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1.
Nat Commun ; 10(1): 3234, 2019 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-31324800

RESUMO

Rearrangement reactions have attracted considerable interest over the past decades due to their high bond-forming efficiency and atom economy in the construction of complex organic architectures. In contrast to the well-established [3,3]-rearrangement, [1,3] O-to-C rearrangement has been far less vigorously investigated, and stereospecific [1,3]-rearrangement is extremely rare. Here, we report a metal-free intramolecular hydroalkoxylation/[1,3]-rearrangement, leading to the practical and atom-economical assembly of various valuable medium-sized lactams with wide substrate scope and excellent diastereoselectivity. Moreover, such an asymmetric cascade cyclization has also been realized by chiral Brønsted acid-catalyzed kinetic resolution. In addition, biological tests reveal that some of these medium-sized lactams displayed their bioactivity as antitumor agents against melanoma cells, esophageal cancer cells and breast cancer cells. A mechanistic rationale for the reaction is further supported by control experiments and theoretical calculations.

2.
J Cell Physiol ; 234(10): 18017-18028, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30825206

RESUMO

Clinical studies have indicated that increased serum cholesterol levels raised the risk of tendinopathy in hypercholesterolemia, but the effect of cholesterol on tendon-derived stem cells (TDSCs) and its underlying mechanism have not been studied. The purpose of this study is to investigate the association between cholesterol and tendinopathy in vitro and in vivo, and its underlying molecular mechanism as well. In TDSCs, the effect of cholesterol was assessed by quantitative polymerase chain reaction, western blot analysis, and immunofluorescence staining. Intracellular levels of reactive oxygen species (ROS) was detected, using flow cytometry. The link between nuclear factor (NF)-κB signaling and the effect of cholesterol was evaluated using a representative IκB kinase (IKK) inhibitor, BAY 11-7082. In addition, Achilles tendons from apolipoprotein E mice fed with a high-fat diet were histologically assessed using hematoxylin and eosin staining and immunohistochemistry. We found that high cholesterol apparently lowered the expression of tendon cell markers (collagen 1, scleraxis, tenomodulin), and elevated ROS levels via the NF-κB pathway both in vitro and in vivo. The ROS scavenger N-acetylcysteine (NAC) and BAY 11-7082 reversed the inhibiting effect of cholesterol on the tendon-related gene expressions of TDSCs. Moreover, NAC blocked cholesterol-induced phosphorylation of IκBα and p65. Significant histological alternation in vivo was shown in Achilles tendon in the hypercholesterolemic group. These results indicated that high cholesterol may inhibit the tendon-related gene expressions in TDSCs via ROS-activated NF-кB signaling, implying pathogenesis of tendinopathy in hypercholesterolemia and suggesting a new mechanism underlying hypercholesterolemia-induced tendinopathy.

3.
Mol Med Rep ; 18(6): 5044-5052, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30320384

RESUMO

Tendon repair follows a slow course of early inflammatory, proliferative and remodeling phases, which commonly results in the failure and loss of normal biomechanical properties. Previous studies have demonstrated that tendon­derived stem cells (TDSCs) are vital healing cells and that mRNA expression of anti­inflammatory cytokine interleukin (IL)­10 is significantly upregulated at the late inflammatory phase. To explore how IL­10 may impact tendon healing, the present study investigated the in vitro effects of IL­10 on TDSCs isolated from rat Achilles tendons. Cellular activities of TDSCs and the expression levels of tendon cell markers were measured treatment with IL­10 and subsequent performance of wound healing assays, reverse transcription­quantitative polymerase chain reaction and western blot analyses. The results demonstrated that IL­10 treatment markedly increased the proliferative capacity of TDSCs. In addition, IL­10 significantly enhanced cell migration when compared with the control cells. Furthermore, IL­10 treatment significantly activated the JAK/Stat3 signaling pathway and inhibited the protein expression of tendon cell markers, including scleraxis and tenomodulin. Notably, IL­10 treatment also reduced the gene expression levels of type 1 collagen, type 3 collagen, lumican and fibromodulin in TDSCs. These findings indicated that IL­10 enhanced cell proliferation and migration, and inhibited tenogenic differentiation in TDSCs in vitro. Reducing the negative effects whilst enhancing the positive effects of IL­10 may be a potential therapeutic target in tendon repair.

