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1.
Artigo em Inglês | MEDLINE | ID: mdl-33740814

RESUMO

PURPOSE: To describe our pharmacy department's plan for conservation of personal protective equipment (PPE) during the coronavirus disease 2019 (COVID-19) pandemic to ensure continued availability of sterile compounded products. SUMMARY: PPE shortages impacted hospitals throughout the nation in the early months of the COVID-19 pandemic response. The PPE requirement for sterile compounding and need to maintain supplies within the pharmacy cleanroom is often overlooked. A sustained supply of PPE is critical to ensure an uninterrupted supply of compounded medications to our patient population. Multiple conservation strategies, including staffing changes, communication, adjustments to training, and even reuse of select PPE, can assist with conservation. CONCLUSION: PPE in pharmacy cleanrooms is critical for the continued provision of sterile compounds with appropriate beyond-use dates and effective patient care. Pharmacy departments must employ multiple conservation strategies to ensure PPE is available for continued compounding of sterile products, and early planning and implementation of conservation strategies are key.

2.
Cancer ; 127(8): 1275-1285, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33320347

RESUMO

BACKGROUND: Little is known about the psychological outcomes of germline multigene panel testing, particularly among diverse patients and those with moderate-risk pathogenic variants (PVs). METHODS: Study participants (N = 1264) were counseled and tested with a 25- or 28-gene panel and completed a 3-month postresult survey including the Multidimensional Impact of Cancer Risk Assessment (MICRA). RESULTS: The mean age was 52 years, 80% were female, and 70% had cancer; 45% were non-Hispanic White, 37% were Hispanic, 10% were Asian, 3% were Black, and 5% had another race/ethnicity. Approximately 28% had a high school education or less, and 23% were non-English-speaking. The genetic test results were as follows: 7% had a high-risk PV, 6% had a moderate-risk PV, 35% had a variant of uncertain significance (VUS), and 52% were negative. Most participants (92%) had a total MICRA score ≤ 38, which corresponded to a mean response of "never," "rarely," or only "sometimes" reacting negatively to results. A multivariate analysis found that mean total MICRA scores were significantly higher (more uncertainty/distress) among high- and moderate-risk PV carriers (29.7 and 24.8, respectively) than those with a VUS or negative results (17.4 and 16.1, respectively). Having cancer or less education was associated with a significantly higher total MICRA score; race/ethnicity was not associated with the total MICRA score. High- and moderate-risk PV carriers did not differ significantly from one another in the total MICRA score, uncertainty, distress, or positive experiences. CONCLUSIONS: In a diverse population undergoing genetic counseling and multigene panel testing for hereditary cancer risk, the psychological response corresponded to test results and showed low distress and uncertainty. Further studies are needed to assess patient understanding and subsequent cancer screening among patients from diverse backgrounds. LAY SUMMARY: Multigene panel tests for hereditary cancer have become widespread despite concerns about adverse psychological reactions among carriers of moderate-risk pathogenic variants (mutations) and among carriers of variants of uncertain significance. This large study of an ethnically and economically diverse cohort of patients undergoing panel testing found that 92% "never," "rarely," or only "sometimes" reacted negatively to results. Somewhat higher uncertainty and distress were identified among carriers of high- and moderate-risk pathogenic variants, and lower levels were identified among those with a variant of uncertain significance or a negative result. Although the psychological response corresponded to risk, reactions to testing were favorable, regardless of results.

3.
Bone Res ; 8(1): 39, 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33298857

RESUMO

Mesenchymal stem cells (MSCs) derived from human embryonic stem cells (hESCs) have significant potential for cell-mediated bone regeneration. Our recent study revealed that inhibiting the epigenetic regulator EZH2 plays a key role in promoting the mesodermal differentiation of hESCs. In this study, an epigenome-wide analysis of hESCs and MSCs revealed that growth differentiation factor 6 (GDF6), which is involved in bone formation, was the most upregulated gene associated with MSCs compared to hESCs. Furthermore, we identified GDF6 as a repressive target of EZH2 and found that ectopic GDF6 selectively promoted hESC differentiation towards the mesodermal lineage and enriched the MSC population. Our results provide molecular insights governing the mesenchymal commitment of hESCs and identify an inducing factor that offers strong promise for the future of regenerative medicine.

