RESUMO
It is widely assumed that as connective tissue, the intervertebral disc (IVD) plays a crucial role in providing flexibility for the spinal column. The disc is comprised of three distinct tissues: the nucleus pulposus (NP), ligamentous annulus fibrous (AF) that surrounds the NP, and the hyaline cartilaginous endplates (CEP). Nucleus pulposus, composed of chondrocyte-like NP cells and its secreted gelatinous matrix, is critical for disc health and function. The NP matrix underwent dehydration accompanied by increasing fibrosis with age. The degeneration of matrix is almost impossible to repair, with the consequence of matrix stiffness and senescence of NP cells and intervertebral disc, suggesting the value of glycoproteins in extracellular matrix (ECM). Here, via database excavation and biological function screening, we investigated a C-type lectin protein, CLEC3A, which could support differentiation of chondrocytes as well as maintenance of NP cells and was essential to intervertebral disc homeostasis. Furthermore, mechanistic analysis revealed that CLEC3A could stimulate PI3K-AKT pathway to accelerate cell proliferation to further play part in NP cell regeneration.
Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Núcleo Pulposo , Proliferação de Células , Humanos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Núcleo Pulposo/metabolismo , Fosfatidilinositol 3-Quinases/metabolismoRESUMO
BACKGROUND: A growing body of studies have indicated that bone marrow mesenchymal stem cells (BMSCs) have powerful analgesic effects in animal models of bone cancer pain. Here, we explored the molecular mechanisms underlying how BMSCs alleviate pain sensation in a mouse model of bone cancer pain. METHODS: C3H/HeN adult male mice were used to generate a bone cancer pain model. BMSCs were isolated from mouse bone marrow, modified by transfection with microRNA-9-5p (miR-9-5p), and infused into the spinal cord. Spontaneous flinches, paw withdrawal latency, limb-use score, and weight-bearing score were used to assess pain-related behaviors. ELISA, RT-PCR, western blot, and luciferase assay were used to assess gene expressions. RESULTS: Our results show that miR-9-5p regulated the expression of both repressor element silencing transcription factor (REST) and µ-opioid receptors (MOR) by targeting REST in primary mouse BMSCs. Overexpression of miR-9-5p reversed the activation of inflammatory pathway in TNF-α- and IL-6-treated BMSCs. In addition, miR-9-5p modified BMSCs alleviated cancer pain in the sarcoma-inoculated mouse model. MiR-9-5p modified BMSCs suppressed cytokine expression in the spinal cord of sarcoma-inoculated mice by suppressing REST gene expression. CONCLUSIONS: Our results indicate that miR-9-5p modified BMSCs can relieve bone cancer pain via modulating neuroinflammation in the central nervous system, suggesting genetically modified BMSCs could be a promising cell therapy in pain management.
Assuntos
Dor do Câncer , Transplante de Células-Tronco Mesenquimais/métodos , MicroRNAs/administração & dosagem , MicroRNAs/metabolismo , Animais , Neoplasias Ósseas/complicações , Dor do Câncer/etiologia , Modelos Animais de Doenças , Regulação da Expressão Gênica/fisiologia , Injeções Espinhais , Masculino , Células-Tronco Mesenquimais , Camundongos , Camundongos Endogâmicos C3H , TransfecçãoRESUMO
Inflammation is one of the major causes of intervertebral disc degeneration (IDD). Emerging evidence has revealed that increase in the levels of pro-inflammatory cytokines, such as interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α), can activate a variety of signaling pathways, eventually resulting in IDD. Here, we show that the two cullin family genes, CUL4A and CUL4B, but not other cullins, are specifically overexpressed in IDD samples compared with healthy controls, and the CUL4A and CUL4B levels are positively correlated with the severity of IDD. In vitro analyses in human osteoblast cells (hFOB1.19), nucleus pulposus cells (hNPCs), and annulus fibrosus cells (hAFCs) indicated that treatment with IL-6 and TNF-α can increase CUL4A and CUL4B levels. By performing a microRNA-based microarray analysis, we found a set of microRNAs (miRNAs) that were differentially expressed in IDD samples compared with samples from healthy controls. Of these miRNAs, miR-194-5p, was significantly downregulated in IDD samples and could bind to the three prime untranslated regions (3'-UTRs) of both CUL4A and CUL4B, thereby downregulating their expression. The in vitro overexpression or downregulation of miR-194-5p, with a miR-194-5p-mimic or with anti-miR-194-5p, can cause the repression or induction of both CUL4A and CUL4B, respectively. Interestingly, treatment with IL-6 and TNF-α inhibitors in primary hNPCs and hAFCs that were isolated from patients with IDD led to the downregulation of CUL4A and CUL4B. Together, these findings provide insight into how the inflammation-dependent downregulation of miR-194-5p contributes to the pathogenesis of IDD, which may aid in the development of new therapeutic approaches for IDD by directly targeting miR-194-5p or CUL4A and CUL4B.
