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1.
Mol Ther ; 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38879755

RESUMO

The extensive degeneration of functional somatic cells and the depletion of endogenous stem/progenitor populations present significant challenges to tissue regeneration in degenerative diseases. Currently, a cellular reprogramming approach enabling directly generating corresponding progenitor populations from degenerative somatic cells remains elusive. The present study focused on intervertebral disc degeneration (IVDD) and identified a three-factor combination (OCT4, FOXA2, TBXT (OFT)) that could induce the dedifferentiation-like reprogramming of degenerative nucleus pulposus cells (dNPCs) toward induced notochordal-like cells (iNCs). Single-cell transcriptomics dissected the transitions of cell identity during reprogramming. Further, OCT4 was found to directly interact with bromodomain PHD-finger transcription factor (BPTF) to remodel the chromatin during the early phases, which was crucial for initiating this dedifferentiation-like reprogramming. In rat models, intradiscal injection of adeno-associated virus carrying OFT generated iNCs from in situ dNPCs and reversed IVDD. These results collectively present a proof-of-concept for dedifferentiation-like reprogramming of degenerated somatic cells into corresponding progenitors through the development of a factor-based strategy, providing a promising approach for regeneration in degenerative disc diseases.

2.
Clin Infect Dis ; 76(3): e1140-e1149, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36037029

RESUMO

BACKGROUND: To provide useful insights into measles elimination progress in China, measles surveillance data were reviewed, and the transmission patterns of measles viruses circulating in China during 1993-2021 were analyzed. METHODS: Measles incidence data from the National Notifiable Disease Reporting System of the China Center for Disease Control and Prevention were analyzed. A total of 17 570 strains were obtained from 30 of 31 provinces in mainland China during 1993-2021. The recommended genotyping window was amplified. Genotyping analysis was conducted for comparison with the reference strains. Phylogenetic analyses were performed to identify genetic relationships among different lineages within the genotypes. RESULTS: With high coverage of routine immunization and intensive supplementary immunization activities, measles incidence has shown a downward trend since 1993, despite 2 resurgences, reaching a historic low level in 2020-2021 (average 0.5 per million). During 1993-2021, 9 genotypes including domestic genotype H1; imported genotypes B3, D4, D8, D9, D11, G3, and H2; and vaccine-associated genotype A were identified. Among them, the genotype H1 strain circulated endemically in China for more than 25 years; the last strain was detected in Yunnan Province in September 2019. Multiple imported genotypes have been identified since 2009 showing different transmission patterns. Since April 2020, no imported strains have been detected, while vaccine-associated genotype A continues to be detected. CONCLUSIONS: The evidence of low incidence during 2020-2021 and virological surveillance data in this study confirm that China is currently approaching measles elimination.


Assuntos
Vírus do Sarampo , Sarampo , Humanos , Vírus do Sarampo/genética , Genótipo , Filogenia , China/epidemiologia , Sarampo/epidemiologia , Sarampo/prevenção & controle
3.
Br J Neurosurg ; 37(3): 503-506, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32552046

RESUMO

Progressive thoracic myelopathy caused by ossification of posterior longitudinal ligament (OPLL) responds poorly to conservative therapy. The most direct decompression is extirpation of ossified posterior longitudinal ligament (PLL). Surgical outcomes of posterior approaches to remove ossified PLL are not always satisfactory because of the risk of neurological deterioration. In this study, we modified the conventional anterior decompression technique via a posterior approach for thoracic OPLL. From an anterior approach, the posterior cortex of vertebral body was exposed and the ossified PLL was removed. Then kyphosis correction was done via posterior instrumentation to reduce cord compression between dura under tension and the anterior canal wall. From the back, the distal end of the ossified PLL was displaced anteriorly to create a gap between ossified PLL and dura, remaining adhesions were divided and the ossified PLL was manipulated through this gap under direct vision. The surgical technique was applied in 20 patients with thoracic myelopathy caused by OPLL. One case of postoperative neurological deterioration was encountered but this recovered fully. Our outcomes were relatively favorable.


