite/complicações , Carragenina , Células Cultivadas , Condrócitos/efeitos dos fármacos , Condrócitos/patologia , Cisteamina/farmacologia , Modelos Animais de Doenças , Edema/complicações , Edema/tratamento farmacológico , Edema/patologia , Humanos , Interleucina-1beta/farmacologia , Camundongos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Proteínas Recombinantes de Fusão/farmacologia , Proteínas Recombinantes de Fusão/uso terapêutico , Transdução Genética
18.
Maxillofac Plast Reconstr Surg ; 37(1): 11, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25821765

RESUMO

Rapid palatal expansion(RPE) with the tooth-born appliance is not sufficient to apply to the patients with periodontal problem or insufficient tooth anchorage, and it leads to tipping of the anchorage teeth and increasing teeth mobility and root resorption. To avoid these disadvantages, we present the case using palatal screws and custommade palatal expander. A 23-year-old patient underwent surgically assisted rapid maxillary expansion with the Hyrax expansion using 4 tent screws. The study models were used to measure the pre-/-post surgical width of the anterior and posterior dental arches with a digital sliding caliper. In the result, the custom-made palatal expander with 4 tent screws is suitable for delivering a force to the mid-palatal suture expansion. And it is low cost, small sized and simply applied. The results indicated that maxillary expansion with the custom-made palatal anchorage device is predictable and stable technique without significant complications in patients.

19.
Am J Orthod Dentofacial Orthop ; 147(3): 381-93, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25726406

RESUMO

Maxillary deficiency is a common feature in patients with repaired cleft lip and palate. Orthognathic surgery has been the conventional approach for the management of cleft-related maxillary hypoplasia. However, for patients with a severe maxillary deficiency, orthognathic surgery alone has many disadvantages, such as high relapse rates of 25% to 40%, instability, limited amount of advancement, and a highly invasive surgical technique. As an alternative treatment method, distraction osteogenesis has been used successfully in the distraction of the mandible, the maxilla, the entire midface, and the orbits as well as the cranial bones, with stable outcomes. The type of distraction device, either external or internal, can be chosen based on the surgical goals set for the patient. In this study, we report on the use of a rigid external distraction device for maxillary advancement in a 22-year-old woman with a repaired unilateral cleft lip and palate and severe maxillary hypoplasia. After the distraction osteogenesis, 2-jaw surgery was performed to correct the maxillary yaw deviation and the mandibular prognathism.


Assuntos
Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Maxila/anormalidades , Procedimentos Cirúrgicos Ortognáticos/métodos , Osteogênese por Distração/métodos , Cefalometria/métodos , Fixadores Externos , Feminino , Mentoplastia/métodos , Humanos , Má Oclusão Classe III de Angle/cirurgia , Maxila/cirurgia , Osteogênese por Distração/instrumentação , Osteotomia de Le Fort/métodos , Osteotomia Sagital do Ramo Mandibular/métodos , Planejamento de Assistência ao Paciente , Prognatismo/cirurgia , Adulto Jovem
20.
J Oral Maxillofac Surg ; 73(2): 340.e1-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25579018

RESUMO

PURPOSE: The aims of this study were to use 3-dimensional cone-beam computed tomography (CBCT) to evaluate how the upper airway and hyoid bone position changed after orthognathic surgery in patients with skeletal Class III malocclusions and to analyze the relations among upper airway changes, the change in the position of the hyoid bone, and postsurgical stability. MATERIALS AND METHODS: CBCT scans were obtained from 15 patients with mandibular prognathism before surgery (T0), 6 months after surgery (T1), 1 year after surgery (T2), and 2 years after surgery (T3). Positional displacement of the hyoid bone was assessed using the coordinates at T0, T1, T2, and T3. In addition, the volume of each patient's pharyngeal airway was measured. Differences in CBCT scans at the established time points were determined by the Wilcoxon signed rank test. The Spearman correlation coefficient was used to determine the relations among changes in hyoid bone position, airway volume, and skeletal reference points. RESULTS: The hyoid bone moved backward at 6 months after surgery (T0 to T1), and the total volume of the pharyngeal airway was considerably decreased at the same time points. At 1 year after surgery (T1 to T2), although the hyoid moved more posteriorly and the total volume of the pharyngeal airway was decreased, the changes were not major. At 2 years after surgery, the hyoid bone moved anteriorly and the size of the upper pharyngeal airway was increased (T2 to T3). CONCLUSION: The hyoid bone moved posteriorly and the pharyngeal airway volume was decreased at 6 months after bimaxillary surgery. These measurements had a tendency to recover at 2 years postoperatively. The decrease in pharyngeal airway volume was not correlated with positional changes of the hyoid bone.


Assuntos
Osso Hioide/patologia , Maxila/cirurgia , Faringe/patologia , Prognatismo/cirurgia , Adulto , Tomografia Computadorizada de Feixe Cônico , Feminino , Seguimentos , Humanos , Osso Hioide/diagnóstico por imagem , Masculino , Má Oclusão Classe III de Angle , Maxila/diagnóstico por imagem , Pessoa de Meia-Idade , Faringe/diagnóstico por imagem , Prognatismo/diagnóstico por imagem , Adulto Jovem
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