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1.
Eur Spine J ; 32(7): 2415-2424, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37156851

RESUMO

PURPOSE: The study aimed to observe cervical intervertebral discs (IVDs) in asymptomatic subjects and to explore the factors associated with cervical intervertebral disc degeneration (IVDD). METHODS: Cervical spine MRI of 5843 subjects was retrospectively analyzed. On the sagittal T2-weighted MR images, the mean signal intensities of the nucleus pulposus were obtained. Standard signal intensity (SSI) of intervertebral discs was defined as the ratio of mean disc signal intensity to mean CSF signal intensity. RESULTS: In subjects under 70 years old, the SSI of IVD was lowest at the C5/6 level. In those over 70, the SSI of IVD was similar among the disc levels from C2/3 to C7/T1. The disc SSI decreased significantly with age in both genders. In subjects under 70 years old, the SSI of the discs at each level was higher in females than in males. In those over 70 years old, no difference was found in disc SSI between two genders at most disc levels. Logistic regression analysis showed that kyphotic and straight cervical spine, obesity and older age were associated with higher risk of having lower disc SSI. CONCLUSION: To our knowledge, this is the largest cross-sectional study using MRI-based quantitative assessment to characterize cervical IVDD in asymptomatic subjects. Cervical IVDD was shown to progress with age and significantly correlated with gender, BMI and cervical alignment. Early intervention of related factors may help delay cervical IVDD and prevent future neck and shoulder pain.


Assuntos
Degeneração do Disco Intervertebral , Disco Intervertebral , Idoso , Feminino , Humanos , Masculino , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/patologia , Estudos Transversais , População do Leste Asiático , Disco Intervertebral/diagnóstico por imagem , Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/epidemiologia , Degeneração do Disco Intervertebral/patologia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos , Doenças Assintomáticas
2.
Rheumatology (Oxford) ; 61(2): 846-855, 2022 02 02.
Artigo em Inglês | MEDLINE | ID: mdl-33982084

RESUMO

OBJECTIVE: To develop and validate a prediction model based on targeted sequencing for glucocorticoid (GC)-associated osteonecrosis of the femoral head (GA-ONFH) in GC-treated adults. METHODS: This two-centre retrospective study was conducted between July 2015 and April 2019 at Zhongshan Hospital (training set) and the Sixth People's Hospital (test set) in Shanghai, China. All patients had a history of GC therapy, with a dose exceeding 2000 mg equivalent prednisone within 6 weeks. Patients were divided into two groups according to whether they were diagnosed with GA-ONFH within 2 years after GC initiation. Blood or saliva samples were collected for targeted sequencing of 358 single nucleotide polymorphisms and genetic risk score (GRS) calculating for developing GA-ONFH prediction model. Receiver operating characteristic (ROC) curve analysis and decision curve analysis (DCA) were performed to evaluate and validate the model. RESULTS: . The training set comprised 117 patients, while the test set comprised 30 patients for external validation. Logistic regression analysis showed that GRS was significantly associated with GA-ONFH (OR 1.87, 95% CI: 1.48, 2.37). The ROC and DCA curves showed that the multivariate model considering GRS, age at GC initial, sex and underlying diseases had a discrimination with area under the ROC curve (AUC) of 0.98 (95% CI: 0.96, 1.00). This model was further externally validated using the test set with an AUC of 0.91 (95% CI: 0.81, 1.00). CONCLUSION: Our prediction model comprising GRS, age, sex and underlying diseases yields valid predictions of GA-ONFH incidence. It may facilitate effective screening and prevention strategies of GA-ONFH.


