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BACKGROUND: Malignant femoral soft tissue tumors are occasionally resected together with the femoral nerves, but this can cause loss of knee extensor muscle activity. To the best of our knowledge, no previous reports have detailed the gait analysis of such cases in combination with electromyography. Herein, we report the gait analysis of a patient who underwent left groin synovial sarcoma and left femoral nerve resection 12 years ago. CASE PRESENTATION: We analyzed the gait of a 38-year-old man who was able to walk unaided after the resection of a synovial sarcoma in the left groin together with the ipsilateral femoral nerve. The muscle activities of the affected medial (MH) and lateral hamstrings (LH), and lateral heads of the gastrocnemius (GL) were increased during 50-75% of the stance phase. The hip flexion angle of the affected limb was smaller, and the ankle plantar flexion angle of the affected limb was larger than that of the non-affected limb. This means that in the affected limb, the hip and ankle angles were adjusted to prevent knee collapse, and the MH, LH, and GL muscles contributed in the mid- and late-stance phases. Moreover, we found that the hamstring and gastrocnemius of the affected limb worked together to keep the ipsilateral knee extended in the mid-stance phase and slightly flexed in the late-stance phase. CONCLUSIONS: Patients capable of walking after femoral nerve resection may control their hamstrings and gastrocnemius muscles collaboratively to prevent ipsilateral knee collapse in the mid- and late-stance phases.
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Sarcoma Sinovial , Sarcoma , Masculino , Humanos , Adulto , Nervo Femoral , Análise da Marcha , Marcha/fisiologia , Caminhada/fisiologia , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/cirurgia , Articulação do Joelho/fisiologia , Músculo Esquelético/cirurgia , Músculo Esquelético/fisiologia , Sarcoma/diagnóstico por imagem , Sarcoma/cirurgia , Fenômenos BiomecânicosRESUMO
Purpose: Myopic choroidal neovascularization (mCNV) is a prevalent cause of vision loss. However, the development of effective therapeutic targets for mCNV has been hindered by the paucity of suitable animal models. Therefore, the aim of this study is to identify potential genes and pathways associated with mCNV and to unearth prospective therapeutic targets that can be utilized to devise efficacious treatments.Methods: Text data mining was used to identify genes linked to choroid, neovascularization, and myopia. g: Profiler was utilized to analyze the biological processes of gene ontology and the Reactome pathways. Protein interaction network analysis was performed using strings and visualized in Cytoscape. MCODE and cytoHubba were used for further screening.Results: Discovery-driven text data mining identified 55 potential genes related to choroid, neovascularization, and myopia. Gene enrichment analysis revealed 11 biological processes and seven Reactome pathways. A protein-protein interaction network with 47 nodes was constructed and analyzed using centrality ranking. Key clusters were identified through algorithm tools. Finally, 14 genes (IL6, FGF2, MMP9, IL10, TNF, MMP2, HGF, MMP3, IGF1, CCL2, CTNNB1, BDNF, NGF, and EDN1), in addition to VEGFA, were evaluated as targets with potential as future therapeutics.Conclusions: This study provides new potential therapeutic targets for mCNV, including IL6, FGF2, MMP9, IL10, TNF, MMP2, HGF, MMP3, IGF1, CCL2, CTNNB1, BDNF, NGF, and EDN1, which correspond to seven potential enriched pathways. These findings provide a basis for further research and offer new possibilities for developing therapeutic interventions for this condition.
