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1.
Am J Pathol ; 194(9): 1737-1751, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38879082

RESUMO

This study investigated the role of apoptosis signal-regulated kinase-1 (ASK1) in intervertebral disc degeneration (IDD). The nucleus pulposus (NP) tissues of non-IDD and IDD patients were subjected to hematoxylin and eosin, Safranin O-fast green, and immunohistochemical staining. Quantitative real-time PCR was used to assess the ASK1 mRNA level within NP tissue samples and cells. The Cell Counting Kit-8 assay, senescence-associated ß-galactosidase staining, and flow cytometry were conducted to assess the viability, senescence, and apoptosis of NP cells, respectively. Extracellular matrix-related factors were detected using Western blot analysis. Furthermore, the effect of ASK1 on the IDD rat model was evaluated. Finally, c-Jun N-terminal kinase (JNK) inhibitors were used to verify the effect of the JNK/p38 signaling on IDD. ASK1 mRNA and protein were up-regulated within NP tissue samples from the IDD group, IL-1ß-stimulated NP cells, and IDD rats. ASK1 inhibition promoted cell viability and repressed the senescence and apoptosis of NP cells, promoted collagen II and aggrecan, inhibited matrix metalloproteinase 3/9 and a disintegrin and metalloproteinase with thrombospondin motifs 4/5 protein levels, and increased NP cells in rat intervertebral disc tissues. ASK1 overexpression exerted the opposite effects of ASK1 inhibition on NP cells. Additionally, JNK/p38 signaling suppression could reverse the ASK1 up-regulation-induced dysfunction. In conclusion, ASK1 facilitated the senescence and apoptosis of NP cells in promoting IDD progression via the JNK/p38 pathway.


Assuntos
Apoptose , Senescência Celular , Degeneração do Disco Intervertebral , MAP Quinase Quinase Quinase 5 , Núcleo Pulposo , Adulto , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Senescência Celular/fisiologia , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , MAP Quinase Quinase Quinase 5/metabolismo , MAP Quinase Quinase Quinase 5/genética , Sistema de Sinalização das MAP Quinases/fisiologia , Núcleo Pulposo/patologia , Núcleo Pulposo/metabolismo
2.
Arch Biochem Biophys ; 756: 109990, 2024 06.
Artigo em Inglês | MEDLINE | ID: mdl-38636690

RESUMO

Nucleus pulposus (NP) cell apoptosis is a significant indication of accelerated intervertebral disc degeneration; however, the precise mechanism is unelucidated as of yet. Ephrin B2 (EFNB2), the only gene down-regulated in the three degraded intervertebral disc tissue microarray groups (GSE70362, GSE147383 and GSE56081), was screened for examination in this study. Subsequently, EFNB2 was verified to be down-regulated in degraded NP tissue samples. Interleukin-1 (IL-1ß) treatment of NP cells to simulate the IDD environment indicated that IL-1ß treatment decreased EFNB2 expression. In degenerative NP cells stimulated by IL-1ß, EFNB2 knockdown significantly increased the rate of apoptosis as well as the apoptosis-related molecules cleaved-caspase-3 and the Bax to Bcl-2 ratio. EFNB2 was found to promote AKT, PI3K, and mTOR phosphorylation; the PI3K/AKT signaling role was investigated using the PI3K inhibitor LY294002. EFNB2 overexpression significantly increased PI3K/AKT pathway activity in IL-1ß-stimulated NP cells than the normal control. Moreover, EFNB2 partially alleviated NP cell apoptosis induced by IL-1ß, reduced the cleaved-cas3 level, and decreased the Bax/Bcl-2 ratio after the addition of the inhibitor LY294002. Additionally, EFNB2 overexpression inhibited the ERK1/2 phosphorylation; the effects of EFNB2 overexpression on ERK1/2 phosphorylation, degenerative NP cell viability, and cell apoptosis were partially reversed by ERK signaling activator Ceramide C6. EFNB2 comprehensively inhibited the apoptosis of NP cells by activating the PI3K/AKT signaling and inhibiting the ERK signaling, obviating the exacerbation of IDD. EFNB2 could be a potential target to protect against degenerative disc changes.


Assuntos
Apoptose , Efrina-B2 , Degeneração do Disco Intervertebral , Núcleo Pulposo , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Núcleo Pulposo/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/genética , Efrina-B2/metabolismo , Efrina-B2/genética , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Interleucina-1beta/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Adulto , Feminino , Serina-Treonina Quinases TOR/metabolismo , Células Cultivadas , Pessoa de Meia-Idade
3.
Neurochem Res ; 48(2): 447-457, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36315370

RESUMO

Spinal cord injury (SCI), resulting in damage of the normal structure and function of the spinal cord, would do great harm to patients, physically and psychologically. The mechanism of SCI is very complex. At present, lots of studies have reported that autophagy was involved in the secondary injury process of SCI, and several researchers also found that calcium ions (Ca2+) played an important role in SCI by regulating necrosis, autophagy, or apoptosis. However, to our best of knowledge, no studies have linked the spinal cord mechanical injury, intracellular Ca2+, and autophagy in series. In this study, we have established an in vitro model of SCI using neural cells from fetal rats to explore the relationship among them, and found that mechanical injury could promote the intracellular Ca2+ concentration, and the increased Ca2+ level activated autophagy through the CaMKKß/AMPK/mTOR pathway. Additionally, we found that apoptosis was also involved in this pathway. Thus, our study provides new insights into the specific mechanisms of SCI and may open up new avenues for the treatment of SCI.