4.
Stat Med ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33120437

RESUMO

Commercialized multigene panel testing brings unprecedented opportunities to understand germline genetic contributions to hereditary cancers. Most genetic testing companies classify the pathogenicity of variants as pathogenic, benign, or variants of unknown significance (VUSs). The unknown pathogenicity of VUSs poses serious challenges to clinical decision-making. This study aims to assess the frequency of VUSs that are likely pathogenic in disease-susceptibility genes. Using estimates of probands' probability of having a pathogenic mutation (ie, the carrier score) based on a family history probabilistic risk prediction model, we assume the carrier score distribution for probands with VUSs is a mixture of the carrier score distribution for probands with positive results and the carrier score distribution for probands with negative results. Under this mixture model, we propose a likelihood-based approach to assess the frequency of pathogenicity among probands with VUSs, while accounting for the existence of possible pathogenic mutations on genes not tested. We conducted simulations to assess the performance of the approach and show that under various settings, the approach performs well with very little bias in the estimated proportion of VUSs that are likely pathogenic. We also estimate the positive predictive value across the entire range of carrier scores. We apply our approach to the USC-Stanford Hereditary Cancer Panel Testing cohort, and estimate the proportion of probands that have VUSs in BRCA1/2 that are likely pathogenic to be 10.12% [95%CI: 0%, 43.04%]. This approach will enable clinicians to target high-risk patients who have VUSs, allowing for early prevention interventions.

5.
Sci Rep ; 10(1): 14454, 2020 09 02.
Artigo em Inglês | MEDLINE | ID: mdl-32879338

RESUMO

The purpose of this study is to evaluate the changes in the palatal alveolar bone thickness and find the factors related to the resorption of the palatal alveolar bone caused by tooth movement after the maxillary incisors were retracted and intruded during orthodontic treatment. The study group comprised of 33 skeletal Class II malocclusion patients who underwent extraction for orthodontic treatment. Palatal alveolar bone thickness changes and resorption factors were identified and analyzed. The changes of maxillary central incisors and palatal alveolar bone thickness were measured, and the corresponding sample t test was performed using SPSS (IBM SPSS version 22). The amount of palatal alveolar bone resorption was measured and various parameters were analyzed to determine which factors affected it. Correlation analysis adopting the amount of palatal alveolar bone resorption as a dependent variable demonstrated that the SNB, mandibular plane angle, and the inclination of the maxillary central incisor were significantly correlated with before treatment. On the other hand, mandibular plane angle, angle of convexity, the inclination of the upper incisor, and the occlusal plane (UOP, POP) were significantly correlated with post-treatment. In addition, the variables related to palatal contour (PP to PAS, SN to PAS, palatal surface angle) and occlusal planes (UOP/POP) were significantly correlated with the difference in palatal bone resorption. During initial diagnosis, high angle class II with normal upper incisor inclination can be signs of high-risk factors. In addition, maintaining the occlusal plane during treatment helps to prevent palatal bone loss.