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Neovascularização de Coroide , Miopia Degenerativa , Humanos , Metaloproteinase 2 da Matriz , Metaloproteinase 3 da Matriz , Metaloproteinase 9 da Matriz , Miopia Degenerativa/diagnóstico , Interleucina-6 , Fator Neurotrófico Derivado do Encéfalo , Fator 2 de Crescimento de Fibroblastos , Interleucina-10 , Neovascularização de Coroide/tratamento farmacológico , Neovascularização de Coroide/genética , Neovascularização de Coroide/diagnósticoRESUMO
The prevalence of myopia has been steadily increasing for several decades, and this condition can cause extensive medical and economic issues in society. Exposure to violet light (VL), a short wavelength (360-400 nm) of visible light from sunlight, has been suggested as an effective preventive and suppressive treatments for the development and progression of myopia. However, the clinical application of VL remains unclear. In this study, we aimed to investigate the preventive and suppressive effects of VL on myopia progression. Various transmittances of VL (40%, 70%, and 100%) were tested in C57BL/6J mice with lens-induced myopia (LIM). Changes in the refractive error, axial length, and choroid thickness during the 3-week LIM were measured. The myopic shift in refractive error and difference in axial length between the 0 and -30 diopter lens was lessened in a transmission-dependent manner. Choroidal thinning, which was observed in myopic conditions, was suppressed by VL exposure and affected by its transmission. The results suggest that myopia progression can be managed using VL transmittance. Therefore, these factors should be considered for the prevention and treatment of myopia.
Assuntos
Cristalino , Miopia , Animais , Camundongos , Camundongos Endogâmicos C57BL , Miopia/prevenção & controle , Luz , Corioide , Comprimento Axial do OlhoRESUMO
INTRODUCTION: Few studies have examined the survival rates of total hip arthroplasty (THA) with the same femoral stem, and the predictive factors leading to the revision of stemmed metal-on-metal (MoM) THA remain unknown. We determined the long-term survival rate of stemmed MoM THA compared with that of metal-on-polyethylene (MoP) bearing THA, the effect of head size and cup placement angle on revision rate, and predictors of revision. MATERIALS AND METHODS: A total of 130 hips in 110 patients who underwent primary THA by the same surgeon were included. M2a-RingLoc with a metal-on-polyethylene bearing (group P, 53 hips), M2a-Taper with MoM bearing (group T, 44 hips), and M2a-Magnum with MoM bearing (group M, 33 hips) were used. The mean age at surgery was 63.1 ± 9.5 years, and the mean postoperative follow-up duration was 133.7 ± 39.1 months. Whole blood metal ion concentrations were measured preoperatively and postoperatively, and magnetic resonance imaging was performed to identify aseptic local tissue reactions (ALTRs). Kaplan-Meier survivorship analysis and multiple logistic regression analysis were performed. RESULTS: The THA survival rate up to the maximum postoperative follow-up period was 96.2% at 173 months, 46.6% at 179 months, and 47.8% at 145 months in groups P, T, and M, respectively, with revision as the endpoint. The stemmed MoM THA recorded a very low survival rate (p < 0.001). The ALTR rates were 70.5% and 63.6% in groups T and M, respectively. The risk factor for revision was the use of MoM bearing, and there was no difference in the results based on the head size in group M. Cobalt levels continued to increase postoperatively, although they were not accurate predictors of revision. CONCLUSIONS: Stemmed MoM THA has a very low survival rate and should be used with caution. It is important to monitor the patient's symptoms and perform appropriate imaging to ensure timely revision.
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Artroplastia de Quadril , Prótese de Quadril , Próteses Articulares Metal-Metal , Humanos , Artroplastia de Quadril/métodos , Taxa de Sobrevida , Reoperação/métodos , Fatores de Risco , Metais , Polietileno , Desenho de Prótese , Falha de PróteseRESUMO
Myopia has become a major public health concern, particularly across much of Asia. It has been shown in multiple studies that outdoor activity has a protective effect on myopia. Recent reports have shown that short-wavelength visible violet light is the component of sunlight that appears to play an important role in preventing myopia progression in mice, chicks, and humans. The mechanism underlying this effect has not been understood. Here, we show that violet light prevents lens defocus-induced myopia in mice. This violet light effect was dependent on both time of day and retinal expression of the violet light sensitive atypical opsin, neuropsin (OPN5). These findings identify Opn5-expressing retinal ganglion cells as crucial for emmetropization in mice and suggest a strategy for myopia prevention in humans.