Assuntos
Proteínas Quinases Ativadas por AMP , Traumatismos da Medula Espinal , Ratos , Animais , Proteínas Quinases Ativadas por AMP/metabolismo , Quinase da Proteína Quinase Dependente de Cálcio-Calmodulina/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Traumatismos da Medula Espinal/metabolismo , Autofagia , Medula Espinal/metabolismo , Apoptose
4.
Eur Spine J ; 24(11): 2560-6, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25870077

RESUMO

PURPOSE: A retrospective study was designed to evaluate clinical outcomes and sagittal alignment following single-level unilateral instrumented transforaminal lumbar interbody fusion (TLIF). METHODS: From November 2008 to December 2010, a total of 139 patients, who suffered from single-level lumbar degenerative disease, were included in this study. Forty-seven males and seventy-two females with a mean age of 57.3 years were enrolled. The average follow-up period was 51.7 months with a range of 41-66 months. The follow-up rate was 85.6 %. Thirty-one patients had diagnosis of discogenic low back pain, ten had recurrent disk herniation, thirty-four had spinal stenosis, and fourty-four had spondylolisthesis. Clinical outcomes were evaluated using the Oswestry disability index (ODI), visual analog scale (VAS) and Japanese Orthopedic Association. Operating time, blood loss, length of stay, and complications were also evaluated. The sagittal alignment and fusion status were assessed by X-ray and three-dimensional computed tomography. RESULTS: The average operating time was 92.1 ± 27.5 min, the average blood loss was 135.1 ± 113.5 ml, and the average length of stay was 12.0 ± 2.9 days. The overall complication rate was 13.4 %, and the fusion rate was 82.4 %. The postoperative clinical outcomes and sagittal alignment were significantly different from the preoperative values. The final lumbar lordosis angle and segment lordosis angle were associated with back pain VAS and ODI scores, respectively. CONCLUSION: Unilateral instrumented TLIF is a safe and effective treatment option for single-level lumbar degenerative disease, and is less invasive, yields good outcomes and has a low complication rate. In addition, the procedure has the potential to partly restore sagittal alignment.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Deslocamento do Disco Intervertebral/cirurgia , Dor Lombar/cirurgia , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Estenose Espinal/cirurgia , Espondilolistese/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Humanos , Imageamento Tridimensional , Degeneração do Disco Intervertebral/complicações , Deslocamento do Disco Intervertebral/complicações , Lordose/diagnóstico por imagem , Dor Lombar/etiologia , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Medição da Dor , Período Pós-Operatório , Estudos Retrospectivos , Estenose Espinal/complicações , Espondilolistese/complicações , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Escala Visual Analógica , Adulto Jovem
5.
Antonie Van Leeuwenhoek ; 105(3): 533-40, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24395034

RESUMO

Inoculated fermentation by selected indigenous yeast strains from a specific location could provide the wine with unique regional sensory characteristics. The identification and differentiation of local yeasts are the first step to understand the function of yeasts and develop a better strain-selection program for winemaking. The indigenous yeasts in five grape varieties, Chardonnay, Cabernet Franc, Cabernet Sauvignon, Marselan, and Merlot cultivated in Xiangning, Shanxi, China were investigated. Eight species of seven genera including Aureobasidium pullulans, Candida zemplinina, Hanseniaspora uvarum, Hanseniaspora occidentalis, Issatchenkia terricola, Metschnikowia pulcherrima, Pichia kluyveri, and Saccharomyces cerevisiae were identified using Wallerstein Laboratory Nutrient medium with sequencing of the 26S rDNA D1/D2 domain. H. uvarum and S. cerevisiae were the predominant species, while most non-Saccharomyces species were present in the whole fermentation process at different levels among the grape varieties. The genotypes of S. cerevisiae from each microvinification were determined by using interdelta sequence analysis. The 102 isolates showed eight different genotypes, and genotype III was the predominant genotype found. The distribution of S. cerevisiae strains during the fermentation of Marselan was also studied. Six genotypes were observed among the 92 strains with different genotypes of competitiveness at different sampling stages. Genotype V demonstrated the potential for organizing starter strains and avoiding inefficient fermentation. In general, this study explored the yeast species in the grapes grown in Xiangning County and provided important information of relationship of local yeast diversity and its regional wine sensory characteristics.