Assuntos
Proteínas Culina/metabolismo , Regulação para Baixo/genética , Inflamação/complicações , Inflamação/genética , Degeneração do Disco Intervertebral/complicações , Degeneração do Disco Intervertebral/genética , MicroRNAs/genética , Anel Fibroso/metabolismo , Linhagem Celular , Células Cultivadas , Proteínas Culina/genética , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-6/farmacologia , Degeneração do Disco Intervertebral/patologia , MicroRNAs/metabolismo , Modelos Biológicos , Núcleo Pulposo/metabolismo , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/genéticaRESUMO
OBJECTIVE: To evaluate the efficacy of unilateral pedicle screw fixation through the pedicle of fractured vertebra in combination with the short segment of pedicle screw in the treatment of thoracolumbar fracture of mild to moderate instability. METHODS: Twenty-six patients with single segment thoracolumbar fracture received unilateral pedicle screw fixation through the pedicle of fractured vertebra in combination with the short segment of pedicle screw from January 2008 to December 2009. There were 16 patients were male and 10 were female with an average age of 47.3 years (range from 39 to 60 years). Fracture severity score was constructed by using the load-sharing classification (4 points for 2 cases, 5 points for 14 cases, 6 points for 10 cases). By Frankel assessment system, 2 cases were in grade C, 3 in grade D, 21 in grade E. The assessment included anterior vertebral body height, the sagittal Cobb angle, the restoration of nervous function, visual analogue score (VAS) and Oswestry disability index (ODI). RESULTS: The follow-up after the surgery was 13 - 26 months, with an average of 18.6 months. There were no fixation failure, defined as implant failure or ≥ 10° correction loss. The neurological status of 4 patients, who had an associated neurologic deficit preoperatively, was completely recovered. The Frankel grade of another case was re-rated D from the original C. The mean anterior vertebral body height increased from 57.0% ± 6.3% before the surgery to 93.1% ± 1.7% at the last follow-up(F = 455.276, P < 0.05). The sagittal Cobb angle decreased from 15.6° ± 4.7° before the surgery to 2.6° ± 5.2° at the last follow-up (F = 34.623, P < 0.05). VAS and ODI were 1.0 ± 0.7 and 17.0 ± 5.9 at the last follow-up. CONCLUSION: Unilateral pedicle screw fixation through the pedicle of fractured vertebra combined with the short segment of pedicle screw is effective for thoracolumbar fracture with mild to moderate instability.
Assuntos
Fixação Interna de Fraturas/métodos , Vértebras Lombares/lesões , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/lesões , Adulto , Parafusos Ósseos , Feminino , Seguimentos , Fixação Interna de Fraturas/instrumentação , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
It is shown by simulations that terahertz (THz) radiation can be produced more efficiently by a mid-infrared laser pulse from a gas target. The THz amplitude is enhanced by 35 times as the laser wavelength increases from 1 µm to 4 µm; a 4 µm laser at 10(15) W cm(-2) produces 5 MV/cm THz radiation. The THz amplitude changes oscillatingly with increasing laser intensity for a given laser wavelength. In addition, the laser intensity threshold for the THz emission is lower for a longer laser wavelength.