Assuntos
Ossificação do Ligamento Longitudinal Posterior , Doenças da Medula Espinal , Estenose Espinal , Humanos , Descompressão Cirúrgica/métodos , Estenose Espinal/cirurgia , Estenose Espinal/complicações , Vértebras Torácicas/cirurgia , Doenças da Medula Espinal/etiologia , Doenças da Medula Espinal/cirurgia , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Ossificação do Ligamento Longitudinal Posterior/complicações
4.
Cell Mol Biol (Noisy-le-grand) ; 68(1): 26-34, 2022 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-35809331

RESUMO

The current experiment was carried out to explore the effect of the miR-146a-mediated TLR4 signaling pathway on the lumbar disc herniation pains. For this aim, a total of 32 rats were divided randomly into 4 groups - the blank group (Group C), Model group (M), miR-146a overexpression group (agomiR-146a group) and negative control group (NC group), with 8 rats in each group. Rats in Group M were prepared for the construction of lumbar disc herniation models, while those in the agomiR-146a group or NC group, in addition to the model construction, would receive the intrathecal injection of agomiR-146a or agomiRNA-146a NC. Thereafter, a series of tests were performed for rats, including the mechanical pain test and heat pain test to measure the pain threshold, RT-PCR to detect the expression of miR-146a, and the transcription of TLR4, IRAK1, TRAF6, IL-6 and TNF-α, Western blot to determine the expression of IRAK1 and TRAF6 and ELISA to determine the expression of IL-6 and TNF-α. Results showed that as compared to the blank group, rats in Group M were more sensitive to the pains, presenting with declines in the thresholds in the pain, and upregulation in the TRL4 signaling pathway (TLR4, IRAK1 and TRAF6) and pro-inflammatory factors, including IL-6 and TNF-α. In comparison with Group M, intrathecal injection of agomiR-146a relieved the pains, with significant upregulation of miR-146a and downregulation of TLR4, IRAK1, TRAF6, IL-6 and TNF-α. Then upregulation of miR-146a could reduce the activity of the TLR4 signaling pathway and the release of pro-inflammatory factors, which may be a potential strategy for the treatment of lumbar disc herniation.


Assuntos
Deslocamento do Disco Intervertebral , MicroRNAs , Animais , Quinases Associadas a Receptores de Interleucina-1/genética , Quinases Associadas a Receptores de Interleucina-1/metabolismo , Interleucina-6/metabolismo , Deslocamento do Disco Intervertebral/genética , MicroRNAs/genética , MicroRNAs/metabolismo , NF-kappa B/metabolismo , Dor , Ratos , Transdução de Sinais , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
Eur Spine J ; 31(12): 3768-3775, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36169729

RESUMO

PURPOSE: Severe cervical axial deformity associated with ankylosing spondylitis (AS) is rare in clinic, and there are little concerns about surgical treatment of axial deformity associated with AS. The case study aims to show the surgical technique to perform cervical rotational osteotomy. METHODS: We present the case of a young AS patient whose neck was fixed in a left-rotational posture at 18°, requiring his trunk to be turned to the right to look forward visually. This made his gait appear to be limping, inconveniencing him with great difficulty. In order to correct this deformity, we performed a novel cervical rotational osteotomy through a one-stage posterior-anterior-posterior approach. Firstly, we performed laminectomies of C7 and T1, followed by a C7/T1 facetectomy with release of the bilateral C8 nerve roots. Next, we performed C7/T1 discectomy, bony resection of the lateral body and uncovertebral joints. The head of the patient was then rotated manually, so that both his face and torso were simultaneously facing frontward. Finally, rods spanning the screws from C6 to T2 were fixed. RESULTS: Postoperatively, the patient's axial malalignment was significantly improved, and he was able to walk normally. Surgical outcomes were well maintained at a 3-year follow-up. CONCLUSION: Through this case, we hope to draw the attention to spinal axial deformity and provide a reference point in the surgical treatment of spinal axial deformity.


Assuntos
Cifose , Espondilite Anquilosante , Humanos , Masculino , Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Espondilite Anquilosante/complicações , Espondilite Anquilosante/diagnóstico por imagem , Espondilite Anquilosante/cirurgia , Osteotomia/métodos , Discotomia , Postura , Cifose/diagnóstico por imagem , Cifose/etiologia , Cifose/cirurgia , Resultado do Tratamento
6.
Int Orthop ; 46(5): 1101-1109, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35132497

