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1.
World Neurosurg ; 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37343670

RESUMO

OBJECTIVE: To identify the risk factors for developing postoperative pulmonary infection in patients with acute cervical spinal cord injury (CSCI), and to develop a nomogram prediction model. METHODS: Patients with CSCI who were admitted to 3 different medical centers between July 2011 and July 2021 were included in this study. All patients underwent cervical spine surgery. Data for patients admitted to the first 2 centers were included in a training set to establish the nomogram prediction model, and data for patients admitted to the third center were included in a validation set to externally verify the efficacy of the prediction model. For the training set, patients were divided into an infected group and a noninfected group (control group). Independent risk factors for postoperative pulmonary infection in patients with CSCI were identified by univariate and multivariate logistic regression analyses. Additionally, a nomogram prediction model was developed and validated based on the risk factors. RESULTS: A total of 689 patients were enrolled, including 574 for the training set and 115 for the validation set. Of the patients included for the training set, 144 developed pulmonary infection, with an incidence of 25.09%; 40 patients included for the validation set developed pulmonary infection (34.78%). Multivariate logistic regression analysis showed that age, American Spinal Injury Association grade, steroid pulse, high-level injury, smoking, multistage surgery, and operation duration were risk factors for the development of postoperative pulmonary infection in patients with CSCI. The area under the curve of the receiver operating characteristic curve of the model built by the training set was 0.905, and that of the receiver operating characteristic curve of the verification set was 0.917. The decision curve indicated that the model was in the range 1%-100%, and the predicted net benefit value of the model was high. CONCLUSIONS: Age, American Spinal Injury Association grade, steroid pulse, CSCI site, smoking history, number of surgical levels, and surgical duration are correlated with the development of postoperative pulmonary infection in patients with CSCI. The risk prediction model of postoperative pulmonary infection has a good prediction efficiency and accuracy.

2.
Eur Spine J ; 32(7): 2448-2458, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37198504

RESUMO

PURPOSE: The purpose of this study was to analyze the clinical and radiological outcomes of two different zero-profile spacers (ROI-C and anchor-C) in contiguous two-level ACDF for CDDD patients. METHODS: We retrospectively analyzed patients who underwent contiguous two-level ACDF due to CDDD between January 2015 and December 2020 in our hospital. Patients who received ROI-C and anchor-C were included as the study groups, and those who underwent plate-cage construct (PCC) were included as the control group. The primary outcome measures were radiographical parameters, and the secondary outcome measures were dysphagia, JOA scores and VAS scores for these patients. RESULTS: A total of 91 patients were enrolled in the study; there were 31, 21 and 39 patients in the ROI-C, anchor-C and PCC groups, respectively. The mean follow-up duration was 24.52 months (range, 18-48 months) in the ROI-C group, 24.38 months (range, 16-52 months) in the anchor-C group and 25.18 months (range, 15-54 months) in the PCC group. The loss of the intervertebral space height and cage subsidence rate in the ROI-C group were significantly higher than those in the anchor-C group and PCC group at the final follow-up (P < 0.05). The ROI-C group showed a lower incidence of adjacent segment degeneration than the anchor-C group and PCC group, but the difference was not significant. The fusion rates were not different among these three groups. The early dysphagia rate was significantly lower in the patients with zero-profile spacers than in the PCC group (P < 0.05), but the difference was not significant at the last follow-up. No relevant differences were found in the JOA scores and VAS scores. CONCLUSIONS: Zero-profile spacers showed promising clinical outcomes in CDDD patients having contiguous two-level ACDF. However, ROI-C resulted in a higher intervertebral space height loss and a higher cage subsidence rate than anchor-C during the follow-up.


Assuntos
Transtornos de Deglutição , Degeneração do Disco Intervertebral , Fusão Vertebral , Humanos , Seguimentos , Resultado do Tratamento , Estudos Retrospectivos , Transtornos de Deglutição/diagnóstico por imagem , Transtornos de Deglutição/etiologia , Discotomia/métodos , Fusão Vertebral/métodos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Degeneração do Disco Intervertebral/cirurgia , Degeneração do Disco Intervertebral/complicações , Placas Ósseas/efeitos adversos , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia
3.
J Orthop Surg Res ; 18(1): 286, 2023 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-37038168

RESUMO

OBJECTIVE: To analyze the association between different postoperative hemoglobin (Hb) levels and postoperative outcomes in patients who have undergone primary lumbar interbody fusion, and to investigate the risk factors and establish a predictive nomogram mode for postoperative Hb < 80 g/L. METHODS: We retrospectively analyzed 726 cases who underwent primary lumbar interbody fusion surgery between January 2018 and December 2021in our hospital. All patients were divided into three groups according to the postoperative Hb levels (< 70 g/L, 70-79 g/L, ≥ 80 g/L). The postoperative outcomes among the three groups were compared, and the risk factors for postoperative Hb < 80 g/L were identified by univariate and multivariable logistic regression analysis. Based on these independent predictors, a nomogram model was developed. Predictive discriminative and accuracy ability of the predicting model was assessed using the concordance index (C-index) and calibration plot. Clinical application was validated using decision curve analysis. Internal validation was performed using the bootstrapping validation. RESULTS: Patients with postoperative Hb < 80 g/L had higher rates of postoperative blood transfusion, a greater length of stay, higher rates of wound complications, and higher hospitalization costs than those with postoperative Hb ≥ 80 g/L. Preoperative Hb, preoperative platelets, fusion segments, body mass index, operation time, and intraoperative blood loss independently were associated with postoperative Hb < 80 g/L. Intraoperative blood salvage was found to be a negative predictor for postoperative Hb < 80 g/L (OR, 0.21 [95% CI 0.09-0.50]). The area under the curve of the nomogram model was 0.950. After internal validations, the C-index of the model was 0.939. The DCA and calibration curve suggested that the nomogram model had a good consistency and clinical utility. CONCLUSIONS: Postoperative Hb < 80 g/L in patients following primary lumbar interbody fusion surgery increased blood transfusions requirement and was independently associated with poor outcomes. A novel nomogram model was established and could conveniently predict the risk of postoperative Hb < 80 g/L in patients after this type of surgery.