RESUMO
Lumbar spinal stenosis (LSS) is a condition wherein patients exhibit age-related fibrosis, elastin-to-collagen ratio reductions, and ligamentum flavum hypertrophy. This study was designed to assess the relationship between SIRT6 and telomerase activity in hypertrophic ligamentum flavum (LFH) cells from LSS patients. We observed significant reductions in SIRT6, TPP1, and POT1 protein levels as well as increases in telomerase reverse transcriptase (TERT) levels and telomerase activity in LFH tissues relative to non- hypertrophic ligamentum flavum (LFN) tissues. When SIRT6 was overexpressed in these LFH cells, this was associated with significant increases in telomerase activity and a significant reduction in fibrosis-related protein expression. These effects were reversed, however, when telomerase activity was inactivated by hTERT knockdown in these same cells. SIRT6 overexpression was further found to reduce the frequency of senescence-associated ß-galactosidase (SA-ß-Gal)-positive LFH cells and to decrease p16, MMP3, and L1 mRNA levels and telomere dysfunction-induced foci (TIFs) in LFH cells. In contrast, hTERT knockdown-induced telomerase inactivation eliminated these SIRT6-dependent effects. Overall, our results indicate that SIRT6 functions as a key protective factor that prevents cellular senescence and telomere dysfunction in ligamentum flavum cells, with this effect being at least partially attributable to SIRT6-dependent telomerase activation.
Assuntos
Dano ao DNA , Hipertrofia , Ligamento Amarelo/patologia , Fatores de Proteção , Sirtuínas/genética , Estenose Espinal/patologia , Telomerase , Envelhecimento , Senescência Celular , Feminino , Fibrose , Humanos , Hipertrofia/patologia , Vértebras Lombares , Masculino , Pessoa de Meia-Idade , Complexo Shelterina , Proteínas de Ligação a TelômerosRESUMO
OBJECTIVE: To introduce a new C(1) screw insertion technique to avoid injury to C(1-2) venous sinus in posterior atlantoaxial fixation. METHODS: 48 cases (96 sides of C(1) screws) undergoing posterior atlantoaxial fixation were retrospectively analyzed, including 28 cases of C(1) or C(2) fresh fracture and 20 cases of congenital malformation or old fracture & dislocation, among which 12 cases (24 sides) were operated by Goel lateral mass screws, 14 cases (28 sides) by TAN Mingsheng C(1) transpedicular screws and 44 sides of C(1) screws in 22 cases were inserted via notch on underside of C(1) posterior arch combined with bone wax column protecting C(1-2) venous sinus. RESULTS: Bleeding was encountered in five sides of C(1) screws among 26 cases (52 sides) whose venous sinuses were not protected by bone wax column, involving 3 cases of Goel lateral screw implant fixation. There was statistical difference in the incidence rate of bleeding between Goel technique and ours (P < 0.05) while there was no statistical difference between C(1) transpedicular technique and ours (P > 0.05) or between Goel sides of Goel lateral mass screws (12.5%) and 2 sides of C(1) transpedicular screws (7.1%). It occurred in none of 22 cases (44 sides) with our presented technique. There was a significant difference between Goel lateral screw implant fixation and C(1) transpedicular technique (P > 0.05). All the screws were implanted successfully. All cases were followed up and there was not any sign of implant failure. CONCLUSIONS: Our presented C(1) screw insertion technique can provide a better bony landmark and vascular protection, stronger bony holding power and more extensive applicability to reduce injury to C(1-2) venous sinus and increase the surgical safety.
Assuntos
Articulação Atlantoaxial/cirurgia , Parafusos Ósseos , Veias Jugulares , Adulto , Idoso , Vértebras Cervicais/irrigação sanguínea , Feminino , Humanos , Fixadores Internos , Masculino , Pessoa de Meia-Idade , Segurança , Resultado do TratamentoRESUMO
The present study aimed to investigate the mechanism of intervertebral disc degeneration (IVDD) and identify an efficient treatment for low back pain. Rabbit annulus fibrosus stem cells (AFSCs) were treated with metformin and lipopolysaccharide (LPS). The results indicated that LPS induced HMGB1 release from the nuclei of AFSCs and caused cell senescence in a concentration-dependent manner. The production of PGE2 and HMGB1 was increased in the medium of the LPS-treated AFSCs. Certain inflammation-associated genes (IL-ß1, IL-6, COX-2 and TNF-α) and proteins (IL-ß1, COX-2 and TNF-α) and specific catabolic genes (MMP-3 and MMP-13) exhibited increased expression in LPS-treated AFSCs. However, the expression levels of other anabolic genes, such as collagen I and collagen II were decreased in LPS-treated AFSCs. Following addition of metformin to LPS-containing medium, HMGB1 was retained in the nuclei of AFSCs and the production of PGE2 and HMGB1 was reduced. The expression levels of the catabolic genes and proteins were decreased and those of the anabolic genes were increased. The findings indicated that metformin exerted an anti-inflammatory effect by blocking the HMGB1 translocation and by inhibiting catabolic production and cell senescence in AFSCs. Therefore, metformin may be used as an efficient treatment for the disc degenerative disease.