RESUMO

PURPOSE: To analyze the predictors for second-stage posterior direct decompression (PDD) after lateral lumbar interbody fusion (LLIF) procedure. METHODS: We studied patients who underwent LLIF for degenerative lumbar spinal stenosis in the last five years, from July 2016 to June 2021. All surgical levels were grouped according to Schizas' central canal stenosis (CCS) classification, Pathria's facet joint degeneration (FJD) classification, Bartynski's lateral recess stenosis (LRS) classification, and Lee's foraminal stenosis (FS) classification. Second-stage PDD rates of each subgroup and their annual change were analyzed. Evaluation of risk factors associated with PDD was investigated. RESULTS: A total of 901 segments from 557 patients were included. The overall PDD rate was 29.97%. An overall PDD rate of 75.21% for grade D CCS, 29.74% for grade C CCS, 41.67% for grade 3 FJD, 37.61% for grade 3 LRS, and 40.70% for grade 3 FS was shown. While there was a continuous decline in annual PDD rate in the past four years, the annual PDD rate for grade D remained at very high levels. Logistic regression analysis had shown grade D CCS as the utmost risk factor for PDD (OR = 17.77). And grade 3 LRS (OR = 4.63), grade 3 FS (OR = 2.42), grade C CCS (OR = 2.41), and grade 3 FJD (OR = 2.04) were also moderately correlated with PDD, which meant they only moderately increased the risk of PDD. CONCLUSION: Extreme severe lumbar CCS (grade D) is the greatest determinant to perform the second-stage PDD procedure after LLIF.


Assuntos
Vértebras Lombares , Fusão Vertebral , Constrição Patológica/etiologia , Constrição Patológica/cirurgia , Descompressão Cirúrgica/efeitos adversos , Descompressão Cirúrgica/métodos , Humanos , Vértebras Lombares/cirurgia , Estudos Retrospectivos , Fusão Vertebral/efeitos adversos , Fusão Vertebral/métodos
7.
Clin Infect Dis ; 73(7): 1157-1164, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33904899

RESUMO

BACKGROUND: To provide a better understanding of the progress on rubella control and elimination in China, a genetic analysis was conducted to examine the transmission pattern of the endemic rubella virus in China during 2010-2019. METHODS: A total of 4895 strains were obtained from 29 of the 31 provinces in mainland China during 2010-2019. The genotyping regions of the strains were amplified, determined, and assembled. Genotyping analysis and lineage division were performed by comparisons with the World Health Organization reference strains and reported lineage reference strains, respectively. Further phylogenetic analyses were performed to compare the genetic relationship. RESULTS: During 2010-2019, the domestic lineage 1E-L1 and multiple imported lineages of rubella viruses including 2B-L1, 1E-L2, and 2B-L2c were identified. Further analysis of the circulation trend of the different lineages indicated that 2 switches occurred among the lineages. The first shift was from lineage 1E-L1 to 2B-L1, which occurred around 2015-2016, followed by the lowest rubella incidence in 2017. The second shift was from lineage 2B-L1 to 1E-L2 and 2B-L2c, which occurred around 2018-2019, coinciding with rubella resurgence and the subsequent nationwide epidemic during 2018-2019. Insufficient genomic information worldwide made it impossible to trace the origin of the imported viruses. CONCLUSIONS: China was moving toward rubella elimination, as evidenced by the fact that previous endemic lineages were not detected. However, rubella reemerged in 2018 2019 due to the newly imported rubella viruses. Therefore, to realize the rubella elimination goal, joint efforts are required for all countries worldwide.


Assuntos
Vírus da Rubéola , Rubéola (Sarampo Alemão) , China/epidemiologia , Genótipo , Humanos , Filogenia , Rubéola (Sarampo Alemão)/epidemiologia , Vírus da Rubéola/genética
8.
FASEB J ; 34(9): 12147-12162, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32686873

RESUMO

Duraplasty after decompression decreases the lesion size and scar formation, promoting better functional recovery, but the underlying mechanism has not been clarified. Here, we fabricated a series of poly(hydroxybutyrate-co-hydroxyvalerate)/polylactic acid/collagen (PHBV/PLA/Col) membranes and cultured them with VSC4.1 motor neurons. The material characteristics and in vitro biological characteristics were evaluated. In the subcutaneous implantation test, PHBV/PLA/COl scaffolds supported the cellular infiltration, microvasculature formation, and decreased CD86-positive macrophage aggregation. Following contusion spinal cord injury at T10 in Sprague-Dawley rats, durotomy was performed with allograft dura mater or PHBV/PLA or PHBV/PLA/Col membranes. At 3 days post-injury, Western blot assay showed decreased the expression of the NLRP3, ASC, cleaved-caspase-1, IL-1ß, TNF-α, and CD86 expression but increased the expression of CD206. Immunofluorescence demonstrated that duraplasty with PHBV/PLA/Col membranes reduced the infiltration of CD86-positive macrophages in the lesion site, decreased the glial fibrillary acidic protein expression, and increased the expression of NF-200. Moreover, duraplasty with PHBV/PLA/Col membranes improved locomotor functional recovery at 8 weeks post-injury. Thus, duraplasty with PHBV/PLA/Col membranes decreased the glial scar formation and promoted axon growth by inhibiting inflammasome activation and modulating macrophage polarization in acute spinal cord injury.