Assuntos
Hospitalização , Nomogramas , Humanos , Estudos Retrospectivos , Hemoglobinas , Região Lombossacral/cirurgia
4.
Int J Gen Med ; 15: 6145-6163, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35855761

RESUMO

Purpose: Pyroptosis plays an important role in the occurrence and progression of many tumors; however, the specific mechanisms involved remain unknown. Here, we construct a pyroptosis-related gene signature that can be used to predict survival prognosis of skin cutaneous melanoma (SKCM) and provide guidance for clinical treatment. Methods: By integrating data from the two databases from the GTEx and TCGA, differentially expressed genes (DEGs) from normal tissues and skin cutaneous tumor tissues were identified. The main signaling pathways and function enrichment of these differential genes were determined. Univariate and multivariate COX regression analysis, and risk score analysis were used to construct a signature to assess its predictive value for overall survival. The mRNA expression of these five genes in melanoma cells was determined by quantitative polymerase chain reaction (qPCR). The pRRophetic algorithm was used to estimate the half-maximal inhibitory concentration (IC50) of chemotherapy drugs in SKCM patients. The expression of multiple immune checkpoint genes also was evaluated. Results: Sixteen DEGs associated with pyroptosis in SKCM and normal skin tissues were identified. Of these, 12 pyroptosis-related DEGs were associated with the prognosis of SKCM. A five-gene signature (GSDMA, GSDMC, IL-18, NLRP6, and AIM2) model was constructed. Patients were divided into high-risk and low-risk groups using the risk scores. Of these, the high-risk group had a worse survival prognosis. There are significant differences in the predicted sensitivity of the high-risk and low-risk groups to chemotherapeutic drugs. In addition, compared with the high-risk group, the low-risk group showed higher expression of PD-1, PDL-1, CTLA-4, LAG-3, and VSIR. Conclusion: In this study, we constructed a novel prognostic pyroptosis-related gene-signature for SKCM. These genes showed good predictive value for patient prognosis and could provide guidance for better treatment of SKCM patients.

5.
Theranostics ; 9(5): 1247-1263, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30867828

RESUMO

Background and Aims: Prostate specific membrane antigen (PSMA) is specifically expressed on prostate epithelial cells and markedly overexpressed in almost all prostate cancers. TRIM24 is also up-regulated from localized prostate cancer to metastatic castration-resistant prostate cancer (CRPC). Because of the high relevance of TRIM24 for cancer development and the universal expression of PSMA in CPRC, we investigated the efficacy of human monoclonal PSMA antibody (PSMAb)-based platform for the targeted TRIM24 siRNA delivery and its therapeutic efficacy in CRPC in vivo and in vitro. Methods: The therapeutic complexes were constructed by conjugating PSMAb and sulfo-SMCC-protamine, and encapsulating TRIM24 siRNA. Flow cytometry, immunofluorescence, and fluorescence imaging were performed to detect the receptor-binding, internalization, and targeted delivery of PSMAb-sulfo-SMCC-protamine (PSP)-FAM-siRNA complex (PSPS) in vitro and in vivo. CCK-8, plate-colony formation, apoptosis, cell cycle, and Transwell assays were performed to evaluate the therapeutic potential of the PSP-TRIM24 siRNA complex in vitro, whereas the in vivo therapeutic efficacy was monitored by small animal imaging, radiography, and micro CT. Results: We confirmed that PSP could efficiently protect siRNA from enzymatic digestion, enable targeted delivery of siRNA, and internalize and release siRNA into PSMA-positive (PSMA+) prostate cancer cells in vitro and in vivo. Silencing TRIM24 expression by the PSP-TRIM24 siRNA complex could dramatically suppress proliferation, colony-formation, and invasion of PSMA+ CRPC cells in vitro, and inhibit tumor growth of PSMA+ CRPC xenografts and bone loss in PSMA+ CRPC bone metastasis model without obvious toxicity at therapeutic doses in vivo. Conclusion: PSMAb mediated TRIM24 siRNA delivery platform could significantly inhibit cell proliferation, colony-formation, and invasion in PSMA+ CRPC in vitro and suppressed tumor growth and bone loss in PSMA+ CRPC xenograft and bone metastasis model.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Antígenos de Superfície/imunologia , Proteínas de Transporte/antagonistas & inibidores , Glutamato Carboxipeptidase II/imunologia , Terapia de Alvo Molecular/métodos , Neoplasias de Próstata Resistentes à Castração/tratamento farmacológico , RNA Interferente Pequeno/administração & dosagem , Animais , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Masculino , Camundongos Nus , Modelos Teóricos , Usos Terapêuticos , Ensaio Tumoral de Célula-Tronco , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Technol Cancer Res Treat ; 18: 1533033819853262, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-31122179

