RESUMO
BACKGROUND: Lipid abnormality and obesity have been proposed to be associated with lumbar disc degeneration, but little is known about the effect of 'lipid healthy but obese' (LH-O) and 'lipid abnormal but not obese' (LA-NO) phenotypes on lumbar disc degeneration in Chinese. The study aims to determine the impact and distinction of LH-O and LA-NO phenotypes on lumbar disc degeneration in Chinese, and to identify the association of related factors with risk of lumbar disc degeneration. METHODS: A total of 678 individuals were included with lumbar magnetic resonance imaging, serum lipid levels and anthropometric measurements. Obesity was defined on the basis of body mass index or waist to hip ratio (WHR). Pfirrmann score and Weishaupt's scale were utilized to assess the degree of disc degeneration and facet joint degeneration. RESULTS: The incidence of the LH-O and LA-NO phenotypes were 11.4% and 18.1%, respectively. LA-NO phenotype demonstrates a high incidence for disc degeneration (P < 0.05), while LH-O phenotype confers a severe disc degeneration grade (P < 0.05). No statistical difference in the percentage of severe facet joint degeneration grade in each group (P > 0.05). Elevated triglycerides and greater WHR may be the risk factors for lumbar disc degeneration in Chinese. CONCLUSION: LH-O and LA-NO phenotypes are common with different status of disc degeneration in Chinese. Elevated triglycerides and abdominal obesity appear to play crucial roles in the development of lumbar disc degeneration.
Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , China , Humanos , Lipídeos , Vértebras Lombares , Imageamento por Ressonância Magnética , Obesidade/complicações , FenótipoRESUMO
PURPOSE: Previous reports revealed a correlation between psychological problems and spinal surgery. There is a lack of knowledge on the effect of anxiety on the percutaneous transforaminal endoscopic discectomy (PTED) outcome at the two year follow-up. The purpose of this study is to investigate changes in anxiety after PTED among patients with lumbar disc herniation (LDH), to compare the effect of anxiety on the prognosis using propensity score matching analysis, and to identify the related parameters of anxiety. METHODS: A total of 145 patients with LDH requiring PTED surgery were included. Twenty-six LDH patients with anxiety were matched with 26 control patients utilizing propensity score matching analysis. The demographic and peri-operative data were collected and analyzed. A correlation analysis was utilized. RESULTS: Both groups achieved significant improvements in visual analogue scale (VAS) scores for pain, Japanese Orthopedic Association (JOA) scores for neurological deficit, and 36-item Short-Form Health Survey (SF-36) scores and Oswestry Disability Index (ODI) scores for quality of life. A statistical difference was detected between the pre-operative and the post-operative Zung Self-Rating Anxiety Scale scores in the anxiety cohort. However, the difference between the anxiety group and the control group was statistically significant in the aforementioned parameters. The VAS, JOA, ODI and the SF-36 scores, and the disease duration were associated with pre-operative anxiety. CONCLUSION: PTED may provide significant improvements in clinical outcomes and symptoms of anxiety. A negative impact on the patient's prognosis may be caused by the presence of anxiety. Pain severity, neurological deficit, disease duration, and quality of life were associated with anxiety.