4.
Am J Sports Med ; 46(9): 2222-2231, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29927623

RESUMO

BACKGROUND: Tendon injuries are common problems among athletes. Complete recovery of the mechanical structure and function of ruptured tendons is challenging. It has been demonstrated that upregulation of glycolysis and lactate production occurs in wounds, inflammation sites, and cancerous tumors, and these metabolic changes also control growth and differentiation of stem and progenitor cells. Similar metabolic changes have been reported in human healing tendons. In addition, lactate production has increased in progenitors isolated from injured tendons after treatment with IL-1ß. It is thought that the metabolic changes play a role in tendon healing after injury. HYPOTHESIS: Glucose metabolism is altered during tendon injury and healing, and modulation of this altered metabolism improves tendon repair. STUDY DESIGN: Controlled laboratory study. METHODS: The authors used the tendon injury model involving a complete incision of the Achilles tendon in C57BL/6J female mice and studied alterations of glucose metabolism in injured tendons with [U-13C]glucose and metabolomics analysis 1 and 4 weeks after surgery. They also examined the effects of dichloroacetate (DCA; an indirect lactate synthesis inhibitor) treatment on the recovery of structure and mechanical properties of injured tendons 4 weeks after surgery in the same mouse model. RESULTS: Significant changes in glucose metabolism in tendons after injury surgery were detected. 13C enrichment of metabolites and intermediates, flux through glycolysis, and lactate synthesis, as well as tricarboxylic acid cycle activity, were acutely increased 1 week after injury. Increased glycolysis and lactate generation were also found 4 weeks after injury. DCA-treated injured tendons showed decreased cross-sectional area and higher values of modulus, maximum stress, and maximum force when compared with vehicle-treated injured tendons. Improved alignment of the collagen fibers was also observed in the DCA group. Furthermore, DCA treatment reduced mucoid accumulation and ectopic calcification in injured tendons. CONCLUSION: The findings indicate that injured tendons acutely increase glycolysis and lactate synthesis after injury and that the inhibition of lactate synthesis by DCA is beneficial for tendon healing. CLINICAL RELEVANCE: Changing metabolism in injured tendons may be a therapeutic target for tendon repair.

5.
Biofabrication ; 10(3): 035013, 2018 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-29882516

RESUMO

Despite the promise of stem cell engineering and the new advances in bioprinting technologies, one of the major challenges in the manufacturing of large scale bone tissue scaffolds is the inability to perfuse nutrients throughout thick constructs. Here, we report a scalable method to create thick, perfusable bone constructs using a combination of cell-laden hydrogels and a 3D printed sacrificial polymer. Osteoblast-like Saos-2 cells were encapsulated within a gelatin methacrylate (GelMA) hydrogel and 3D printed polyvinyl alcohol pipes were used to create perfusable channels. A custom-built bioreactor was used to perfuse osteogenic media directly through the channels in order to induce mineral deposition which was subsequently quantified via micro-CT. Histological staining was used to verify mineral deposition around the perfused channels, while COMSOL modeling was used to simulate oxygen diffusion between adjacent channels. This information was used to design a scaled-up construct containing a 3D array of perfusable channels within cell-laden GelMA. Progressive matrix mineralization was observed by cells surrounding perfused channels as opposed to random mineral deposition in static constructs. Micro-CT confirmed that there was a direct relationship between channel mineralization within perfused constructs and time within the bioreactor. Furthermore, the scalable method presented in this work serves as a model on how large-scale bone tissue replacement constructs could be made using commonly available 3D printers, sacrificial materials, and hydrogels.

