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1.
Genomics ; 115(2): 110574, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36758878

RESUMO

Chondrocyte senescence is a decisive component of age-related osteoarthritis, however, the function of small noncoding RNAs (sncRNAs) in chondrocyte senescence remains underexplored. Human hip joint cartilage chondrocytes were cultivated up to passage 4 to induce senescence. RNA samples were extracted and then analyzed using small RNA sequencing and qPCR. ß-galactosidase staining was used to detect the effect of sncRNA on chondrocyte aging. Results of small RNA sequencing showed that 279 miRNAs, 136 snoRNAs, 30 snRNAs, 102 piRNAs, and 5 rasiRNAs were differentially expressed in senescent chondrocytes. The differential expression of 150 sncRNAs was further validated by qPCR. Transfection of sncRNAs and ß-galactosidase staining were also performed to further revealed that hsa-miR-135b-5p, SNORA80B-201, and RNU5E-1-201 have the function to restrain chondrocyte senescence, while has-piR-019102 has the function to promote chondrocyte senescence. Our data suggest that sncRNAs have therapeutic potential as novel epigenetic targets in age-related osteoarthritis.


Assuntos
MicroRNAs , Osteoartrite , Pequeno RNA não Traduzido , Humanos , Condrócitos/metabolismo , Osteoartrite/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Pequeno RNA não Traduzido/metabolismo , beta-Galactosidase/genética , beta-Galactosidase/metabolismo , Epigênese Genética , Senescência Celular
2.
Cell Biol Int ; 46(10): 1588-1603, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35762224

RESUMO

To provide a basis for promising exosome-based therapies against intervertebral disc degeneration (IDD), our present research aimed to identify a mechanism underlying the vesicle release from nucleus pulposus cells (NPCs). Scutellarin (SC) is a natural chemotherapeutic agent isolated from Erigeron breviscapus with a variety of biological activities. Here, we observed the significantly elevated autophagy levels in rat NPCs under the stimulation of SC, leading to a concomitant enhancement of intracellular vesicle release, which could be attributed to the inactivation of the phosphoinositide 3-kinase (PI3K)/phosphatase and tensin homolog (PTEN)/protein kinase B (Akt) pathway. To ensure that exosome release was driven by SC via the autophagic pathway, we implemented gain-of-function and loss-of-function studies by additionally using insulin-like growth factor-1 (IGF-1) and small-interfering RNA of autophagy-related gene 5 (ATG5), and the exosome secretion decreased in the case of attenuated autophagy. Evidently, the treatment with SC exerted the remarkable upregulation of Rab8a through the overexpression of ATG5. After the respective knockdown of ATG5 and Rab8a, the increased release of exosomes induced by SC was reversed, whereas the number of intracellular vesicles was restored. Overall, it can be concluded that SC contributes to the autophagy activation in NPCs by acting on the PI3K/PTEN/Akt pathway, which upregulates the expression of Rab8a and promotes the release of exosomes, inspiring novel therapeutic strategies in preventing IDD that might be fruitfully investigated.


Assuntos
Exossomos , Degeneração do Disco Intervertebral , Núcleo Pulposo , Animais , Apigenina , Apoptose/genética , Autofagia/genética , Proteína 5 Relacionada à Autofagia/metabolismo , Exossomos/metabolismo , Glucuronatos , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Núcleo Pulposo/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos
3.
Exp Cell Res ; 395(2): 112239, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-32828826

RESUMO

Our present study investigated whether exosome secretion of nucleus pulposus cells (NPCs) is regulated by autophagy. Different autophagic states of NPCs were induced by rapamycin (Rap), bafilomycin A1 (Baf) and other agents, and it was found that exosomes were secreted in an autophagy-dependent manner. Activation or inhibition of autophagy increased or decreased, respectively, the amount of exosomes that were released into the extracellular space. In addition, in order to confirm that Rap-promoted release of exosomes was mediated by autophagy rather than other pathways, we used autophagy associated gene 5 (ATG5) small-interfering RNA (siRNA) to silence the expression of ATG5 gene, which is indispensable for autophagy. The results showed that siRNA against ATG5 (siATG5) induced an accumulation of intraluminal vesicles (ILVs) in NPCs and a concomitant decrease in the amount of exosomes isolated from supernatant. Ras homolog gene (Rho) and Rho-associated coiled-coil forming protein kinase (ROCK) family molecules are capable of cytoskeletal remodeling and affecting vesicle transport. Therefore, we carried out targeted interventions and evaluated the effects of the RhoC/ROCK2 pathway on the secretion of exosomes within autophagic environment. Knockdown of RhoC and ROCK2 with corresponding siRNA significantly inhibited the secretion of exosomes originating from ILVs in NPCs, even when NPCs were subsequently treated with Rap. Taken together, our findings suggest that autophagy positively regulates expression levels of RhoC and ROCK2, and that the RhoC/ROCK2 pathway exerts a key function on NPCs-derived exosome secretion.