Assuntos
Vitis/microbiologia , Leveduras/classificação , China , Fermentação , Variação Genética , Genótipo , Dados de Sequência Molecular , RNA Ribossômico/genética , Saccharomyces cerevisiae/classificação , Saccharomyces cerevisiae/genética
6.
Sci Rep ; 14(1): 14023, 2024 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890348

RESUMO

The mechanism of spinal cord injury (SCI) is highly complex, and an increasing number of studies have indicated the involvement of pyroptosis in the physiological and pathological processes of secondary SCI. However, there is limited bioinformatics research on pyroptosis-related genes (PRGs) in SCI. This study aims to identify and validate differentially expressed PRGs in the GEO database, perform bioinformatics analysis, and construct regulatory networks to explore potential regulatory mechanisms and therapeutic targets for SCI. We obtained high-throughput sequencing datasets of SCI in rats and mice from the GEO database. Differential analysis was conducted using the "limma" package in R to identify differentially expressed genes (DEGs). These genes were then intersected with previously reported PRGs, resulting in a set of PRGs in SCI. GO and KEGG enrichment analyses, as well as correlation analysis, were performed on the PRGs in both rat and mouse models of SCI. Additionally, a protein-protein interaction (PPI) network was constructed using the STRING website to examine the relationships between proteins. Hub genes were identified using Cytoscape software, and the intersection of the top 5 hub genes in rats and mice were selected for subsequent experimentally validated. Furthermore, a competing endogenous RNA (ceRNA) network was constructed to explore potential regulatory mechanisms. The gene expression profiles of GSE93249, GSE133093, GSE138637, GSE174549, GSE45376, GSE171441_3d and GSE171441_35d were selected in this study. We identified 10 and 12 PRGs in rats and mice datasets respectively. Six common DEGs were identified in the intersection of rats and mice PRGs. Enrichment analysis of these DEGs indicated that GO analysis was mainly focused on inflammation-related factors, while KEGG analysis showed that the most genes were enriched on the NOD-like receptor signaling pathway. We constructed a ceRNA regulatory network that consisted of five important PRGs, as well as 24 miRNAs and 34 lncRNAs. This network revealed potential regulatory mechanisms. Additionally, the three hub genes obtained from the intersection were validated in the rat model, showing high expression of PRGs in SCI. Pyroptosis is involved in secondary SCI and may play a significant role in its pathogenesis. The regulatory mechanisms associated with pyroptosis deserve further in-depth research.


Assuntos
Biologia Computacional , Redes Reguladoras de Genes , Mapas de Interação de Proteínas , Piroptose , Traumatismos da Medula Espinal , Animais , Traumatismos da Medula Espinal/genética , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Camundongos , Piroptose/genética , Ratos , Biologia Computacional/métodos , Mapas de Interação de Proteínas/genética , Perfilação da Expressão Gênica
7.
Front Surg ; 9: 860564, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35478724

RESUMO

Objective: To establish a regression formula for LL based on individual PI and TK in asymptomatic population aged over 50 years and evaluate its predictive power for the occurrence of postoperative mechanical complications in patients with adult spinal deformity (ASD). Methods: A total of 178 asymptomatic adults were recruited for the study. The association between LL and PI, LL and TK, was investigated to establish a predictive formula for ideal LL based on PI and TK. Additionally, 93 ASD patients undergoing posterior correction surgery were retrospectively analyzed. The absolute value of the gap between postoperative actual LL and theoretical LL was defined as ΔLL. Patients were classified into two groups depending on the presence or absence of mechanical complications. The demographic and radiological data of patients were compared between the two groups. Results: A significant association was found between LL and PI (r = 0.599, P < 0.001), LL and TK (r = 0.523, P < 0.001). A novel formula was developed as follows: LL = 0.7*PI + 0.4*TK + 1 (R 2 = 0.524). In the validation cohort, 29 patients developed mechanical complications. Postoperative ΔLL (12.5 ± 7.6° vs. 7.0 ± 5.4°, P = 0.001) significantly increased the incidence of mechanical complications. The most appropriate threshold of ΔLL for predicting mechanical complications was 9.8°. For patients whose ΔLL were <9.8° and >9.8°, the incidence of mechanical complications was 19.4% and 54.8%, respectively. Conclusion: Ideal lumbar lordosis should be matched for PI and TK. The developed prediction formula for LL based on PI and TK in asymptomatic adults may help surgeons to understand the mechanisms of lumbar alignment generation and predict occurrence of mechanical complications after ASD surgery.