6.
Med Sci Monit ; 24: 1567-1573, 2018 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-29547593

RESUMO

BACKGROUND Previous studies demonstrated that tendon-derived stem cells (TDSCs) were vital healing cells and that mRNA expression of anti-inflammatory cytokine IL-6 was significantly upregulated in injured tendons. The aim of the present study was to investigate the effects of IL-6 on the TDSCs in vitro. MATERIAL AND METHODS TDSCs isolated from the Achilles tendons in SD rats were co-cultured with various concentrations of IL-6. Cell proliferation, cell cycle analysis, quantitative real-time PCR, western blotting analysis, and statistical analysis were used in the study. RESULTS The result showed that IL-6 strongly increased proliferation capability, and induced cell cycle activation and transition into G2/M phase from G1 phase in TDSCs. However, IL-6 treatment strongly inhibited gene expression of Scleraxis, Collagen 1, Tenomodulin, Collagen 3, Early Growth Response Protein 1, Decorin, Lumican, Biglycan and Fibromodulin in TDSCs. It also strongly inhibited protein expression of tendon cell markers like scleraxis, collagen 1, collagen 3, and tenomodulin. IL-6 treatment strongly activated the JAK/Stat3 signaling pathway in TDSCs. Furthermore, WP1066, a JAK/Stat3 signaling pathway inhibitor, abrogated the effects of IL-6 on TDSCs. CONCLUSIONS These findings indicated that IL-6 might exert dual effects on TDSCs in vitro: strongly enhancing their proliferation but inhibiting their tenogenic differentiation via the JAK/Stat3 pathway.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Interleucina-6/farmacologia , Janus Quinases/metabolismo , Transdução de Sinais , Células-Tronco/citologia , Células-Tronco/metabolismo , Tendões/citologia , Animais , Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/efeitos dos fármacos
7.
Arthritis Rheumatol ; 70(2): 230-241, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29024567

RESUMO

OBJECTIVE: To establish an unbiased, 3-dimensional (3-D) approach that quantifies subchondral bone plate (SBP) changes in mouse joints, and to investigate the mechanism that mediates SBP sclerosis at a late stage of osteoarthritis (OA). METHODS: A new micro-computed tomography (micro-CT) protocol was developed to characterize the entire thickness of the SBP in the distal femur of a normal mouse knee. Four mouse models of severe joint OA were generated: cartilage-specific Egfr-knockout (Egfr-CKO) mice at 2 months after surgical destabilization of the medial meniscus (DMM), Egfr-CKO mice with aging-related spontaneous OA, wild-type (WT) mice at 10 months after DMM, and WT mice at 14 weeks after DMM plus hemisectomy of the meniscus (DMMH) surgery. As an additional model, mice with knockout of the sclerostin gene (Sost-KO) were subjected to DMMH surgery. Knee joints were examined by micro-CT, histology, and immunohistochemical analyses. RESULTS: Examination of the mouse distal femur by 3-D micro-CT revealed a positive correlation between SBP thickness and the loading status in normal knees. In all 4 mouse models of late-stage OA, SBP sclerosis was restricted to the areas under severely eroded articular cartilage. This was accompanied by elevated bone formation at the bone marrow side of the SBP and a drastic reduction in the levels of sclerostin in osteocytes within the SBP. Unlike in WT mice, no further increase in the thickness of the SBP was observed in response to DMMH in Sost-KO mice. CONCLUSION: Since focal stress on the SBP underlying sites of cartilage damage increases during late stages of OA, these findings establish mechanical loading-induced attenuation of sclerostin expression and elevation of bone formation along the SBP surface as the major mechanisms characterizing subchondral bone phenotypes associated with severe late-stage OA in mice.

8.
Sci Rep ; 7(1): 13413, 2017 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-29042643

RESUMO

The extracellular matrix (ECM) is a fibrillar protein-based network, the physical and chemical properties of which can influence a multitude of cellular processes. Despite having an important role in cell and tissue signaling, a complete chemo-mechanical characterization of ECM proteins such as fibronectin (FN) is lacking. In this study, we engineered monodisperse FN nanofibers using a surface-initiated assembly technique in order to provide new insight into the elastic behavior of this material over large deformations. FN nanofibers were patterned on surfaces in a pre-stressed state and when released from the surface underwent rapid contraction. We found that the FN nanofibers underwent 3.3-fold and 9-fold changes in length and width, respectively, and that the nanofiber volume was conserved. Volume was also conserved following uniaxial extension of the FN nanofibers of ~2-fold relative to the patterned state. This data suggests that the FN networks we engineered formed an incompressible material with a Poisson's ratio of ~0.5. While the Poisson's ratio of cells and other biological materials are widely estimated as 0.5, our experimental results demonstrate that for FN networks this is a reasonable approximation.