Assuntos
Cristalino/metabolismo , Luz , Proteínas de Membrana/metabolismo , Miopia/prevenção & controle , Opsinas/metabolismo , Animais , Camundongos , Camundongos Endogâmicos C57BL , Miopia/metabolismo , Refração Ocular , Tomografia de Coerência Óptica , Corpo VítreoRESUMO
The knee extension mechanism including the quadriceps femoris muscles and patella plays a crucial role in the stance phase of a normal gait cycle. We performed gait analysis of a patient who had undergone complete resection of the knee extension mechanism. An 8-month-old boy developed infantile fibrosarcoma of the right knee and underwent resection of the quadriceps femoris muscles, patella, and patellar tendon. The gait analysis performed at 8 years of age demonstrated that he could maintain the knee joint extension position during the stance phase. Increased muscle activities in the hamstring and gastrocnemius were observed. The results suggest that the hamstring and gastrocnemius muscles might play a role in maintaining the knee extension position during the stance phase. We suggest the importance of reinforcing these muscles in rehabilitation for patients who lost the knee extension mechanism.
Assuntos
Fibrossarcoma/cirurgia , Análise da Marcha , Patela/cirurgia , Ligamento Patelar/cirurgia , Músculo Quadríceps/cirurgia , Fenômenos Biomecânicos , Fibrossarcoma/patologia , Humanos , Lactente , Masculino , Patela/patologia , Ligamento Patelar/patologia , Músculo Quadríceps/patologiaRESUMO
Recent studies have reported an association between myopia development and local ocular inflammation. Lactoferrin (LF) is an iron-binding protein present in saliva, tears, and mother's milk. Furthermore, sequestering iron by LF can cause its antibacterial property. Moreover, LF has an anti-inflammatory effect. We aimed to determine the suppressive effect of LF against the development and progress of myopia using a murine lens-induced myopia (LIM) model. We divided male C57BL/6J mice (3 weeks old) into two groups. While the experimental group was orally administered LF (1600 mg/kg/day, from 3-weeks-old to 7-weeks-old), a similar volume of Ringer's solution was administered to the control group. We subjected the 4-week-old mice to -30 diopter lenses and no lenses on the right and left eyes, respectively. We measured the refraction and the axial length at baseline and 3 weeks after using a refractometer and a spectral domain optical coherence tomography (SD-OCT) system in both eyes. Furthermore, we determined the matrix metalloproteinase-2 (MMP-2) activity, and the amount of interleukin-6 (IL-6), MMP-2, and collagen 1A1 in the choroid or sclera. The eyes with a minus lens showed a refractive error shift and an axial length elongation in the control group, thus indicating the successful induction of myopia. However, there were no significant differences in the aforementioned parameters in the LF group. While LIM increased IL-6 expression and MMP-2 activity, it decreased collagen 1A1 content. However, orally administered LF reversed these effects. Thus, oral administration of LF suppressed lens-induced myopia development by modifying the extracellular matrix remodeling through the IL-6-MMP-2 axis in mice.