RESUMO

Our previous study indicated that knockdown of Aurora-B inhibit the proliferation of osteosarcoma cells. But the function and molecular mechanisms of Aurora-B in osteosarcoma cells growth and metastasis remains unclear. The aim of this study was to investigate the molecular mechanisms of Aurora-B in the progression of osteosarcoma. Osteosarcoma cells (U2-OS and 143B) were treated with specific Lentivirus-Vectors (up or downregulation Aurora-B). The ability of cells proliferation, migration, and invasion was measured using Cell-Counting Kit-8, wound healing and transwell invasion assays. Furthermore, based on label-free quantitative proteomic analysis of potential molecular mechanisms of Aurora-B in human 143B cells. A total of 25 downregulated and 76 upregulated differentially expressed proteins were screened in terms of the change in their expression abundance. We performed functional annotation and functional enrichment analyses. Gene ontology enrichment, KEGG analysis, and protein-protein interaction networks were constructed and analyzed. We found that the PTK2 may play an important role in the progression of osteosarcoma cells. Finally, Western blot revealed that expression of PTK2, AKT, PI3K, and nuclear factor-kappaB increased after over expression of Aurora-B. Overall, these data highlight that Aurora-B may promote the malignant phenotype of osteosarcoma cells by activating the PTK2/PI3K/AKt/nuclear factor-KappaB pathway.


Assuntos
Aurora Quinase B/genética , Neoplasias Ósseas/genética , Neoplasias Ósseas/patologia , Carcinogênese/genética , Osteossarcoma/genética , Osteossarcoma/patologia , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Progressão da Doença , Quinase 1 de Adesão Focal/genética , Ontologia Genética , Humanos , NF-kappa B/genética , Fosfatidilinositol 3-Quinases/genética , Mapas de Interação de Proteínas/genética , Proteômica , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais/genética
7.
Theranostics ; 7(19): 4791-4804, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29187904

RESUMO

Background and Aims: Angiogenesis is an important pathological process during progression of plaque formation, which can result in plaque hemorrhage and vulnerability. This study aims to explore non-invasive imaging of angiogenesis in atherosclerotic plaque through magnetic resonance imaging (MRI) and positron emission tomography (PET) by using GEBP11 peptide targeted magnetic iron oxide nanoparticles in a rabbit model of atherosclerosis. Methods: The dual-modality imaging probe was constructed by coupling 2, 3-dimercaptosuccinnic acid-coated paramagnetic nanoparticles (DMSA-MNPs) and the PET 68Ga chelator 1,4,7-triazacyclononane-N, N', N''-triacetic acid (NOTA) to GEBP11 peptide. The atherosclerosis model was induced in New Zealand white rabbits by abdominal aorta balloon de-endothelialization and atherogenic diet for 12 weeks. The plaque areas in abdominal artery were detected by ultrasound imaging and Oil Red O staining. Immunofluorescence staining and Prussian blue staining were applied respectively to investigate the affinity of GEBP11 peptide. MTT and flow cytometric analysis were performed to detect the effects of NGD-MNPs on cell proliferation, cell cycle and apoptosis in Human umbilical vein endothelial cells (HUVECs). In vivo MRI and PET imaging of atherosclerotic plaque were carried out at different time points after intravenous injection of nanoparticles. Results: The NGD-MNPs with hydrodynamic diameter of 130.8 nm ± 7.1 nm exhibited good imaging properties, high stability, low immunogenicity and little cytotoxicity. In vivo PET/MR imaging revealed that 68Ga-NGD-MNPs were successfully applied to visualize atherosclerotic plaque angiogenesis in the rabbit abdominal aorta. Prussian blue and CD31 immunohistochemical staining confirmed that NGD-MNPs were well co-localized within the blood vessels' plaques. Conclusion:68Ga-NGD-MNPs might be a promising MR and PET dual imaging probe for visualizing the vulnerable plaques.


Assuntos
Aterosclerose/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Imagem Multimodal/métodos , Nanopartículas/metabolismo , Peptídeos/química , Tomografia por Emissão de Pósitrons/métodos , Compostos Radiofarmacêuticos/farmacocinética , Animais , Feminino , Radioisótopos de Gálio/química , Compostos Heterocíclicos/química , Compostos Heterocíclicos com 1 Anel , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nanopartículas/química , Neovascularização Fisiológica , Coelhos , Compostos Radiofarmacêuticos/efeitos adversos , Compostos Radiofarmacêuticos/síntese química , Succímero/química , Distribuição Tecidual
8.
Oncotarget ; 8(39): 64853-64866, 2017 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-29029396