Assuntos
Deslocamento do Disco Intervertebral , Qualidade de Vida , Ansiedade/diagnóstico , Ansiedade/epidemiologia , Ansiedade/etiologia , Discotomia , Humanos , Deslocamento do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Medição da Dor , Prognóstico , Pontuação de Propensão , Estudos Retrospectivos , Resultado do TratamentoRESUMO
The intervertebral disc (IVD) is the largest avascular structure in the body, and IVD cells reside in vivo in an environment that is considered to be hypoxic. However, the role of oxygen in IVD cell biology remains an issue of debate. By reviewing the available literature about the effect of oxygen tension on regulating the phenotype, energy metabolism, matrix production, and survival of IVD cells, as well as on the expression and function of hypoxia-inducible factor in IVD cells, we conclude that hypoxia is essential in maintaining the physiological function of IVD cells. Modulating the oxygen tension of the IVD or the activity of hypoxia-inducible factor in IVD cells may be a promising strategy for the prevention and treatment of IVD degeneration.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia Celular/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/citologia , Animais , Bovinos , Sobrevivência Celular/fisiologia , Matriz Extracelular/metabolismo , Glicólise/fisiologia , Humanos , Disco Intervertebral/irrigação sanguínea , Oxigênio/fisiologiaRESUMO
BACKGROUND/AIMS: Apoptosis and autophagy are two patterns of programmed cell death which play important roles in the intervertebral disc degeneration. Oxidative stress is an important factor for the induction of programmed cell death. However, the cellular reactions linking autophagy to apoptosis of disc cells under oxidative stress have never been described. This study investigated the responses of autophagy and apoptosis and their interactions in the nucleus pulposus cells (NP cells) under oxidative stress, with the aim to better understand the mechanism of disc degeneration. METHODS: NP cells isolated from rat lumbar discs were subjected to different concentrations of H2O2 for various time periods. Cell viability was determined by CCK-8 assay, and their apoptosis and autophagy responses were evaluated by fluorescent analysis, flow cytometry and western blotting, et al. The interactions of autophagy and apoptosis and the possible signaling pathways were also investigated by using autophagy modulators. RESULTS: H2O2 increased the lysosomal membrane permeability in the NP cells and induced apoptosis through the mitochondrial pathway subsequently. Meanwhile, H2O2 stimulated an early autophagy response through the ERK/m-TOR signaling pathway. Autophagy inhibition significantly decreased the apoptosis incidence in the cells insulted by H2O2. CONCLUSION: These results suggested that controlling the autophagy response in the NP cells under oxidative stress should be beneficial for the survival of the cells and probably delay the process of disc degeneration.
Assuntos
Apoptose/fisiologia , Autofagia/fisiologia , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/patologia , Estresse Oxidativo/fisiologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Peróxido de Hidrogênio/farmacologia , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismoRESUMO
Age-related bone loss is a major cause of osteoporosis and osteoporotic fractures in the elderly. However, the underlying molecular mechanism of age-related bone loss is still poorly understood. The aim of this study was to clarify whether autophagy in osteocytes was involved in age-related bone loss. Male Sprague-Dawley (SD) rats in 3, 9, and 24 month old were used to mimic the age-related bone loss in men. Micro-CT evaluation, histomorphometric analysis, and measurement of bone turnover rate verified age-related bone loss in the male SD rats. Immunofluorescent histochemistry, RT-PCR, and Western blot assessment demonstrated that the expression of LC3-II, LC3-II/I, Beclin-1, and Ulk-1 in the osteocytes decreased with age, while SQSTM1/p62 and apoptosis in the osteocytes increased. A significant correlation between the markers of osteocyte autophagy and bone mineral density in the proximal tibia was revealed. However, osteocyte autophagy was not correlated with osteocyte apoptosis in the process of aging. These results suggested that osteocyte autophagy was possibly involved in the age-related bone loss. Decreased activity of osteocyte autophagy independent of apoptosis might contribute to the age-related bone loss in senile osteoporosis.