Assuntos
Autofagia/fisiologia , Exossomos/metabolismo , Núcleo Pulposo/metabolismo , Proteína de Ligação a GTP rhoC/genética , Animais , Secreções Corporais/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Ratos Sprague-Dawley , Quinases Associadas a rho/metabolismo , Proteína de Ligação a GTP rhoC/metabolismo
4.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 42(1): 37-46, 2020 Feb 28.
Artigo em Zh | MEDLINE | ID: mdl-32131938

RESUMO

Objective To study the gene expression of cardiac mesenchymal cells in patients with type 2 diabetes mellitus (T2DM)based on a whole-genome high-throughput sequencing dataset,screen differentially expressed genes,analyze the genetics signature of cardiac mesenchymal cells in T2DM patients by bioinformatics analysis,and explore the environmental chemicals related to the key differentially expressed genes. Methods The dataset GSE106177 was obtained from Gene Expression Omnibus (GEO) database.The dataset was pre-processed and analyzed by Network Analyst,Cytoscape 3.7.1,String11.0,CTD,and HMDD for screening for differentially expressed genes,enrichment analysis,establishment of protein-protein interaction (PPI) networks,and screening for relevant environmental chemicals. Results The gene expression pattern of cardiac mesenchymal cells in T2DM patients was significantly different from that in the control group.There were 135 differentially expressed genes,of which 58 (42.96%) were up-regulated and 77 (57.04%) were down-regulated.The differentially expressed genes mainly participated in biological processes such as multicellular organism development,anatomical structure development,and system development and were mainly involved in hepatocellular carcinoma,Cushing's syndrome,and cholesterol metabolism.PPI network showed that UBC was the core protein node.The microRNA-Gene interaction network showed that seven microRNAs,represented by hsa-mir-8485,interacted with the differentially expressed genes.Key T2DM related genes such as UBC,DNER,and CNTN1 interacted with bisphenol A. Conclusions The gene expression profile of cardiac mesenchymal cells markedly changes in T2DM patients,during which UBC may play an important biological role.Bisphenol A exposure may also affect the development and normal function of cardiac cells in T2DM patients.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Células-Tronco Mesenquimais/metabolismo , MicroRNAs/genética , Miocárdio/citologia , Transcriptoma , Biologia Computacional , Perfilação da Expressão Gênica , Humanos
5.
Med Sci Monit ; 25: 10136-10153, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31885034

RESUMO

BACKGROUND The incidence and prognostic factors of chondrosarcoma patients have been reported in early studies. However, the association between risk factors and the incidence or prognosis of chondrosarcoma patients with pulmonary metastasis remains unclear. Therefore, we assessed these risk factors among chondrosarcoma patients with pulmonary metastasis. MATERIAL AND METHODS From 1365 chondrosarcoma patients in the Surveillance, Epidemiology, and End Results (SEER) database, we collected the information of 69 patients with pulmonary metastasis at the initial diagnosis of chondrosarcoma from 2010 to 2016. We investigated the incidence, risk factors, and prognostic factors for pulmonary metastasis patients by using multivariate logistic regression and multivariate Cox regression analyses. RESULTS Data from a total of 69 (6.8%) chondrosarcoma patients with pulmonary metastasis at initial diagnosis were extracted. Patients with the following characteristics were positively associated with higher risk of pulmonary metastasis: dedifferentiated subtype, high grade of malignancy, extracompartmental tumor (Enneking B), presence of regional lymph nodes, local recurrence, large tumor size (larger than 15 cm), and being married. Older patients (older than 67 years), and patients with clear cell chondrosarcoma or large tumor size (larger than 15 cm) exhibited the worse prognosis and survival (overall and cancer-specific). Resection of the primary tumor tended to be correlated with a better prognosis. CONCLUSIONS The incidence of pulmonary metastasis in chondrosarcoma was approximately 6.8%, with poor prognosis. Identifying risk factors and their associations with the incidence and prognosis in chondrosarcoma patients with pulmonary metastasis could provide a reference for clinical surveillance and guide the design of personalized treatment plans.


Assuntos
Condrossarcoma/diagnóstico , Condrossarcoma/epidemiologia , Neoplasias Pulmonares/epidemiologia , Neoplasias Pulmonares/secundário , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Feminino , Humanos , Incidência , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Prognóstico , Modelos de Riscos Proporcionais , Fatores de Risco , Análise de Sobrevida , Adulto Jovem
6.
Eur Spine J ; 26(4): 1162-1172, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-27885472