8.
Front Surg ; 9: 912357, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36248369

RESUMO

Objective: The main aim of this study was to comprehensively explore the relationship among pelvic incidence (PI), inflection point (IP), and apex of lumbar lordosis (LLA), and establish a predictive formula for LLA based on individual PI and IP in asymptomatic Chinese adults. Methods: A total of 385 asymptomatic adults with average age 38.3 ± 11.9 years (range 20-73 years) were recruited between November 2020 and October 2021. Full-spine, standing x-rays were then obtained from each participant. Next, the following sagittal parameters were measured: PI, IP, LLA, the horizontal offset between the plumb line of the lumbar apex and that of the posterosuperior corner of S1 (LASO), the upper lumbar lordosis (ULL) and lower lumbar lordosis (LLL), lumbar lordosis (LL), and thoracic kyphosis (TK). Moreover, the association among PI, IP, and the other sagittal parameters was evaluated, followed by linear regression analyses. A P-value of <0.05 was considered statistically significant. Results: PI showed statistically significant correlations with LLA (rs = -0.629; P < 0.01), LASO (rs = 0.537; P < 0.01), LLL (rs = 0.788; P < 0.01), and LL (rs = 0.663; P < 0.01). On the other hand, IP also showed statistically significant correlations with LLA (rs = 0.671; P < 0.01), LASO (rs = -0.493; P < 0.01), LLL (rs = -0.402; P < 0.01), and LL (rs = -0.283; P < 0.01). The corresponding predictive formulae were displayed as follows: LLA = -0.03 * PI + 0.23 * IP + 14.45 (R 2 = 0.669); LASO = 0.38 * PI-2.09 * IP + 53.62 (R 2 = 0.460); and LLL = 0.58 * PI-0.88 * IP + 18.86 (R 2 = 0.659). Conclusion: The specific lumbar shape should be modulated by pelvic morphology and IP level. In addition, we established predictive formulae for ideal sagittal lumbar profile based on individual PI and IP, with the overarching goal of helping surgeons to better comprehend the regulatory mechanisms of the individual sagittal lumbar alignment, and design a precise and personalized corrective plan.

9.
Front Surg ; 9: 961582, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36684332

RESUMO

Purpose: This study aimed to summarize the characteristics of the 100 most-cited articles on adult spinal deformity (ASD) and to analyze past and current research hotspots and trends. Methods: Literature searches (from inception to 28 April 2022) using Web of Science databases were conducted to identify ASD-related articles. The top 100 most-cited articles were collected for further analysis. Meanwhile, author keywords from articles published in the last 5 years were selected for further analysis. Results: The top 100 most-cited articles on ASD were selected from 3,354 papers. The publication year ranged from 1979 to 2017, and all papers were written in English. The citation count among them ranged from 100 to 1,145, and the mean citation number was 215.2. The foremost productive first author was Schwab F. University of Washington had the largest number of publications. The United States of America had the largest number of published articles (n = 84) in this field. Spine was the most popular journal. Complications were the most studied themes. The visualization analysis of author keywords from the literature in the recent 5 years showed that complications, sagittal plane parameters, and surgical techniques are still the research hotspots, and minimally invasive surgery will continue to develop rapidly. Conclusion: Based on a comparative analysis of the results of bibliometric and visualization, complications and sagittal plane parameters are still the major topics of research at present and even later, and minimally invasive surgery has a growth trend in this field of ASD.

10.
Mol Immunol ; 135: 294-303, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33957479

RESUMO

Increasing evidence suggests that endoplasmic reticulum (ER) stress activates several pro-inflammatory signaling pathways in many diseases, including acute lung injury (ALI). We have reported that blocking triggering receptor expressed on myeloid cells 1 (TREM-1) protects against ALI by suppressing pulmonary inflammation in mice with ALI induced by lipopolysaccharides (LPS). However, the molecular mechanism underlying the TREM-1-induced pro-inflammatory microenvironment in macrophages remains unclearly. Herein, we aimed to determine whether TREM-1 regulates the inflammatory responses induced by LPS associated with ER stress activation. We found that the activation of TREM-1 by a monoclonal agonist antibody (anti-TREM-1) increased the mRNA and protein levels of IL-1ß, TNF-α, and IL-6 in primary macrophages. Treatment of the anti-TREM-1 antibody increased the expression of ER stress markers (ATF6, PERK, IRE-1α, and XBP-1s) in primary macrophages. While pretreatment with 4-PBA, an inhibitor of ER stress, significantly inhibited the expression of ER stress markers and pro-inflammatory cytokines and reduced LDH release. Furthermore, inhibiting the activity of the IRE-1α/XBP-1s pathway by STF-083010 significantly mitigated the increased levels of IL-1ß, TNF-α, and IL-6 in macrophages treated by the anti-TREM-1 antibody. XBP-1 silencing attenuated pro-inflammatory microenvironment evoked by activation of TREM-1. Besides, we found that blockade of TREM-1 with LR12 ameliorated ER stress induced by LPS in vitro and in vivo. In conclusion, we conclude that TREM-1 activation induces ER stress through the IRE-1α/XBP-1s pathway in macrophages, contributing to the pro-inflammatory microenvironment.