6.
Prog Orthod ; 20(1): 47, 2019 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-31867679

RESUMO

BACKGROUND: Maxillary incisor protrusion is a prevalent dental deformity and is often treated by upper incisor intrusion and retraction. The mechanical loading triggers the resorption and apposition of the bone. Alveolar bone remodeling is expected to follow orthodontic tooth movement in a one-to-one relationship. However, in many cases, the outcomes are different. Alveolar bone might still remain thick causing lip protrusion and other aesthetic problems after treatment. Additional corrective procedures such as alveoloplasty. On the other hand, if the labial bone becomes too thin, periodontal problems like gingival recession might occur. The unpredictability of the treatment result and the risk of requiring corrective procedures pose significant challenges to both the providers and patients. The aim of this study is to determine factors that can help to predict the alveolar bone reaction before maxillary incisor intrusion and retraction. METHODS: The cohort included 34 female patients (mean age 25.8 years) who were diagnosed with skeletal class II malocclusion with upper incisor protrusion. These patients underwent extraction and orthodontic treatment with upper incisor intrusion and retraction. Lateral cephalograms at pre-treatment and post-treatment were taken. Linear and angular measurements were analyzed to evaluate the alveolar bone changes based on initial conditions. RESULTS: The study found that the relative change, calculated as change in alveolar bone thickness after treatment divided by the initial alveolar thickness, was inversely correlated with the initial thickness. There was a significant increase of labial alveolar bone thickness at 9-mm apical from cementoenamel junction (B3) (P < 0.05) but no statistically significant change in the thickness at other levels. In addition, the change in angulation between the incisor and alveolar bone was inversely correlated with several initial angulations: between the initial palatal plane and upper incisor angle, between the initial palatal plane and upper incisor labial surface angle, and between the initial palatal plane and bone labial surface angle. On the other hand, the change in labial bone thickness was neither significantly correlated with the initial thickness nor significantly correlated to the amount of retraction. CONCLUSION: The unpredictability of alveolar bone remodeling after upper incisor intrusion and retraction poses significant challenges to treatment planning and patient experience. The study showed that the initial angulation between the incisor and alveolar bone is correlated with the change in angulation after treatment, the initial thickness of the alveolar bone was correlated with the relative change of the alveolar bone thickness (defined as change in thickness after treatment divided by its initial thickness), and the amount of intrusion was correlated with the alveolar bone thickness change at 9-mm apical from the cementoenamel junction after treatment. The results of the present study also revealed that the change in labial alveolar bone thickness was neither significantly correlated with the initial thickness nor significantly correlated to the amount of retraction.


Assuntos
Estética Dentária , Incisivo , Adulto , Remodelação Óssea , Cefalometria , Feminino , Humanos , Maxila , Técnicas de Movimentação Dentária
7.
Am J Orthod Dentofacial Orthop ; 156(1): 113-124, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31256824

RESUMO

Scissor bite often remains unnoticed by patients although it can adversely affect facial symmetry, jaw growth, and mastication. This case report illustrates the efficacy of temporary skeletal anchorage devices (TSADs) and a modified lingual arch in correcting severe scissor bite. A 28-year-old woman presented with severe scissor bite in the mandibular right posterior segment. To treat this condition, TSADs were used for maxillary posterior intrusion and a modified lingual arch for buccally uprighting mandibular posterior teeth. Long-term retention records demonstrate stable treatment results.


Assuntos
Oclusão Dentária , Má Oclusão de Angle Classe II/terapia , Má Oclusão de Angle Classe I/terapia , Ortodontia Corretiva/métodos , Adulto , Cefalometria/métodos , Modelos Dentários , Feminino , Humanos , Má Oclusão de Angle Classe I/diagnóstico por imagem , Má Oclusão de Angle Classe I/cirurgia , Má Oclusão de Angle Classe II/diagnóstico por imagem , Má Oclusão de Angle Classe II/cirurgia , Mandíbula/diagnóstico por imagem , Mandíbula/patologia , Mandíbula/cirurgia , Maxila/diagnóstico por imagem , Maxila/patologia , Maxila/cirurgia , Procedimentos de Ancoragem Ortodôntica/instrumentação , Procedimentos de Ancoragem Ortodôntica/métodos , Desenho de Aparelho Ortodôntico , Aparelhos Ortodônticos , Fios Ortodônticos , Ortodontia Corretiva/instrumentação , Técnica de Expansão Palatina , Planejamento de Assistência ao Paciente , Fatores de Tempo , Resultado do Tratamento
9.
Int J Oral Sci ; 11(1): 5, 2019 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-30602776

RESUMO

In the original version of this Article, Figure 1c was inadvertently assembled with a duplicate of Figure 1b. The correct image for Figure 1c, shown below, has been added in the HTML and PDF versions of the Article. This does not affect the conclusions of the study. We sincerely apologize for any inconvenience this may have caused our readers.