Assuntos
Envelhecimento/patologia , Autofagia , Osteócitos/metabolismo , Osteoporose/metabolismo , Osteoporose/patologia , Animais , Densidade Óssea , Masculino , Osteócitos/patologia , Ratos , Ratos Sprague-DawleyRESUMO
Autophagy and apoptosis are important in maintaining the metabolic homeostasis of intervertebral disc cells, and transforming growth factor-ß1 (TGF-ß1) is able to delay intervertebral disc degeneration. This study determined the effect of TGF-ß1 on the crosstalk between autophagy and apoptosis in the disc cells, with the aim to provide molecular mechanism support for the prevention and treatment of disc degeneration. Annulus fibrosus (AF) cells were isolated and cultured under serum starvation. 10 ng/mL TGF-ß1 reduced the apoptosis incidence in the cells under serum starvation for 48 h, down-regulated the autophagy incidence in the cells pretreated with 3-methyladenine (3-MA) or Bafilomycin A (Baf A), partly rescued the increased apoptosis incidence in the cells pretreated with 3-MA, while further reduced the decreased apoptosis incidence in the cells pretreated with Baf A. Meanwhile, TGF-ß1 down-regulated the expressions of autophagic and apoptotic markers in the cells under starvation, partly down-regulated the expressions of Beclin-1, LC3 II/I and cleaved caspase-3 in the cells pretreated with 3-MA or Baf A, while significantly decreased the expression of Bax/Bcl-2 in the cells pretreated with Baf A. 3-MA blocked the phosphorylation of both AKT and mTOR and partly reduced the inhibitory effect of TGF-ß1 on the expression of LC3 II/I and cleaved caspase-3. TGF-ß1 enhanced the expression of p-ERK1/2 and down-regulated the expressions of LC3 II/I and cleaved caspase-3. U0126 partly reversed this inhibitory effect of TGF-ß1. In conclusion, TGF-ß1 protected against apoptosis of AF cells under starvation through down-regulating excessive autophagy. PI3K-AKT-mTOR and MAPK-ERK1/2 were the possible signaling pathways involved in this process.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Disco Intervertebral/citologia , Fator de Crescimento Transformador beta1/farmacologia , Animais , Meios de Cultura Livres de Soro , Citoproteção/efeitos dos fármacos , Imunofluorescência , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/ultraestrutura , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fagossomos/efeitos dos fármacos , Fagossomos/ultraestrutura , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: Diagnosis and treatment decisions of cervical instability are made, in part, based on the clinician's assessment of sagittal rotation on flexion and extension radiographs. The objective of this study is to evaluate the intraobserver and interobserver reliability of three measurement techniques in assessing cervical sagittal rotation. METHODS: Fifty lateral radiographs of patients with single-level cervical degenerative disc were selected and measured on two separate occasions by three spine surgeons using three different measurement techniques. Cervical sagittal rotation was measured using three different techniques. RESULTS: Intraclass correlation coefficients were most consistent for Method 2 (ICC 0.93-0.96) followed by Method 1 (ICC 0.88-0.91) and Method 3 (ICC 0.81-0.87). Intraobserver agreement (% of repeated measures within 0.5° of the original measurement) ranged between 76% and 96% for all techniques, with Method 2 showing the best agreement (92%-96%). Paired comparisons between observers varied considerably with interobserver reliability correlation coefficients ranging from 0.54 to 0.89. Method 2 showed the highest interobserver reliability coefficient (0.82, range 0.73-0.88). Method 2 was also more reliable for the classification of "instability". Intraobserver percent agreements ranged from 94 to 98% for Method 2 versus 84% to 90% for Method 1 and 78% to 86% for Method 3, while interobserver percent agreements ranged from 90% to 98% for Method 2 versus 86% to 94% for Method 1 and 74% to 84% for Method 3. CONCLUSIONS: Method 2 (measuring the angle from the inferior endplate of the vertebra above the degenerative disc and the inferior endplate of the vertebra below the degenerative disc) showed the best intraobserver and interobserver reliability overall in assessing cervical sagittal rotation.
Assuntos
Vértebras Cervicais/diagnóstico por imagem , Degeneração do Disco Intervertebral/diagnóstico por imagem , Intensificação de Imagem Radiográfica/normas , Rotação , Cirurgiões/normas , Humanos , Variações Dependentes do Observador , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos TestesRESUMO