RESUMO

OBJECTIVE: For three or more involved cervical levels, there is a debate over which approach yields the best outcomes for the treatment of multilevel cervical degenerative disease. Our objective is to compare the radiological and clinical outcomes of two treatments for multilevel cervical degenerative disease: anterior cervical discectomy and fusion (ACDF) versus plate-only open-door laminoplasty (laminoplasty). METHODS: Patients were randomized on a 1:1 randomization schedule with 17 patients in the ACDF group and 17 patients in the laminoplasty group. Clinical outcomes were assessed by a visual analog scale (VAS), Japanese Orthopedic Association (JOA) scores, operative time, blood loss, rates of complications, drainage volume, discharge days after surgery, and complications. The cervical spine curvature index (CI) and range of motion (ROM) were assessed with radiographs. RESULTS: The mean VAS score, the mean JOA score, and the rate of complications did not differ significantly between groups. The laminoplasty group had greater blood loss, a longer operative time, more drainage volume, and a longer hospital stay than the ACDF group. There were no significant differences in the CI and ROM between the two groups at baseline and at each follow-up time point. ROM in both groups decreased significantly after surgery. CONCLUSIONS: Both ACDF and laminoplasty are effective and safe treatments for multilevel cervical degenerative disease. ACDF causes fewer traumas than laminoplasty.


Assuntos
Placas Ósseas , Vértebras Cervicais/cirurgia , Discotomia , Laminoplastia , Estenose Espinal/cirurgia , Adulto , Idoso , Discotomia/efeitos adversos , Discotomia/métodos , Discotomia/estatística & dados numéricos , Feminino , Humanos , Laminoplastia/efeitos adversos , Laminoplastia/métodos , Laminoplastia/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
7.
Med Sci Monit ; 22: 1022-7, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-27021044

RESUMO

BACKGROUND: The purpose of this biomechanical in vitro study was to compare the kinematics and intradiscal pressure achieved with 2 methods: L4-L5 pedicle screw-rod fixation (PSRF) with an upper L3-L4 Coflex device and L4-L5 PSRF alone. The results were used to characterize the biomechanics of the topping-off operation with a Coflex device for the lumbar motion segment adjacent to single-level rigid fixation. MATERIAL/METHODS: Six human cadaveric spine specimens were biomechanically tested in vitro (6 males, 0 females). The 3-dimensional specimen motion in response to applied loads during flexibility tests was determined. Loads were applied along anatomic axes to induce flexion-extension, lateral bending, and axial rotation. All specimens were first studied with intact lumbar motion segments, then with L4-L5 PSRF alone, and finally with L4-L5 PSRF with an upper L3-L4 Coflex device. A non-paired comparison of the 3 configurations under 3 different conditions was made. RESULTS: PSRF, with or without a Coflex device, significantly increased the range of motion (ROM) in the upper adjacent motion segments in all directions of loading. The intradiscal pressure (IDP) changed slightly. A correlation analysis showed that the ROM and IDP are significantly positively correlated. The application of the upper motion segment of the Coflex device provided greater stability in all directions of motion than did PSRF alone, particularly for extension (p<0.05), while use of a Coflex device did not significantly decrease the IDP compared with PSRF alone (p>0.05). CONCLUSIONS: These results suggest that L4-L5 PSRF with an L3-L4 Coflex device is more stable than L4-L5 PSRF alone. PSRF with an upper Coflex device is a promising alternative to PSRF alone. Based on these biomechanical tests, it might be considered a protective method to prevent adjacent segment degeneration (ASD), although some limitations with this in vitro study must be addressed in the future.


Assuntos
Vértebras Lombares/fisiologia , Dispositivos de Fixação Ortopédica , Adulto , Fenômenos Biomecânicos , Feminino , Humanos , Disco Intervertebral/fisiologia , Vértebras Lombares/diagnóstico por imagem , Masculino , Amplitude de Movimento Articular , Torque
8.
Eur Spine J ; 24 Suppl 4: S514-21, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25337858

RESUMO

PURPOSE: Adamantinoma is a low-grade primary malignant bone tumour with slow growth and local recurrence. Its occurrence in the spine is extremely rare, particularly with multilevel involvement. This paper wants to present the first case involving a patient with recurrent thoracolumbar spinal adamantinoma, who underwent a successful three-level spondylectomy for en bloc resection. METHODS: A 24-year-old man with osteolytic masses of T11 and T12 vertebral bodies was performed curettage by a posterior approach in 2008. The pathology report showed the excised neoplasm was a rare adamantinoma. This patient underwent a tumorectomy again because of its local recurrence nearly 3 years later. In 2012, it was unfortunately revealed that the excised tumour had relapsed and had spread to the L1 vertebral body. Due to its repeated recurrence and aggressive lesion, total en bloc spondylectomy (TES) for this malignant tumour was thought to be the best option for preventing repeated recurrence and possible cure. TES for T11-L1 thoracolumbar spine was performed and spinal reconstruction was completed with instrumentation and a titanium mesh cage through a one-stage single posterior approach. RESULTS: After three-level TES, neurological deficits of the patient demonstrated good recovery and no evidence of adamantinoma recurrence or deformity was found at 2-year follow-up. CONCLUSIONS: This is the first case involving multilevel thoracolumbar spinal adamantinoma with repeated recurrence to be successfully treated by three-level TES by a single posterior approach.


