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1.
Phytomedicine ; 68: 153186, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32088353

RESUMO

BACKGROUND: Osteosarcoma is the most common type of primary malignant bone tumor. This disease has exhibited a progressively lower survival rate over the past several decades, which has resulted in it becoming a main cause of death in humans. Rosmarinic acid (RA), a water-soluble polyphenolic phytochemical, exerts powerful anticancer effects against multiple types of cancer; however, its potential effects on osteosarcoma remain unknown. Hence, the present study investigated the efficacy of RA against osteosarcoma and aimed to clarify the mechanisms underlying this process. METHODS: The effects of RA on cell viability, apoptosis, cell cycle distribution, migration, invasion, and signaling molecules were analyzed by CCK-8 assay, flowcytometric analysis, wound healing assay, Transwell assay, proteomic analysis, and use of shRNAs. RESULTS: RA exerted anti-proliferation and pro-apoptotic effects on U2OS and MG63 osteosarcoma cells. Apoptosis was induced via extrinsic and intrinsic pathways by increasing the Bax/Bcl-2 ratio, triggering the intracellular production of reactive oxygen species (ROS), reducing the mitochondrial membrane potential (MMP), and upregulating the cleavage rates of caspase-8, caspase-9, and caspase-3. Additionally, RA suppressed the migration and invasion of osteosarcoma cells by inhibiting the expression levels of matrix metalloproteinase-2 and -9 (MMP-2 and -9), which are associated with a weakening of the epithelial-mesenchymal transition (EMT). Moreover, proteomic analyses identified DJ-1 as a potential target for RA. Several studies have indicated an oncogenic role for DJ-1 using knockdowns via the lentiviral-mediated transfection of shRNA, which caused the conspicuous suppression of cell proliferation, migration, and invasion as well as the arrest of cell cycle progression. At the molecular level, the expression levels of DJ-1, p-PI3K, and p-Akt were reduced, whereas the protein levels of phosphatase and tensin homologue (PTEN) were increased. CONCLUSION: In conjunction with the high levels of DJ-1 expression in osteosarcoma tissues and cell lines, the present results suggested that RA exhibited anticancer effects in osteosarcoma cells by inhibiting DJ-1 via regulation of the PTEN-PI3K-Akt signaling pathway. Therefore, DJ-1 might be a biological target for RA in osteosarcoma cells.

2.
Oncol Lett ; 18(6): 6431-6442, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31807166

RESUMO

Ewing's sarcoma (ES) is a common malignant bone tumor in children and adolescents. Although great efforts have been made to understand the pathogenesis and development of ES, the underlying molecular mechanism remains unclear. The present study aimed to identify new key genes as potential biomarkers for the diagnosis, targeted therapy or prognosis of ES. mRNA expression profile chip data sets GSE17674, GSE17679 and GSE45544 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened using the R software limma package, and functional and pathway enrichment analyses were performed using the enrichplot package and GSEA software. The NetworkAnalyst online tool, as well as Cytoscape and its plug-ins cytoHubba and NetworkAnalyzer, were used to construct a protein-protein interaction network (PPI) and conduct module analysis to screen key (hub) genes. LABSO COX regression and overall survival (OS) analysis of the Hub genes were performed. A total of 211 DEGs were obtained by integrating and analyzing the three data sets. The functions and pathways of the DEGs were mainly associated with the regulation of small-molecule metabolic processes, cofactor-binding, amino acid, proteasome and ribosome biosynthesis in eukaryotes, as well as the Rac1, cell cycle and P53 signaling pathways. A total of one important module and 20 hub genes were screened from the PPI network using the Maximum Correlation Criteria algorithm of cytoHubba. LASSO COX regression results revealed that titin (TTN), fast skeletal muscle troponin T, skeletal muscle actin α-actin, nebulin, troponin C type 2 (fast), myosin light-chain 3 (MYL3), slow skeletal muscle troponin T (TNNT1), myosin-binding protein C1 slow-type, tropomyosin 3 and myosin heavy-chain 7 were associated with prognosis in patients with ES. The Kaplan-Meier curves demonstrated that high mRNA expression levels of TNNT1 (P<0.001), TTN (P=0.049), titin-cap (P=0.04), tropomodulin 1 (P=0.011), troponin I2 fast skeletal type (P=0.021) and MYL3 (P=0.017) were associated with poor OS in patients with ES. In conclusion, the DEGs identified in the present study may be key genes in the pathogenesis of ES, three of which, namely TNNT1, TTN and MYL3, may be potential prognostic biomarkers for ES.