12.
Am J Pathol ; 188(10): 2318-2327, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30059656

RESUMO

Medication-related osteonecrosis of the jaw (MRONJ) is a rare but detrimental intraoral lesion that predominantly occurs in patients with long-term use of antiresorptive agents, such as bisphosphonate and denosumab, a human anti-receptor activator of NF-κB ligand (RANKL) monoclonal antibody (Ab). Surgical intervention, such as tooth extraction, is a known risk factor for MRONJ, which is often performed to eliminate preexiting pathologic inflammatory conditions, such as periodontal diseases. Nonetheless, it remains unknown whether pre-existing periodontal disease condition exacerbates, or removal of such condition ameliorates, MRONJ development after tooth extraction. In this study, we combined the ligature-induced periodontitis and the tooth extraction mouse models under the administration of zoledronic acid (ZOL) or anti-RANKL Ab, and provide experimental evidence that a pre-existing pathologic inflammatory condition exacerbates MRONJ development after tooth extraction in mice. Under ZOL administration, tooth extraction alone induced ONJ lesions; however, extraction of a ligature-placed tooth further exacerbated ONJ development. When the ligature was removed and the inflammatory condition was deescalated, ONJ development was ameliorated. Anti-RANKL Ab administration resulted in similar outcomes. Interestingly, unlike ZOL-administered mice, anti-RANKL Ab-administered mice exhibited complete absence of osteoclasts, suggesting that physical presence of osteoclasts is not directly involved in ONJ development. Collectively, our study demonstrated that periodontal disease is a functionally linked risk factor that predisposes ONJ development after tooth extraction in the presence of bisphosphonate and denosumab.


Assuntos
Doenças Maxilomandibulares/prevenção & controle , Osteonecrose/prevenção & controle , Periodontite/terapia , Extração Dentária , Animais , Osteonecrose da Arcada Osseodentária Associada a Difosfonatos/prevenção & controle , Conservadores da Densidade Óssea/toxicidade , Denosumab/toxicidade , Modelos Animais de Doenças , Feminino , Doenças Maxilomandibulares/induzido quimicamente , Ligadura , Camundongos Endogâmicos C57BL , Osteonecrose/induzido quimicamente
13.
Cell Stem Cell ; 23(2): 193-209.e5, 2018 Aug 02.
Artigo em Inglês | MEDLINE | ID: mdl-30017591

RESUMO

Aberrant lineage specification of skeletal stem cells (SSCs) contributes to reduced bone mass and increased marrow adipose tissue (MAT) in osteoporosis and skeletal aging. Although master regulators of osteoblastic and adipogenic lineages have been identified, little is known about factors that are associated with MAT accumulation and osteoporotic bone loss. Here, we identify peroxisome-proliferator-activated receptor γ coactivator 1-α (PGC-1α) as a critical switch of cell fate decisions whose expression decreases with aging in human and mouse SSCs. Loss of PGC-1α promoted adipogenic differentiation of murine SSCs at the expense of osteoblastic differentiation. Deletion of PGC-1α in SSCs impaired bone formation and indirectly promoted bone resorption while enhancing MAT accumulation. Conversely, induction of PGC-1α attenuated osteoporotic bone loss and MAT accumulation. Mechanistically, PGC-1α maintains bone and fat balance by inducing TAZ. Our results suggest that PGC-1α is a potentially important therapeutic target in the treatment of osteoporosis and skeletal aging.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Tecido Adiposo/citologia , Envelhecimento/metabolismo , Osso e Ossos/citologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Músculo Esquelético/citologia , Osteoporose/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Células-Tronco/citologia , Fatores de Transcrição/metabolismo , Tecido Adiposo/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Osso e Ossos/metabolismo , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Músculo Esquelético/metabolismo , Osteoporose/patologia , Domínios PDZ , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/deficiência , Células-Tronco/metabolismo , Transativadores , Adulto Jovem
14.
Proc Natl Acad Sci U S A ; 115(24): E5566-E5575, 2018 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-29844188

RESUMO

Although significant progress has been made in understanding epigenetic regulation of in vitro adipogenesis, the physiological functions of epigenetic regulators in metabolism and their roles in obesity remain largely elusive. Here, we report that KDM4B (lysine demethylase 4B) in adipose tissues plays a critical role in energy balance, oxidation, lipolysis, and thermogenesis. Loss of KDM4B in mice resulted in obesity associated with reduced energy expenditure and impaired adaptive thermogenesis. Obesity in KDM4B-deficient mice was accompanied by hyperlipidemia, insulin resistance, and pathological changes in the liver and pancreas. Adipocyte-specific deletion of Kdm4b revealed that the adipose tissues were the main sites for KDM4B antiobesity effects. KDM4B directly controlled the expression of multiple metabolic genes, including Ppargc1a and Ppara Collectively, our studies identify KDM4B as an essential epigenetic factor for the regulation of metabolic health and maintaining normal body weight in mice. KDM4B may provide a therapeutic target for treatment of obesity.