Assuntos
Adamantinoma/cirurgia , Vértebras Lombares/cirurgia , Recidiva Local de Neoplasia/cirurgia , Procedimentos Ortopédicos/métodos , Procedimentos de Cirurgia Plástica/métodos , Neoplasias da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Humanos , Masculino , Procedimentos Ortopédicos/instrumentação , Próteses e Implantes , Procedimentos de Cirurgia Plástica/instrumentação , Adulto Jovem
9.
J Spinal Disord Tech ; 27(8): E309-14, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25093646

RESUMO

STUDY DESIGN: This was a prospective study on the clinical outcomes of single-stage surgery for thoracic and lumbar spine tuberculosis patients with bilateral paraspinal or bilateral psoas abscesses. OBJECTIVE: The aim of this study was to investigate the feasibility of, indications for, and clinical effects of single-stage posterior surgery for the treatment of thoracic and lumbar spinal tuberculosis with bilateral paraspinal or bilateral psoas abscesses. SUMMARY OF BACKGROUND DATA: An increasing number of articles have been published on the use of single-stage surgery for spinal tuberculosis; however, none of these articles have discussed the use of such surgery in patients with bilateral abscesses. METHODS: Between January 2003 and January 2011, 41 patients with thoracic and lumbar spinal tuberculosis and bilateral paraspinal or bilateral psoas abscesses were treated with single-stage posterior surgery. All of the patients were treated preoperatively with 1-2 weeks of antituberculosis drugs. All patients were managed postoperatively with standard courses of chemotherapy with triple or quadruple antituberculosis drugs. The clinical symptoms, complications, and laboratory and image indicators were recorded. RESULTS: There were no local recurrences except in one L3-L4 tuberculosis patient. Two patients presented with extraspinal tuberculosis in the third year. There were no incision complications. Bone fusion was observed 6 months after the operation. The erythrocyte sedimentation rate was normal at 3 weeks-3 months postoperatively. There were no internal fixation failures. The internal fixations in 6 young patients were removed after the spinal tuberculosis was cured. CONCLUSIONS: Single-stage posterior surgery with instrumentation results in less operative trauma and can be a suitable alternative for treating thoracic and lumbar tuberculosis with bilateral paraspinal or bilateral psoas abscesses.


Assuntos
Abscesso/cirurgia , Abscesso do Psoas/cirurgia , Tuberculose da Coluna Vertebral/cirurgia , Abscesso/etiologia , Adulto , Antituberculosos/uso terapêutico , Transplante Ósseo , Desbridamento , Feminino , Humanos , Ílio/cirurgia , Fixadores Internos , Vértebras Lombares/cirurgia , Região Lombossacral , Masculino , Pessoa de Meia-Idade , Cuidados Pós-Operatórios , Estudos Prospectivos , Abscesso do Psoas/etiologia , Recidiva , Vértebras Torácicas/cirurgia , Resultado do Tratamento , Tuberculose da Coluna Vertebral/complicações , Tuberculose da Coluna Vertebral/tratamento farmacológico , Adulto Jovem
10.
Int J Mol Sci ; 15(12): 22365-73, 2014 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-25479080

RESUMO

Extracellular acidification occurs under physiologic and pathologic conditions, such as exercise, ischemia, and inflammation. It has been shown that acidosis has various adverse effects on bone. In recent years there has been increasing evidence which indicates that ovarian cancer G protein-coupled receptor 1 (OGR1) is a pH-sensing receptor and mediates a variety of extracellular acidification-induced actions on bone cells and other cell types. Recent studies have shown that OGR1 is involved in the regulation of osteoclast differentiation, survival, and function, as well as osteoblast differentiation and bone formation. Moreover, OGR1 also regulates acid-induced apoptosis of endplate chondrocytes in intervertebral discs. These observations demonstrate the importance of OGR1 in skeletal development and metabolism. Here, we provide an overview of OGR1 regulation ofosteoclasts, osteoblasts, and chondrocytes, and the molecular actions of OGR1 induced by extracellular acidification in the maintenance of bone health.


Assuntos
Ácidos/metabolismo , Osso e Ossos/metabolismo , Espaço Extracelular/metabolismo , Neoplasias Ovarianas/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Animais , Feminino , Humanos , Prótons
11.
Diagn Microbiol Infect Dis ; 109(3): 116278, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38723451

RESUMO

The aim of this study was to evaluate the influence factors of metagenomic next-generation sequencing (mNGS) negative results in the diagnosed patients with spinal infection. mNGS test was applied in a cohort of 114 patients with suspected spinal infection, among which 56 patients had a final diagnosis of spinal infection. mNGS achieved a sensitivity of 75.0% (95% CI, 61.6% to 85.6%) and a specificity of 84.5% (95% CI, 72.6% to 92.7%), using histopathology and culture results as reference. Diagnosed patients with a negative culture result had lower white blood cell account, percentage of neutrophilic granulocyte, C-reactive protein (all P<0.05) and relatively higher rate of prior antimicrobial treatment history (P=0.059). However, diagnosed patients with a negative mNGS result did not have such difference with mNGS-positive patients, suggesting that mNGS was not strictly limited by the above indicators, which presented the advantages of this technique from another point of view.