RESUMO

The poor survival of cells in ischemic sites diminishes the therapeutic efficacy of stem cell therapy. Previously we and others have reported that Cannabinoid receptor type II (CB2) is protective during heart ischemic injury for its anti-oxidative activity. However, whether CB2 activation could improve the survival and therapeutic efficacy of stem cells in ischemic myocardium and the underlying mechanisms remain elusive. Here, we showed evidence that CB2 agonist AM1241 treatment could improve the functional survival of adipose-derived mesenchymal stem cells (AD-MSCs) in vitro as well as in vivo. Moreover, AD-MSCs adjuvant with AM1241 improved cardiac function, and inhibited cardiac oxidative stress, apoptosis and fibrosis. To unveil possible mechanisms, AD-MSCs were exposed to hydrogen peroxide/serum deprivation to simulate the ischemic environment in myocardium. Results delineated that AM1241 blocked the apoptosis, oxidative damage and promoted the paracrine effects of AD-MSCs. Mechanistically, AM1241 activated signal transducers and activators of transcription 3 (Stat3) through the phosphorylation of Akt and ERK1/2. Moreover, the administration of AM630, LY294002, U0126 and AG490 (inhibitors for CB2, Akt, ERK1/2 and Stat3, respectively) could abolish the beneficial actions of AM1241. Our result support the promise of CB2 activation as an effective strategy to optimize stem cell-based therapy possibly through Stat3 activation.

9.
Free Radic Biol Med ; 113: 291-303, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28993270

RESUMO

Myocardial injury and dysfunction are critical manifestations of sepsis. Previous studies have reported that liver X receptor (LXR) activation is protective during sepsis. However, whether LXR activation protects against septic heart injury and its underlying mechanisms remain elusive. This study was designed to determine the role of LXR activation in the septic heart with a focus on SIRT1 (silent information regulator 1) signaling. Male cardiac-specific SIRT1 knockout mice (SIRT1-/-) and their wild-type littermates were subjected to sepsis by cecal ligation and puncture (CLP) in the presence or absence of LXR agonist T0901317. The survival rate of mice was recorded during the 7-day period post CLP. Our results demonstrated that SIRT1-/- mice suffered from exacerbated mortality and myocardial injury in comparison with their wild-type littermates. Meanwhile, T0901317 treatment improved mice survival, accompanied by significant ameliorations of myocardial injury and dysfunction in wild-type mice but not in SIRT1-/- mice. Furthermore, the levels of myocardial inflammatory cytokines (TNF-α, IL-6, IL-1ß, MCP-1, MPO and HMGB1), oxidative stress (ROS generation, MDA), endoplasmic-reticulum (ER) stress (protein levels of CHOP, GRP78, GRP94, IRE1α, and ATF6), and cardiac apoptosis following CLP were inhibited by T0901317 treatment in wild-type mice but not in SIRT1-/- mice. Mechanistically, T0901317 enhanced SIRT1 signaling and the subsequent deacetylation and activation of antioxidative FoxO1 and anti-ER stress HSF1, as well as the deacetylation and inhibition of pro-inflammatory NF-ΚB and pro-apoptotic P53, thereby alleviating sepsis-induced myocardial injury and dysfunction. Our data support the promise of LXR activation as an effective strategy for relieving heart septic injury.


Assuntos
Anticolesterolemiantes/farmacologia , Traumatismos Cardíacos/tratamento farmacológico , Hidrocarbonetos Fluorados/farmacologia , Receptores X do Fígado/genética , Sepse/tratamento farmacológico , Sirtuína 1/genética , Sulfonamidas/farmacologia , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Chaperona BiP do Retículo Endoplasmático , Proteína Forkhead Box O1/genética , Proteína Forkhead Box O1/metabolismo , Regulação da Expressão Gênica , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Traumatismos Cardíacos/genética , Traumatismos Cardíacos/mortalidade , Traumatismos Cardíacos/patologia , Fatores de Transcrição de Choque Térmico/genética , Fatores de Transcrição de Choque Térmico/metabolismo , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Receptores X do Fígado/agonistas , Receptores X do Fígado/metabolismo , Masculino , Camundongos , Camundongos Knockout , Miocárdio/metabolismo , Miocárdio/patologia , Peroxidase/genética , Peroxidase/metabolismo , Sepse/genética , Sepse/mortalidade , Sepse/patologia , Transdução de Sinais , Sirtuína 1/deficiência , Análise de Sobrevida , Fator de Transcrição CHOP/genética , Fator de Transcrição CHOP/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
10.
World Neurosurg ; 101: 568-576, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28238873

RESUMO

BACKGROUND: Scoliosis surgery usually is associated with large volume of intraoperative blood loss, and cell salvage is used commonly to filter and retranfusion autologous blood to patients. The efficacy of using cell salvage in scoliosis surgery, however, is still controversial. OBJECTIVE: The purpose of this study is to make clear that intraoperative use of cell salvage is effective to decrease the volume of perioperative allogenic blood transfusion in scoliosis surgery. METHODS: A meta-analysis was conducted to identify the relevant studies from PubMed, Embase, Medline, Cochrane library, and Google scholar until July 2016. All randomized trials and controlled clinical studies comparing the clinical outcomes of using cell salvage versus noncell salvage in scoliosis surgery were retrieved for the meta-analysis. The data were analyzed by RevMan 5.3. RESULTS: A total of 7 studies with 562 patients were included in this meta-analysis. Based on the analysis, the volumes of perioperative and postoperative allogenic red blood cell (RBC) transfusion in cell salvage group were significantly less than those in control group (P = 0.04 and P = 0.01); however, no significant difference was detected in the amount of intraoperative allogenic RBC transfusion and the risk of patients needing allogenic blood transfusion between the 2 groups (P = 0.14 and P = 0.61). Both the hemoglobin and hematocrit levels on the first day after surgery were significantly greater in cell salvage group than those in control group (P = 0.002 and P < 0.001). No significant differences, however, were noted in neither hemoglobin nor hematocrit level at the time of discharge between the 2 groups (P = 0.76 and P = 0.32). One of the included study reported the number of patients with complications related to transfusion in the two groups, which was not significant different (P = 0.507). CONCLUSIONS: Cell salvage significantly reduced the volumes of perioperative and postoperative allogenic RBC transfusion in scoliosis surgery and increased the hemoglobin and hematocrit levels on the first day postoperatively. In addition, it seemed not to increase the rate of transfusion complications during the surgery.