Assuntos
Estresse do Retículo Endoplasmático/fisiologia , Macrófagos/patologia , Proteínas de Membrana/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Receptor Gatilho 1 Expresso em Células Mieloides/metabolismo , Proteína 1 de Ligação a X-Box/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Anticorpos Monoclonais/imunologia , Microambiente Celular/imunologia , Inflamação/imunologia , Interleucina-1beta/análise , Interleucina-6/análise , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Pneumonia/induzido quimicamente , Pneumonia/prevenção & controle , Interferência de RNA , Receptor Gatilho 1 Expresso em Células Mieloides/antagonistas & inibidores , Fator de Necrose Tumoral alfa/análise , Proteína 1 de Ligação a X-Box/genética
11.
Neurosurgery ; 85(6): E1095-E1110, 2019 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-31501892

RESUMO

BACKGROUND: Currently, little is known about the clinical relevance of tumor-stroma ratio (TSR) in chordoma and data discussing the relationship between TSR and immune status of chordoma are lacking. OBJECTIVE: To characterize TSR distribution in spinal chordoma, and investigated its correlation with clinicopathologic or immunological features of patients and outcome. METHODS: TSR was assessed visually on hematoxylin and eosin-stained sections from 54 tumor specimens by 2 independent pathologists. Multiplex immunofluorescence was used to quantify the expression levels of microvessel density, Ki-67, Brachyury, and tumor as well as stromal PD-L1. Tumor immunity status including the Immunoscore and densities of tumor-infiltrating lymphocytes (TILs) subtypes were obtained from our published data and reanalyzed. RESULTS: Bland-Altman plot showed no difference between mean TSR derived from the two observers. TSR was positively associated with stromal PD-L1 expression, the Immunoscore and CD3+ as well as CD4+ TILs density, but negatively correlated with tumor microvessel density, Ki-67 index, surrounding muscle invasion by tumor and number of Foxp3+ and PD-1+ TILs. Low TSR independently predicted poor local recurrence-free survival and overall survival. Moreover, patients with low TSR and low Immunoscore chordoma phenotype were associated with the worst survival. More importantly, combined TSR and Immunoscore accurately reflected prognosis and enhanced the ability of TSR or Immunoscore alone for outcome prediction. CONCLUSION: These data reveal the significant impact of TSR on tumor progression and immunological response of patients. Subsequent use of agents targeting the stroma compartment may be an effective strategy to treat chordoma especially in combination with immune-based drugs.


Assuntos
Cordoma/imunologia , Cordoma/mortalidade , Neoplasias da Coluna Vertebral/imunologia , Neoplasias da Coluna Vertebral/mortalidade , Microambiente Tumoral/imunologia , Idoso , Cordoma/diagnóstico por imagem , Progressão da Doença , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Neoplasias da Coluna Vertebral/diagnóstico por imagem , Taxa de Sobrevida/tendências
12.
Mol Med Rep ; 17(2): 2957-2963, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29257287

RESUMO

This study is to reveal the characteristics of autophagy and the effect of neuroserpin (NSP) treatment on autophagy during the process of functional recovery following spinal cord injury (SCI). After the clip compress rat model of SCI had been made, autophagy­associated proteins, including LC3­II, beclin­1 and p62, were evaluated at 2, 4, 24, 72 h, and 168 h in the experimental group, and the sham group as control. Transmission electron microscopy (TEM) was further used for autophagy detection at 4 and 72 h. All the male rats were randomly divided into three groups: Sham, vehicle and NSP group. NSP or an equal volume of saline vehicle was administered via intrathecal injection immediately after SCI. Each group was further divided into subgroups for the following experiments: i)Western blot (LC3­II and p62); ii) Immunofluorescent double staining (LC3/MAP­2/DAPI); iii) Nissl staining and Basso Beattie Bresnahan (BBB score) for NSP neuroprotection evaluation. Our results revealed both LC3­II and p62 expression trended upward at 24, 72 and 168 h after SCI. The LC3­II peaked at 72 h, while p62 peaked at 24 h. Beclin­1 dropped significantly at 72 and 168 h. TEM results showed that autophagosomes largely accumulated at 72 h after SCI when compared with the sham group. Western blot analysis showed that LC3­II and p62 were markedly decreased with NSP treatment at 72 h after injury compared with that of the vehicle­group. Immunofluorescent double labeling indicated that accumulation of autophagosomes was reduced in the NSP group. Further, post­SCI treatment with NSP improved the BBB scale and increased the number of anterior horn motor neurons. Together, this study demonstrates that autophagic flux is impaired, meanwhile NSP restores autophagic flux and promotes functional recovery after SCI in rats.