Assuntos
Necrose da Cabeça do Fêmur/induzido quimicamente , Glucocorticoides/efeitos adversos , Adolescente , Adulto , Fatores Etários , Idoso , Feminino , Necrose da Cabeça do Fêmur/genética , Predisposição Genética para Doença/genética , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Estatísticos , Reprodutibilidade dos Testes , Estudos Retrospectivos , Fatores de Risco , Análise de Sequência de DNA , Fatores Sexuais , Adulto Jovem
3.
Lab Invest ; 101(9): 1238-1253, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34059758

RESUMO

Spinal cord injury (SCI) is one common neurological condition which involves primary injury and secondary injury. Neuron inflammation and apoptosis after SCI is the most important pathological process of this disease. Here, we tried to explore the influence and mechanism of miRNAs on the neuron inflammatory response and apoptosis after SCI. First, by re-analysis of Gene Expression Omnibus dataset (accession GSE19890), miR-182 was selected for further study because of its suppressive effects on the inflammatory response in the various types of injuries. Functional experiments demonstrated that miR-182 overexpression promoted functional recovery, reduced histopathological changes, and alleviated spinal cord edema in mice. It was also observed that miR-182 overexpression reduced apoptosis and attenuated the inflammatory response in spinal cord tissue, as evidenced by the reduction of tumor necrosis factor (TNF)-α, interleukin (IL)-6, and IL-1ß, and the induction of IL-10. Using a lipopolysaccharide (LPS)-induced SCI model in BV-2 cells, we found that miR-182 was downregulated in the BV-2 cells following LPS stimulation, and upregulation of miR-182 improved LPS-induced cell damage, as reflected by the inhibition of apoptosis and the inflammatory response. IκB kinase ß (IKKß), an upstream target of the NF-κB pathway, was directly targeted by miR-182 and miR-182 suppressed its translation. Further experiments revealed that overexpression of IKKß reversed the anti-apoptosis and anti-inflammatory effects of miR-182 in LPS stimulated BV-2 cells. Finally, we found that miR-182 overexpression blocked the activation of the NF-κB signaling pathway in vitro and in vivo, as demonstrated by the downregulation of phosphorylated (p­) IκB-α and nuclear p-p65. Taken together, these data indicate that miR-182 improved SCI-induced secondary injury through inhibiting apoptosis and the inflammatory response by blocking the IKKß/NF-κB pathway. Our findings suggest that upregulation of miR-182 may be a novel therapeutic target for SCI.


Assuntos
Apoptose/efeitos dos fármacos , Inflamação/metabolismo , MicroRNAs/farmacologia , Traumatismos da Medula Espinal/metabolismo , Animais , Modelos Animais de Doenças , Feminino , Quinase I-kappa B/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Transdução de Sinais/efeitos dos fármacos
4.
Med Sci Monit ; 26: e927107, 2020 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-33149108

RESUMO

BACKGROUND Spinal cord injury (SCI) is a serious nervous system condition that can cause lifelong disability. The aim of this study was to identify potential molecular mechanisms and therapeutic targets for SCI. MATERIAL AND METHODS We constructed a weighted gene coexpression network and predicted which hub genes are involved in SCI. A compression model of SCI was established in 45 Sprague-Dawley rats, which were divided into 5 groups (n=9 per group): a sham operation group, and 1, 3, 5, and 7 days post-SCI groups. The spinal cord tissue on the injured site was harvested on 1, 3, 5, and 7 days after SCI and 3 days after surgery in the sham operation group. High-throughput sequencing was applied to investigate the expression profile of the mRNA in all samples. Differentially expressed genes were screened and included in weighted gene coexpression network analysis (WGCNA). Co-expressed modules and hub genes were identified by WGCNA. The biological functions of each module were investigated using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. RESULTS According to the RNA-seq data, a total of 1965 differentially expressed genes were screened, and WGCNA identified 10 coexpression modules and 5 hub genes. Module function analysis revealed that SCI was associated with immune response, cell division, neuron projection development, and collagen fibril organization. CONCLUSIONS Our study revealed dynamic changes in a variety of biological processes following SCI and identified 5 hub genes via WGCNA. These results provide insights into the molecular mechanisms and therapeutic targets of SCI.