Assuntos
Histona Desmetilases com o Domínio Jumonji/metabolismo , Doenças Metabólicas/metabolismo , Obesidade/metabolismo , Adipócitos/metabolismo , Adipogenia/fisiologia , Tecido Adiposo/metabolismo , Animais , Peso Corporal/fisiologia , Dieta Hiperlipídica/efeitos adversos , Metabolismo Energético/fisiologia , Epigênese Genética/fisiologia , Resistência à Insulina/fisiologia , Lipólise/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução , Termogênese/fisiologia
15.
Transl Behav Med ; 8(1): 85-94, 2018 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-29385580

RESUMO

Research on the communication of genetic test results has focused predominately on non-Hispanic White (NHW) mutation-positive families with high-risk hereditary cancer conditions. Little is known about this process for racially and ethnically diverse individuals or for those with mutations in moderate risk genes. The communication behaviors of study participants who carry a gene mutation were analyzed 3 months after disclosure of genetic test results. Participants were queried about communication of their results, as part of a prospective study of multi-gene panel genetic testing. The responses of particpants who tested positive were analyzed by race/ethnicity and by level of cancer risk (high vs. moderate). Of the 216 mutation-positive study participants, 136 (63%) responded. Self-reported race/ethnicity was 46% NHW, 41% Hispanic, 10% Asian, and 2% Black. The majority (99.0%, n = 135) had shared their results with someone and 96% had told a family member (n = 130). Hispanic respondents were less likely to have told a healthcare provider about their results than NHW (29% vs. 68%, p < .0001). Asian respondents were less likely than NHW to encourage family members to undergo testing (OR = 0.1, p = .03); but Asian family members were more likely to undergo testing (OR = 8.0, p = .03). There were no differences in communication between those with a mutation in a high- or moderate-risk gene. Three months post genetic testing, communication of results was very high; 30% reported a family member underwent genetic testing. Further studies are needed to better understand the communication process in individuals from diverse racial/ethnic backgrounds.


Assuntos
Predisposição Genética para Doença , Testes Genéticos , Comunicação em Saúde , Neoplasias/genética , Neoplasias/psicologia , Comportamento Social , Família/etnologia , Família/psicologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Neoplasias/etnologia
16.
PLoS One ; 13(1): e0190901, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29304080

RESUMO

A majority of patients with orofacial cleft deformity requires cleft repair through a bone graft. However, elevated amount of bone resorption and subsequent bone graft failure remains a significant clinical challenge. Bisphosphonates (BPs), a class of anti-resorptive drugs, may offer great promise in enhancing the clinical success of bone grafting. In this study, we compared the effects of systemic and local delivery of BPs in an intraoral bone graft model in rats. We randomly divided 34 female 20-week-old Fischer F344 Inbred rats into four groups to repair an intraoral critical-sized defect (CSD): (1) Control: CSD without graft (n = 4); (2) Graft/Saline: bone graft with systemic administration of saline 1 week post-operatively (n = 10); (3) Graft/Systemic: bone graft with systemic administration of zoledronic acid 1 week post-operatively (n = 10); and (4) Graft/Local: bone graft pre-treated with zoledronic acid (n = 10). At 6-weeks post-operatively, microCT volumetric analysis showed a significant increase in bone fraction volume (BV/TV) in the Graft/Systemic (62.99 ±14.31%) and Graft/Local (69.35 ±13.18%) groups compared to the Graft/Saline (39.18±10.18%). Similarly, histological analysis demonstrated a significant increase in bone volume in the Graft/Systemic (78.76 ±18.00%) and Graft/Local (89.95 ±4.93%) groups compared to the Graft/Saline (19.74±18.89%). The local delivery approach resulted in the clinical success of bone grafts, with reduced graft resorption and enhanced osteogenesis and bony integration with defect margins while avoiding the effects of BPs on peripheral osteoclastic function. In addition, local delivery of BPs may be superior to systemic delivery with its ease of procedure as it involves simple soaking of bone graft materials in BP solution prior to graft placement into the defect. This new approach may provide convenient and promising clinical applications towards effectively managing cleft patients.