Estradiol could protect osteoblast against apoptosis, and apoptosis and autophagy were extensively and intimately connected. The aim of the present study was to test the hypothesis that autophagy was present in osteoblasts under serum deprivation and estrogen protected against osteoblast apoptosis via promotion of autophagy. MC3T3-E1 osteoblastic cells were cultured in a serum-free and phenol red-free minimal essential medium (α-MEM). Ultrastructural analysis, lysosomal activity assessment and monodansycadaverine (MDC) staining were employed to determine the presence of autophagy, and real time PCR was used to evaluate the expression of autophagic markers. Meanwhile, the osteoblasts were transferred in a serum-free and phenol red-free α-MEM containing either vehicle or estradiol. Apoptosis and autophagy was assessed by using the techniques of real-time PCR, Western blot, immunofluorescence assay, and flow cytometry. The possible pathway through which estrogen promoted autophagy in the serum-deprived osteoblasts was also investigated. Real-time PCR demonstrated the expression of LC3, beclin1 and ULK1 genes in osteoblasts under serum deprivation, and immunofluorescence assay verified high expression of proteins of these three autophagic bio-markers. Lysosomes and autolysosomes accumulated in the cytoplasm of osteoblasts were also detected under transmission electron microscopy, MDC staining and lysosomal activity assessment. Meanwhile, estradiol significantly decreased the expression of proteins of the bio-markers of apoptosis, and at the same time increased the expression of proteins of the bio-markers of autophagy in the serum-deprived osteoblasts. Furthermore, the estradiol-promoted autophagy in serum-deprived osteoblasts could be blocked by estrogen receptor (ER) antagonist (ICI 182780), and estradiol failed to rescue the cells pretreated with an inhibitor of vacuolar ATPase (bafilomycin A) from apoptosis. Serum deprivation resulted in apoptosis through activation of Caspase-3 and induced autophagy through inhibition of phospho-mammalian target of rapamycin (p-mTOR). Both 3-methyladenine (3MA) and U0126 led to increase of apoptosis in osteoblasts with serum deprivation. Estradiol failed to over-ride the inhibitory effect of 3MA on phosphorylation of AKT but directly led to dephosphorylation of mTOR and upregulation of LC3 protein expression. However, the estradiol-enhanced LC3 protein expression was significantly suppressed by U0126 through inhibition of phosphorylation of extracellular signal-regulated kinase (ERK). Estradiol rescued osteoblast apoptosis via promotion of autophagy through the ER-ERK-mTOR pathway.
Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Estradiol/farmacologia , Osteoblastos/efeitos dos fármacos , Receptores de Estrogênio/genética , Serina-Treonina Quinases TOR/genética , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Proteína Beclina-1 , Butadienos/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Meios de Cultura , Estradiol/análogos & derivados , Antagonistas de Estrogênios/farmacologia , Fulvestranto , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Regulação da Expressão Gênica , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Macrolídeos/farmacologia , Camundongos , Nitrilas/farmacologia , Osteoblastos/citologia , Osteoblastos/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismoRESUMO
BACKGROUND: The pathogenesis of osteoporosis after spinal cord injury (SCI) may be different from disuse osteoporosis. OBJECTIVE: To investigate whether there is the differential anabolic response to mechanical loading between osteoblasts from SCI rats and those from hindlimb-immobilized rats. METHODS: Femoral bone-marrow was harvested for osteoblast culture from SCI rats, hindlimb-immobilized rats, and control rats 3 weeks after animal model creation. At the stage of differentiation, rat osteoblasts were plated in six-well plates for stretching. Cyclic strains were applied for 48 hours, and then alkaline phosphatase (ALPase) activity, procollagen, and osteocalcin production, and gene expression of osteocalcin, runt-related transcription factor 2 (Runx2), and osterix were measured in osteoblasts from SCI rats, hindlimb-immobilized rats, and control rats. RESULTS: ALPase activity, procollagen, and osteocalcin production, and gene expression of osteocalcin, Runx2, and osterix were significantly lower in osteoblasts after stretching from SCI rats compared with those from hindlimb-immobilized rats. However, there was no significant difference of these parameters between isolated osteoblasts from hindlimb-immobilized rats and those from control rats. CONCLUSION: The activity of isolated osteoblasts from SCI rats was lower than control rats, and this suggested that osteoblasts from SCI rats responded less to mechanical loading as compared with those from control rats.