Assuntos
Complicações Intraoperatórias/prevenção & controle , Recuperação de Sangue Operatório/métodos , Escoliose/cirurgia , Humanos , Complicações Intraoperatórias/diagnóstico , Recuperação de Sangue Operatório/tendências , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Escoliose/diagnóstico , Resultado do Tratamento
11.
World Neurosurg ; 90: 109-115, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26944885

RESUMO

BACKGROUND: Closed wound suction drainage after spine surgery is commonly used in clinical practice. However, no consensus has been reached for using drainage versus nondrainage after lumbar spinal surgery until now. OBJECTIVE: The purpose of this study was to determine the clinical outcomes of using closed suction drainage versus nondrainage after lumbar spinal surgery. METHODS: We conducted a systematic review and meta-analysis to identify relevant studies from PubMed, MEDLINE, EMBASE, Cochrane Library, and Google scholar up to September 2015. All randomized, quasi-randomized, and controlled clinical studies, which compared the clinical outcomes of using closed suction drainage versus nondrainage in patients who underwent lumbar spinal surgery, were included. Data extraction and quality assessment were according to Cochrane Collaboration guidelines. RESULTS: Five studies involving 1295 patients were included in this meta-analysis. By pooling the clinical outcomes, there were no significant differences between patients with drainage and nondrainage in terms of the incidence of wound infection (odds ratio [OR], 1.48; 95% confidence interval [CI], 0.47-4.71; P = 0.50), wound hematoma (OR, 0.45; 95% CI, 0.01-29.31, P = 0.71), and reoperation (OR, 1.36; 95% CI, 0.22-8.27; P = 0.74). Drainage after lumbar surgery was associated with more blood loss and significantly greater blood transfusions (OR, 3.68; 95% CI, 1.80-7.54; P < 0.01) compared with nondrainage. However, more patients contracted postoperative fever in the nondrainage group than did those in drainage group. CONCLUSIONS: Based on this systematic review and meta-analysis, there is insufficient evidence to suggest routine use of prophylactic closed suction drainage after lumbar spinal surgery. However, a decision to use or not use drainage should be individualized for each patient because many factors affect the outcomes.


Assuntos
Hematoma Epidural Espinal/epidemiologia , Hematoma Epidural Espinal/prevenção & controle , Vértebras Lombares/cirurgia , Fusão Vertebral/estatística & dados numéricos , Sucção/estatística & dados numéricos , Infecção da Ferida Cirúrgica/epidemiologia , Infecção da Ferida Cirúrgica/prevenção & controle , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Reoperação/estatística & dados numéricos , Fatores de Risco , Resultado do Tratamento , Adulto Jovem
12.
Int J Biochem Cell Biol ; 59: 1-10, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25456445

RESUMO

Nucleus pulposus (NP) cells reside in a hypoxic environment in vivo, while the mechanisms of how NP cells maintain survival under hypoxia are not clear. Autophagy is an important physiological response to hypoxia and implicated in the survival regulation in most types of cells. This study was designed to investigate the role of autophagy in the survival of NP cells under hypoxia. We found that appropriate autophagy activity was beneficial to the survival of NP cells in serum deprivation, while excessive autophagy led to death of the NP cells. Hypoxia facilitated the survival of NP cells in serum deprivation by down-regulating excessive autophagy. Hypoxia down-regulated the autophagy activity of NP cells through restricting the production of reactive oxygen species (ROS) and inactivating the AMPK/mTOR signaling pathway, and possibly through a pathway involving HIF-1α. We believed that understanding the autophagy response of NP cells to hypoxia and its role in cell survival had important clinical significance in the prevention and treatment of degenerative discogenic diseases.


Assuntos
Autofagia , Regulação para Baixo , Disco Intervertebral/citologia , Espécies Reativas de Oxigênio/metabolismo , Adenilato Quinase/metabolismo , Animais , Apoptose , Hipóxia Celular , Sobrevivência Celular , Meios de Cultura Livres de Soro , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Fagossomos/metabolismo , Fagossomos/ultraestrutura , Ratos , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
13.
Cell Physiol Biochem ; 34(4): 1175-89, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25277442

RESUMO

BACKGROUND/AIMS: Apoptosis and autophagy are two patterns of programmed cell death which play important roles in the intervertebral disc degeneration. Oxidative stress is an important factor for the induction of programmed cell death. However, the cellular reactions linking autophagy to apoptosis of disc cells under oxidative stress have never been described. This study investigated the responses of autophagy and apoptosis and their interactions in the nucleus pulposus cells (NP cells) under oxidative stress, with the aim to better understand the mechanism of disc degeneration. METHODS: NP cells isolated from rat lumbar discs were subjected to different concentrations of H2O2 for various time periods. Cell viability was determined by CCK-8 assay, and their apoptosis and autophagy responses were evaluated by fluorescent analysis, flow cytometry and western blotting, et al. The interactions of autophagy and apoptosis and the possible signaling pathways were also investigated by using autophagy modulators. RESULTS: H2O2 increased the lysosomal membrane permeability in the NP cells and induced apoptosis through the mitochondrial pathway subsequently. Meanwhile, H2O2 stimulated an early autophagy response through the ERK/m-TOR signaling pathway. Autophagy inhibition significantly decreased the apoptosis incidence in the cells insulted by H2O2. CONCLUSION: These results suggested that controlling the autophagy response in the NP cells under oxidative stress should be beneficial for the survival of the cells and probably delay the process of disc degeneration.