Assuntos
Biologia Computacional , Redes Reguladoras de Genes , Transdução de Sinais/genética , Compressão da Medula Espinal/complicações , Compressão da Medula Espinal/genética , Traumatismos da Medula Espinal/complicações , Traumatismos da Medula Espinal/genética , Animais , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Ontologia Genética , Masculino , Ratos Sprague-Dawley , Compressão da Medula Espinal/patologia , Traumatismos da Medula Espinal/patologia
5.
Chin Med Sci J ; 31(3): 185-191, 2016 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-27733227

RESUMO

Degenerative disc disease is a multifaceted progressive irreversible condition and an inevitable part of aging, which has been found to be a contributing factor for low back pain and might cause radiculopathy, myelopathy, spinal stenosis, degenerative spondylolisthesis, and herniations. Its etiology is complex and multifactorial. Although genetics influence more dominant, the occupational and mechanical influences still persist as a major risk factor. This review emphasizes up-to-date knowledge regarding etiology of disc degeneration with special consideration on occupational, lifestyle factors, and genetic polymorphisms.


Assuntos
Degeneração do Disco Intervertebral/etiologia , Humanos , Degeneração do Disco Intervertebral/genética , Estilo de Vida , Doenças Profissionais/etiologia
6.
Eur Spine J ; 24(11): 2607-13, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-26174232

RESUMO

PURPOSE: This paper is to evaluate the efficacy and safety of transforaminal lumbar interbody fusion (TLIF) using unilateral pedicle screws along with contralateral translaminar facet joint screw (UPS+TFS) fixation in comparison with the method using bilateral pedicle screws fixation (BPS) in degenerative lumbar diseases. METHODS: Forty patients with single-level lumbar diseases were divided into two groups randomly. One group was treated by TLIF with BPS fixation while the other group was treated by the new technique with UPS+TFS fixation. The preoperative and postoperative ODI, JOA, VAPS scores, mean operation time, mean operation blood loss, fusion rate and complications were collected for comparison under two surgical methods. In terms of complications, only two cases of superficial infection in the BPS group and one case of urinary tract infection in the other group was found. RESULTS: The mean operation time and blood loss was significantly less in UPS+TFS group than in BPS group. The preoperation and postoperative ODI, JOA and VAPS at the intervals of 6 weeks, 3, 6 months and 1 year between the BPS and UPS+TFS group showed no significant disparities. Only one patient in UPS+TFS group was not fused with pseudoarthrosis formation. CONCLUSIONS: The clinical efficacy and safety of TLIF with UPS+TFS fixation were comparable to BPS fixation; however, the soft tissue injury and the corresponding operation cost were reduced with unilateral pedicle screw plus translaminar facet screw fixation.


Assuntos
Vértebras Lombares/cirurgia , Parafusos Pediculares , Fusão Vertebral/métodos , Articulação Zigapofisária/cirurgia , Parafusos Ósseos , Custos e Análise de Custo , Humanos , Imageamento Tridimensional , Vértebras Lombares/diagnóstico por imagem , Duração da Cirurgia , Período Pós-Operatório , Lesões dos Tecidos Moles/etiologia , Fusão Vertebral/efeitos adversos , Fusão Vertebral/economia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Articulação Zigapofisária/diagnóstico por imagem
7.
Eur Spine J ; 23 Suppl 2: 228-35, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24232695

RESUMO

INTRODUCTION: Synovial sarcomas of the spine are very rare, most rare of which was occurring in the thoracic vertebral body. The diagnosis of synovial sarcomas was very difficult. It depends on the radiological examination, immunohistochemical examination and gene examination. The best treatment to them was completely surgical resection with negative margins. Other treatments such as radiation therapy and chemotherapy were just adjuvant. The prognosis of synovial sarcomas was disappointing. CASE PRESENTATION: A 26-year-old male patient had low back pain. The radiological examination showed bony erosion of the T7 vertebral body and no soft tissue mass around the spine. He underwent T7 resection en bloc and internal fixation with two levels above T7 and two levels below T7. Then histopathological and gene examination revealed high malignant synovial sarcoma. So he was treated by chemotherapy and external beam radiation therapy after surgery. CONCLUSION: Primary vertebral body synovial sarcoma is very rare and difficult to diagnose and treat.