9.
Biomater Sci ; 5(8): 1629-1639, 2017 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-28612067

RESUMO

Fibronectin (FN) is an extracellular matrix (ECM) glycoprotein that plays an important role in a wide range of biological processes including embryonic development, wound healing, and fibrosis. Recent evidence has demonstrated that FN is mechanosensitive, where the application of force induces conformational changes within the FN molecule to expose otherwise cryptic binding domains. However, it has proven technically challenging to dynamically monitor how the nanostructure of FN fibers changes as a result of force-induced extension, due in part to the inherent complexity of FN networks within tissue and cell-generated extracellular matrix (ECM). This has limited our understanding of FN matrix mechanobiology and the complex bi-directional signaling between cells and the ECM, and de novo FN fiber fabrication strategies have only partially addressed this. Towards addressing this need, we have developed a modified surface-initiated assembly (SIA) technique to engineer FN nanofibers that we can uniaxially stretch to >7-fold extensions and subsequently immobilize them in the stretched state for high resolution atomic force microscopy (AFM) imaging. Using this approach, we analyzed how the nanostructure of FN molecules within the nanofibers changed with stretch. In fully contracted FN nanofibers, we observed large, densely packed, isotropically-oriented nodules. With intermediate extension, uniaxially-aligned fibrillar regions developed and nodules became progressively smaller. At high extension, the nanostructure consisted of highly aligned fibrils with small nodules in a beads-on-a-string arrangement. In summary, we have established a methodology to uniaxially stretch FN fibers and monitor changes in nanostructure using AFM. Our results provide new insight into how FN fiber extension can affect the morphology of the constituent FN molecules.


Assuntos
Fibronectinas/química , Fenômenos Mecânicos , Nanofibras/química , Nanotecnologia , Teste de Materiais , Conformação Molecular
10.
PLoS One ; 11(6): e0156783, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27280771

RESUMO

Osteoarthritis (OA) is one of most common skeletal disorders and can affect synovial joints such as knee and ankle joints. α5 integrin, a major fibronectin receptor, is expressed in articular cartilage and has been demonstrated to play roles in synovial joint development and in the regulation of chondrocyte survival and matrix degradation in articular cartilage. We hypothesized that α5 integrin signaling is involved in pathogenesis of OA. To test this, we generated compound mice that conditionally ablate α5 integrin in the synovial joints using the Gdf5Cre system. The compound mice were born normally and had an overall appearance similar to the control mice. However, when the mutant mice received the OA surgery, they showed stronger resistance to osteoarthritic changes than the control. Specifically the mutant knee joints presented lower levels of cartilage matrix and structure loss and synovial changes and showed stronger biomechanical properties than the control knee joints. These findings indicate that α5 integrin may not be essential for synovial joint development but play a causative role in induction of osteoarthritic changes.


Assuntos
Cartilagem Articular/patologia , Integrina alfa5/fisiologia , Articulação do Joelho/fisiopatologia , Osteoartrite do Joelho/fisiopatologia , Líquido Sinovial/metabolismo , Animais , Cartilagem Articular/metabolismo , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transdução de Sinais
11.
Matrix Biol ; 52-54: 315-324, 2016 May-Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26825318

RESUMO

Ectopic tendon mineralization can develop following tendon rupture or trauma surgery. The pathogenesis of ectopic tendon mineralization and its clinical impact have not been fully elucidated yet. In this study, we utilized a mouse Achilles tendon injury model to determine whether ectopic tendon mineralization alters the biomechanical properties of the tendon and whether BMP signaling is involved in this condition. A complete transverse incision was made at the midpoint of the right Achilles tendon in 8-week-old CD1 mice and the gap was left open. Ectopic cartilaginous mass formation was found in the injured tendon by 4weeks post-surgery and ectopic mineralization was detected at 8 to 10weeks post-surgery. Ectopic mineralization grew over time and volume of the mineralized materials of 25-weeks samples was about 2.5 fold bigger than that of 10-weeks samples, indicating that injury-induced ectopic tendon mineralization is progressive. In vitro mechanical testing showed that max force, max stress and mid-substance modulus in the 25-weeks samples were significantly lower than the 10-weeks samples. We observed substantial increases in expression of bone morphogenetic protein family genes in injured tendons 1week post-surgery. Immunohistochemical analysis showed that phosphorylation of both Smad1 and Smad3 was highly increased in injured tendons as early as 1week post-injury and remained high in ectopic chondrogenic lesions 4-weeks post-injury. Treatment with the BMP receptor kinase inhibitor (LDN193189) significantly inhibited injury-induced tendon mineralization. These findings indicate that injury-induced ectopic tendon mineralization is progressive, involves BMP signaling and associated with deterioration of tendon biomechanical properties.