Assuntos
Osteoblastos/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Animais , Modelos Animais de Doenças , Elevação dos Membros Posteriores , História Antiga , Masculino , Osteoporose/etiologia , Osteoporose/fisiopatologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Traumatismos da Medula Espinal/complicaçõesRESUMO
OBJECTIVE: To investigate the clinical utility of multiplex ligation-dependent probe amplification (MLPA) for detecting 22q11 deletion and duplication in congenital heart disease (CHD) cases and to study the incidence of 22q11 deletion and duplicaton in different kinds of CHD. METHODS: Forty eight probes of which 25 located in 22q11 low copy number region (LCR 22s A-H), 7 in 22q11 surrounding region (CES, 22q13) and 16 in chromosomes 4, 8, 10 and 17 were selected to detect 22q11 deletion and duplication in 181 preoperative children with CHD and 14 fetuses with serious CHD or CHD with multiple malformations. In these cases, karyotype analysis was also performed. RESULTS: MLPA demonstrated that 7 cases had 22q11 deletion [6 cases from CLTCL1 to LZTR1(LCR A-D) and 1 case from CLTCL1 to PCQAP (LCR A-C)] and that 1 case had 22q11 duplication,spanning from ZNF74 to LZTR1(LCR B-D). The phenotypes of heart defect included ventricular septal defect, atrioventricular septal defect, pulmonary stenosis and tetralogy of Fallot. Karyotype analysis showed that 1 case had 21q deletion [46, XY, 21q], 1 case had mosaic trisomy 8 [47,XY, +8/46, XY(1:2)] and 4 cases had trisomy 21. One of the 4 cases with trisomy 21 had concurrent 22q11 duplication. CONCLUSIONS: MLPA is a rapid, sensitive, site specific and relatively inexpensive method for diagnosis of 22q11 deletion and duplication in CHD. 22q11 deletion and duplication may cause various kinds of CHD, suggesting that genetic detection should be performed routinely in CHD patients.
Assuntos
Deleção Cromossômica , Cromossomos Humanos Par 22 , Duplicação Gênica , Cardiopatias Congênitas/genética , Técnicas de Amplificação de Ácido Nucleico/métodos , Adolescente , Feminino , Humanos , Recém-Nascido , MasculinoRESUMO
R-spondin proteins are identified as secreted agonists of the canonical Wnt/ß-catenin signaling pathway, and leucine-rich repeat-containing G-protein-coupled receptors (LGR) are recognized as R-spondin receptors. The potential role of R-spondin 2 (Rspo2) and LGR4 in mediating osteogenesis remains poorly understood. In our in vitro experiments, we found that Rspo2 could promote osteogenesis through activating the Wnt signaling pathway in MC3T3-E1 cells. However, this effect of Rsop2 disappeared in the cells with functional disruption of LGR4. Meanwhile, Rspo2 significantly inhibited osteoclastogenesis and this effect of Rspo2 was dependent on the presence of osteoblasts with normal function of LGR4. In our in vivo experiments, we found that application of exogenous Rspo2 rescued the bone loss and improved the microarchitecture of bone in OVX mice. Rspo2 could be a positive regulator of bone metabolism through activating the canonical Wnt/ß-catenin signaling, and LGR4 acted as a key receptor for Rspo2 to promote osteogenesis.
Assuntos
Osteogênese , Receptores Acoplados a Proteínas G/metabolismo , Trombospondinas/metabolismo , Via de Sinalização Wnt , Animais , Reabsorção Óssea/metabolismo , Reabsorção Óssea/patologia , Calcificação Fisiológica , Diferenciação Celular , Linhagem Celular , Feminino , Inativação Gênica , Proteína-5 Relacionada a Receptor de Lipoproteína de Baixa Densidade/metabolismo , Camundongos Endogâmicos C57BL , Osteoblastos/citologia , Osteoblastos/metabolismo , Osteoclastos/citologia , Osteoclastos/metabolismo , Ovariectomia , Estabilidade Proteica , beta Catenina/metabolismoRESUMO
Radiotherapy is widely used in esophageal squamous cell carcinoma (ESCC) treatment. Promoting the radiation sensitivity of cancer cells is required. Recent studies have shown that sunitinib can inhibit the growth of several cancer lines. However, few studies on the radiosensitive effect of sunitinib on ESCC cells under hypoxic conditions have been conducted. In the present study, the radiosensitive effects of sunitinib on human ESCC cells were assessed, and the underlying mechanisms were explored. ESCC cells were exposed to hypoxia and treated with sunitinib at different concentrations prior to irradiation. Sunitinib potently inhibited ESCC cell proliferation in an MTT assay. In a clonogenic survival assay, sunitinib sensitized hypoxic ESCC cells to radiation, with sensitizing enhancement ratios of 1.31-1.59. In addition, sunitinib promoted the apoptosis of ESCC cells, but did not alter their cell cycle distribution. Radiosensitization was accompanied by inhibition of the radiation-induced upregulation of hypoxia-inducible factor (HIF)-1α and vascular endothelial growth factor (VEGF) expression. Thus, sunitinib confers radiosensitivity to esophageal cancer cells, which is associated with the downregulation of HIF-1α and VEGF expression. Sunitinib can be a promising radiosensitizer for esophageal cancer radiotherapy.