Assuntos
Axônios/metabolismo , Macrófagos/metabolismo , Membranas Artificiais , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Regeneração , Traumatismos da Medula Espinal , Animais , Axônios/patologia , Colágeno/química , Colágeno/farmacologia , Feminino , Macrófagos/patologia , Poliésteres/química , Poliésteres/farmacologia , Ratos , Ratos Sprague-Dawley , Traumatismos da Medula Espinal/metabolismo , Traumatismos da Medula Espinal/patologia , Traumatismos da Medula Espinal/terapia
9.
Small ; 16(8): e1906415, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32003924

RESUMO

Spinal cord injury (SCI) is a devastating disorder, leading to permanent motor and sensory deficit. Despite recent advances in neurosciences, the treatment efficacy on SCI patients remains unsatisfactory, mainly due to the poor accumulation, short retention, and lack of controlled release of therapeutics in lesion tissue. Herein, an injured spinal cord targeting prodrug polymer micelle is built. An esterase-responsive bond is used to link apocynin (APO) monomer, because of the enhanced esterase activity found in microglia cells after activation, which ensures a controlled degradation of APO prodrug (Allyloxypolyethyleneglycol-b-poly [2-(((4-acetyl-2-methoxyphenoxy)carbonyl)oxy)ethyl methacrylate], APEG-PAPO or PAPO) by activated microglia cells. A scar tissue-homing peptide (cysteine-alanine-glutamine-lysine, CAQK) is introduced to the PAPO to endow the polymer micelle the lesion tissue-targeting ability. As a result, this CAQK-modified prodrug micelle (cPAM) exhibits an improved accumulation and prolonged retention in lesion tissue compared to the control micelle. The cPAM also leads to superior tissue protection and sustained motor function recovery than the control groups in a mouse model of SCI. In conclusion, the cPAM induces an effective treatment of SCI by the lesion tissue specific delivery of the prodrug polymer via its robust scar binding effect, making the scar tissue a drug releasing platform for sustained treatment of SCI.


Assuntos
Cicatriz , Micelas , Polímeros , Traumatismos da Medula Espinal , Animais , Camundongos , Microglia/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Fármacos Neuroprotetores/química , Polímeros/química , Traumatismos da Medula Espinal/tratamento farmacológico
10.
Cytotherapy ; 22(4): 193-203, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32173261

RESUMO

Spinal cord injury (SCI) is a common disease and a major cause of paralysis, carrying much burden around the world. Despite the progress made with growth factors therapy, the response rate of acute SCI treatment still remains unsatisfactory, due largely to complex and severe inflammatory reactions. Herein, we prepare a MFG-E8-loaded copolymer system-based anti-inflammation therapy for SCI treatment. It is shown that the MFG-E8-loaded copolymer system can decrease pro-inflammatory cytokine expression and neuron death. In a rat model of crush-caused SCI, the copolymer system shows significant therapeutic efficacy by ameliorating inflammation, decreasing fibrotic scar, promoting myelin regeneration and suppressing overall SCI severity.


Assuntos
Antígenos de Superfície/administração & dosagem , Morte Celular/efeitos dos fármacos , Sistemas de Liberação de Medicamentos/métodos , Proteínas do Leite/administração & dosagem , Bainha de Mielina/metabolismo , NF-kappa B/metabolismo , Polietilenoglicóis/administração & dosagem , Poliglactina 910/administração & dosagem , Traumatismos da Medula Espinal/tratamento farmacológico , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Hidrogéis/administração & dosagem , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Injeções , Regeneração Nervosa/efeitos dos fármacos , Células PC12 , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Resultado do Tratamento
11.
Mol Cell Biochem ; 472(1-2): 157-171, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32594337

RESUMO

Adipose-derived stem cells (ADSCs) are an ideal source of cells for intervertebral disc (IVD) regeneration, but the effect of an increased osmotic microenvironment on ADSC differentiation remains unclear. Here, we aimed to elucidate whether hyperosmolarity facilitates ADSC nucleus pulposus (NP)-like differentiation and whether histone demethylase KDM4B is involved in this process. ADSCs were cultured under standard and increased osmolarity conditions for 1-3 weeks, followed by analysis for proliferation and viability. Differentiation was then quantified by gene and protein analysis. Finally, KDM4B knockdown ADSCs were generated using lentiviral vectors. The results showed that increasing the osmolarity of the differentiation medium to 400 mOsm significantly increased NP-like gene expression and the synthesis of extracellular matrix (ECM) components during ADSC differentiation; however, further increasing the osmolarity to 500 mOsm suppressed the NP-like differentiation of ADSCs. KDM4B, as well as the IVD formation regulators forkhead box (Fox)a1/2 and sonic hedgehog (Shh), were found to be significantly upregulated at 400 mOsm. KDM4B knockdown reduced Foxa1/2, Shh, and NP-associated markers' expression, as well as the synthesis of ECM components. The reduction in NP-like differentiation caused by KDM4B knockdown was partially rescued by Purmorphamine, a specific agonist of Shh. Moreover, we found that KDM4B can directly bind to the promoter region of Foxa1/2 and decrease the content of H3K9me3/2. In conclusion, our results indicate that a potential optimal osmolarity window might exist for successful ADSC differentiation. KDM4B plays an essential role in regulating the osmolarity-induced NP-like differentiation of ADSCs by interacting with Foxa1/2-Shh signaling.