Assuntos
Sequenciamento de Nucleotídeos em Larga Escala , Metagenômica , Sensibilidade e Especificidade , Humanos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Masculino , Feminino , Metagenômica/métodos , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Adulto Jovem , Doenças da Coluna Vertebral/microbiologia , Doenças da Coluna Vertebral/diagnóstico
12.
J Spinal Disord Tech ; 26(7): E286-92, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23381180

RESUMO

STUDY DESIGN: Retrospectively study. OBJECTIVES: To evaluate clinical and radiologic outcomes of skip-level anterior cervical discectomy and fusion (ACDF) with self-locking stand-alone polyetheretherketone (PEEK) cages for the treatment of 2 noncontiguous levels of cervical disk degenerative disease (CDDD). SUMMARY OF BACKGROUND DATA: The use of stand-alone PEEK cages in ACDF has been proved to be safe and effective to treat CDDD. For 2 noncontiguous levels of CDDD, skip-level ACDF with self-locking stand-alone PEEK cages, which fuses only the involved levels without anterior plates, may be the optimal treatment choice. METHODS: Sixteen consecutive patients with 2 noncontiguous levels of CDDD underwent skip-level ACDF with self-locking stand-alone PEEK cages. Clinical outcomes were evaluated using Japanese Orthopaedic Association scores and Odom criteria. Fusion rate and time, cages subsidence, spinal curvature, intervertebral height at the operated level, and adjacent disk degeneration were assessed. RESULTS: Patients were followed up for average 43.6 months (range, 24-78 mo). The mean operative time was 113 minutes (range, 98-134 min) with an average blood loss of 62 mL (range, 47-76 mL). The Japanese Orthopaedic Association score, degree of spinal curvature, and intervertebral height were significantly increased at the final follow-up examination compared with preoperatively (P<0.05). Fifteen patients (93.8%) achieved solid fusion in an average time of 5.1 months. Three cages (9.38%) in 2 patients subsided. Radiologic evidence of adjacent segment degeneration was observed in 3 segments (6.25%; 2 infra-adjacent segments and 1 intermediate segment). No case had neurological deterioration postoperatively. No implant failure or migration was observed during follow-up. CONCLUSIONS: Treatment of 2 noncontiguous levels of CDDD with skip-level ACDF with self-locking stand-alone cages achieved good clinical and radiologic outcomes including a high fusion rate, low complication rate, and excellent maintenance of spinal curvature and intervertebral height.


Assuntos
Vértebras Cervicais/cirurgia , Discotomia/métodos , Cetonas/farmacologia , Polietilenoglicóis/farmacologia , Fusão Vertebral/métodos , Espondilose/cirurgia , Adulto , Idoso , Benzofenonas , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/efeitos dos fármacos , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Polímeros , Radiografia , Estudos Retrospectivos , Espondilose/diagnóstico por imagem , Resultado do Tratamento
13.
J Orthop Res ; 41(7): 1555-1564, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36448180

RESUMO

Oxidative stress can lead to nucleus pulposus cell (NPC) apoptosis, which is considered to be one of the main contributors to intervertebral disc degeneration (IVDD). Procyanidin B2 is a natural antioxidant that protects against oxidative stress. However, whether procyanidin B2 protects NPCs from oxidative stress remains unknown. In this study, we demonstrated that procyanidin B2 could reduce tert-butyl hydroperoxide-induced reactive oxygen species in rat NPCs and attenuate rat NPC apoptosis. Further experiments revealed that procyanidin B2 upregulated the expression of both nuclear factor erythroid 2-related factor 2 (Nrf2) and phosphorylation of protein kinase B (Akt). We then used silencing of Nrf2 and LY294002 to silence Nrf2 expression and block the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, respectively, and found that the protective roles of procyanidin B2 in NPCs were inhibited. Therefore, we demonstrated that procyanidin B2 alleviated rat NPC apoptosis induced by oxidative stress by upregulating Nrf2 via activation of the PI3K/Akt signaling pathway. This study provides a potential therapeutic approach for procyanidin B2 in IVDD, which might help in the development of new drugs for IVDD treatment.