Assuntos
Anel Fibroso/efeitos dos fármacos , Anti-Inflamatórios/farmacologia , Proteína HMGB1/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Metformina/farmacologia , Animais , Anel Fibroso/metabolismo , Senescência Celular/efeitos dos fármacos , Proteína HMGB1/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Coelhos , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismoRESUMO
The inflammatory-associated factors interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) are widely reported to be associated with intervertebral disc (IVD) degeneration (IVDD). N-acetyl-5-methoxytryptamine (melatonin) is a natural hormone secreted by the pineal gland which has been shown to participate in several physiological and pathological progresses, such as aging, anti-inflammation, anti-apoptosis and autophagy regulation. However, the effects of melatonin on IVD remain unclear. In the present study, we treated human nucleus pulposus cells (NPCs) with melatonin and discovered that melatonin could modulate extracellular matrix (ECM) remodeling induced by IL-1ß by enhancing collagen II and aggrecan expression levels and by downregulating matrix metalloproteinase-3 (MMP-3) levels. These findings were verified by western blot and immunofluorescence assays. Intraperitoneal injection of melatonin mitigated IVDD in the rat tail puncture model. X-ray and magnetic resonance imaging (MRI), as well as hematoxylin-eosin (H&E), Safranine O-Green, Alcian blue and Celium red staining methods were adopted to evaluate IVDD grades, the structural integrity of nucleus pulposus (NP) and annulus fibrosus (AF) and the damage and calcification of the cartilage endplate. Melatonin reduced inflammatory cell aggregation and the release of the inflammatory factors IL-1ß, IL-6, TNF-α as determined by immunohistochemistry. In conclusion, the present study demonstrated that melatonin could modulate ECM remodeling by IL-1ß in vitro and attenuate the IVDD and induction of inflammation in a rat tail puncture model in vivo. The data demonstrated that melatonin may contribute to the restoration processs of IVD following damage and may be used as a potential novel therapy for IVDD.
Assuntos
Matriz Extracelular/efeitos dos fármacos , Interleucina-1beta/metabolismo , Degeneração do Disco Intervertebral , Melatonina/farmacologia , Núcleo Pulposo/efeitos dos fármacos , Animais , Matriz Extracelular/metabolismo , Matriz Extracelular/patologia , Feminino , Humanos , Inflamação/metabolismo , Interleucina-1beta/efeitos dos fármacos , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Núcleo Pulposo/patologia , Ratos , Ratos Sprague-DawleyRESUMO
The present study was aimed at the investigation of the effects of melatonin on spinal cord injury (SCI) and the role of IGFBP3 in SCI both in vivo and in vitro. The rats received treatment with 100 mg kg-1 melatonin or both melatonin and pGenesil-1-si-IGFBP3 (50 µg per g bw) after SCI surgery. The motor function in rats was measured using the Basso-Beattie-Bresnahan (BBB) scale score; perfusion vessel area was determined by injecting FITC-conjugated lycopersicon esculentum agglutinin lectin (FITC-LEA), whereas the blood-spinal cord barrier permeability was measured using Evans blue. The pericytes were isolated, and the cells were cultured under hypoxia, treated with melatonin or transfected with si-IGFBP3. RT-qPCR and western blotting were conducted for the determination of IGFBP3, VEGF, MMP-2, ICAM-1 and Ang1. The expression of IGFBP3 was significantly down-regulated in the SCI rats, and melatonin significantly enhanced the IGFBP3 level. Melatonin improved the motor function, reduced the neuron injury, and improved the microcirculation in rats. However, the down-regulation of IGFBP3 significantly reversed these effects. Moreover, in both the SCI rat spinal cord tissues and the in vitro pericytes under hypoxia, the expressions of IGFBP3 and Ang1 were significantly down-regulated, whereas those of the proteins MMP-2, VEGF and ICAM-1 were significantly up-regulated, and melatonin dramatically inhibited these changes. Melatonin could protect the rats from SCI by improving the microcirculation through the up-regulation of IGFBP3.