Assuntos
Autofagia/efeitos dos fármacos , Neuropeptídeos/uso terapêutico , Fármacos Neuroprotetores/uso terapêutico , Inibidores de Serina Proteinase/uso terapêutico , Serpinas/uso terapêutico , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Autofagossomos/efeitos dos fármacos , Autofagossomos/patologia , Modelos Animais de Doenças , Masculino , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/fisiopatologia , Neuroserpina
13.
Cell Death Dis ; 9(10): 1020, 2018 10 03.
Artigo em Inglês | MEDLINE | ID: mdl-30282965

RESUMO

Huntingtin interaction protein 2 (HIP2) is an E2 ubiquitin-conjugating enzyme associated with neurodegenerative diseases, and HIP2 mRNA has been implicated as a potential blood biomarker for Parkinson's disease (PD). However, it is unclear whether the alteration of HIP2 expression may contribute to the development of PD, and whether the change of HIP2 in blood could reflect its expression in the brain or motor functions in PD patients. In this study, we established a mouse line with HIP2 haploinsufficiency. The reduction of the HIP2 expression led to spontaneous motor function impairment and dopaminergic neuronal loss. Furthermore, HIP2 haploinsufficiency increased the susceptibility of mice to 6-hydroxydopamine (6-OHDA) and caused severe loss of dopaminergic neurons. Interestingly, in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model for PD, we observed concurrent, highly correlated decrease of HIP2 expression in the brain and in the blood. Using blood samples from more than 300 patients, we validated the decreased HIP2 mRNA in PD patients, including de novo patients. Finally, in a 1-year, 20-patient study, we observed reversed blood HIP2 mRNA levels accompanying improved motor and overall daily functions in 75% of the PD patients with instructed Tai Chi training. Therefore, our in vivo studies have indicated HIP2 insufficiency as a contributing factor for PD, and functionally validated blood HIP2 as a useful and reversible biomarker for PD.


Assuntos
Dopamina/metabolismo , Neurônios Dopaminérgicos/metabolismo , Atividade Motora/fisiologia , Doença de Parkinson/metabolismo , Enzimas de Conjugação de Ubiquitina/metabolismo , 1-Metil-4-Fenil-1,2,3,6-Tetra-Hidropiridina/farmacologia , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/efeitos dos fármacos , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Atividade Motora/efeitos dos fármacos , Oxidopamina/farmacologia
14.
Clin Spine Surg ; 30(6): E776-E783, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27404853

RESUMO

STUDY DESIGN: A retrospective clinical study. OBJECTIVE: This study sought to retrospectively compare the mid-term to long-term outcomes between unilateral pedicle screw (UPS) and bilateral pedicle screw (BPS) augmented transforaminal lumbar interbody fusion (TLIF) in lumbar degenerative diseases. SUMMARY OF BACKGROUND DATA: Recently, UPS fixation has been applied in TLIF, for its satisfactory clinical outcome, less implants and less invasiveness. However, only short-term outcome has been reported, the mid-term to long-term outcome has not been well characterized. MATERIALS AND METHODS: From June 2007 to February 2011, 215 of 348 consecutive patients suffering from lumbar degenerative diseases were operated in our hospital and accomplished a minimum of 4-year follow-up. These patients were divided into 2 groups according to the operative techniques: UPS group (n=109), and bilateral pedicle screw group (n=106). Operative time, blood loss, length of hospital stay, hospital bill, fusion status, and complications were recorded and analyzed statistically. Visual analog scale, Oswestry disability index, and Japanese Orthopaedic Association scores were used to assess the preoperative and postoperative pain and functional outcome. RESULTS: The mean follow-up duration was 52.2 months. A significant decrease occurred in operative time, blood loss, and hospital bill in unilateral group, compared with bilateral group (P<0.05). The average postoperative visual analog scale, Oswestry disability index, and Japanese Orthopaedic Association scores improved significantly in each group than the preoperative counterparts (P<0.05); however, there were no significant difference between groups at any follow-up time point (P>0.05). No statistically difference was detected regarding fusion rate and complication rate between the 2 groups (P>0.05), except the cage migration rate (P<0.05). CONCLUSIONS: UPS fixation could achieve satisfactory clinical outcome similar to bilateral fixation in TLIF at a mid-term to long-term follow-up. To avoid cage migration, bullet-shaped cages should not be used in the unilateral group.


Assuntos
Forame Magno/cirurgia , Vértebras Lombares/cirurgia , Parafusos Pediculares , Fusão Vertebral , Demografia , Avaliação da Deficiência , Feminino , Seguimentos , Forame Magno/diagnóstico por imagem , Humanos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Parafusos Pediculares/efeitos adversos , Assistência Perioperatória , Complicações Pós-Operatórias/etiologia , Escoliose/diagnóstico por imagem , Escoliose/cirurgia , Fusão Vertebral/efeitos adversos , Tomografia Computadorizada por Raios X , Escala Visual Analógica
15.
Clin Biomech (Bristol, Avon) ; 49: 91-95, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28898815