Assuntos
Lactoferrina/administração & dosagem , Lactoferrina/uso terapêutico , Metaloproteinase 2 da Matriz/metabolismo , Leite/química , Miopia/tratamento farmacológico , Administração Oral , Animais , Bovinos , Corioide/metabolismo , Colágeno/metabolismo , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Interleucina-6/metabolismo , Cristalino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Esclera/metabolismoRESUMO
BACKGROUND: Delay in fracture healing or non-union can be devastating complication. Recent studies have reported that teriparatide (TP) demonstrated effectively on callus formation and mechanical strength and zoledronate (ZA) increased the callus size and resistance at the fracture site in rat fracture model. In this study, the effects of combination therapy with low dose TP and ZA on fracture healing was evaluated. METHODS: From 1 week post-operation, TP (5 times a week administration) and ZA (0.1 mg/kg single administration) were administered by dividing the rats into the following five groups: TP 1 µg group {T(1): TP 1 µg/kg}, ZA group (ZA:0.1 mg/kg), TP1 µg+ZA group {T(1)+ZA: TP 1 µg/kg+ZA}, TP 10 µg+ZA group {T(10)+ZA: TP 10 µg/kg + ZA}, and control group (C: administered saline). Rt femurs were excised 7 weeks after the surgery; bone fusions were evaluated with soft X-ray images on a 4-point scale. And the histopathological examination was performed in demineralized and non-demineralized specimens. Furthermore, the Radiographic Union Scale was conducted in all specimens. RESULTS: About the bone fusions rates, C, T(1), ZA, T(1)+ZA, and T(10)+ZA groups demonstrated 20.0%, 55.6%, 70.0%, 70.0%, and 80.0%, respectively, and with 4-point scale, each group was 0.50, 1.56, 2.00, 2.60, and 2.80 points, respectively. The callus volume was significantly increased to 16.66 mm2 and 17.75 mm2 in the T(1)+ZA and T(10)+ZA groups, respectively, while 10.65 mm2 (p < 0.05) in the C group. Furthermore, the callus area in the T(10)+ZA group was also observed to have significantly increased to 78.78%, compared with 54.63% and 44.11% in the C and T(1)+ZA groups, respectively (p < 0.01). Histopathologically, cartilage tissue and immature callus formation were observed at the bone junction in the C group; however, the osseous bridge formation of mature callus was observed in the ZA, T(1)+ZA, and T(10)+ZA groups. CONCLUSION: It is suggested that administration of low dose TP and ZA in combination may lead to the treatment of delayed union of fracture. We hope the combination treatment may become one of new therapeutic strategy.
Assuntos
Conservadores da Densidade Óssea/uso terapêutico , Fraturas do Fêmur/tratamento farmacológico , Consolidação da Fratura/efeitos dos fármacos , Teriparatida/uso terapêutico , Ácido Zoledrônico/uso terapêutico , Animais , Conservadores da Densidade Óssea/administração & dosagem , Conservadores da Densidade Óssea/farmacologia , Calo Ósseo/efeitos dos fármacos , Calo Ósseo/patologia , Modelos Animais de Doenças , Esquema de Medicação , Avaliação Pré-Clínica de Medicamentos/métodos , Quimioterapia Combinada , Fraturas do Fêmur/diagnóstico por imagem , Fraturas do Fêmur/patologia , Fraturas do Fêmur/fisiopatologia , Masculino , Radiografia , Ratos Sprague-Dawley , Teriparatida/administração & dosagem , Teriparatida/farmacologia , Ácido Zoledrônico/administração & dosagem , Ácido Zoledrônico/farmacologiaRESUMO
BACKGROUND: The standard for rotational alignment of the tibial component in total knee arthroplasty (TKA) remains unclear. Cases often require positioning of the tibial component, prioritizing adequate coverage of resected bone surface rather than alignment with the tibial rotational axis. We investigated tibial component position in TKA, prioritizing maximum coverage of resected bone surface, and evaluated the correlation with the tibial anteroposterior (AP) axis. METHODS: We analyzed preoperative computed tomography images for primary TKA in 106 cases and 157 knees, using three-dimensional planning software. Tibial component position prioritizing maximum coverage of resected bone surface was simulated, and results were compared with the AP axis. Rotational alignment angle was defined as that between a line perpendicular to the tibial AP axis and a line connecting the posterior edge of the tibial component. RESULTS: The simulated tibial component was more externally rotated by a mean 4.5° ± 4.2°. The alignment angle showed normal distribution, but variability was large, ranging from 5.1° internal rotation to 16.2° external rotation. In 138 of 157 (87.9 %) knees, the tibial component was positioned in the externally rotated position with respect to the AP axis. The tibial component was aligned within the medial one-third of the patellar tendon in 122 of 157 (77.7 %) knees. CONCLUSIONS: The tibial component aligned using coverage prioritizing was externally rotated, although large variability was observed. Rotational alignment was optimal in 79 % of cases when the tibial component was aligned with coverage prioritizing, but hyperexternal rotation was observed in patients with severe knee deformation.