RESUMO
BACKGROUND: Osteoporotic vertebral compression fracture (OVCF) is a common type of fracture, and percutaneous kyphoplasty (PKP) is an eligible solution to it. Previous studies have revealed that both the volume and filling pattern of bone cement correlate with the clinical outcomes after PKP procedure. However, the role of bone cement distribution remains to be illustrated. METHODS: To retrospectively evaluate the relationship between the bone cement distribution and the clinical outcomes of unilateral PKP, we enrolled 73 OVCF patients receiving unilateral PKP treatment. All the intervened vertebrae were classified into three groups based on the bone cement distribution observed on postoperative X-ray films. Preoperative and postoperative radiographic parameters including the vertebral height and kyphotic Cobb angle were recorded, and anterior vertebral height restoration rate (AVHRR) and Cobb angle correction (CR) were then calculated to assess the vertebral height reconstruction. Preoperative and postoperative Oswestry Disability Index (ODI) and visual analogue scale (VAS) were adopted by interviewing patients to assess the mobility improvement and pain relief. Demographic data, body mass index (BMI), lumbar bone mineral density (evaluated by BMD T-score) of each patient, bone cement volume (BV), and bone cement extravasation (BE) were also recorded. Between- and within-group comparisons and multivariable correlation analysis were carried out to analyze the data. RESULTS: VAS and ODI scores were both significantly improved in all of the enrolled cases with no significant differences between groups. Among the three groups, the average age, AVHRR, and BV were significantly different. Occurrence of BE was significantly different between two of the three groups. AVHRR was demonstrated to correlate negatively with preoperative anterior vertebral height ratio and positively with preoperative Cobb angle, CR, diffusion score, and ODI changes. CONCLUSIONS: Bone cement distribution is a potential predictor to the reconstructive effects in unilateral PKP for OVCFs. Bone cement distribution is associated with AVHRR and BV, as well as the risk of BE occurrence. Greater bone cement distribution may indicate better vertebral restoration along with a higher BE risk.
Assuntos
Cimentos Ósseos , Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Idoso , Feminino , Fraturas por Compressão/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Fraturas por Osteoporose/cirurgia , Estudos Retrospectivos , Fraturas da Coluna Vertebral , Resultado do TratamentoRESUMO
OBJECTIVE: To investigate the effects of menopause on redox balance in the intervertebral disc and to examine whether oxidative stress and autophagy were associated with disc degeneration in menopause rats. METHODS: Thirty female Sprague-Dawley rats were randomly divided into three groups (sham, ovariectomized with vehicle, and ovariectomized with estrogen). At the end of the 3-month treatment, the rats were examined by 3.0 T MRI. Serum estradiol (E2) level was measured. Redox balance of nucleus pulposus was determined by measuring total antioxidant capacity (T-AOC), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH-Px), glutathione (GSH), and oxidized glutathione (GSSG). Transmission electron microscopy (TEM), immunohistochemical staining, and Western blot were used to determine the nucleus pulposus autophagy level. At the same time, Spearman's correlation coefficient was used to describe the relationship between intervertebral disc grade, oxidative stress status, serum E2, and autophagy level. RESULTS: The level of serum E2 was significantly decreased by ovariectomy and can be corrected by the estrogen replacement therapy (ERT). In OVX rats, an increased oxidative stress and high level of autophagy were observed in nucleus pulposus tissue. ERT prevented the intervertebral disc degeneration (IVDD), restored the redox balance, and reduced autophagy level. CONCLUSION: Ovariectomy induced oxidative stress, autophagy, and intervertebral disc degeneration. Autophagy of the intervertebral disc was negatively correlated with oxidative stress, and the level of autophagy can be reduced by ERT through modulating the redox balance and downregulating the autophagy level. Regulating the redox balance of IVD may be a potential therapeutic option for degeneration of the disc in the postmenopausal women.