Assuntos
Doenças Raras/patologia , Sarcoma Sinovial/patologia , Neoplasias da Coluna Vertebral/patologia , Vértebras Torácicas/patologia , Adulto , Quimioterapia Adjuvante , Humanos , Ílio/transplante , Dor Lombar/etiologia , Masculino , Parestesia/etiologia , Radioterapia Adjuvante , Doenças Raras/terapia , Sarcoma Sinovial/terapia , Neoplasias da Coluna Vertebral/terapia
8.
Artigo em Inglês | MEDLINE | ID: mdl-38805325

RESUMO

The process of labeling medical text plays a crucial role in medical research. Nonetheless, creating accurately labeled medical texts of high quality is often a time-consuming task that requires specialized domain knowledge. Traditional methods for generating labeled data typically rely on rigid rule-based approaches, which may not adapt well to new tasks. While recent machine learning (ML) methodologies have mitigated the manual labeling efforts, configuring models to align with specific research requirements can be challenging for labelers without technical expertise. Moreover, automated labeling techniques, such as transfer learning, face difficulties in in directly incorporating expert input, whereas semi-automated methods, like data programming, allow knowledge integration through rules or knowledge bases but may lack continuous result refinement throughout the entire labeling process. In this study, we present a collaborative human-ML teaming workflow that seamlessly integrates visual cluster analysis and active learning to assist domain experts in labeling medical text with high efficiency. Additionally, we introduce an innovative neural network model called the embedding network, which incorporates expert insights to generate task-specific embeddings for medical texts. We integrate the workflow and embedding network into a visual analytics tool named KMTLabeler, equipped with coordinated multi-level views and interactions. Two illustrative case studies, along with a controlled user study, provide substantial evidence of the effectiveness of KMTLabeler in creating an efficient labeling environment for medical text classification.

9.
IEEE Trans Vis Comput Graph ; 30(1): 1238-1248, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37874707

RESUMO

Simulation-based Medical Education (SBME) has been developed as a cost-effective means of enhancing the diagnostic skills of novice physicians and interns, thereby mitigating the need for resource-intensive mentor-apprentice training. However, feedback provided in most SBME is often directed towards improving the operational proficiency of learners, rather than providing summative medical diagnoses that result from experience and time. Additionally, the multimodal nature of medical data during diagnosis poses significant challenges for interns and novice physicians, including the tendency to overlook or over-rely on data from certain modalities, and difficulties in comprehending potential associations between modalities. To address these challenges, we present DiagnosisAssistant, a visual analytics system that leverages historical medical records as a proxy for multimodal modeling and visualization to enhance the learning experience of interns and novice physicians. The system employs elaborately designed visualizations to explore different modality data, offer diagnostic interpretive hints based on the constructed model, and enable comparative analyses of specific patients. Our approach is validated through two case studies and expert interviews, demonstrating its effectiveness in enhancing medical training.


Assuntos
Gráficos por Computador , Educação Médica , Humanos , Aprendizagem , Retroalimentação , Prontuários Médicos
10.
Neural Regen Res ; 19(5): 1142-1149, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-37862220

RESUMO

Recent studies have revealed that lipid droplets accumulate in neurons after brain injury and evoke lipotoxicity, damaging the neurons. However, how lipids are metabolized by spinal cord neurons after spinal cord injury remains unclear. Herein, we investigated lipid metabolism by spinal cord neurons after spinal cord injury and identified lipid-lowering compounds to treat spinal cord injury. We found that lipid droplets accumulated in perilesional spinal cord neurons after spinal cord injury in mice. Lipid droplet accumulation could be induced by myelin debris in HT22 cells. Myelin debris degradation by phospholipase led to massive free fatty acid production, which increased lipid droplet synthesis, ß-oxidation, and oxidative phosphorylation. Excessive oxidative phosphorylation increased reactive oxygen species generation, which led to increased lipid peroxidation and HT22 cell apoptosis. Bromocriptine was identified as a lipid-lowering compound that inhibited phosphorylation of cytosolic phospholipase A2 by reducing the phosphorylation of extracellular signal-regulated kinases 1/2 in the mitogen-activated protein kinase pathway, thereby inhibiting myelin debris degradation by cytosolic phospholipase A2 and alleviating lipid droplet accumulation in myelin debris-treated HT22 cells. Motor function, lipid droplet accumulation in spinal cord neurons and neuronal survival were all improved in bromocriptine-treated mice after spinal cord injury. The results suggest that bromocriptine can protect neurons from lipotoxic damage after spinal cord injury via the extracellular signal-regulated kinases 1/2-cytosolic phospholipase A2 pathway.