Assuntos
Tendão do Calcâneo/lesões , Proteínas Morfogenéticas Ósseas/metabolismo , Calcinose/fisiopatologia , Proteínas Smad/metabolismo , Traumatismos dos Tendões/fisiopatologia , Tendão do Calcâneo/patologia , Tendão do Calcâneo/fisiopatologia , Animais , Fenômenos Biomecânicos , Calcinose/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Humanos , Camundongos , Fosforilação , Transdução de Sinais , Traumatismos dos Tendões/patologia , Cicatrização
12.
Biochem Biophys Res Commun ; 463(4): 667-72, 2015 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-26051275

RESUMO

Tendon injuries are common, and the damaged tendon often turns into scar tissue and never completely regains the original biomechanical properties. Previous studies have reported that the mRNA levels of inflammatory cytokines such as IL-1ß are remarkably up-regulated in injured tendons. To examine how IL-1ß impacts tendon repair process, we isolated the injured tendon-derived progenitor cells (inTPCs) from mouse injured Achilles tendons and studied the effects of IL-1ß on the inTPCs in vitro. IL-1ß treatment strongly reduced expression of tendon cell markers such as scleraxis and tenomodulin, and also down-regulated gene expression of collagen 1, collagen 3, biglycan and fibromodulin in inTPCs. Interestingly, IL-1ß stimulated lactate production with increases in hexokinase II and lactate dehydrogenase expression and a decrease in pyruvate dehydrogenase. Inhibition of lactate production restored IL-1ß-induced down-regulation of collagen1 and scleraxis expression. Furthermore, IL-1ß significantly inhibited adipogenic, chondrogenic and osteogenic differentiation of inTPCs. Interestingly, inhibition of tenogenic and adipogenic differentiation was not recovered after removal of IL-1ß while chondrogenic and osteogenic differentiation abilities were not affected. These findings indicate that IL-1ß strongly and irreversibly impairs tenogenic potential and alters glucose metabolism in tendon progenitors appearing in injured tendons. Inhibition of IL-1ß may be beneficial for maintaining function of tendon progenitor cells during the tendon repair process.


Assuntos
Diferenciação Celular/fisiologia , Interleucina-1beta/fisiologia , Células-Tronco/metabolismo , Tendões/metabolismo , Animais , Sequência de Bases , Primers do DNA , Feminino , Glucose/metabolismo , Técnicas In Vitro , Camundongos , Reação em Cadeia da Polimerase , Tendões/citologia
13.
Med Sci Monit ; 21: 1162-72, 2015 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-25904398

RESUMO

BACKGROUND: We studied the biological safety, biomechanics, and tissue compatibility of calcium phosphate cement and Polymethyl Methacrylate composite bone cement mixed in different ratios. MATERIAL/METHODS: CPC and PMMA were mixed in different ratios (3:1, 2:1, 1:1, 1:2, 1:5, 1:10, 1:15, and 1:20). PMMA solvent is a general solvent containing a dissolved preparation of the composite bone cement specific to a given specimen to determine biological safety, biomechanics, and tissue compatibility. RESULTS: The CPC/PMMA (33%) group, CPC/PMMA (50%) group, CPC/PMMA (67%) group, and CPC/PMMA (75%) group were more in line with the composite bone cement without cytotoxicity requirements. The compressive strength of the CPC/PMMA (67%) group and CPC/PMMA (75%) group was 20 Mpa-30 Mpa, while that of the CPC/PMMA (4.8%) group, CPC/PMMA (6.25%) group, CPC/PMMA (9.1%) group, CPC/PMMA (16.7%) group, CPC/PMMA (33%) group, and CPC/PMMA (50%) group was 40 Mpa-70 Mpa. Curing time was longer in the CPC group (more than 11 min) and shorter in the PMMA group (less than 2 min). The results of weight loss rate showed that there were no significant differences between the CPC/PMMA group (4.8%, 6.25%, 9.1%, 16.7%, 33%) and PMMA control group (p>0.05). With the decrease of CPC content, the rate of weight loss gradually decreased. CONCLUSIONS: The CPC/PMMA (50%) group, CPC/PMMA (67%) group, and CPC/PMMA (75%) group provide greater variability and selectivity for the composite bone cement in obtaining better application.