Assuntos
Antioxidantes/metabolismo , Autofagia/efeitos dos fármacos , Estradiol/farmacologia , Degeneração do Disco Intervertebral/tratamento farmacológico , Menopausa/metabolismo , Oxirredutases/metabolismo , Animais , Modelos Animais de Doenças , Estradiol/farmacocinética , Feminino , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Low bone mass in patients with adolescent idiopathic scoliosis has been well reported. Poor bone quality was regarded as a new and unique prognostic factor in aggravating curve progression. However, the potential biomechanical correlation between them remains unclear. METHODS: Three-dimensional finite element models of idiopathic scoliotic spine with different bone mineral status were created for axial loading simulation. An axial load of 3 different body weights was applied on different bone mineral mass models. The mechanical responses of the vertebral cortical and cancellous bone, facet joints, end plate, and intervertebral disc were analyzed. RESULTS: Accompanied with the low bone mineral status, thoracic scoliosis produced asymmetric and higher stress in the cortical bone, lumbar facet joints, and end plate at the concave side of the thoracic structure curve. Stress increased in the disc at the apex of the scoliosis, whereas it mildly decreased in the L4-5 and L5-S1 disc. Body weight gain increased the stress in scoliotic spine structures in all bone mineral statues. CONCLUSIONS: Biomechanical simulations indicated that low bone mineral mass might aggravate curve progression and induce more serious lumbar compensatory scoliosis in patients with adolescent idiopathic scoliosis. Weight gain was also a risk factor for curve progression.
Assuntos
Densidade Óssea , Doenças Ósseas Metabólicas/fisiopatologia , Escoliose/fisiopatologia , Adolescente , Fenômenos Biomecânicos , Peso Corporal , Doenças Ósseas Metabólicas/complicações , Simulação por Computador , Análise de Elementos Finitos , Humanos , Disco Intervertebral/fisiopatologia , Vértebras Lombares/fisiopatologia , Masculino , Modelos Biológicos , Escoliose/complicações , Estresse Fisiológico , Vértebras Torácicas/fisiopatologiaRESUMO
OBJECTIVE: To evaluate the nitric oxide (NO) levels in rat brain cortex and hippocampus after chronic mild stress. METHODS: Sixteen male Sprague-Dawley rats were allocated into control group and model group randomly. Model rats were induced by consecutive chronic mild stress; weight gain, open field test and sucrose solution consumption were investigated before and after procedure. Nitric oxide contents in prefrontal cortex and hippocampus were determined by spectrophotometric assays. RESULT: Decreased locomotion, loss of interest and anhedonia were observed in chronic mild stress rat model group. Nitric oxide contents in prefrontal cortex and hippocampus were significantly higher in chronic mild stress group [(31.00 +/-2.55)nmol/mg.pro and (38.11 +/-1.73)nmol/mg.pro, respectively] than those in control group [(26.97 +/-1.38)nmol/mg.pro and (36.06 +/-0.87)nmol/mg.pro, respectively] (P <0.05). CONCLUSION: Chronic stress can stimulate NO release, and dysfunction of nitric oxide pathway may be involved in development of depression.
Assuntos
Córtex Cerebral/metabolismo , Hipocampo/metabolismo , Óxido Nítrico/biossíntese , Estresse Psicológico/fisiopatologia , Animais , Depressão/etiologia , Depressão/fisiopatologia , Masculino , Atividade Motora/fisiologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Estresse Psicológico/complicaçõesRESUMO
STUDY DESIGN: A retrospective technical report. OBJECTIVE: To assess the effect of bilateral C1 laminar hooks combined with C2 pedicle screw fixation for the treatment of C1-C2 instability. SUMMARY OF BACKGROUND DATA: Various posterior atlantoaxial fixations for C1-C2 instability have been developed. However, due to anatomic anomalies of the vertebral artery, the smallness of the pedicle, trajectories of broken screws, or a lack of surgical experience, a simple atlantoaxial fixation technique with good safety and effectiveness is urgently needed. MATERIALS AND METHODS: From January 2007 to September 2012, 18 patients with C1-C2 instability who underwent posterior bilateral C1 laminar hooks combined with C2 pedicle screw fixation were evaluated. Six patients had acute odontoid fractures (Anderson IIc type), 8 patients had odontoid pseudarthrosis, 3 had os odontoideum, and 1 had a traumatic rupture of the transverse ligament. The mean age at the time of surgery was 34.1 years. The clinical and radiographic analyses were performed before and after the operation and at follow-up. RESULTS: The follow-up period was 12-78 months (with an average follow-up period of 25.6 mo). All patients were relieved of pain and their neurological symptoms were substantially improved. The postoperative JOA score improved significantly (t=-7.234, P<0.001). No neurological or vascular complications occurred in these cases. The device was placed well and had not loosened or broken and plain radiographs revealed bony fusion in 17 patients. One patient had C1 posterior arch fracture 3 weeks postoperatively and she was followed up for 18 months without revision surgery. CONCLUSIONS: When appropriate patients were selected, bilateral C1 laminar hooks combined with C2 pedicle screw fixation can be an alternative method to treat C1-C2 instability effectively with a relatively simple procedure. Preoperative planning and evaluation were crucial for the solid atlantoaxial fusion.