11.
Mol Biol Rep ; 40(2): 779-85, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23111454

RESUMO

ATP-binding cassette transporter A1 (ABCA1) is a membrane-associated protein which has attracted considerable attention as a candidate gene for Alzheimer's disease (AD) based on its function as a key factor in lipid metabolism by mediating cellular cholesterol efflux, the rate-limiting step in the production of nascent high-density lipoprotein (HDL) particles. The relationship between ABCA1 common variations (R219 K rs2230806, I883 M rs4149313 and R1587 K rs2230808) and AD has been reported in various ethnic groups; however, these studies have yielded contradictory results. To investigate this inconsistency, we performed a meta-analysis of 13 studies involving a total of 12,248 subjects to evaluate the effect of ABCA1 on genetic susceptibility for AD. Overall, the summary OR of AD was 1.01 (95 % CI: 0.93-1.10; P = 0.77), 1.10 (95 % CI: 0.96-1.26; P = 0.16), and 1.08 (95 % CI: 0.96-1.23; P = 0.21) for R219 K, I883 M and R1587 K polymorphism, respectively. No significant results were observed in dominant and recessive when compared with wild genotype for these polymorphisms. In the stratified analyses by ethnicity and sample size, no evidence of any gene-disease association was obtained. In conclusion, the present meta-analysis does not support the notion that common SNPs on ABCA1 is a major genetic risk factor for AD.


Assuntos
Transportadores de Cassetes de Ligação de ATP/genética , Doença de Alzheimer/genética , Polimorfismo de Nucleotídeo Único , Transportador 1 de Cassete de Ligação de ATP , Substituição de Aminoácidos , Estudos de Casos e Controles , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Fatores de Risco
12.
J Orthop Surg Res ; 18(1): 162, 2023 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-36864451

RESUMO

BACKGROUND: Despite extensive research, there is still a need for safe and effective agents to promote spinal fusion. Interleukin (IL)-1ß is an important factor which influences the bone repair and remodelling. The purpose of our study was to determine the effect of IL-1ß on sclerostin in osteocytes and to explore whether inhibiting the secretion of sclerostin from osteocytes can promote spinal fusion at early stages. METHODS: Small-interfering RNA was used to suppress the secretion of sclerostin in Ocy454 cells. MC3T3-E1 cells were cocultured with Ocy454 cells. Osteogenic differentiation and mineralisation of MC3T3-E1 cells were evaluated in vitro. SOST knock-out rat generated using the CRISPR-Cas9 system and rat spinal fusion model was used in vivo. The degree of spinal fusion was assessed by manual palpation, radiographic analysis and histological analysis at 2 and 4 weeks. RESULTS: We found that IL-1ß level had a positive association with sclerostin level in vivo. IL-1ß promoted the expression and secretion of sclerostin in Ocy454 cells in vitro. Inhibition of IL-1ß-induced secretion of sclerostin from Ocy454 cells could promote the osteogenic differentiation and mineralisation of cocultured MC3T3-E1 cells in vitro. The extent of spinal graft fusion was greater in SOST-knockout rats than in wild-type rats at 2 and 4 weeks. CONCLUSIONS: The results demonstrate that IL-1ß contributes to a rise in the level of sclerostin at early stages of bone healing. Suppressing sclerostin may be an important therapeutic target capable of promoting spinal fusion at early stages.


Assuntos
Calcinose , Fusão Vertebral , Animais , Ratos , Calcificação Fisiológica , Diferenciação Celular , Osteócitos , Osteogênese , Interleucina-1beta/farmacologia
13.
Global Spine J ; 13(3): 630-635, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33896208