Assuntos
Diferenciação Celular , Proliferação de Células , Histona Desmetilases com o Domínio Jumonji/metabolismo , Células-Tronco Mesenquimais/citologia , Núcleo Pulposo/citologia , Animais , Células Cultivadas , Histona Desmetilases com o Domínio Jumonji/genética , Células-Tronco Mesenquimais/metabolismo , Núcleo Pulposo/metabolismo , Concentração Osmolar , Ratos , Ratos Sprague-Dawley
12.
BMC Musculoskelet Disord ; 21(1): 259, 2020 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-32312254

RESUMO

BACKGROUND: Extreme lumbar spinal stenosis was thought to be a relative contraindication for lateral lumbar interbody fusion (LLIF) and was excluded in most studies. This is a retrospective study to analyze the radiographic and clinical outcome of LLIF for extreme lumbar spinal stenosis of Schizas grade D. METHODS: For radiographic analysis, we included 181 segments from 110 patients who underwent LLIF between June 2017 and December 2018. Lumbar spinal stenosis was graded according to Schizas' classification. Anterior and posterior disc heights, disc angle, foramen height, spinal canal diameter and central canal area were measured on CT and MRI. For clinical analysis, 18 patients with at least one segment of grade D were included. Visual analogue scale (VAS) and Oswestry disability index (ODI) scores were used to evaluate clinical outcome. Continuous variables were compared using Student's t-test, with P-values < 0.05 considered to indicate statistically significant differences. RESULTS: Among the 181 segments included for radiological evaluation, there were 23 grade A segments, 37 grade B segments, 103 grade C segments and 18 grade D segments. Postoperatively, the average change of midsagittal canal diameter of grade D was significantly greater than that of grade A, and not significantly different compared to grades B and C. As to the average change of disc height, bilateral foraminal height, disc angle and central canal area (CCA), grade D was not significantly different from the others. The average postoperative CCA of grade D was significantly smaller than the average preoperative CCA of grade C. Eighteen patients with grade D stenosis were followed up for an average of 19.61 ± 6.32 months. Clinical evaluation revealed an average improvement in the ODI and VAS scores for back and leg pain by 20.77%, 3.67 and 4.15 points, respectively. Sixteen of 18 segments with grade D underwent posterior decompression. CONCLUSION: The radiographic decompression effect of LLIF for Schizas grade D segments was comparable with that of other grades. Posterior decompression was necessary for LLIF to achieve a satisfactory clinical outcome for extreme lumbar spinal stenosis of Schizas grade D.


Assuntos
Descompressão Cirúrgica/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Complicações Pós-Operatórias/diagnóstico por imagem , Fusão Vertebral/métodos , Estenose Espinal/diagnóstico por imagem , Estenose Espinal/cirurgia , Idoso , Feminino , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Escala Visual Analógica
13.
Hum Mol Genet ; 26(8): 1577-1583, 2017 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-28334814

RESUMO

The genetic architecture of adolescent idiopathic scoliosis (AIS) remains poorly understood. Here we present the result of a 4-stage genome-wide association study composed of 5,953 AIS patients and 8,137 controls. Overall, we identified three novel susceptible loci including rs7593846 at 2p14 near MEIS1 (Pcombined = 1.19 × 10-13, OR = 1.21, 95% CI = 1.10-1.32), rs7633294 at 3p14.1 near MAGI1 (Pcombined = 1.85 × 10-12, OR = 1.20, 95% CI = 1.09-1.32), and rs9810566 at 3q26.2 near TNIK (Pcombined = 1.14 × 10-11, OR = 1.19, 95% CI = 1.08-1.32). We also confirmed a recently reported region associated with AIS at 20p11.22 (Pcombined = 1.61 × 10-15, OR = 1.22, 95% CI = 1.12-1.34). Furthermore, we observed significantly asymmetric expression of Wnt/beta-catenin pathway in the bilateral paraspinal muscle of AIS patients, including beta-catenin, TNIK, and LBX1. This is the first study that unveils the potential role of Wnt/beta-catenin pathway in the development of AIS, and our findings may shed new light on the etiopathogenesis of AIS.