Assuntos
Degeneração do Disco Intervertebral , Núcleo Pulposo , Ratos , Animais , Proteínas Proto-Oncogênicas c-akt/fisiologia , Fosfatidilinositol 3-Quinase/metabolismo , Fosfatidilinositol 3-Quinase/uso terapêutico , Fosfatidilinositol 3-Quinases , Núcleo Pulposo/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Fator 2 Relacionado a NF-E2/uso terapêutico , Estresse Oxidativo , Degeneração do Disco Intervertebral/tratamento farmacológico , Degeneração do Disco Intervertebral/metabolismo , Apoptose
14.
J Clin Neurosci ; 114: 32-37, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37290140

RESUMO

Spine surgeons should weigh the risks of anticoagulants against their benefits in preventing deep venous thrombosis (DVT), as they may increase the risk of bleeding. Spinal metastasis patients undergoing decompression with fixation are at a high risk for DVT, which may occur preoperatively. Therefore, anticoagulants should be administered preoperatively. This study aimed to evaluate the safety of the administration of anticoagulants in treating spinal metastasis patients with preoperative DVT. Therefore, we prospectively investigated the prevalence of DVT in these patients. Patients who were diagnosed with preoperative DVT were included in an anticoagulant group. Subcutaneous low-molecular-weight heparin (LMWH) was administered. Patients without DVT were included in a non-anticoagulant group. Data on patient information, clinical parameters, blood test results, and bleeding complications were also collected. Moreover, the safety of anticoagulants was analyzed. The prevalence of preoperative DVT was 8.0%. None of the patients developed pulmonary thromboembolism. Furthermore, no significant differences in blood loss, drainage volume, hemoglobin levels, number of transfusions, or preoperative trans-catheter arterial embolization were observed between the two groups. None of the patients developed major bleeding. However, two patients experienced wound hematoma and one experienced incisional bleeding in the non-anticoagulant group. Therefore, LMWH is safe for spinal metastasis patients. Future randomized controlled trials should be conducted to evaluate the validity of perioperative prophylactic anticoagulation therapy in these patients.


Assuntos
Neoplasias da Coluna Vertebral , Trombose Venosa , Humanos , Heparina de Baixo Peso Molecular/efeitos adversos , Estudos Prospectivos , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/cirurgia , Anticoagulantes/efeitos adversos , Hemorragia/induzido quimicamente , Trombose Venosa/epidemiologia , Trombose Venosa/tratamento farmacológico , Heparina/uso terapêutico
15.
Adv Healthc Mater ; 12(32): e2301724, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37767893

RESUMO

The bone matrix has distinct architecture and biochemistry which present a barrier to synthesizing bone-mimetic regenerative scaffolds. To mimic the natural structures and components of bone, biomimetic structural decellularized extracellular matrix (ECM)/regenerated silk fibroin (RSF) scaffolds incorporated with magnetic nanoparticles (MNP) are prepared using a facile synthetic methodology. The ECM/RSF/MNP scaffold is a hierarchically organized and interconnected porous structure with silk fibroin twined on the collagen nanofibers. The scaffold demonstrates saturation magnetization due to the presence of MNP, along with good cytocompatibility. Moreover, the ß-sheet crystalline domain of RSF and the chelated MNP could mimic the deposition of hydroxyapatite and enhance compressive modulus of the scaffold by ≈20%. The results indicate that an external static magnetic field (SMF) with a magnetic responsive scaffold effectively promotes cell migration, osteogenic differentiation, neogenesis of endotheliocytes in vitro, and new bone formation in a critical-size femur defect rat model. RNA sequencing reveals that the molecular mechanisms underlying this osteogenic effect involve calsequestrin-2-mediated Ca2+ release from the endoplasmic reticulum to activate Ca2+ /calmodulin/calmodulin-dependent kinase II signaling axis. Collectively, bionic magnetic scaffolds with SMF stimulation provide a potent strategy for bone regeneration through internal structural cues, biochemical composition, and external physical stimulation on intracellular Ca2+ homeostasis.


Assuntos
Fibroínas , Alicerces Teciduais , Ratos , Animais , Alicerces Teciduais/química , Fibroínas/química , Osteogênese , Cálcio , Biomimética , Calmodulina , Regeneração Óssea/fisiologia , Fenômenos Magnéticos , Engenharia Tecidual/métodos
16.
Inflamm Res ; 61(3): 207-15, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22159524

RESUMO

OBJECTIVE: To investigate nano-hydroxyapatite (nHA) pellets as carriers for vancomycin in the treatment of chronic osteomyelitis and bone defects due to methicillin-resistant Staphylococcus aureus (MRSA) strains. METHODS: Chronic osteomyelitis was induced in 45 New Zealand white rabbits. After 3 weeks (chronic infection), all animals were treated with debridement. The rabbits were divided into an experimental group (the bone was filled with vancomycin-loaded nHA pellets), a control group (the bone was filled with nHA pellets alone), and a blank group. The drug release profiles were determined in vitro and in vivo. X-rays, bone specimens, and microorganism cultures were used to evaluate the efficacy of the treatments. RESULTS: Following a rapid initial release into the circulation, the drug concentration remained effective in the osseous and soft tissues for 12 weeks after debridement. Within 3 months, all rabbits in the experimental group recovered from osteomyelitis without a recurrence of the infection and the bone defects were partially repaired, whereas the infection and bone defects persisted in the control and blank groups. CONCLUSIONS: The results demonstrate that vancomycin-loaded nHA pellets successfully repair bone defects and control infection in MRSA-induced chronic osteomyelitis. In addition, nHA is an effective and safe controlled-release vancomycin carrier for chronic osteomyelitis with bone defects that is induced by MRSA.