RESUMO

STUDY DESIGN: Retrospective study. OBJECTIVE: Lumbar magnetic resonance imaging (MRI) findings are believed to be associated with low back pain (LBP). This study sought to develop a new predictive classification system for low back pain. METHOD: Normal subjects with repeated lumbar MRI scans were retrospectively enrolled. A new classification system, based on the radiological features on MRI, was developed using an unsupervised clustering method. RESULTS: One hundred and fifty-nine subjects were included. Three distinguishable clusters were identified with unsupervised clustering that were significantly correlated with LBP (P = .017). The incidence of LBP was highest in cluster 3 (57.14%), nearly twice the incidence in cluster 1 (30.11%). There were obvious differences in the sagittal parameters among the 3 clusters. Cluster 3 had the smallest intervertebral height. Based on follow-up findings, 27% of subjects changed clusters. More subjects changed from cluster 1 to clusters 2 or 3 (14.5%) than changed from cluster 2 or cluster 3 to cluster 1 (5%). Participation in sport was more frequent in subjects who changed from cluster 3 to cluster 1. CONCLUSION: Using an unsupervised clustering method, we developed a new classification system comprising 3 clusters, which were significantly correlated with LBP. The prediction of LBP is independent of age and better than that based on individual sagittal parameters derived from MRI. A change in cluster during follow-up may partially predict lumbar degeneration. This study provides a new system for the prediction of LBP that should be useful for its diagnosis and treatment.

14.
Clin Lab ; 58(9-10): 891-6, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23163103

RESUMO

BACKGROUND: Neuroserpin (NSP) is a neuroprotective factor in the situation of ischemia of a brain, such as stroke. However, it has never been reported in the spinal cord, which is part of the central nervous system (CNS). METHODS: The expression of NSP was detected using Western blotting and neuron apoptosis detected by TUNEL staining following spinal cord ischemia caused by sustained compression in rats. RESULTS: The results showed that NSP was upregulated in the injury area of spinal cord, accompanied with the activation of micorglia and tissue plasminogen activator (tPA), which suggested that NSP also plays a neuroprotective role in spinal cord compression since neuronal apoptosis appears when NSP returns to normal levels or even lower. CONCLUSIONS: NSP upregulates in early periods of sustained spinal cord compression.


Assuntos
Neuropeptídeos/metabolismo , Fármacos Neuroprotetores/metabolismo , Inibidores de Serina Proteinase/metabolismo , Serpinas/metabolismo , Compressão da Medula Espinal/patologia , Regulação para Cima , Animais , Apoptose , Biomarcadores/metabolismo , Proliferação de Células , Modelos Animais de Doenças , Masculino , Microglia/metabolismo , Microglia/patologia , Neurônios Motores/metabolismo , Neurônios Motores/patologia , Ratos , Ratos Sprague-Dawley , Medula Espinal/metabolismo , Medula Espinal/patologia , Compressão da Medula Espinal/metabolismo , Ativador de Plasminogênio Tecidual/metabolismo , Neuroserpina
15.
J Orthop Res ; 40(10): 2350-2361, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35005809

RESUMO

Diabetes mellitus contributes to intervertebral disc degeneration. Nucleus pulposus cell senescence plays an important role in intervertebral disc degeneration. However, the effects of hyperglycemia on human nucleus pulposus cells and the underlying process remains poorly understood. In the current study, we evaluated the effects of high glucose levels on human nucleus pulposus cell senescence in vitro and the effects of hyperglycemia on rat nucleus pulposus aging in vivo. Human nucleus pulposus cells were cultured in high-glucose medium (200 mM glucose) for 48 h. Senescence-associated ß-galactosidase staining, western blot analysis, and enzyme-linked immunosorbent assays were performed to evaluate human nucleus pulposus cell senescence. Flow cytometry and enzyme-linked immunosorbent assays were used to evaluate reactive oxygen species and advanced glycation end-product levels. Transcriptome sequencing followed by bioinformatics analysis was used to understand the abnormal biological processes of nucleus pulposus cells cultured in high-glucose medium. Diabetes mellitus rat models were established and histopathological and immunohistochemical analysis was conducted to examine nucleus pulposus tissue senescence in vivo. Exposure to a high glucose concentration promoted human nucleus pulposus cell senescence and increased the senescence-related secretion phenotype in human nucleus pulposus cells in vitro and in rat nucleus pulposus tissue in vivo. Bioinformatics analysis showed that hub genes were involved in nucleus pulposus cell cycle activities and cell senescence. The results suggest that appropriate blood glucose control may be key to preventing intervertebral disc degeneration in diabetic patients.