Assuntos
Apoptose/fisiologia , Autofagia/fisiologia , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/patologia , Estresse Oxidativo/fisiologia , Animais , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Permeabilidade da Membrana Celular/efeitos dos fármacos , Permeabilidade da Membrana Celular/fisiologia , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Peróxido de Hidrogênio/farmacologia , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Serina-Treonina Quinases TOR/metabolismo
14.
BMC Musculoskelet Disord ; 15: 332, 2014 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-25281011

RESUMO

BACKGROUND: Diagnosis and treatment decisions of cervical instability are made, in part, based on the clinician's assessment of sagittal rotation on flexion and extension radiographs. The objective of this study is to evaluate the intraobserver and interobserver reliability of three measurement techniques in assessing cervical sagittal rotation. METHODS: Fifty lateral radiographs of patients with single-level cervical degenerative disc were selected and measured on two separate occasions by three spine surgeons using three different measurement techniques. Cervical sagittal rotation was measured using three different techniques. RESULTS: Intraclass correlation coefficients were most consistent for Method 2 (ICC 0.93-0.96) followed by Method 1 (ICC 0.88-0.91) and Method 3 (ICC 0.81-0.87). Intraobserver agreement (% of repeated measures within 0.5° of the original measurement) ranged between 76% and 96% for all techniques, with Method 2 showing the best agreement (92%-96%). Paired comparisons between observers varied considerably with interobserver reliability correlation coefficients ranging from 0.54 to 0.89. Method 2 showed the highest interobserver reliability coefficient (0.82, range 0.73-0.88). Method 2 was also more reliable for the classification of "instability". Intraobserver percent agreements ranged from 94 to 98% for Method 2 versus 84% to 90% for Method 1 and 78% to 86% for Method 3, while interobserver percent agreements ranged from 90% to 98% for Method 2 versus 86% to 94% for Method 1 and 74% to 84% for Method 3. CONCLUSIONS: Method 2 (measuring the angle from the inferior endplate of the vertebra above the degenerative disc and the inferior endplate of the vertebra below the degenerative disc) showed the best intraobserver and interobserver reliability overall in assessing cervical sagittal rotation.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Degeneração do Disco Intervertebral/diagnóstico por imagem , Intensificação de Imagem Radiográfica/normas , Rotação , Cirurgiões/normas , Humanos , Variações Dependentes do Observador , Intensificação de Imagem Radiográfica/métodos , Reprodutibilidade dos Testes
15.
Free Radic Biol Med ; 77: 10-20, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25224042

RESUMO

Oxidative stress can damage various cellular components of osteoblasts, and is regarded as a pivotal pathogenic factor for bone loss. Increasing evidence indicates a significant role of cell autophagy in response to oxidative stress. However, the role of autophagy in the osteoblasts under oxidative stress remains to be clarified. In this study, we verified that hydrogen peroxide induced autophagy and apoptosis in a dose- and time-dependent manner in osteoblastic Mc3T3-E1 cells. Both 3-methyladenine (the early steps of autophagy inhibitor) and bafilomycin A1 (the last steps of autophagy inhibitor) enhanced the cell apoptosis and reactive oxygen species level in the osteoblasts insulted by hydrogen peroxide. However, promotion of autophagy with either a pharmacologic inducer (rapamycin) or the Beclin-1 overexpressing technique rescued the cell apoptosis and reduced the reactive oxygen species level in the cells. Treatment with H2O2 significantly increased the levels of carbonylated proteins, malondialdehyde and 8-hydroxy-2'-deoxyguanosine, decreased the mitochondrial membrane potential, and increased the mitochondria-mediated apoptosis markers. The damaged mitochondria were cleared by autophagy. Furthermore, the molecular levels of the endoplasmic reticula stress signaling pathway changed in hydrogen peroxide-treated Mc3T3-E1 cells, and blocking this stress signaling pathway by RNA interference against candidates of glucose-regulated protein 78 and protein kinase-like endoplasmic reticulum kinase decreased autophagy while increasing apoptosis in the cells. In conclusion, oxidative damage to osteoblasts could be alleviated by early autophagy through the endoplasmic reticulum stress pathway. Our findings suggested that modulation of osteoblast autophagy could have a potentially therapeutic value for osteoporosis.