Assuntos
Vértebras Cervicais/cirurgia , Instabilidade Articular/cirurgia , Parafusos Pediculares , Instrumentos Cirúrgicos , Adolescente , Adulto , Vértebra Cervical Áxis/cirurgia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto JovemRESUMO
Cell cycle progression in mammals is strictly controlled by a number of cyclin-dependent kinases (CDKs) and CDK inhibitors (CKIs), the expression of which is often dysregulated in cancer cells. Our previous work revealed that Cullin 4B (CUL4B), a critical component of the Cullin4B-RING E3 ligase complex (CRL4B), is overexpressed in human osteosarcoma cells through an unknown mechanism. Here, we demonstrated that CUL4B forms an E3 ligase with RBX1 (RING-box 1), DDB1 (DNA damage binding protein 1), and DCAF11 (DDB1 and CUL4 associated factor 11) in human osteosarcoma cells. In vitro and in vivo ubiquitination analyses indicated that CRL4BDCAF11 E3 ligase was able to specifically ubiquitinate a CDK inhibitor-p21Cip1 at K16, K154, K161 and K163 but not at K75 and K141. Knocking down any component of the CRL4BDCAF11 complex, including CUL4B, DDB1 or DCAF11, using short hairpin RNAs (shRNAs) attenuated the ubiquitination level of p21Cip1, inhibited osteosarcoma cell proliferation, led to cell cycle arrest at S phase, and decreased colony formation rate. Taken together, our data suggest that the CRL4BDCAF11 complex represents a unique E3 ligase that promotes the ubiquitination of p21Cip1 and regulates cell cycle progression in human osteosarcoma cells.
Assuntos
Proteínas de Transporte/metabolismo , Ciclo Celular , Proteínas Culina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Proteínas de Ligação a DNA/metabolismo , Osteossarcoma/patologia , Processamento de Proteína Pós-Traducional , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Técnicas de Silenciamento de Genes , Humanos , UbiquitinaçãoRESUMO
OBJECTIVES: To evaluate the feasibility and reliability of C(1) lateral-mass screw-C(2) pedicle screw and crosslink compression fixation for Jefferson fracture. METHODS: Seventeen patients with atlas fracture, 12 males and 5 females, aged 42.5 (25 - 67), 4 of which with unstable atlas fracture, were treated. 11 cases underwent C(1) lateral mass and C(2) pedicle screws and crosslink fixation, 6 of which had axial instability and rupture of atlas transverse ligament, 1 had C(2) luminal fracture, and the other 4 had axial instability. With the assistant of regional anatomy study and fluoroscopy the C(1) lateral mass screw and C(2) pedicle screw were inserted properly. Connecting rods were applied into the two screws on each side. Crosslink between the two rods were applied, compressing to achieve the realignment of the C(1) lateral mass fracture and C(0)-C(1)-C(2) into anatomical position. C(1)-C(2) fusions with posterior bone graft were performed in the patients with axial instability or transverse ligament discontinuity. RESULTS: The operative time ranged from 90 to 176 min with an average of 124 min. The intra-operative blood loss ranged from 270 to 1200 ml with an average of 432 ml. Fluoroscopic examination was used for 18 seconds on average. There were no neurological deficits, vertebral artery related complications or other complications in all the patients. No neurological deficit was aggravated after the patient's mobilization with brace 5 days after operation. One case of vertebral artery rupture happened because of the use of electrocautery. The bleeding was stopped by the use of hemostatic sponge and bone cement without causing cerebral hemodynamic deficit. X-ray examination showed bone fusion and stability in all the patients three months after the operation. The restoration of the C(2) fracture was confirmed by CT scan. CONCLUSION: Osteosynthesis of the atlas by C(1) lateral-mass screw-C(2) pedicle screw and crosslink compression fixation is an ideal option for C(1) burst fracture with or without rupture of transverse ligament. The procedure allows a physiological reconstruction of the C(0)-C(1)-C(2) joint and short segmental solid fusion for Jefferson fracture.