3.
J Orthop Surg Res ; 14(1): 443, 2019 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-31842920

RESUMO

BACKGROUND: Scoliosis causes thoracic deformities, and it is necessary to assess these changes in pulmonary function test (PFT). To determine how measurements of spinal and thoracic cage deformities are related to pulmonary function. METHODS: Seventy-two patients with main right thoracic curvature in adolescent idiopathic scoliosis (AIS) underwent a PFT and a radiological parameter evaluation of spinal and thoracic cage deformities. Simple and multiple linear regressions were also used to note whether a combination of variables might better predict PFT values. Means were compared using the two-sample t test or one-way ANOVA with Tukey's multiple comparison methods. RESULTS: Forced vital capacity (FVC)% predicted had significantly negative correlations with main thoracic curve Cobb (MT-Cobb) (R2 = 0.648, p < 0.001), main thoracic curve-rib hump (MT-RH) (R2 = 0.522, p < 0.001), main thoracic curve apical vertebral body-to-rib ratio (MT-AVB-R) (R2 = 0.536, p < 0.001), and main thoracic curve apical vertebra translation (MT-AVT) (R2 = 0.383, p < 0.001). Multiple regression analysis was performed with FVC% predicted as the dependent variable and MT-Cobb, MT-RH, MT-AVB-R, and MT-AVT as the independent variables. MT-Cobb, MT-RH, MT-AVB-R, and MT-AVT were factors with a significant effect on FVC% predicted (p < 0.001). For 45 patients who had preoperative FVC impairment (FVC% predicted < 80%), their MT-Cobb averaged 76.71°. Twenty-seven patients with normal preoperative FVC (FVC% predicted ≥ 80%) had a smaller mean MT-Cobb of 52.03° (p < 0.001). In other radiological parameters, the impaired FVC group had a MT-AVT of 54.29 mm compared to 38.06 mm for the normal FVC group (p < 0.001). MT-AVB-R averaged 2.92 for the impaired FVC group and 1.78 for the normal FVC group (p < 0.001). MT-RH averaged 28.79 mm for the impaired group and 16.62 mm for the normal group (p < 0.001). Further stratification of preoperative PFT results is divided into three groups. The three groups also showed significant differences in MT-Cobb, MT-RH, MT-AVB-R, and MT-AVT (p < 0.001). CONCLUSION: Severe scoliosis leads to an increased degree of thoracic deformity, which increases the risk of lung damage in AIS. Moreover, a more accurate assessment of pulmonary function is achieved through radiological parameters and PFTs.

4.
Medicine (Baltimore) ; 98(50): e18277, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31852100

RESUMO

The aim of the study was to evaluate the clinical effect of the limited area decompression, intervertebral fusion, and pedicle screw fixation for treating degenerative lumbar spinal stenosis (DLSS) with instability. Hemilaminectomy decompression, intervertebral fusion, and pedicle screw fixation for treating DLSS with instability as the control group.Follow-up of 54 patients (26 males and 28 females; average age, 59.74 ±â€Š10.38 years) with DLSS with instability treated by limited area decompression, intervertebral fusion, and pedicle screw fixation (LIFP group), and 52 patients as control group with hemilaminectomy decompression, intervertebral fusion, and pedicle screw fixation (HIFP group). We assessed clinical effect according to the patients' functional outcome grading (good to excellent, fair, or poor), Oswestry Disability Index (ODI) and visual analogue scale (VAS) for low back pain and lower limb pain, which was administered preoperatively and at 3, 6, and 12 months postoperatively. Fusion status was assessed by radiologists at the last follow-up. Treatment satisfaction was assessed according to the subjective evaluations of the patients.At the 12-month follow-up, 96.2% (52/54) and 90.3% (47/52) of group LIFP and HIFP belonged to good to excellent outcome categories, respectively, while 3.7% (2/54) and 9.6% (5/52) of group LIFP and HIFP belonged to fair respectively, neither group belonged to poor. Satisfaction rates of patients in group LIFP and group HIFP were 98.1% (53/54) and 92.3% (48/52), respectively. The patients' functional outcome grading and satisfaction rate in group LIFP were better than that in group HIFP. The VAS for low back and lower limb pain and the ODI improved significantly during the 12 months after surgery (all P < .001) in 2 groups. The VAS for low back and lower limb pain were no difference between two groups, however, the ODI of group LIFP was lower than that of group HIFP (P < .001). All patients achieved radiological fusion.The limited area decompression, intervertebral fusion, and pedicle screw fixation had a satisfactory effect on patients with DLSS with instability.