RESUMO
Smad-7 inhibited the transforming growth factor beta (TGF-ß)-induced proteoglycan synthesis in chondrocytes and completely antagonized the effect of TGF-ß on the proliferation of the cells. The aim of this study was to evaluate the contribution of Smad-7 to the pathophysiology of disc degeneration by determining the expression of Smad-7 in the degenerative intervertebral discs and its effect on the extracellular matrix metabolism of disc cells. Instability of the lumbar spine produced by imbalanced dynamic and static forces was used to induce intervertebral disc degeneration in rats. The expression of Smad-7 was assessed by the immunohistochemical method. Disc cell apoptosis was detected by in situ TUNEL staining. The effect of Smad-7 overexpression on the matrix metabolism of disc cells was analyzed in vitro by real-time polymerase chain reaction (PCR) and Western blotting. Finally, intradiscal injection of the Smad-7 overexpression lentivirus was performed to evaluate the in vivo effect of Smad-7 on disc degeneration. Radiographic and histomorphological examinations showed that lumbar disc degeneration became more and more severe in the rats with induced instability. Immunohistochemical observation demonstrated increasing protein expression of Smad-7 in the degenerative discs. A significantly positive correlation was found between Smad-7 expression and the degree of disc degeneration and between Smad-7 expression and disc cell apoptosis. Overexpression of Smad-7 in disc cells inhibited the expression of TGF-ß1, collagen type-I, collagen type-II, and aggrecan and promoted the expression of MMP-13, but did not change the expression of ADAMTS-5. The in vivo findings illustrated that intradiscal injection of lentivirus vector with Smad-7 overexpression accelerated the progress of disc degeneration. In conclusion, Smad-7 was highly expressed in the degenerative discs. Overexpression of Smad-7 weakened the protective role of TGF-ß and accelerated the progress of disc degeneration. Interference on Smad-7 might be a potential therapeutic method for the prevention and treatment of degenerative disc diseases.
Assuntos
Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Proteína Smad7/metabolismo , Animais , Western Blotting , Separação Celular , Matriz Extracelular/metabolismo , Vértebras Lombares/metabolismo , Masculino , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , TransfecçãoRESUMO
Oxidative stress can damage various cellular components of osteoblasts, and is regarded as a pivotal pathogenic factor for bone loss. Increasing evidence indicates a significant role of cell autophagy in response to oxidative stress. However, the role of autophagy in the osteoblasts under oxidative stress remains to be clarified. In this study, we verified that hydrogen peroxide induced autophagy and apoptosis in a dose- and time-dependent manner in osteoblastic Mc3T3-E1 cells. Both 3-methyladenine (the early steps of autophagy inhibitor) and bafilomycin A1 (the last steps of autophagy inhibitor) enhanced the cell apoptosis and reactive oxygen species level in the osteoblasts insulted by hydrogen peroxide. However, promotion of autophagy with either a pharmacologic inducer (rapamycin) or the Beclin-1 overexpressing technique rescued the cell apoptosis and reduced the reactive oxygen species level in the cells. Treatment with H2O2 significantly increased the levels of carbonylated proteins, malondialdehyde and 8-hydroxy-2'-deoxyguanosine, decreased the mitochondrial membrane potential, and increased the mitochondria-mediated apoptosis markers. The damaged mitochondria were cleared by autophagy. Furthermore, the molecular levels of the endoplasmic reticula stress signaling pathway changed in hydrogen peroxide-treated Mc3T3-E1 cells, and blocking this stress signaling pathway by RNA interference against candidates of glucose-regulated protein 78 and protein kinase-like endoplasmic reticulum kinase decreased autophagy while increasing apoptosis in the cells. In conclusion, oxidative damage to osteoblasts could be alleviated by early autophagy through the endoplasmic reticulum stress pathway. Our findings suggested that modulation of osteoblast autophagy could have a potentially therapeutic value for osteoporosis.
Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Osteoblastos/fisiologia , Animais , Apoptose , Linhagem Celular , Sobrevivência Celular , Humanos , Potencial da Membrana Mitocondrial , Camundongos , Osteoporose/metabolismo , Osteoporose/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismoRESUMO
OBJECTIVE: Liposarcoma (LPS) is the most common soft tissue sarcoma and accounts for approximately 20% of all mesenchymal malignancies, often occurring in deep soft tissue of retroperitoneal space. Accurate preoperative diagnosis is therefore necessary. We explored whether computed tomography (CT) could be used to differentiate between the various types of retroperitoneal liposarcoma (RPLS). METHOD: Forty-seven cases of RPLS, diagnosed surgically and histologically, were analyzed retrospectively. CT features were correlated with postoperative pathological appearance. RESULTS: The study radiologist identified 29, 11, 2, 2 and 3 RPLS as atypical lipomatous tumor/well-differentiated liposarcoma (ALT/WDL), dedifferentiated liposarcoma (DDL), myxoid/round cell liposarcoma (ML/RCL), pleomorphic liposarcoma (PL) and mixed-type liposarcoma. Analysis of CT scans revealed the following typical findings of the different subtypes of RPLS: ALT/WDL was mainly visible as a well-delineated fatty hypodense tumor with uniform density and integrity margin; DDL was marked by the combination of focal nodular density and hypervascularity. ML/RCL, PL and mixed liposarcoma showed malignant biological behaviour and CT findings need further studies. CONCLUSIONS: CT scanning can reveal important details including internal components, margins and surrounding tissues. Based on CT findings, tumor type can be roughly evaluated and biopsy location and therapeutic scheme guided.
Assuntos
Lipossarcoma/diagnóstico por imagem , Lipossarcoma/patologia , Recidiva Local de Neoplasia/diagnóstico por imagem , Recidiva Local de Neoplasia/patologia , Neoplasias Retroperitoneais/diagnóstico por imagem , Neoplasias Retroperitoneais/patologia , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Lipossarcoma/classificação , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Neoplasias Retroperitoneais/classificação , Estudos RetrospectivosRESUMO
Radiation therapy is an important treatment for head and neck squamous cell carcinoma (HNSCC). However, how to promote radiation sensitivity in HNSCC remains a challenge. This study aimed to investigate the radiosensitizing effects of fenofibrate on HNSCC and explore the underlying mechanisms. HNSCC cell lines CNE-2 and KB were subjected to ionizing radiation (IR), in the presence or absence of fenofibrate treatment. Cell growth and survival, apoptosis and cell cycle were evaluated. In addition, CNE-2 cells were xenografted into nude mice and subjected to IR and/ or fenofibrate treatment. The expression of cyclinB and CDK1 was detected by Western blotting. Our results showed that fenofibrate efficiently radiosensitized HNSCC cells and xenografts in mice, and induced apoptosis and G2/M arrest via reducing the activity of the CDK1/cyclinB1 kinase complex. These data suggest that fenofibrate could be a promising radiosensitizer for HNSCC radiotherapy.
Assuntos
Apoptose/efeitos da radiação , Carcinoma de Células Escamosas/radioterapia , Fenofibrato/farmacologia , Neoplasias de Cabeça e Pescoço/radioterapia , Pontos de Checagem da Fase M do Ciclo Celular/efeitos dos fármacos , Radiossensibilizantes/farmacologia , Animais , Apoptose/efeitos dos fármacos , Proteína Quinase CDC2 , Caspase 3/biossíntese , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos da radiação , Ciclina B1/antagonistas & inibidores , Ciclina B1/metabolismo , Quinases Ciclina-Dependentes/antagonistas & inibidores , Quinases Ciclina-Dependentes/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Radiação Ionizante , Carcinoma de Células Escamosas de Cabeça e Pescoço , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
INTRODUCTION: Proximal femoral nail antirotation (PFNA) and third-generation Gamma nail (Gamma 3) are widely used in the treatment of intertrochanteric fractures. However, it remains unclear which device achieves better clinical and radiographic outcomes when treating intertrochanteric fractures. METHODS: This study comprised 239 patients with intertrochanteric fractures treated with either PFNA or Gamma 3 for a minimum of 12 months. During surgery, the operative time, image intensifier time and amount of blood loss were recorded. Following surgery, we assessed reduction quality and implant position. At the final follow-up, postoperative complications, including femoral shaft fracture, cutout, reoperation, pneumonia, urinary tract infection, cerebral infarction, cardiac infarction and decubital ulcer, were recorded. In addition, walking ability was assessed using the Parker-Palmer mobility score. RESULTS: No difference was found in the operative time, image intensifier time and amount of blood loss between patients treated with PFNA and those treated with Gamma 3. The reduction quality of fractures treated with Gamma 3 was better than those treated with PFNA. However, there were no significant differences in implant position, walking ability and postoperative complications between the two groups. Although Gamma 3 resulted in better reduction quality, it did not provide any advantages in walking ability and postoperative complications when compared with PFNA. CONCLUSION: Therefore, we conclude that both PFNA and Gamma 3 are safe and reliable devices for the treatment of intertrochanteric fractures.