Assuntos
Cimentos para Ossos/química , Fosfatos de Cálcio/química , Polimetil Metacrilato/química , Células 3T3 , Animais , Fenômenos Biomecânicos , Cimentos para Ossos/toxicidade , Fosfatos de Cálcio/toxicidade , Força Compressiva , Humanos , Teste de Materiais , Camundongos , Microscopia Eletrônica de Varredura , Osteoblastos/efeitos dos fármacos , Polimetil Metacrilato/toxicidade , Radiografia , Ratos , Ratos Sprague-Dawley , Resistência à Tração , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/patologia , Fraturas da Tíbia/terapia , Engenharia Tecidual , Difração de Raios X
14.
Int Immunopharmacol ; 24(2): 408-415, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25576403

RESUMO

Proinflammatory cytokine interleukin-1ß (IL-1ß) plays a crucial role in the pathogenesis of Osteoarthritis (OA) by stimulating several mediators contributed to cartilage degradation. Aucubin, a natural compound derived from plants which has been shown to possess diverse biological activities including anti-inflammatory property, may benefit the IL-1ß stimulated chondrocytes. The present study was aimed to investigate the effects of Aucubin on IL-1ß stimulated rat chondrocytes. Rat chondrocytes were cultured and pretreated with Aucubin (1, 10, 20, 50µM), and then stimulated with or without IL-1ß (10ng/ml). Gene and protein expression of MMP-3, MMP-9, MMP-13, cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS) was determined by real-time PCR and Western blotting respectively. Nitric oxide (NO) production was quantified by Griess reagent. Phosphorylation and nuclear translocation of p65 were detected by western blotting and immunofluorescence, respectively. We found that Aucubin significantly reversed the elevated gene and protein expression of MMP-3, MMP-9, MMP-13, iNOS, COX-2 and the production of NO induced by IL-1ß challenge in rat chondrocytes. Furthermore, Aucubin was able to suppress the IL-1ß-mediated phosphorylation and nuclear translocation of p65, indicating Aucubin may possibly act via the NF-κB signaling pathway. The present study proposes that Aucubin may be a potential therapeutic choice in the treatment of OA due to its anti-inflammatory and chondroprotective features.


Assuntos
Anti-Inflamatórios/farmacologia , Condrócitos/efeitos dos fármacos , Glucosídeos Iridoides/farmacologia , NF-kappa B/antagonistas & inibidores , Animais , Cartilagem Articular/citologia , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Condrócitos/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Interleucina-1beta , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Metaloproteinase 3 da Matriz/genética , Metaloproteinase 3 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/genética , Óxido Nítrico Sintase Tipo II/metabolismo , RNA Mensageiro/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
15.
Med Sci Monit ; 20: 1628-33, 2014 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-25213190

RESUMO

BACKGROUND: The aim of this meta-analysis was to compare the outcomes of proximal femoral nail (PFN) and dynamic hip screw (DHS) in treatment of intertrochanteric fractures. MATERIAL AND METHODS: Relevant randomized or quasi-randomized controlled studies comparing the effects of PFN and DHS were searched for following the requirements of the Cochrane Library Handbook. Six eligible studies involving 669 fractures were included. Their methodological quality was assessed and data were extracted independently for meta-analysis. RESULTS: The results showed that the PFN group had significantly less operative time (WMD: -21.15, 95% CI: -34.91 - -7.39, P=0.003), intraoperative blood loss (WMD: -139.81, 95% CI: -210.39 - -69.22, P=0.0001), and length of incision (WMD: -6.97, 95% CI: -9.19 - -4.74, P<0.00001) than the DHS group. No significant differences were found between the 2 groups regarding postoperative infection rate, lag screw cut-out rate, or reoperation rate. CONCLUSIONS: The current evidence indicates that PFN may be a better choice than DHS in the treatment of intertrochanteric fractures.