Assuntos
Transplante Ósseo , Fissura Palatina/cirurgia , Difosfonatos/administração & dosagem , Animais , Fissura Palatina/tratamento farmacológico , Feminino , Osteoclastos/efeitos dos fármacos , Ratos , Ratos Endogâmicos F344 , Microtomografia por Raio-X
17.
Proc Natl Acad Sci U S A ; 114(35): E7218-E7225, 2017 08 29.
Artigo em Inglês | MEDLINE | ID: mdl-28808036

RESUMO

Patients with cleft lip and/or palate (CLP), who undergo numerous medical interventions from infancy, can suffer from lifelong debilitation caused by underdeveloped maxillae. Conventional treatment approaches use maxillary expansion techniques to develop normal speech, achieve functional occlusion for nutrition intake, and improve esthetics. However, as patients with CLP congenitally lack bone in the cleft site with diminished capacity for bone formation in the expanded palate, more than 80% of the patient population experiences significant postexpansion relapse. While such relapse has been a long-standing battle in craniofacial care of patients, currently there are no available strategies to address this pervasive problem. Estrogen, 17ß-estradiol (E2), is a powerful therapeutic agent that plays a critical role in bone homeostasis. However, E2's clinical application is less appreciated due to several limitations, including its pleiotropic effects and short half-life. Here, we developed a treatment strategy using an injectable system with photo-cross-linkable hydrogel (G) and nanodiamond (ND) technology to facilitate the targeted and sustained delivery of E2 to promote bone formation. In a preclinical expansion/relapse model, this functionalized E2/ND/G complex substantially reduced postexpansion relapse by nearly threefold through enhancements in sutural remodeling compared with unmodified E2 administration. The E2/ND/G group demonstrated greater bone volume by twofold and higher osteoblast number by threefold, compared with the control group. The E2/ND/G platform maximized the beneficial effects of E2 through its extended release with superior efficacy and safety at the local level. This broadly applicable E2 delivery platform shows promise as an adjuvant therapy in craniofacial care of patients.


Assuntos
Estrogênios/farmacologia , Nanodiamantes/uso terapêutico , Técnica de Expansão Palatina/instrumentação , Animais , Fenda Labial/cirurgia , Fissura Palatina/terapia , Modelos Animais de Doenças , Feminino , Hidrogel de Polietilenoglicol-Dimetacrilato/farmacologia , Nanoestruturas/uso terapêutico , Ratos , Ratos Sprague-Dawley , Recidiva , Prevenção Secundária/métodos , Resultado do Tratamento
18.
Stem Cell Reports ; 9(3): 752-761, 2017 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-28826853

RESUMO

Mesoderm derived from human embryonic stem cells (hESCs) is a major source of the mesenchymal stem/stromal cells (MSCs) that can differentiate into osteoblasts and chondrocytes for tissue regeneration. While significant progress has been made in understanding of molecular mechanisms of hESC differentiation into mesodermal cells, little is known about epigenetic factors controlling hESC fate toward mesoderm and MSCs. Identifying potential epigenetic factors that control hESC differentiation will undoubtedly lead to advancements in regenerative medicine. Here, we conducted an epigenome-wide analysis of hESCs and MSCs and uncovered that EZH2 was enriched in hESCs and was downregulated significantly in MSCs. The specific EZH2 inhibitor GSK126 directed hESC differentiation toward mesoderm and generated more MSCs by reducing H3K27me3. Our results provide insights into epigenetic landscapes of hESCs and MSCs and suggest that inhibiting EZH2 promotes mesodermal differentiation of hESCs.


Assuntos
Diferenciação Celular , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Histonas/metabolismo , Células-Tronco Embrionárias Humanas/citologia , Células-Tronco Embrionárias Humanas/metabolismo , Lisina/metabolismo , Mesoderma/citologia , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Reprogramação Celular/efeitos dos fármacos , Ontologia Genética , Células-Tronco Embrionárias Humanas/efeitos dos fármacos , Humanos , Indóis/farmacologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Metilação , Família Multigênica , Piridonas/farmacologia , Transcriptoma/genética
19.
Am J Orthod Dentofacial Orthop ; 151(5): 887-897, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28457266