Assuntos
Descompressão Cirúrgica/métodos , Instabilidade Articular/cirurgia , Laminectomia/métodos , Vértebras Lombares , Parafusos Pediculares , Fusão Vertebral/métodos , Estenose Espinal/cirurgia , Feminino , Fluoroscopia , Seguimentos , Humanos , Instabilidade Articular/complicações , Instabilidade Articular/diagnóstico , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estenose Espinal/complicações , Estenose Espinal/diagnóstico , Cirurgia Assistida por Computador/métodos , Fatores de Tempo , Resultado do Tratamento
5.
J Coll Physicians Surg Pak ; 29(12): S135-S137, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31779768

RESUMO

Ankylosing spondylitis (AS) with an Andersson lesion may cause kyphosis. As the disease progresses, kyphosis gradually worsens. When conservative treatment does not improve the symptoms, surgery is often needed to correct the deformity. The optimal surgical approach for ankylosing spondylitis with kyphosis remains controversial. Here, we introduce our surgical procedure of pseudoarticular debridgement and osteotomy of the apical vertebrae of the Cobb angle. We found that both the kyphosis and associated symptoms improved significantly after 13 months of follow-up.

6.
Regen Med ; 14(9): 887-898, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31436130

RESUMO

Spinal cord injury (SCI) is one of the leading causes of global disability. However, there are currently no effective clinical treatments for SCI. Repair of SCI is essential but poses great challenges. As a comprehensive treatment program combining biological scaffolds, seed cells and drugs or biological factors, tissue engineering has gradually replaced the single transplantation approach to become a focus of research that brings new opportunities for the clinical treatment of SCI.

7.
Zhongguo Gu Shang ; 32(3): 269-277, 2019 Mar 25.
Artigo em Chinês | MEDLINE | ID: mdl-30922012

RESUMO

OBJECTIVE: To systematically evaluate the efficacy and safety of anterior decompression and posterior decompression in the treatment of thoracolumbar fractures with spinal cord injury, so as to provide a good scientific basis for more effective treatment of thoracolumbar fractures with spinal cord injury. METHODS: A clinical data about comparative study of anterior decompression and posterior decompression in the treatment of thoracolumbar fractures with spinal cord injury was searched and collected. The databases of Pubmed, Embase, Cochrane Library, CNKI, CBM, Wanfang Medical Network were searched by computer. Artificially collected journals included Spine, European Spine Journal, The Journal of Bone and Joint Surgery. Two spine surgeons independently screened the literature according to established inclusion and exclusion criteria and assessed the quality of the included studies. Meta-analysis was performed on the data using Review Manager 5.3 software, the indicators included operative time, intraoperative blood loss, postoperative tactile score, postoperative motor score, postoperative vertebral height, hospitalization time, neurological function recovery, efficiency of treatment, postoperative complications. RESULTS: Fifteen randomized controlled trials (RCTs) were enrolled in a total of 1 360 patients, including 680 anterior decompression and 680 posterior decompression. The results of Meta-analysis showed that the anterior decompression group had longer operation time [MD=80.09, 95% CI(36.83, 123.34), P=0.000 3], more intraoperative blood loss [MD=225.21, 95%CI(171.07, 279.35), P<0.000 01], longer hospitalization time [MD=2.31, 95% CI(0.32, 4.31), P=0.02]. And the postoperative tactile score [MD=13.39, 95% CI(9.86, 16.92), P<0.000 01], postoperative motor score [MD=13.15, 95% CI(7.02, 19.29), P<0.000 1], vertebral height [MD=1.36, 95% CI(0.79, 1.92), P<0.000 01] in anterior decompression were higher than that in posterior decompression. There was no statistically significant differences in the efficacy of treatment [OR=1.14, 95% CI(0.56, 2.31), P=0.72], neurological recovery [OR=0.87, 95% CI(0.57, 1.33), P=0.52] between two groups. CONCLUSIONS: Compared with posterior decompression, the anterior decompression has the advantages of longer operating time, more intraoperative blood loss, longer hospitalization time, higher postoperative tactile score, higher postoperative motor score, and higher injury vertebral height, But there was no significant difference in the treatment efficiency and nerve function recovery between two groups.