Assuntos
Artroplastia do Joelho/métodos , Tíbia/diagnóstico por imagem , Idoso , Idoso de 80 Anos ou mais , Mau Alinhamento Ósseo/diagnóstico por imagem , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Ligamento Patelar/diagnóstico por imagem , Ligamento Cruzado Posterior/diagnóstico por imagem , Cuidados Pré-Operatórios , Rotação , Tomografia Computadorizada por Raios XRESUMO
A single bout of exercise is known to increase the insulin sensitivity of skeletal muscle; however, the underlying mechanism of this phenomenon is not fully understood. Because a single bout of exercise induces a transient increase in blood interleukin-6 (IL-6) level, we hypothesized that the enhancement of insulin sensitivity after a single bout of exercise in skeletal muscle is mediated at least in part through IL-6-dependent mechanisms. To test this hypothesis, C57BL6J mice were intravenously injected with normal IgG or an IL-6 neutralizing antibody before exercise. Twenty-four hours after a single bout of exercise, the plantaris muscle was harvested to measure insulin sensitivity and glucose transporter (GLUT)-4 expression levels by ex-vivo insulin-stimulated 2-deoxyglucose (2-DG) uptake and Western blotting, respectively. Compared with sedentary mice, mice that performed exercise showed enhanced IL-6 concentration, insulin-stimulated 2-DG uptake, and GLUT-4 expression in the plantaris muscle. The enhanced insulin sensitivity and GLUT4 expression were canceled by injection of the IL-6 neutralizing antibody before exercise. In addition, IL-6 injection increased GLUT4 expression, both in the plantaris muscle and the soleus muscle in C57BL6J mice. Furthermore, a short period of incubation with IL-6 increased GLUT4 expression in differentiated C2C12 myotubes. In summary, these results suggested that IL-6 increased GLUT4 expression in muscle and that this phenomenon may play a role in the post-exercise enhancement of insulin sensitivity in skeletal muscle.
Assuntos
Transportador de Glucose Tipo 4/metabolismo , Insulina/farmacologia , Interleucina-6/fisiologia , Músculo Esquelético/metabolismo , Condicionamento Físico Animal , Animais , Células Cultivadas , Interleucina-6/antagonistas & inibidores , Interleucina-6/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/enzimologia , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
The effects of dendritic cells (DCs) with low dose doxorubicin on the enhancement of the systemic immune response, including the effects on calreticulin (CRT) expression, heat shock protein 70 (HSP70) on the cell surface expression, and the enhancement of high mobility group box 1 (HMGB1) release from cancer cells, remain unclear. The present study investigated whether the combination of DCs and doxorubicin (ADM) induces immune cell death, and leads to tumor growth inhibition in a murine osteosarcoma model. To evaluate immune response activation in vivo, 4 groups of mice were established: i) untreated mice, ii) DC-treated mice, iii) ADM-treated mice, and iv) DC and ADM-treated mice. Immunological cell death and CRT, HSP70, and HMGB1 expression levels were higher in doxorubicin-treated cells than those in untreated or those treated with DCs alone. NF-κB expression was higher in the DCs after ligand activation using CRT, HSP70, or HMGB1 in vitro. Mice treated with DCs and ADM displayed an increased number of CD8+ T-lymphocytes within metastatic tumors and inhibition of metastatic growth. The expression of CRT and the release of HMGB1 from tumor tissues were increased in the ADM-treated groups. Treatment with DCs and ADM resulted in the highest serum interferon-γ levels. Combining ADM, which can induce immunogenic cell death, with DCs enhanced the systemic immune response. The findings of the present study provide further support for the continued development of antitumor agents that induce cell death and the immune response to target osteosarcoma.