Assuntos
Pinos Ortopédicos , Parafusos Ósseos , Fêmur/cirurgia , Fraturas do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Reoperação
16.
Stem Cells ; 32(12): 3266-77, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25220576

RESUMO

To study the cellular mechanism of the tendon repair process, we used a mouse Achilles tendon injury model to focus on the cells recruited to the injured site. The cells isolated from injured tendon 1 week after the surgery and uninjured tendons contained the connective tissue progenitor populations as determined by colony-forming capacity, cell surface markers, and multipotency. When the injured tendon-derived progenitor cells (inTPCs) were transplanted into injured Achilles tendons, they were not only integrated in the regenerating area expressing tenogenic phenotype but also trans-differentiated into chondrogenic cells in the degenerative lesion that underwent ectopic endochondral ossification. Surprisingly, the micromass culture of the inTPCs rapidly underwent chondrogenic differentiation even in the absence of exogenous bone morphogenetic proteins or TGFßs. The cells isolated from human ruptured tendon tissues also showed connective tissue progenitor properties and exhibited stronger chondrogenic ability than bone marrow stromal cells. The mouse inTPCs contained two subpopulations one positive and one negative for CD105, a coreceptor of the TGFß superfamily. The CD105-negative cells showed superior chondrogenic potential in vitro and induced larger chondroid degenerative lesions in mice as compared to the CD105-positive cells. These findings indicate that tendon progenitor cells are recruited to the injured site of tendons and have a strong chondrogenic potential and that the CD105-negative population of these cells would be the cause for chondroid degeneration in injured tendons. The newly identified cells recruited to the injured tendon may provide novel targets to develop therapeutic strategies to facilitate tendon repair.


Assuntos
Diferenciação Celular/fisiologia , Células-Tronco Mesenquimais/citologia , Células-Tronco/citologia , Tendões/citologia , Animais , Células Cultivadas , Condrogênese/fisiologia , Endoglina , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Camundongos , Osteogênese/fisiologia , Tendões/metabolismo
17.
J Clin Anesth ; 26(5): 350-9, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25066879

RESUMO

STUDY OBJECTIVE: To compare intra-articular lidocaine (IAL) with intravenous analgesia and sedation (IVAS) for manual closed reduction of acute anterior shoulder dislocation. DESIGN: Meta-analysis. SETTING: Metropolitan medical university. MEASUREMENTS: A literature search was conducted of PubMed, Ovid and Cochrane Library, to identify randomized controlled trials (RCTs) published from January 1, 1990 to September 1, 2012, that compared IAL with IVAS for manual closed reduction of acute anterior shoulder dislocation. Effective data were pooled using fixed-effects or random-effects models with mean differences (MDs) and risk ratios (RRs) for continuous and dichotomous variables, respectively. MAIN RESULTS: Nine RCTs comprising 438 patients were analyzed. Statistical analyses showed that IAL was superior to IVAS with respect to lower complication risk (P < 0.00001) and shorter mean hospital length of stay (P = 0.03). No significant differences were noted in success of joint reduction (P = 0.16), patient satisfaction (P = 0.12), or postreduction pain relief (P = 0.76). However, IAL required more time than IVAS from injection to reduction (P < 0.00001). Subgroup analyses showed that IVAS was associated with higher risks of respiratory depression (P < 0.0001), vomiting (P = 0.04), and thrombophlebitis (P = 0.008), but no statistical differences were identified in nausea (P = 0.06), hypotension (P = 0.10), drowsiness (P = 0.45), or headache (P = 0.29). CONCLUSIONS: Intra-articular lidocaine injection may be safer than IVAS because there are fewer risks of postoperative complications with IAL. Both techniques are similarly effective for manual closed reduction of acute anterior shoulder dislocation.


Assuntos
Analgésicos/administração & dosagem , Anestésicos Locais/administração & dosagem , Lidocaína/administração & dosagem , Luxação do Ombro/terapia , Analgesia/métodos , Analgésicos/efeitos adversos , Anestésicos Locais/efeitos adversos , Humanos , Hipnóticos e Sedativos/administração & dosagem , Hipnóticos e Sedativos/efeitos adversos , Injeções Intra-Articulares , Injeções Intravenosas , Tempo de Internação , Lidocaína/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Tempo
18.
Biochem Biophys Res Commun ; 450(1): 762-6, 2014 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-24953691