RESUMO

BACKGROUNDS: A variety of improved surgical methods were adopted in the transforaminal lumbar interbody fusion. A mechanical stability provides an ideal environment for the formation of a fusion mass and is the basis of their good outcomes. The object of this study is to evaluate the initial similarities and differences of four commonly-used posterior surgical procedures biomechanically. METHODS: Biomechanical testing was performed at L3-4 motion segment in 6 fresh-frozen human cadaveric lumbar spines (L2-L5), including the following sequentially tested configurations: 1) intact motion segment; 2) bilateral pedicle screw fixation; 3) unilateral pedicle screw fixation; 4) unilateral pedicle screw plus contralateral translaminar facet joint screw fixation according to the Magerl technique; and 5) bilateral pedicle screw fixation with bilateral facetectomies. The range of motion, neutral zone and stiffness of each method and intact segment were collected and compared. FINDINGS: All of four methods reduce the range of motion significantly in flexion and extension and lateral bending but not in axial torsion compared with the native segment. There is no significant difference among four procedures about the range of motion in all loading modes. All of methods increase the stiffness of segmental motion compared with intact segment in all loading modes, but only bilateral pedicle screw fixation showed significant increases in stiffness in flexion and extension(p=0.02) and lateral bending(p=0.023). The stiffness offered by instrumented constructs in different methods showed no significant difference in all loading modes. INTERPRETATION: The stiffness offered by four different posterior fixations in single segmental transforaminal lumbar interbody fusion is not significantly different.


Assuntos
Vértebras Lombares/cirurgia , Amplitude de Movimento Articular/fisiologia , Fusão Vertebral/métodos , Fenômenos Biomecânicos , Parafusos Ósseos , Cadáver , Humanos , Vértebras Lombares/fisiopatologia , Região Lombossacral , Parafusos Pediculares , Articulação Zigapofisária/cirurgia
16.
Biomed Res Int ; 2016: 7261027, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27885358

RESUMO

The aim of this study was to evaluate the risk factors between ipsilateral and contralateral reherniation and to compare the effectiveness of miniopen transforaminal lumbar interbody fusion (TLIF) with unilateral fixation for each group. From November 2007 to December 2014, clinical and radiographic data of each group (ipsilateral or contralateral reherniation) were collected and compared. Functional assessment (Visual Analog Scale (VAS) score and Japanese Orthopaedic Association (JOA)) and radiographic evaluation (fusion status, disc height, lumbar lordosis (LL), and functional spine unit (FSU) angle) were applied to compare surgical effect for each group preoperatively and at final followup. MacNab questionnaire was applied to further evaluate the satisfactory rate after the discectomy and fusion. No difference except pain-free interval was found between ipsilateral and contralateral groups. There was a significant difference in operative time between two groups. No differences were found in clinical and radiographic data for assessment of surgical effect between two groups. The satisfactory rate was decreasing in both groups with time passing after discectomy. Difference in pain-free interval may be a distinction for ipsilateral and contralateral reherniation. Miniopen TLIF with unilateral pedicle screw fixation can be a recommendable way for single level reherniation regardless of ipsilateral or contralateral reherniation.


Assuntos
Deslocamento do Disco Intervertebral/cirurgia , Vértebras Lombares/cirurgia , Fusão Vertebral/métodos , Feminino , Humanos , Deslocamento do Disco Intervertebral/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Satisfação do Paciente , Parafusos Pediculares , Fatores de Risco , Inquéritos e Questionários , Resultado do Tratamento
17.
J Neurosurg Spine ; 24(3): 375-80, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26637067

RESUMO

OBJECT: This study sought to make a biomechanical comparison of 3 different posterior fixation techniques for 2-level lumbar spinal disorders. METHODS: Eight fresh-frozen human cadaver lumbar spines (4 from L-1 to L-5, 4 from L-1 to S-1) were tested by applying pure moments of ± 8 Nm. Each specimen was first tested intact, and then the left facetectomies of L3-4 and L4-5 were performed to establish an unstable condition without removal of discs. Three instrumentation systems were then tested randomly: unilateral pedicle screw (UPS), UPS with contralateral translaminar facet screw (UPSFS), and bilateral pedicle screw (BPS). The range of motion (ROM) and the neutral zone (NZ) of L3-5 were measured. RESULTS: All fixation types could reduce the ROM of L3-5 significantly in flexion, extension, and lateral bending, compared with the intact state. In axial torsion, only BPS reduced the ROM significantly, compared with the intact state. The UPSFS technique provided intermediate stability, which was superior to the UPS in flexion-extension and lateral bending, and inferior to the BPS in lateral bending. Compared with the intact state, the NZs decreased significantly for UPS, UPSFS, and BPS in flexion-extension, while not significantly in lateral bending and axial torsion. CONCLUSIONS: In this study, among the 3 fixation techniques, BPS offered the highest stability, UPSFS provided intermediate stability, and UPS was the least stable for 2-level lumbar spinal disorders. UPSFS appeared to be able to offer a less invasive choice than BPS in well-selected patients with 2-level lumbar spinal disorders.