Assuntos
Traumatismos da Medula Espinal , Fraturas da Coluna Vertebral , Descompressão Cirúrgica , Humanos , Vértebras Lombares , Vértebras Torácicas , Resultado do Tratamento
8.
J Neuroinflammation ; 15(1): 220, 2018 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-30075820

RESUMO

BACKGROUND: The glutamine synthetase (GS), an astrocyte-specific enzyme, is involved in lipopolysaccharide (LPS)-induced inflammation which activates the mitogen-activated protein kinase (MAPK) signaling. Endocannabinoid 2-arachidonyl glycerol (2-AG) has been described to serve as an endogenous mediator of analgesia and neuroprotection. However, whether 2-AG can directly influence astrocytic GS and MAPK expressions remains unknown. METHODS: In the present study, the effects of 2-AG on astrocytic GS expression, p38 and ERK1/2 expression, cell viability, and apoptosis following LPS exposure were investigated. RESULTS: The results revealed that LPS exposure increased GS expression with p38 activation in the early phase and decreased GS expression with activation of ERK1/2, decrease of cell viability, and increase of apoptosis in the late phase. Inhibition of p38 reversed GS increase in the early phase while inhibition of ERK1/2 reversed GS decrease in the late phase induced by LPS exposure. 2-AG protected astrocytes from increase of apoptosis and decrease of cell viability induced by the late phase of LPS exposure. In the early phase of LPS exposure, 2-AG could suppress the increase of GS expression and activation of p38 signaling. In the late phase of LPS exposure, 2-AG could reverse the decrease of GS expression and activation of ERK1/2 induced by LPS. CONCLUSION: These findings suggest that 2-AG could maintain the GS expression in astrocytes to a relatively stable level through modulating MAPK signaling and protect astrocytes from LPS exposure.


Assuntos
Ácidos Araquidônicos/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Agonistas de Receptores de Canabinoides/farmacologia , Endocanabinoides/farmacologia , Glutamato-Amônia Ligase/metabolismo , Glicerídeos/farmacologia , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Células Cultivadas , Córtex Cerebral/citologia , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteína Glial Fibrilar Ácida/metabolismo , Lipopolissacarídeos/farmacologia , Fosforilação/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Fatores de Tempo
9.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 30(9): 1061-1064, 2016 Sep 08.
Artigo em Chinês | MEDLINE | ID: mdl-29786355

RESUMO

OBJECTIVE: To evaluate the accuracy of using smartphone to measure the angle of acetabular component in total hip arthroplasty (THA). METHODS: Between June 2012 and September 2015, the acetabular abduction and anteversion angles were measured in 50 patients undergoing THA. There were 24 males and 26 females, aged 37 to 83 years (mean, 71 years). The left hip was involved in 22 cases and the right hip in 28 cases. Of 50 patients, 34 suffered from fracture of the femoral neck, and 16 suffered from avascular necrosis of the femoral head. Acetabular dysplasia was excluded in all cases. A smartphone was used to measure the acetabular abduction and anteversion angles during operation; standard Picture Archiving and Communication Systems (PACS) was used to measured the acetabular abduction and anteversion angles on the X-ray film at 1 week after operation. It was defined as positive that the component angle values by PACS measurement were greater than those by the smartphone measurement, whereas as negative. The two measurement methods were compared, and intra-observer variability was assessed by analyzing the intraclass correlation coefficient (ICC), the Mann-Whitney U-test was used to analyze difference. RESULTS: The ICC was 0.84 in the acetabular component angles by smartphone and PACS measurement methods. The acetabular component abduction angle was (44.02±1.33)° and the anteversion angle was (17.62±2.20)° by smartphone measurement. The acetabular component abduction angle was (44.74±4.05)° and the anteversion angle was (17.22±5.57)° by PACS measurement. There was no significant difference between two measurement methods (Z=-1.977, P=0.482; Z=-0.368, P=0.713). The acetabular component angle was in the safe zone in 44 cases; and the acetabular component anteversion angle was beyond safe range of 1 to 5°, and the abduction angle was beyond safe range of 1 to 3° in 6 cases. Intra-measurement variability was -21 to +10° for the anteversion angle and -10 to + 9° for the abduction angle, indicating that the acetabular component anteversion angle by smartphone measurement was greater than that by the PACS measurement, and the abduction angle was less than that by PACS measurement. CONCLUSIONS: Smartphone is a convenient tool to measure the acetabular component angle in THA.