RESUMO

INTRODUCTION: Bone-borne palatal expansion relies on mini-implant stability for successful orthopedic expansion. The large magnitude of applied force experienced by mini-implants during bone-borne expansion may lead to high failure rates. Use of bicortical mini-implant anchorage rather than monocortical anchorage may improve mini-implant stability. The aims of this study were to analyze and compare the effects of bicortical and monocortical anchorages on stress distribution and displacement during bone-borne palatal expansion using finite element analysis. METHODS: Two skull models were constructed to represent expansion before and after midpalatal suture opening. Three clinical situations with varying mini-implant insertion depths were studied in each skull model: monocortical, 1-mm bicortical, and 2.5-mm bicortical. Finite element analysis simulations were performed for each clinical situation in both skull models. Von Mises stress distribution and transverse displacement were evaluated for all models. RESULTS: Peri-implant stress was greater in the monocortical anchorage model compared with both bicortical anchorage models. In addition, transverse displacement was greater and more parallel in the coronal plane for both bicortical models compared with the monocortical model. Minimal differences were observed between the 1-mm and the 2.5-mm bicortical models for both peri-implant stress and transverse displacement. CONCLUSIONS: Bicortical mini-implant anchorage results in improved mini-implant stability, decreased mini-implant deformation and fracture, more parallel expansion in the coronal plane, and increased expansion during bone-borne palatal expansion. However, the depth of bicortical mini-implant anchorage was not significant.


Assuntos
Procedimentos de Ancoragem Ortodôntica/métodos , Técnica de Expansão Palatina , Tomografia Computadorizada de Feixe Cônico , Análise de Elementos Finitos , Humanos , Maxila/anatomia & histologia , Maxila/diagnóstico por imagem , Modelos Anatômicos , Palato/anatomia & histologia , Palato/diagnóstico por imagem , Crânio/anatomia & histologia , Crânio/diagnóstico por imagem
20.
Cleft Palate Craniofac J ; 54(6): 687-698, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28094562

RESUMO

OBJECTIVE: Bone grafts in patients with cleft lip and palate can undergo a significant amount of resorption. The aim of this study was to investigate the effects of bisphosphonates (BPs) on the success of bone grafts in rats. DESIGN: Thirty-five female 15-week-old Fischer F344 Inbred rats were divided into the following experimental groups, each receiving bone grafts to repair an intraoral CSD: (1) Graft/saline: systemic administration of saline and (2) systemic administration of zoledronic acid immediately following surgery (graft/BP/T0), (3) 1 week postoperatively (graft/BP/T1), and (4) 3 weeks postoperatively (graft/BP/T2). As an additional control, the defect was left empty without bone graft. MAIN OUTCOME MEASURES: Microcomputed tomography and histologic analyses were performed in addition to evaluation of osteoclasts through tartrate-resistant acid phosphatase staining. RESULTS: Bone volume fraction (bone volume/tissue volume) for the delayed BP treatment groups (graft/BP/T1 = 45.4% ± 8.8%; graft/BP/T2 = 46.1% ± 12.4%) were significantly greater than that for the graft/saline group (31.0% ± 7.9%) and the graft/BP/T0 (27.6% ± 5.9%) 6 weeks postoperatively (P < .05). Hematoxylin and eosin staining confirmed an evident increase in bone volume and fusion of defect margins with existing palatal bone in the graft/BP/T1 and graft/BP/T2 groups. The graft/BP/T0 group showed the lowest bone volume with signs of acute inflammation. CONCLUSIONS: Delayed BP administration following cleft bone graft surgery led to significant increase in bone volume and integration compared with saline controls. However, BP injection immediately after the surgery did not enhance bone volume, and rather, may negatively affect bone graft incorporation.


Assuntos
Processo Alveolar/efeitos dos fármacos , Processo Alveolar/cirurgia , Difosfonatos/administração & dosagem , Difosfonatos/farmacologia , Imidazóis/administração & dosagem , Imidazóis/farmacologia , Processo Alveolar/diagnóstico por imagem , Animais , Reabsorção Óssea , Transplante Ósseo/métodos , Feminino , Fêmur/transplante , Ílio/transplante , Ratos , Ratos Endogâmicos F344 , Microtomografia por Raio-X , Ácido Zoledrônico
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