Assuntos
Antibacterianos/uso terapêutico , Portadores de Fármacos/uso terapêutico , Staphylococcus aureus Resistente à Meticilina , Osteomielite/tratamento farmacológico , Infecções Estafilocócicas/tratamento farmacológico , Vancomicina/uso terapêutico , Animais , Antibacterianos/sangue , Antibacterianos/farmacocinética , Carga Bacteriana , Modelos Animais de Doenças , Implantes de Medicamento/uso terapêutico , Durapatita/uso terapêutico , Nanoestruturas/uso terapêutico , Osteomielite/diagnóstico por imagem , Osteomielite/microbiologia , Osteomielite/patologia , Coelhos , Radiografia , Infecções Estafilocócicas/diagnóstico por imagem , Infecções Estafilocócicas/microbiologia , Infecções Estafilocócicas/patologia , Tíbia/metabolismo , Vancomicina/sangue , Vancomicina/farmacocinética
17.
Acta Neurochir (Wien) ; 154(4): 731-8, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22297398

RESUMO

BACKGROUND: Zoledronic acid (ZOL) has been shown to significantly increase bone mineral density and to decrease the incidence of osteoporotic fractures. However, its safety when used after lumbar interbody fusion surgery remains unclear. We sought to determine whether ZOL infusion 3 days after transforaminal lumbar interbody fusion (TLIF) affects the risk of nonunion. METHODS: This was a randomized, double-blind, placebo-controlled trial involving subjects who underwent TLIF surgery. Eighty-two subjects (≥50 years of age) were randomly assigned to receive either 5 mg intravenous ZOL (N=41) or placebo (N=41) 3 days after surgery. Each patient received a lumbar computed tomography scan 6 months and 12 months postoperatively. We evaluated interbody fusion using the multiplanar reconstruction technique. Clinical outcome was evaluated with the Oswestry Disability Index. Bone turnover markers (amino terminal propeptides of type I collagen and C-telopeptide of type I collagen) were measured to investigate the biological effects of ZOL on spinal fusion. RESULTS: In the ZOL group, 7 levels (11.5%) exhibited non-union; in the placebo group, 9 levels (14.5%) exhibited nonunion at 12 months postoperatively. This difference was not statistically significant (P=0.82). The difference in ODI scores between two groups was not statistically significant at any of the follow-up times. However, ZOL decreased bone turnover markers significantly. CONCLUSIONS: There was no association between ZOL treatment and nonunion of the lumbar spinal bone. Thus, undergoing lumbar interbody fusion surgery is not a valid reason to suspend or avoid treatment with ZOL.


Assuntos
Conservadores da Densidade Óssea/administração & dosagem , Difosfonatos/administração & dosagem , Imidazóis/administração & dosagem , Vértebras Lombares/efeitos dos fármacos , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Idoso , Densidade Óssea/efeitos dos fármacos , Densidade Óssea/fisiologia , Terapia Combinada/métodos , Feminino , Humanos , Infusões Intravenosas/métodos , Degeneração do Disco Intervertebral/cirurgia , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Radiografia , Ácido Zoledrônico
18.
Zhonghua Yi Xue Za Zhi ; 92(13): 904-8, 2012 Apr 03.
Artigo em Zh | MEDLINE | ID: mdl-22781532

RESUMO

OBJECTIVE: To compare the safety and efficacies of traditional open versus percutaneous monosegmental pedicle screw fixation in the treatment of incomplete thoracolumbar spinal fracture. METHODS: A retrospective analysis was conducted for 44 inpatients with a diagnosis of incomplete thoracolumbar spinal fracture (AO classification: A3.1 and A3.2) undergoing monosegmental pedicle instrumentation (MSPI) from September 2008 to January 2011. There were 24 cases in percutaneous group and 20 cases in traditional open group. The mean operative duration, blood loss, blood drainage, visual analogue scale/score (VAS) and vertebral kyphotic angle at pre- and post-operation were evaluated. RESULTS: No significant differences existed in operative durations between two groups (P > 0.05). Significant differences between two groups were observed in terms of intra-operative blood loss and VAS scores at Week 1 postoperation (P < 0.05). There were no significant differences in VAS score preoperation, 1 year postoperation or pre-and post-operative vertebral kyphotic angle (P > 0.05). No complications of iatrogenic neurological injury or hardware failure occurred. CONCLUSION: The application of percutaneous monosegment pedicle instrumentation in the treatment of thoracolumbar fractures in type of A 3.1 and A 3.2 is both feasible and safe. Its postoperative therapeutic effect is comparable to that of traditional open monosegmental fixation.