Assuntos
Acetábulo/anatomia & histologia , Artroplastia de Quadril/métodos , Mau Alinhamento Ósseo/prevenção & controle , Cabeça do Fêmur/cirurgia , Smartphone , Feminino , Colo do Fêmur/cirurgia , Fraturas Ósseas , Humanos , Masculino , Osteonecrose , Resultado do Tratamento
10.
Int J Mol Med ; 36(3): 776-82, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26165148

RESUMO

Aplasia Ras homologue member Ⅰ (ARHI), an imprinted tumor-suppressor gene, is downregulated in various types of cancer. However, the expression, function and specific mechanisms of ARHI in human osteosarcoma (OS) cells remain unclear. The aim of the present study was to assess the effect of ARHI on OS cell proliferation and apoptosis and its associated mechanism. In the study, ARHI mRNA and protein levels were markedly downregulated in OS cells compared with the human osteoblast precursor cell line hFOB1.19. By generating stable transfectants, ARHI was overexpressed in OS cells that had low levels of ARHI. Overexpression of ARHI inhibited cell viability and proliferation and induced apoptosis. However, caspase­3 activity was not changed by ARHI overexpression. In addition, phosphorylated Akt protein expression decreased in the ARHI overexpression group compared to that in the control vector group. The knockdown of ARHI also resulted in the promotion of cell proliferation and the attenuation of apoptosis in MG­63 cells. Additionally, ARHI silencing increased the level of p­Akt. The present results indicate that ARHI inhibits OS cell proliferation and may have a key role in the development of OS.


Assuntos
Neoplasias Ósseas/genética , Osso e Ossos/patologia , Osteossarcoma/genética , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Proteínas rho de Ligação ao GTP/genética , Apoptose , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Osso e Ossos/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Sobrevivência Celular , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Humanos , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Interferência de RNA , RNA Interferente Pequeno/genética , Regulação para Cima
11.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 24(10): 1164-7, 2010 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-21046799

RESUMO

OBJECTIVE: To discuss the selection of anterior or posterior or a combination of anterior and posterior surgical treatment of lower cervical dislocation. METHODS: A retrospectively study was performed on 28 patients with lower cervical dislocation who received operative treatment between January 2005 and October 2008. There were 19 males and 9 females with an average age of 38 years (range, 19-57 years), including 21 cases of fresh dislocation and 7 cases of old dislocation. The time from injury to hospitalization was 3 hours to 58 days. According to Allen classification, all cases had flexion injury, including 19 cases of degree I dislocation, 2 cases of degree II, 5 cases of degree III, and 2 cases of degree IV. At admission according to Frankel classification, 7 cases were rated as grade A, 4 as grade B, 9 as grade C, 3 as grade D, and 5 as grade E. All patients received open reduction, internal fixation, and iliac bone graft spinal fusion. Of them, combined anterior and posterior approach operation were given in 4 cases, single anterior operation in 22 cases, and single posterior operation in 2 cases. RESULTS: All operations were completed successfully and the spinal cord injury did not deteriorate after operation. Esophageal fistula occurred in 1 case receiving anterior approach operation and was cured after 1 month. Infection of wound occurred in 1 case and was cured after dressing change. The other incisions healed by first intention. One case (Frankel grade A) died of pulmonary infection 6 weeks after operation. Twenty-seven patients were followed up 21-38 months. Two cases suffered from shoulder pain 12 months after operation. X-ray films showed complete reduction, normal height of vertebral space and normal sequence of cervical spine after operation. All cases obtained bone fusion after 3.5-6.0 months of operation (4.2 months on average). Frankel grades were improved in different degrees after operation. CONCLUSION: The operation plan of lower cervical dislocation should be determined by the neurologic status of the patient, and the classification of the injury as a unilateral or bilateral dislocation.


Assuntos
Vértebras Cervicais , Luxações Articulares/cirurgia , Adulto , Feminino , Fixação Interna de Fraturas/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fusão Vertebral/métodos , Adulto Jovem
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