Assuntos
Pinos Ortopédicos , Fraturas do Fêmur/cirurgia , Fixação Interna de Fraturas/instrumentação , Fraturas do Quadril/cirurgia , Idoso , Idoso de 80 Anos ou mais , Feminino , Consolidação da Fratura , Humanos , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias , Recuperação de Função Fisiológica , RotaçãoRESUMO
OBJECTIVE: The aim of this study was to investigate the effect of a substance P (SP) receptor (NK1 receptor [NK1-R]) antagonist on hyperalgesia and bone metabolism in ovariectomized mice. METHODS: Thirty-six 9-week-old mice were subjected to either bilateral ovariectomy or sham surgery. Three weeks after the operation, the mice were treated with either a single-dose injection or 2-week repeated daily administration of L-703606, an NK1-R antagonist. Behavioral tests were performed for pain assessment; tibiae and the third lumbar vertebrae were dissected and assessed for microarchitectural or biomechanical properties. The expressions of SP and NK1-R in the dorsal root ganglia and spinal cord were also evaluated. RESULTS: Both single-dose injection and 2-week repeated injections of L-703606 led to a significant increase in nociceptive threshold in ovariectomized mice. However, the antihyperalgesic effect faded at 2 hours and almost disappeared at 5 hours after a single-dose injection. With the 14-day repeated treatment of ovariectomized mice, the effect was not detectable at 24 hours after the first injection but was obvious at 24 hours after 1-week and 2-week administrations and still existed at 48 hours after the last injection. Ovariectomized mice at the hyperalgesic state had enhanced SP immunoreactivity in the dorsal root ganglia and up-regulated SP and NK1-R expressions in the spinal cord. However, no significant change in serum SP level was detected. Two-week treatment with L-703606 could down-regulate these expressions but failed to salvage the deteriorated trabecular microstructure and reduced compressive strength in ovariectomized mice. CONCLUSIONS: Estrogen deficiency-induced hyperalgesia is achieved through up-regulation of SP and NK1-R expressions. Blockade of SP receptor can alleviate pain but cannot ameliorate bone loss. NK1-R antagonist is not recommended for the treatment of estrogen deficiency osteoporosis.
Assuntos
Antagonistas dos Receptores de Neurocinina-1/administração & dosagem , Osteoporose/tratamento farmacológico , Osteoporose/fisiopatologia , Ovariectomia , Dor/tratamento farmacológico , Receptores da Neurocinina-1/fisiologia , Analgesia , Analgésicos , Animais , Feminino , Camundongos , Camundongos Endogâmicos C57BL , Quinuclidinas/administração & dosagemRESUMO
OBJECTIVE: To discuss the unsuccessful reasons and the preventive methods of the unsuccessful clinic cases. METHODS: The retrospective analysis was carried on the 80 prosthesis in 70 patients from 1994 to 2001 which were suffered with unsuccessful results after the restoration of the metal crowns and bridges. RESULTS: There were 68 teeth which had collapsed or broken. 20 teeth had the post loosing or shedding. Root breaking, food impaction, unharmony colors of porcelain and the changing color of gingival were 3, 3, 6 and 2 teeth. CONCLUSION: It is necessary to select suitable repairing materials and operate correctly for preventing the occurring of the unsuccessful results in the porcelain-fused-to-metal-crowns and bridges.