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Short non-coding RNAs, called microRNAs (miRNAs), regulate cell biology by affecting the expression of target genes. However, we know little about the miRNAs regulating the growth and progression of Ewing's sarcoma (ES). To identify possible oncogenic factors in ES, we used a microarray-based approach to profile the changes in the expression of miRNAs and the downstream mRNAs in five ES cell lines. One miRNA, miR138, was significantly downregulated, whereas the expression of focal adhesion kinase (FAK) was significantly upregulated in all tested ES cells. When miR138 was transfected into ES cell lines, the expression of FAK in these cells was greatly suppressed and inhibited the proliferation and mobility of ES cells. Overexpression of miR138 in vitro resulted in further inhibition of the cell cycle at the G1 phase and in the induction of anoikis, in a dose- and time-dependent manner. Moreover, miR138 overexpression in ES cells significantly suppressed the number of distant metastases in vivo. The data in the present study demonstrates for the first time a novel mechanism that regulates the expression of FAK via miR138 in ES cells.
Assuntos
Quinase 1 de Adesão Focal/metabolismo , Regulação Neoplásica da Expressão Gênica , MicroRNAs/metabolismo , Sarcoma de Ewing/metabolismo , Animais , Apoptose , Ciclo Celular , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , DNA Complementar/metabolismo , Fase G1 , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Metástase Neoplásica , Transplante de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Oligonucleotídeos/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Aberrant microRNA (miRNA) expression plays an essential role in osteosarcoma (OS) pathogenesis. Recent studies have shown that dysregulation of miRNA expression is associated with increased tumorigenesis and poor prognosis in several types of cancers, including OS. The aim of this study was to investigate the relevant microRNAs involved in the development of OS. METHODS: To explore possible oncogenic factors in OS, we used a microarray-based approach to profile changes in the expression of miRNAs and their target mRNAs in five OS cell lines and human mesenchymal stem cells (hMSCs). An miRNA, miR-93, was significantly up-regulated, whereas phosphatase and tensin homologue (PTEN) expression was significantly down-regulated in all tested OS cells, when compared with hMSCs. RESULTS: When anti-miR-93 was transfected into OS cell lines, PTEN expression was greatly increased, suggesting that PTEN might be a target of miR-93 in ES cells. The expression of phosphorylated Akt protein, which is known to be inversely correlated with that of PTEN, was significantly down-regulated in anti-miR-93-transfected cells. Furthermore, transfection of anti-miR-93 inhibited the proliferation and cell cycle progression of ES cells. In addition, the down-regulation of miR-93 in these cells significantly suppressed tumor growth in vivo. CONCLUSION: Ectopic expression of miR-93 decreased PTEN protein levels. Furthermore, miR-93 increased proliferation and decreased apoptosis in OS cells, whereas its silencing in these cells inhibited such carcinogenic processes. Taking these observations together, miR-93 can be seen to play a critical role in carcinogenesis through suppression of PTEN, and may serve as a therapeutic target for the treatment of OS.
Assuntos
MicroRNAs/genética , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Osteossarcoma/patologia , TransfecçãoRESUMO
We attempted to enhance the antitumor effects of tumor lysate-pulsed dendritic cells by eliminating regulatory T cells. The combinatorial effects of dendritic cells and agonist anti-glucocorticoid-induced tumor necrosis factor receptor (anti-GITR) antibodies were investigated with respect to enhancement of the systemic immune response, elimination of regulatory T cells, and inhibition of tumor growth. To determine whether the combination of dendritic cells and antiGITR antibodies could enhance systemic immune responses and inhibit primary tumor growth in a murine osteosarcoma (LM8) model. We established the following 4 groups of C3H mice (20 mice in total): i), control IgG-treated mice; ii), tumor lysate-pulsed dendritic celltreated mice; iii), agonist anti-GITR antibody-treated mice; and iv), agonist anti-GITR antibody- and tumor lysate-pulsed dendritic celltreated mice.The mice that received the agonist anti-GITR antibodies and tumor lysate-pulsed dendritic cells displayed inhibited primary growth, prolonged life time, reduced numbers of regulatory T lymphocytes in the spleen, elevated serum interferon-γ levels, increased number of CD8+ T lymphocytes. The mice that received combined therapy had reduced level of immunosuppressive cytokines in tumor tissue and serum. Combining agonist anti-GITR antibodies with tumor lysate-pulsed dendritic cells enhanced the systemic immune response. These findings provide further support for the continued development of agonist anti-GITR antibodies as an immunotherapeutic strategy for osteosarcoma. We suggest that our proposed immunotherapy could be developed further to improve osteosarcoma treatment.