Assuntos
Autofagia , Estresse do Retículo Endoplasmático , Osteoblastos/fisiologia , Animais , Apoptose , Linhagem Celular , Sobrevivência Celular , Humanos , Potencial da Membrana Mitocondrial , Camundongos , Osteoporose/metabolismo , Osteoporose/patologia , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo
16.
Cytokine ; 70(2): 87-96, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25127907

RESUMO

Autophagy and apoptosis are important in maintaining the metabolic homeostasis of intervertebral disc cells, and transforming growth factor-ß1 (TGF-ß1) is able to delay intervertebral disc degeneration. This study determined the effect of TGF-ß1 on the crosstalk between autophagy and apoptosis in the disc cells, with the aim to provide molecular mechanism support for the prevention and treatment of disc degeneration. Annulus fibrosus (AF) cells were isolated and cultured under serum starvation. 10 ng/mL TGF-ß1 reduced the apoptosis incidence in the cells under serum starvation for 48 h, down-regulated the autophagy incidence in the cells pretreated with 3-methyladenine (3-MA) or Bafilomycin A (Baf A), partly rescued the increased apoptosis incidence in the cells pretreated with 3-MA, while further reduced the decreased apoptosis incidence in the cells pretreated with Baf A. Meanwhile, TGF-ß1 down-regulated the expressions of autophagic and apoptotic markers in the cells under starvation, partly down-regulated the expressions of Beclin-1, LC3 II/I and cleaved caspase-3 in the cells pretreated with 3-MA or Baf A, while significantly decreased the expression of Bax/Bcl-2 in the cells pretreated with Baf A. 3-MA blocked the phosphorylation of both AKT and mTOR and partly reduced the inhibitory effect of TGF-ß1 on the expression of LC3 II/I and cleaved caspase-3. TGF-ß1 enhanced the expression of p-ERK1/2 and down-regulated the expressions of LC3 II/I and cleaved caspase-3. U0126 partly reversed this inhibitory effect of TGF-ß1. In conclusion, TGF-ß1 protected against apoptosis of AF cells under starvation through down-regulating excessive autophagy. PI3K-AKT-mTOR and MAPK-ERK1/2 were the possible signaling pathways involved in this process.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Disco Intervertebral/citologia , Fator de Crescimento Transformador beta1/farmacologia , Animais , Meios de Cultura Livres de Soro , Citoproteção/efeitos dos fármacos , Imunofluorescência , Disco Intervertebral/efeitos dos fármacos , Disco Intervertebral/ultraestrutura , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Masculino , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Fagossomos/efeitos dos fármacos , Fagossomos/ultraestrutura , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo
17.
Crit Rev Eukaryot Gene Expr ; 24(3): 193-204, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25072146

RESUMO

The intervertebral disc (IVD) is the largest avascular structure in the body, and IVD cells reside in vivo in an environment that is considered to be hypoxic. However, the role of oxygen in IVD cell biology remains an issue of debate. By reviewing the available literature about the effect of oxygen tension on regulating the phenotype, energy metabolism, matrix production, and survival of IVD cells, as well as on the expression and function of hypoxia-inducible factor in IVD cells, we conclude that hypoxia is essential in maintaining the physiological function of IVD cells. Modulating the oxygen tension of the IVD or the activity of hypoxia-inducible factor in IVD cells may be a promising strategy for the prevention and treatment of IVD degeneration.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Hipóxia Celular/fisiologia , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Degeneração do Disco Intervertebral/patologia , Disco Intervertebral/citologia , Animais , Bovinos , Sobrevivência Celular/fisiologia , Matriz Extracelular/metabolismo , Glicólise/fisiologia , Humanos , Disco Intervertebral/irrigação sanguínea , Oxigênio/fisiologia
18.
J Spinal Cord Med ; 36(3): 220-4, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-23809592

RESUMO

BACKGROUND: The pathogenesis of osteoporosis after spinal cord injury (SCI) may be different from disuse osteoporosis. OBJECTIVE: To investigate whether there is the differential anabolic response to mechanical loading between osteoblasts from SCI rats and those from hindlimb-immobilized rats. METHODS: Femoral bone-marrow was harvested for osteoblast culture from SCI rats, hindlimb-immobilized rats, and control rats 3 weeks after animal model creation. At the stage of differentiation, rat osteoblasts were plated in six-well plates for stretching. Cyclic strains were applied for 48 hours, and then alkaline phosphatase (ALPase) activity, procollagen, and osteocalcin production, and gene expression of osteocalcin, runt-related transcription factor 2 (Runx2), and osterix were measured in osteoblasts from SCI rats, hindlimb-immobilized rats, and control rats. RESULTS: ALPase activity, procollagen, and osteocalcin production, and gene expression of osteocalcin, Runx2, and osterix were significantly lower in osteoblasts after stretching from SCI rats compared with those from hindlimb-immobilized rats. However, there was no significant difference of these parameters between isolated osteoblasts from hindlimb-immobilized rats and those from control rats. CONCLUSION: The activity of isolated osteoblasts from SCI rats was lower than control rats, and this suggested that osteoblasts from SCI rats responded less to mechanical loading as compared with those from control rats.