Assuntos
Diabetes Mellitus , Hiperglicemia , Degeneração do Disco Intervertebral , Núcleo Pulposo , Animais , Senescência Celular , Diabetes Mellitus/metabolismo , Glucose/metabolismo , Humanos , Hiperglicemia/complicações , Hiperglicemia/metabolismo , Hiperglicemia/patologia , Degeneração do Disco Intervertebral/patologia , Núcleo Pulposo/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo , beta-Galactosidase/metabolismo , beta-Galactosidase/farmacologia
16.
Front Cell Neurosci ; 15: 646788, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34054430

RESUMO

A secondary injury induced by a spinal cord injury (SCI) remains the main cause of devastating neural dysfunction; therefore, it has been the subject of focused research for many years. Long noncoding RNA (lncRNA) has been found to participate in the SCI process, and this finding presents a high potential for diagnosis and treatment; however, the role of lncRNA in a secondary injury induced by SCI remains unclear. The aim of this study was to investigate the regulatory effect of lncRNA growth arrest-specific transcript 5 (GAS5) in secondary injury during SCI. The SCI mice model and hypoxic cellular model were established to research the roles of lncRNA GAS5 during SCI. Reverse transcription quantitative polymerase chain reaction (qRT-PCR) was conducted to determine the expression levels of microR-93 (miR-93) and lncRNA GAS5. Western blot analysis of the apoptosis regulator protein and terminal deoxynucleotidyl transferase dUTP nick end labeling assay was conducted to evaluate neuron cell apoptosis. Basso, Beattie, and Bresnahan (BBB) scores were calculated to assess neurological function. Flow cytometry was used to determine neuron cell apoptosis. The associations among GAS5, miR-93, and the phosphatase and tensin homolog (PTEN) were disclosed using RNA immunoprecipitation (RIP) assay, RNA pulldown assay, and dual-luciferase reporter assay. QRT-PCR demonstrated that GAS5 was significantly upregulated in both the SCI mice and hypoxic cellular models. GAS5 knockdown suppressed neuron cell apoptosis and inflammatory response in the SCI mice model. Further studies have indicated that GAS5 functions as a competing endogenous RNA (ceRNA) by sponging miR-93 in neuronal cells. In addition, PTEN was a target of miR-93, and GAS5 knockdown exhibited its anti-apoptotic and anti-inflammatory effects through the miR-93/PTEN axis. These findings suggest that the GAS5/miR-93/PTEN axis may be a promising therapeutic target for SCI.

17.
Bone ; 145: 115844, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33453444

RESUMO

The adverse effects of glucocorticoids (GCs) on bone marrow stromal stem cells (BMSCs) play an important role in steroid-induced osteonecrosis of the femoral head (ONFH). Our previous miRNA microarray analysis indicated that microRNA-224-5p (miR-224-5p) could be a potential regulator; however, the underlying mechanism remains unclear. In the present study, we demonstrated that miR-224-5p was upregulated in GC-treated BMSCs, and functional experiments revealed that miR-224-5p could suppress osteogenic but promote adipogenic differentiation of BMSCs. Smad4 was identified as a direct target gene of miR-224-5p, and the Smad4-Taz axis was confirmed as the regulatory pathway for adipo-osteogenic differentiation of BMSCs. Our in vivo experiments further confirmed that the miR-224-5p antagomir could alleviate the inhibitory effects of GCs and facilitate bone formation in steroid-induced ONFH models. Therefore, these findings provide insight into the function of miR-224-5p as a reciprocal regulator of the adipo-osteogenic differentiation of BMSCs, and it could serve as a novel therapeutic target for steroid-induced ONFH.