Assuntos
Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Fraturas da Coluna Vertebral/cirurgia , Adulto , Parafusos Ósseos , Feminino , Humanos , Vértebras Lombares/lesões , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Vértebras Torácicas/lesões , Resultado do Tratamento
19.
Yi Chuan ; 34(11): 1456-64, 2012 Nov.
Artigo em Zh | MEDLINE | ID: mdl-23208143

RESUMO

Based on the cDNA sequence of GPX in Hyriopsis cumingii, the complete genomic DNA of GPX gene and it's 5'-flanking region were identified from H. cumingii using PCR and genome walking technique. The length of the complete genomic sequence was 6 708 bp including the 5'-flanking region, two exons, and one intron. Sequence analysis of the 992 bp 5'-flanking region revealed that it contained a core promoter element (TATA-box) and other transcription regulation elements such as AP1, C/EBP, and CdxA. The sequence lengths of the two exons were 273 bp and 991 bp, respectively, and the intron was 4 491 bp in length. Sixteen single nucleotide polymorphisms (SNPs) were detected in the GPX gene from resistant stock (RS) and susceptible stock (SS) of H. cumingii. These polymorphisms were analyzed with regard to resistance to Aeromonas hydrophila. Among them, three SNPs including A-99G, A-86C, and A-49C in GPX promoter and five SNPs including A2841T, C2847T, G3146C, A3150G, and G4645T in GPX introns were associated with resistance/susceptibility of H. cumingii to A. hydrophila, both in genotype and allele frequency. Linkage disequilibrium analysis revealed that A-86C, A-49C, C2847T, A3150G, G4645T, A2841T, and G3146C were in high linkage disequilibrium, and haplotype analysis revealed that the frequency of two major predominant haplotypes (ACTGT and TG) in the resistant group was significantly higher than that in the susceptible group. The results suggest that the polymorphic loci in the GPX gene could be potential genetic markers for future molecular selection of strains resistant to diseases.


Assuntos
Genoma , Glutationa Peroxidase/genética , Polimorfismo de Nucleotídeo Único , Unionidae/genética , Região 5'-Flanqueadora , Animais , Sequência de Bases , Estruturas Genéticas , Haplótipos , Desequilíbrio de Ligação , Dados de Sequência Molecular
20.
Clin Neurol Neurosurg ; 214: 107154, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35151059

RESUMO

OBJECTIVE: re is paucity in the literature on the epidemiological evidence of pulmonary thromboembolism (PE) and deep venous thrombosis (DVT) in spinal metastatic tumor patients. The aim of our study was to identify the incidence and risk factors for VTE in spinal metastasis patients treated with decompression with internal instruments. METHODS: We prospectively investigated the occurrence of VTE after decompression with internal fixations in 80 spinal metastasis patients. DVT was diagnosed by using a duplex ultrasonographical. PE was diagnosed by multidetector computed tomographic (CT) pulmonary angiography. Patient information and clinical parameters were collected. Risk factors were analyzed by comparing the difference between VTE and non-VTE cases. RESULTS: The incidence of developing a DVT was 6.3% (5/80). No patient suffered PE. In univariate analysis, the mean length of hospital stay after surgery until discharge for VTE group was longer than non-VTE group, ODI scores and AIS in VTE group were significantly worse than non-VTE group, D-dimer one-day postoperatively for VTE group was significantly higher than non-VTE group. In logistic regression, D-dimer at one-day postoperatively was the only risk factor. The areas under the ROC curves for the D-dimer (post) to distinguish between non-VTE and VTE was 0.971(P value=0.000). By means of the ROC analysis, the optimum thresholds of D-dimer(post) were determined to be 9.51 mg/L. The sensitivity and specificity for the optimum threshold were 100.0% and 92.0%. CONCLUSION: The prospective study of 80 patients with spinal metastasis who underwent decompression with internal fixation revealed an incidence of DVT of 6.3%, patients with increasingly D-dimer level at one-day postoperatively had a higher risk of DVT, and the optimum thresholds of D-dimer(post) were determined to be 9.51 mg/L.


Assuntos
Embolia Pulmonar , Neoplasias da Coluna Vertebral , Tromboembolia Venosa , Descompressão/efeitos adversos , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Humanos , Incidência , Prevalência , Estudos Prospectivos , Embolia Pulmonar/epidemiologia , Fatores de Risco , Neoplasias da Coluna Vertebral/complicações , Tromboembolia Venosa/diagnóstico , Tromboembolia Venosa/epidemiologia , Tromboembolia Venosa/etiologia
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