Assuntos
Moléculas de Adesão Celular Neuronais/genética , Proteínas de Homeodomínio/genética , Proteínas de Neoplasias/genética , Proteínas Serina-Treonina Quinases/genética , Escoliose/genética , Proteínas Adaptadoras de Transdução de Sinal , Adolescente , Moléculas de Adesão Celular , Feminino , Regulação da Expressão Gênica , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Genótipo , Quinases do Centro Germinativo , Guanilato Quinases , Proteínas de Homeodomínio/biossíntese , Humanos , Masculino , Proteína Meis1 , Polimorfismo de Nucleotídeo Único , Escoliose/patologia , Fatores de Transcrição/biossíntese , Via de Sinalização Wnt , beta Catenina/biossíntese , beta Catenina/genética
14.
FASEB J ; : fj201800373R, 2018 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-29890089

RESUMO

Adipose tissue-derived stem cell (ADSC)-based therapy is promising for the treatment of intervertebral disc (IVD) degeneration, but the difficulty in inducing nucleus pulposus (NP)-like differentiation limits its clinical applications. Forkhead box (Fox)-A2 is an essential transcription factor for the formation of a normal NP. We demonstrated that type II collagen stimulates NP-like differentiation of ADSCs, partly by increasing the expression of FoxA2. We constructed FoxA2-overexpressing and -knockdown ADSCs by using lentiviral vectors. FoxA2 overexpression significantly enhanced NP-specific gene expression and the synthesis of glycosaminoglycan and collagen, whereas FoxA2 knockdown decreased NP-like differentiation and the expression of aggrecan and collagen II. The enhanced NP-like differentiation related to FoxA2 overexpression was partially rescued by an Shh signaling pathway inhibitor. In addition, FoxA2 inhibited the expression of Itg-α2 and further promoted NP-like differentiation induced by type II collagen. Furthermore, FoxA2-overexpressing ADSCs combined with type II collagen hydrogels promoted regeneration of degenerated NP in vivo. Our findings suggest that FoxA2 plays an essential role in the NP-like differentiation of ADSCs by activating the Shh signaling pathway.-Zhou, X., Ma, C., Hu, B., Tao, Y., Wang, J., Huang, X., Zhao, T., Han, B., Li, H., Liang, C., Chen, Q., Li, F. FoxA2 regulates the type II collagen-induced nucleus pulposus-like differentiation of adipose-derived stem cells by activation of the Shh signaling pathway.

15.
Cells Tissues Organs ; 205(3): 178-188, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30064140

RESUMO

Nucleus pulposus-derived mesenchymal stem cells (NP-MSCs) are suitable cell candidates for intervertebral disc (IVD) regeneration. However, little work has been done to determine the proliferation and chondrogenic differentiation of NP-MSCs in the hyperosmotic microenvironment of IVD. This study aimed to investigate the influence of the hyperosmolarity of IVD on the proliferation and chondrogenic differ-entiation of NP-MSCs. NP-MSCs were cultured in media of 300, 400, 430, and 500 mOsm/L, mimicking the osmotic pressures of serious degenerative, moderately degenerative, and healthy IVD. Cell proliferation was measured by CCK-8 assay. The expression of aggrecan, collagen I, and collagen II were measured by gene and protein expression analysis. Alcian blue and dimethylmethylene blue assay were used to investigate the accumulation of sulfate glycosaminoglycan. The regulation role of extracellular signal-regulated kinase (ERK) pathway was also analyzed. The results showed that, compared to 300 mOsm/L, hyperosmolarity of healthy IVD (430 and 500 mOsm/L) inhibited the proliferation and chondrogenic differentiation of NP-MSCs. The relative hypoosmotic condition of moderately degenerative IVD (400 mOsm/L) led to great proliferation and chondrogenic differentiation capacity. The ERK pathway was activated by the hyperosmolarity; inhibition of the ERK pathway abolished the difference in cell proliferation between the 300 mOsm/L and the hyperosmotic conditions, and enhanced chondrogenic differentiation. In conclusion, hyperosmolarity of IVD had a significant impact on the proliferation and chondrogenic differentiation of NP-MSCs. The ERK pathway was involved in the inhibition of proliferation and chondrogenic differentiation of NP-MSCs by the hyperosmolarity of IVD. The relative hypo-osmotic condition prevailing in degenerative discs offers a more permissive microenvironment for NP-MSCs.