Assuntos
Vértebras Lombares/fisiopatologia , Vértebras Lombares/cirurgia , Doenças da Coluna Vertebral/fisiopatologia , Doenças da Coluna Vertebral/cirurgia , Adulto , Fenômenos Biomecânicos , Cadáver , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Dispositivos de Fixação Ortopédica , Amplitude de Movimento Articular
19.
Clin Neurol Neurosurg ; 141: 1-6, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26691785

RESUMO

OBJECTIVES: This study sought to retrospectively compare three different posterior fixation techniques in transforaminal lumbar interbody fusion for two-level lumbar degenerative diseases. PATIENTS AND METHODS: This was a retrospective single-center study including 84 patients who underwent TLIF instrumented with unilateral pedicle screws (UPS), unilateral pedicle screws plus contra-lateral translaminar facet screws (UPSFS), or bilateral pedicle screws (BPS) between June 2008 and May 2012. These patients were divided into three groups: UPS (n=22), UPSFS (n=28) and BPS (n=34) group. Operative time, blood loss, length of hospital stay, hospital bill, fusion status and complications were recorded and analyzed statistically. Visual analog scale (VAS), Oswestry Disability Index (ODI), and Japanese Orthopaedic Association Scores (JOA) were used to assess the preoperative and postoperative pain and functional outcome. Sagittal alignment was evaluated by the segment lordosis (SL) and whole lumbar spine lordosis (LL). RESULTS: The mean follow up duration was 46.2 (ranging from 36 to 60) months. A significant decrease occurred in operative time, blood loss and hospital bill in UPS and UPSFS group, compared with BPS group (p<0.05). The average postoperative VAS, ODI and JOA scores improved significantly in each group than the preoperative counterparts (p<0.05), however, there were no significant difference between groups at any follow-up time point (p>0.05). No statistically difference was detected regarding fusion rate and complication rate between groups (p>0.05), except the screw/rod failure rate (p<0.05). Radiographic analysis showed that the LLs in all these groups got improved (p<0.05) and the SLs maintained (p>0.05). CONCLUSION: UPS or UPSFS instrumented TLIF could achieve satisfactory mid-term clinical outcome comparable to BPS's, with less surgical time, less blood loss, and lower cost; UPS should be prudently performed for two-level cases in case of lower fusion rate, and cannulated screws should be replaced by stronger solid screws in UPSFS to reduce facet screw breakage.


Assuntos
Parafusos Ósseos/normas , Vértebras Lombares/cirurgia , Doenças Neurodegenerativas/cirurgia , Fusão Vertebral/métodos , Fusão Vertebral/normas , Idoso , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Fixadores Internos/normas , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Doenças Neurodegenerativas/diagnóstico por imagem , Radiografia , Estudos Retrospectivos , Fusão Vertebral/instrumentação , Fatores de Tempo
20.
Indian J Orthop ; 48(4): 374-9, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25143640

RESUMO

BACKGROUND: Transforaminal lumbar interbody fusion (TLIF) has been used in lumbar degenerative diseases. Some researchers have applied unilateral fixation in TLIF to reduce operational trauma without compromising the clinical outcome, but it is always suspected biomechanically unstable. The supplementary contralateral translaminar facet screw (cTLFS) seemed to be able to overcome the inherent drawbacks of unilateral pedicle screw (uPS) fixation theoretically. This study evaluates the safety, feasibility and efficacy of TLIF using uPS with cTLFS fixation in the treatment of lumbar degenerative diseases (LDD). MATERIALS AND METHODS: 50 patients (29 male) underwent the aforementioned surgical technique for their LDD between December 2009 and April 2012. The results were evaluated based on visual analogue scale (VAS) of the leg and back, Japanese Orthopedic Association (JOA) score and Oswestry Disability Index (ODI) were recorded. The radiographic examinations in form of X-ray, computed tomography (CT) or magnetic resonance imaging was done preoperatively and 1 week, 3 months, 6 months, 12 months and 24 months postoperatively. The student t-test was used for comparison between the preoperative values and postoperative counterparts. P < 0.05 was considered to be statistically significant. RESULTS: Among 50 patients, 22 received one level fusion and 28 two level's, with corresponding operation time and estimated blood loss being approximately 90 min, 150 ml and 120 min, 200 ml, respectively. No severe complications happened perioperatively. The mean VAS (back, leg) scores dropped from (7.6, 7.5) preoperatively to (2.1, 0.6) at 12 months' followup, ODI from 49.1 preoperatively to 5.6 and JOA score raised from 10.6 preoperatively to 28.5, all P < 0.001, suggesting of good clinical outcome. From the three-dimensional reconstructed CT, 62 out of 70 segments displayed solid fusion with fusion rate of 88.6% at 12 months postoperatively. CONCLUSIONS: TLIF using uPS fixation plus cTLFS fixation is a safe, feasible and effective technique in the treatment of one or two level lumbar degenerative diseases short termly.

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