RESUMO

NSAIDs are often ingested to reduce the pain and improve regeneration of tendon after tendon injury. Although the effects of NSAIDs in tendon healing have been reported, the data and conclusions are not consistent. Recently, tendon-derived stem cells (TDSCs) have been isolated from tendon tissues and has been suggested involved in tendon repair. Our study aims to determine the effects of COX-2 inhibitor (celecoxib) on the proliferation and tenocytic differentiation of TDSCs. TDSCs were isolated from mice Achilles tendon and exposed to celecoxib. Cell proliferation rate was investigated at various concentrations (0.1, 1, 10 and 100 µg/ml) of celecoxib by using hemocytometer. The mRNA expression of tendon associated transcription factors, tendon associated collagens and tendon associated molecules were determined by reverse transcription-polymerase chain reaction. The protein expression of Collagen I, Collagen III, Scleraxis and Tenomodulin were determined by Western blotting. The results showed that celecoxib has no effects on TDSCs cell proliferation in various concentrations (p>0.05). The levels of most tendon associated transcription factors, tendon associated collagens and tendon associated molecules genes expression were significantly decreased in celecoxib (10 µg/ml) treated group (p<0.05). Collagen I, Collagen III, Scleraxis and Tenomodulin protein expression were also significantly decreased in celecoxib (10 µg/ml) treated group (p<0.05). In conclusion, celecoxib inhibits tenocytic differentiation of tendon-derived stem cells but has no effects on cell proliferation.


Assuntos
Colágeno/metabolismo , Pirazóis/administração & dosagem , Células-Tronco/citologia , Células-Tronco/fisiologia , Sulfonamidas/administração & dosagem , Tendões/citologia , Tendões/fisiologia , Animais , Celecoxib , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/fisiologia , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Inibidores de Ciclo-Oxigenase 2/administração & dosagem , Relação Dose-Resposta a Droga , Camundongos , Camundongos Endogâmicos C57BL
19.
Orthopedics ; 36(3): e288-94, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23464935

RESUMO

The goal of this study was to compare the outcomes of unstable trochanteric fractures treated with the InterTan nail (Smith & Nephew, Memphis, Tennessee) and the Proximal Femoral Nail Antirotation (PFNA-II) (Synthes, Solothurn, Switzerland). A total of 132 consecutive patients with unstable trochanteric fractures of the femur were enrolled in the study. The only intervention was InterTan nail or PFNA-II fixation of the unstable trochanteric fractures. Follow-up occurred at 1, 3, 6, and 12 months postoperatively and yearly thereafter. Radiographs were obtained at each follow-up, and all implant position changes, complications, and fixation failures were recorded. A total of 113 patients meeting the criteria were evaluated at a mean last follow-up of 18.36 months (range, 12-30 months). Intraoperative complications and length of hospital stay were comparable between the groups. Patients treated with the PFNA-II experienced shorter fluoroscopy and operative times, less intraoperative blood loss, and less femoral neck shortening. The incidence of thigh pain was significantly higher in the PFNA-II group (30.4%) than in the InterTan group (10.3%) (P=.001). No statistically significant differences existed in general complications, local complications, walking ability, Harris Hip Scores, or hip range of motion at final follow-up.


Assuntos
Pinos Ortopédicos , Fixação Intramedular de Fraturas/instrumentação , Fraturas do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
ScientificWorldJournal ; 2013: 978485, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23431263

RESUMO

OBJECTIVE: The aim of this study was to use three-dimensional (3D) computational modeling to compare the geometric fitness of these two kinds of proximal femoral intramedullary nails in the Chinese femurs. Computed tomography (CT) scans of a total of 120 normal adult Chinese cadaveric femurs were collected for analysis. With the three-dimensional (3D) computational technology, the anatomical fitness between the nail and bone was quantified according to the impingement incidence, maximum thicknesses and lengths by which the nail was protruding into the cortex in the virtual bone model, respectively, at the proximal, middle, and distal portions of the implant in the femur. The results showed that PFNA-II may fit better for the Chinese proximal femurs than InterTan, and the distal portion of InterTan may perform better than that of PFNA-II; the anatomic fitness of both nails for Chinese patients may not be very satisfactory. As a result, both implants need further modifications to meet the needs of the Chinese population.


Assuntos
Pinos Ortopédicos , Fêmur/anatomia & histologia , Fixação Intramedular de Fraturas/instrumentação , Modelos Anatômicos , Grupo com Ancestrais do Continente Asiático , Cadáver , Simulação por Computador , Humanos , Tomografia Computadorizada por Raios X
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