Assuntos
Diferenciação Celular , Condrogênese , Disco Intervertebral/citologia , Células-Tronco Mesenquimais/citologia , Núcleo Pulposo/citologia , Animais , Diferenciação Celular/genética , Proliferação de Células , Condrogênese/genética , Matriz Extracelular/metabolismo , Regulação da Expressão Gênica , Glicosaminoglicanos/metabolismo , Sistema de Sinalização das MAP Quinases , Células-Tronco Mesenquimais/metabolismo , Concentração Osmolar , Ratos Sprague-Dawley
16.
Med Sci Monit ; 24: 6742-6749, 2018 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-30248086

RESUMO

BACKGROUND Cantharidin (CTD) is one of the major active ingredients of blister beetles and has significant antitumor activity in many cancer cell lines. The aim of our study was to evaluate the effect of CTD on the apoptosis of human osteosarcoma cells MG-63 and MNNG/HOS, and to explore the possible molecular mechanism. MATERIAL AND METHODS Osteosarcoma cells MG-63 and MNNG/HOS were treated with varying concentrations of CTD. The proliferation inhibition of cells was detected by MTS. Flow cytometry and Hoechst 33258 staining were used to determine cell cycle arrest and apoptosis, and apoptosis-related protein levels were analyzed by Western blotting. RESULTS Our current findings suggest that CTD could inhibit the proliferation of these 2 osteosarcoma cells. The cells treated with CTD showed an obvious apoptotic morphology, and CTD promoted cells apoptosis in a dose-dependent manner. In addition, cantharidin-induced apoptosis was accompanied by increased expression of Bax and PARP and decreased expression of Bcl-2, p-Akt, and p-Cdc2. CONCLUSIONS CTD accelerates the apoptosis of MG-63 and MNNG/HOS cells in a concentration-dependent manner through the mitochondria-dependent pathway, suggesting that use of CTD is a novel approach for the treatment of osteosarcoma.


Assuntos
Cantaridina/farmacologia , Mitocôndrias/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Ciclo Celular/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/metabolismo , Osteossarcoma/tratamento farmacológico , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
17.
Eur Spine J ; 26(Suppl 1): 202-206, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28365857

RESUMO

BACKGROUND: Thoracic spinal stenosis caused by ossification of ligamentum flavum (OLF) is frequently seen, but long segmental thoracic spinal cord compressed by consequent thickened ligament posteriorly was rarely reported. OBJECT: To report a case of thoracic spinal cord compression caused by atypical long segmental thoracic hypertrophic pachymeningitis (HP) with OLF. METHODS: A 55-year-old woman presenting with weakness and numbness in lower extremities was admitted to our department. Combined with physical examination and MRI results, diagnosis of HP with OLF was considered. Due to progressive neurological symptoms, thoracic decompression with internal fixation was performed. RESULTS: The patient felt a reduced numbness and improvement in motor functions 5 days after surgery. Pathological examination suggested the diagnosis of HP with OLF. CONCLUSIONS: HP is a rare condition characterized as thickening and enhancement of the dura mater on contrast-enhanced MRI and chronic inflammatory hyperplasia changes on biopsy. A case of atypical HP complicated with OLF is described. Chondrocytes infiltration in histological examination indicates the potential of ossification in HP.


Assuntos
Ligamento Amarelo/diagnóstico por imagem , Meningite/complicações , Ossificação Heterotópica/complicações , Compressão da Medula Espinal/etiologia , Adulto , Descompressão Cirúrgica/métodos , Dura-Máter/diagnóstico por imagem , Dura-Máter/cirurgia , Feminino , Humanos , Ligamento Amarelo/patologia , Imageamento por Ressonância Magnética , Masculino , Meningite/diagnóstico por imagem , Pessoa de Meia-Idade , Ossificação Heterotópica/diagnóstico por imagem , Ossificação Heterotópica/patologia , Compressão da Medula Espinal/diagnóstico por imagem , Compressão da Medula Espinal/cirurgia , Vértebras Torácicas/diagnóstico por imagem , Vértebras Torácicas/cirurgia , Tomografia Computadorizada por Raios X
18.
Eur Spine J ; 26(Suppl 1): 9-16, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27188182