Assuntos
Necrose da Cabeça do Fêmur , MicroRNAs , Adipogenia/genética , Diferenciação Celular , Cabeça do Fêmur , Necrose da Cabeça do Fêmur/induzido quimicamente , Necrose da Cabeça do Fêmur/genética , Humanos , MicroRNAs/genética , Osteogênese/genética , Esteroides/efeitos adversos
18.
J Int Med Res ; 48(2): 300060519867828, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31507223

RESUMO

OBJECTIVE: In this retrospective study, a modified measurement method was used to analyze cage migration during follow-up after unilateral instrumented transforaminal lumbar interbody fusion (TLIF) and identify associated factors. METHODS: We retrospectively evaluated 75 patients who had been treated with unilateral instrumented TLIF. Cage migration was quantitatively defined as anterior-posterior or lateral displacement of the cage. RESULTS: Five patients had significant cage migration (6.7%), but none developed severe neural symptoms during follow-up or underwent reoperation. The cages tended to migrate posteriorly or toward the side of surgery. The initial cage position and patient age were strongly associated with migration. Migration was less frequent when the cages were initially placed closer to the side of surgery. Patients of advanced age were more likely to develop anterior-posterior migration than were young patients. CONCLUSION: Cage migration is related to the initial position of the cage. Particular attention is required when performing unilateral instrumented TLIF in patients of advanced age because they are most likely to develop cage migration. Quantification of cage migration is an effective method of exploring the associated factors.


Assuntos
Vértebras Lombares , Fusão Vertebral , Humanos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Região Lombossacral , Reoperação , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
19.
J Orthop Surg Res ; 15(1): 314, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787876

RESUMO

OBJECTIVE: To compare the spinal stability with different fixation methods after thoracic TES using finite element analysis METHODS: The spinal finite element model was established from a healthy volunteer, and the validity was verified. The models of T8 thoracic total en bloc spondylectomy (TES) with and without artificial vertebral body were established combination with different fixation methods: the first was long segment fixation with fixed segments T5-7, T9-11; the second was short segment fixation with fixed segments T6-7, T9-10; the third was modified short segment with a pair of vertebral body screws on T7 and T9 added on the basis of short segment fixation. The motions of each model in standing state were simulated in software. The range of motion (ROM) and internal fixation stress changes were analyzed. RESULTS: When anterior support was effective, the three fixation methods could effectively maintain the stability of the spine. However, when anterior support failed, the ROM of the long segment fixation group and the short segment fixation group in the flexion-extension directions was significantly higher than that of when the anterior support existed, while the modified short segment fixation group had no significant changes. Meanwhile, the stress of internal fixation in the long segment fixation group and the short segment fixation group were greatly increased. However, there were no significant changes in modified short segment fixation group. CONCLUSION: After TES, the presence of the thoracic cage gives partial anterior stabilization. When the anterior support failed, the modified short segment fixation method can provide better stability.


Assuntos
Fusão Vertebral/métodos , Vértebras Torácicas/cirurgia , Fenômenos Biomecânicos , Análise de Elementos Finitos , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Fusão Vertebral/instrumentação , Neoplasias da Coluna Vertebral/cirurgia
20.
Biomaterials ; 247: 119962, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32251929

RESUMO

Magnesium and Mg-based alloys are promising biomaterials for orthopedic implants because of their degradability, osteogenic effects, and biocompatibility. However, the drawbacks of these materials include high hydrogen gas production, unexpected corrosion resistance, and insufficient mechanical strength duration. Surface modification can protect these biomaterials and induce osteogenesis. In this work, a SrHPO4 coating was developed for our patented biodegradable Mg-Nd-Zn-Zr alloy (abbr. JDBM) through a chemical deposition method. The coating was characterized by in vitro immersion, ion release, and cytotoxicity tests, which showed a slower corrosion behavior and excellent cell viability. RNA sequencing of MC3T3E1 cells treated with SrHPO4-coated JDBM ion release test extract showed increased Tlr4, followed by the activation of the downstream PI3K/Akt signaling pathway, causing proliferation and growth of pre-osteoblasts. An intramedullary nail (IMN) was implanted in a femoral fracture rat model. Mechanical test, radiological and histological analysis suggested that SrHPO4-coated JDBM has superior mechanical properties, induces more bone formation, and decreases the degradation rate compared with uncoated JDBM and the administration of TLR4 inhibitor attenuated the new bone formation for fracture healing. SrHPO4 is a promising coating for JDBM implants, particularly for long-bone fractures.


Assuntos
Fraturas do Fêmur , Osteogênese , Ligas , Animais , Materiais Revestidos Biocompatíveis , Corrosão , Teste de Materiais , Fosfatidilinositol 3-Quinases , Ratos
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