Assuntos
Anticorpos Anti-Idiotípicos/administração & dosagem , Células Dendríticas/imunologia , Proteína Relacionada a TNFR Induzida por Glucocorticoide/imunologia , Imunidade Inata/imunologia , Osteossarcoma/imunologia , Animais , Anticorpos Anti-Idiotípicos/imunologia , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células/genética , Terapia Baseada em Transplante de Células e Tecidos , Proteína Relacionada a TNFR Induzida por Glucocorticoide/antagonistas & inibidores , Humanos , Imunoterapia , Camundongos , Osteossarcoma/patologia , Osteossarcoma/terapia , Linfócitos T Reguladores/imunologiaRESUMO
Quorum sensing is a cell-to-cell communication mechanism, which is responsible for regulating a number of bacterial virulence factors and biofilm maturation and therefore plays an important role for establishing wound infection. Quorum-sensing signals may induce inflammation and predispose wounds to infection by Pseudomonas aeruginosa; however, the interaction has not been well investigated. We examined the effects of the P. aeruginosa las quorum-sensing signal, N-3-oxo-dodecanoyl homoserine lactone (3OC12-HSL), on matrix metalloproteinase (MMP) 9 expression in Rat-1 fibroblasts. 3OC12-HSL upregulated the expression of the MMP9 gene bearing an activator protein-1 (AP-1) binding site in the promoter region. We further investigated the mechanism underlying this effect. c-Fos gene expression increased rapidly after exposure to 3OC12-HSL, and nuclear translocation of c-Fos protein was observed; both effects were reduced by pretreatment with an AP-1 inhibitor. These results suggest that 3OC12-HSL can alter MMP9 gene expression in fibroblasts via the AP-1 signaling pathway.
Assuntos
4-Butirolactona/análogos & derivados , Fibroblastos/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Homosserina/análogos & derivados , Metaloproteinase 9 da Matriz/genética , Pseudomonas aeruginosa/química , Fator de Transcrição AP-1/genética , 4-Butirolactona/farmacologia , Abietanos/farmacologia , Animais , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Homosserina/farmacologia , Metaloproteinase 9 da Matriz/metabolismo , Regiões Promotoras Genéticas , Transporte Proteico , Proteínas Proto-Oncogênicas c-fos/genética , Proteínas Proto-Oncogênicas c-fos/metabolismo , Pseudomonas aeruginosa/metabolismo , Percepção de Quorum , Ratos , Transdução de Sinais , Fator de Transcrição AP-1/antagonistas & inibidores , Fator de Transcrição AP-1/metabolismoRESUMO
Exercise enhances insulin sensitivity in skeletal muscle, but the underlying mechanism remains obscure. Recent data suggest that alternatively activated M2 macrophages enhance insulin sensitivity in insulin target organs such as adipose tissue and liver. Therefore, the aim of this study was to determine the role of anti-inflammatory M2 macrophages in exercise-induced enhancement of insulin sensitivity in skeletal muscle. C57BL6J mice underwent a single bout of treadmill running (20 m/min, 90 min). Twenty-four hours later, ex vivo insulin-stimulated 2-deoxy glucose uptake was found to be increased in plantaris muscle. This change was associated with increased number of CD163-expressing macrophages (i.e. M2-polarized macrophages) in skeletal muscle. Systemic depletion of macrophages by pretreatment of mice with clodronate-containing liposome abrogated both CD163-positive macrophage accumulation in skeletal muscle as well as the enhancement of insulin sensitivity after exercise, without affecting insulin-induced phosphorylation of Akt and AS160 or exercise-induced GLUT4 expression. These results suggest that accumulation of M2-polarized macrophages is involved in exercise-induced enhancement of insulin sensitivity in mouse skeletal muscle, independently of the phosphorylation of Akt and AS160 and expression of GLUT4.