Assuntos
Osteoblastos/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Animais , Modelos Animais de Doenças , Elevação dos Membros Posteriores , História Antiga , Masculino , Osteoporose/etiologia , Osteoporose/fisiopatologia , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Traumatismos da Medula Espinal/complicações
19.
Apoptosis ; 18(11): 1363-1375, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-23743762

RESUMO

Estradiol could protect osteoblast against apoptosis, and apoptosis and autophagy were extensively and intimately connected. The aim of the present study was to test the hypothesis that autophagy was present in osteoblasts under serum deprivation and estrogen protected against osteoblast apoptosis via promotion of autophagy. MC3T3-E1 osteoblastic cells were cultured in a serum-free and phenol red-free minimal essential medium (α-MEM). Ultrastructural analysis, lysosomal activity assessment and monodansycadaverine (MDC) staining were employed to determine the presence of autophagy, and real time PCR was used to evaluate the expression of autophagic markers. Meanwhile, the osteoblasts were transferred in a serum-free and phenol red-free α-MEM containing either vehicle or estradiol. Apoptosis and autophagy was assessed by using the techniques of real-time PCR, Western blot, immunofluorescence assay, and flow cytometry. The possible pathway through which estrogen promoted autophagy in the serum-deprived osteoblasts was also investigated. Real-time PCR demonstrated the expression of LC3, beclin1 and ULK1 genes in osteoblasts under serum deprivation, and immunofluorescence assay verified high expression of proteins of these three autophagic bio-markers. Lysosomes and autolysosomes accumulated in the cytoplasm of osteoblasts were also detected under transmission electron microscopy, MDC staining and lysosomal activity assessment. Meanwhile, estradiol significantly decreased the expression of proteins of the bio-markers of apoptosis, and at the same time increased the expression of proteins of the bio-markers of autophagy in the serum-deprived osteoblasts. Furthermore, the estradiol-promoted autophagy in serum-deprived osteoblasts could be blocked by estrogen receptor (ER) antagonist (ICI 182780), and estradiol failed to rescue the cells pretreated with an inhibitor of vacuolar ATPase (bafilomycin A) from apoptosis. Serum deprivation resulted in apoptosis through activation of Caspase-3 and induced autophagy through inhibition of phospho-mammalian target of rapamycin (p-mTOR). Both 3-methyladenine (3MA) and U0126 led to increase of apoptosis in osteoblasts with serum deprivation. Estradiol failed to over-ride the inhibitory effect of 3MA on phosphorylation of AKT but directly led to dephosphorylation of mTOR and upregulation of LC3 protein expression. However, the estradiol-enhanced LC3 protein expression was significantly suppressed by U0126 through inhibition of phosphorylation of extracellular signal-regulated kinase (ERK). Estradiol rescued osteoblast apoptosis via promotion of autophagy through the ER-ERK-mTOR pathway.


Assuntos
Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Estradiol/farmacologia , Osteoblastos/efeitos dos fármacos , Receptores de Estrogênio/genética , Serina-Treonina Quinases TOR/genética , Animais , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteína Homóloga à Proteína-1 Relacionada à Autofagia , Proteína Beclina-1 , Butadienos/farmacologia , Caspase 3/genética , Caspase 3/metabolismo , Linhagem Celular , Meios de Cultura , Estradiol/análogos & derivados , Antagonistas de Estrogênios/farmacologia , Fulvestranto , Galactosiltransferases/genética , Galactosiltransferases/metabolismo , Regulação da Expressão Gênica , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Macrolídeos/farmacologia , Camundongos , Nitrilas/farmacologia , Osteoblastos/citologia , Osteoblastos/metabolismo , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Receptores de Estrogênio/antagonistas & inibidores , Receptores de Estrogênio/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo
20.
J Cell Mol Med ; 16(12): 2968-77, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-22947224

RESUMO

It has long been recognized that spinal cord injury (SCI) leads to a loss of bone mineral. However, the mechanisms of bone loss after SCI remain poorly understood. The aim of this study was to investigate whether SCI causes a shift in skeletal balance between osteoblastogenesis and adipogenesis. Eighty male Sprague-Dawley rats at 6 weeks of age were randomly divided into two groups: sham-operated (SHAM) group and SCI group. The rats were killed after 3 weeks, 3 months and 6 months, and their femora, tibiae and humeri were collected for mesenchymal stem cells (MSCs) culture, bone mineral density (BMD) measurement, RNA analysis and Western Blot analysis. Osteogenic and adipogenic differentiation potential of MSCs from SCI rats and SHAM rats was evaluated. We found increased marrow adiposity in sublesional tibiae of SCI rats. SCI caused increased peroxisome proliferator-activated receptor-γ (PPARγ) expression and diminished Wnt signalling in sublesional tibiae. Interestingly, in MSCs from SCI rats treated with the PPARγ inhibitor GW9662, the ratios of RANKL to OPG expression were significantly decreased. On the contrary, in MSCs from SCI rats treated with the PPARγ ligand troglitazone, the ratios of RANKL to OPG expression in SCI rats were significantly increased. High expression of PPARγ may lead to increased bone resorption through the RANKL/OPG axis after SCI. In addition, high expression also results in the suppression of osteogenesis and enhancement of adipogenesis in SCI rats. SCI causes a shift in skeletal balance between osteoblastogenesis and adipogenesis, thus leading to bone loss after SCI.


Assuntos
Adipogenia , Reabsorção Óssea , Osteogênese , PPAR gama/metabolismo , Traumatismos da Medula Espinal/fisiopatologia , Via de Sinalização Wnt , Anilidas/farmacologia , Animais , Densidade Óssea , Osso e Ossos/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Cromanos/farmacologia , Masculino , Células-Tronco Mesenquimais/fisiologia , Osteoblastos/metabolismo , Osteoprotegerina/biossíntese , Ligante RANK/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Tiazolidinedionas/farmacologia , Troglitazona , Proteínas Wnt/antagonistas & inibidores , Proteínas Wnt/metabolismo
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