RESUMO

BACKGROUND: Idiopathic intracranial hypertension (IIH) is a relatively rare syndrome of increased intracranial pressure of unknown etiology. It is characterized by cerebrospinal fluid (CSF) opening pressure more than 250 mmH2O, with normal cranial imaging and CSF content. IIH occurred after spinal surgery is extremely rare. METHODS: We present two IIH cases occurred after spinal surgery and conduct a systematic review of articles reporting IIH occurred after spinal surgery. RESULTS: The first patient underwent a posterior decompression and fixation for cervical fractures. IIH symptoms appeared 3 days postoperatively and gradually resolved with appropriate medication. The second patient underwent posterior spinal fusion with segmental instrumentation for congenital scoliosis. IIH symptoms appeared 5 days postoperatively and the patient died due to the irreversible intracranial hypertension although underwent intensive care and treatment. The literature review revealed that there were only five cases of IIH occurred after spinal surgery reported till date. CONCLUSIONS: IIH occurred after spinal surgery is relatively rare; the diagnosis is based upon exclusion of other diseases. IIH should be kept in mind in patients underwent spinal surgery as it could develop into irreversible intracranial hypertension.


Assuntos
Hipertensão Intracraniana/etiologia , Fusão Vertebral/efeitos adversos , Pressão do Líquido Cefalorraquidiano/fisiologia , Descompressão Cirúrgica/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem
19.
Eur Spine J ; 26(7): 1862-1870, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28281005

RESUMO

BACKGROUND: Postural deformities in the coronal plane were frequent and disabling complications of PD, which reduces the quality of life of patients. This study aimed to garner greater attention to the Parkinson disease (PD)-related postural trunk deviations in the coronal plane by exploring a method for diagnosis because of the lack of any uniform diagnostic criteria and epidemiological studies. It also aimed to provide correlation data in the Chinese PD patients. METHODS: In this cross-sectional study, 503 consecutive outpatients with PD were enrolled who underwent standardized clinical evaluation. The study recruited 83 PD patients diagnosed with Pisa syndrome (PS). Scoliosis and coronal imbalance were diagnosed accurately by radiographic data. The PD patients were compared based on the Cobb angle and coronal balance for several demographic and clinical variables. RESULTS: PD patients with PS had a prevalence of 16.5%. The prevalence of coronal imbalance and scoliosis was 10.34 and 7.75%, respectively. PD patients with PS were older and had a more severe disease, significantly longer disease duration and treatment duration, and reduced quality of life. The most important finding was that the different morphology of the spinal level had an effect on the severity of coronal balance or Cobb angle. CONCLUSIONS: The present study indicated that the postural deformities in the coronal plane were related to the morphology of the spinal level, especially the position of the Cobb angle. To benefit the PD patients with PS, the full-length standing spine radiographs should be performed as early as possible.


Assuntos
Doença de Parkinson/complicações , Escoliose/diagnóstico , Escoliose/etiologia , Idoso , China , Estudos Transversais , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Radiografia , Fatores de Risco , Escoliose/epidemiologia
20.
Emerg Infect Dis ; 22(11): 1930-1936, 2016 11.
Artigo em Inglês | MEDLINE | ID: mdl-27767007

RESUMO

In 2015, a novel influenza A(H1N1) virus was isolated from a boy in China who had severe pneumonia. The virus was a genetic reassortant of Eurasian avian-like influenza A(H1N1) (EA-H1N1) virus. The hemagglutinin, neuraminidase, and matrix genes of the reassortant virus were highly similar to genes in EA-H1N1 swine influenza viruses, the polybasic 1 and 2, polymerase acidic, and nucleoprotein genes originated from influenza A(H1N1)pdm09 virus, and the nonstructural protein gene derived from classical swine influenza A(H1N1) (CS H1N1) virus. In a mouse model, the reassortant virus, termed influenza A/Hunan/42443/2015(H1N1) virus, showed higher infectivity and virulence than another human EA-H1N1 isolate, influenza A/Jiangsu/1/2011(H1N1) virus. In the respiratory tract of mice, virus replication by influenza A/Hunan/42443/2015(H1N1) virus was substantially higher than that by influenza A/Jiangsu/1/2011(H1N1) virus. Human-to-human transmission of influenza A/Hunan/42443/2015(H1N1) virus has not been detected; however, given the circulation of novel EA-H1N1 viruses in pigs, enhanced surveillance should be instituted among swine and humans.


Assuntos
Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/diagnóstico , Influenza Humana/virologia , Vírus Reordenados , Animais , Linhagem Celular , China/epidemiologia , Genes Virais , História do Século XXI , Humanos , Lactente , Vírus da Influenza A Subtipo H1N1/isolamento & purificação , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/epidemiologia , Influenza Humana/história , Tipagem de Sequências Multilocus , Filogenia , RNA Viral , Testes Sorológicos , Índice de Gravidade de Doença , Virulência , Replicação Viral
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