Assuntos
Polaridade Celular/efeitos dos fármacos , Insulina/farmacologia , Macrófagos/citologia , Músculo Esquelético/citologia , Condicionamento Físico Animal , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Ácido Clodrônico/administração & dosagem , Ácido Clodrônico/farmacologia , Desoxiglucose/metabolismo , Proteínas Ativadoras de GTPase/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Lipossomos , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fosforilação/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores de Superfície Celular/metabolismoRESUMO
Masticatory muscle tendon-aponeurosis hyperplasia (MMTAH) is a new disease entity characterized by limited mouth opening due to contracture of the masticatory muscles resulting from hyperplasia of tendons and aponeuroses. The other clinical feature is that the face of the patient with this disease displays a square mandible configuration. Muscle relaxants provide no relief for the limited mouth-opening ability. Anesthesiologists need to suspect difficult airway when patients have limited mouth opening with square mandible configuration. MMTAH can therefore be a possible cause of difficult intubation.
Assuntos
Anestesia , Laringoscopia , Músculos da Mastigação/patologia , Tendões/patologia , Idoso , Feminino , Humanos , Hiperplasia/patologia , Intubação Intratraqueal , Mandíbula/anormalidades , Boca/anatomia & histologiaRESUMO
A new structure for an adenine-selective host molecule, featuring the pertinent link of five-six-five-membered heteroaromatic rings and two carbamoyl NH sites, was developed. This structure provides a correctly oriented array of complementary hydrogen bonding sites for the adenine nucleobase, which exploits both Watson-Crick and Hoogsteen-type interactions. The complexation with adenine nucleobases by multiple hydrogen bonding was supported by (1)H NMR spectroscopy. This type of host displayed high selectivity in complexation, with an accompanying fluorescent response to lipophilized adenosine in CHCl(3). Furthermore, a remarkably selective potentiometric response was attained for adenosine 5'-monophosphate over 5'-GMP, 5'-CMP, and 5'-UMP by using an ion-selective electrode with a PVC-supported solvent polymeric membrane. This indicates recognition of water-soluble nucleotide guests through the membrane-water interface. These findings are expected to form a reliable basis for the development of artificial sensing systems for mononucleotides in biological systems.
Assuntos
Adenina/química , Compostos Heterocíclicos/química , Adenina/análogos & derivados , Técnicas Biossensoriais/métodos , Eletroquímica , Ligação de Hidrogênio , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Nucleotídeos/química , SolubilidadeRESUMO
The Ni-catalyzed coupling of allyl chlorides and enynes has been developed; the cyclization of enynes was triggered by the addition of pi-allylnickel species to the alkyne part, followed by the incorporation of the alkene part.
Assuntos
Alcinos/química , Compostos Alílicos/química , Níquel/química , Catálise , Ciclização , Estrutura Molecular , Compostos Organometálicos/química , Oxirredução , EstereoisomerismoRESUMO
Catalytic cycloisomerization of enynes has been accomplished in the presence of an Ni0-PPh3-Zn-carboxylic acid or -ZnCl2 system. A nickel(I)-hydride complex, thought to be generated by reduction of the protonated nickel(II) complex with Zn, is proposed as the catalytic species. This cycloisomerization shows reactivity behavior that is different from that of a conventional metal-catalyzed reaction. In particular, in the reaction with (E)-enynes, the catalytic system has a selectivity that favors the formation of the 1,3-diene over the 1,4-diene. In addition, this catalytic system has been applied to the domino cyclization of dienynes for the construction of tricyclic compounds.