Assuntos
Atlas Cervical/lesões , Fixação Interna de Fraturas , Fraturas da Coluna Vertebral/cirurgia , Adulto , Idoso , Feminino , Seguimentos , Humanos , Instabilidade Articular/cirurgia , Masculino , Pessoa de Meia-Idade , Radiografia , Fraturas da Coluna Vertebral/diagnóstico por imagem , Fusão VertebralRESUMO
The purpose of this study was to describe the clinical features of noncontiguous cervical degenerative disc disease (cDDD), investigate the efficacy and complications of a stand-alone anchored spacer (SAAS) for patients with noncontiguous cDDD, and present radiologic analysis of the intermediate segment (IS) after skip-level fusion. Nineteen consecutive patients with noncontiguous cDDD who underwent skip-level anterior cervical discectomy and fusion (ACDF) with SAAS from January 2010 to December 2012 were enrolled in this study. Clinical outcomes were assessed preoperatively and at 24 months postoperatively using the Japanese Orthopaedic Association score, Neck Disability Index, and Visual Analog Scale. Overall cervical alignment (OCA) of the cervical spine, and the range of motion (ROM), intervertebral disc height (IDH), disc signal intensity and disc protrusion of IS were measured and compared before and after surgery. Clinical outcomes significantly improved compared to preoperative scores. The OCA was corrected and maintained at 24 months postoperatively compared with preoperative values (p<0.05). There were no significant differences in the ROM and IDH of the IS at each follow-up (p>0.05). However, decreased signal intensity on T2-weighted MRI was evidenced in three mobile IS at final follow-up (20.0%). Skip-level ACDF with SAAS may be an efficacious option for the treatment of noncontiguous cDDD.
Assuntos
Degeneração do Disco Intervertebral/cirurgia , Fusão Vertebral/instrumentação , Adulto , Idoso , Vértebras Cervicais/cirurgia , Discotomia/instrumentação , Discotomia/métodos , Feminino , Seguimentos , Humanos , Disco Intervertebral/cirurgia , Masculino , Pessoa de Meia-Idade , Medição da Dor , Período Pós-Operatório , Amplitude de Movimento Articular , Fusão Vertebral/métodos , Resultado do TratamentoRESUMO
OBJECTIVE: The lumbar ligamentum ï¬avum (LF) is an important part of the spine to maintain the stability of the spine. In this study we aimed to examine whether mechanical force by cyclic stretch could induce apoptosis in human LF cells and investigate the underlying mechanism. METHODS: LF cells were isolated from six young patients undergoing spinal surgery and then cultured in vitro. LF cells were subjected to cyclic stretch and the poptosis was detected by flow cytometry. The level of intracellular reactive oxygen species (ROS) and caspase-9 activity were measured. RESULTS: Cyclic stretch at a frequency of 0.5â Hz with 20% elongation induced the apoptosis of human LF cells in vitro, and this was correlated with increased ROS generation and activation of caspase-9. CONCLUSION: Our study suggests that cyclic stretch-induced apoptosis in human LF cells may be mediated by ROS generation and the activation of caspase-9.
Assuntos
Apoptose , Ligamento Amarelo/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estresse Mecânico , Caspase 9/genética , Caspase 9/metabolismo , Células Cultivadas , Humanos , Ligamento Amarelo/citologiaRESUMO
Optical modulators can have high modulation speed and broad bandwidth, while being compact. However, these optical modulators usually work for low-intensity light beams. Here we present an ultrafast, plasma-based optical modulator, which can directly modulate high-power lasers with intensity up to 10(16) W cm(-2) to produce an extremely broad spectrum with a fractional bandwidth over 100%, extending to the mid-infrared regime in the low-frequency side. This concept relies on two co-propagating laser pulses in a sub-millimetre-scale underdense plasma, where a drive laser pulse first excites an electron plasma wave in its wake while a following carrier laser pulse is modulated by the plasma wave. The laser and plasma parameters suitable for the modulator to work are based on numerical simulations.