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1.
J Orthop Translat ; 28: 108-117, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33868923

RESUMO

Background: Surgery for Ewing sarcoma involving acetabulum in children is challenging. Considering the intrinsic structure of immature pelvis, trans-acetabular osteotomy through triradiate cartilage might be applied. The study was to describe the surgical technique and function outcomes of trans-acetabular osteotomy through triradiate cartilage and reconstruction with customized, 3D-printed prosthesis. Methods: Two children with periacetabular ES were admitted to our hospital. The pre-operative imaging showed the triradiate cartilage was not penetrated or wholly affected by tumor. After neoadjuvant chemotherapy, the tumor was excised by trans-acetabular osteotomy basing on "triradiate cartilage strategy" and the acetabulum was reconstructed with the customized, 3D-printed prosthesis. The prosthesis was designed in Mimics software basing on the images from CT, optimized by topology technique, and examined in FE model. After implantation, the oncological and functional outcomes were evaluated with radiography, CT, and MSTS score. Results: The operation time and intra-operative blood loss in these two children were 3.5h, 2.5h and 300 ml, 600 ml, respectively. The postoperative specimen showed the tumor was en bloc removed with safe margin. In the latest follow-up (48 months and 24 months), both patients were free of disease and had satisfactory function according to MSTS score. The radiography indicated the prosthesis fit the defect well without loosening. Conclusion: The customized, 3D-printed prosthesis could provide optimal reconstruction of pelvic ring and satisfactory hip function after trans-acetabular osteotomy in children. The translational potential of this article: This study provides promising results of implantation of customized 3D printing prosthesis in children's pelvic sarcoma, which may bring a new design method for orthopaedic implants.

2.
Ann Transl Med ; 9(3): 249, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33708876

RESUMO

Background: Osteoarthritis (OA) is a common degenerative disease with multifactorial etiology. The dedifferentiation of chondrocytes can accelerate the progress of OA. Tanshinone IIA (TIIA) has been widely used to treat OA for many years and has proved to be effective in inhibiting chondrocyte dedifferentiation. Until now, the precise mechanism of TIIA's effect against dedifferentiation has not been well understood. Methods: The targets of TIIA were explored from public databases using various methods. The related targets of OA were obtained from the GeneCards database and the Online Mendelian Inheritance in Man (OMIM) database. The potential targets and signaling pathways were determined using protein-protein interaction (PPI), Gene Ontology (GO), and the Kyoto Encyclopedia of Genes and Genomes (KEGG). Cell viability, proliferation, and metabolic activity were analyzed in vitro. The effects of TIIA on chondrocyte dedifferentiation were evaluated by assessing morphological changes, glycosaminoglycan (GAG) production, and messenger RNA (mRNA) levels of cartilage-related genes. After 48 hours of culture in medium with 100 µg/mL TIIA, chondrocytes/hydrogel spheres were implanted to repair cartilage defects in a rat model. The harvested specimens were examined with hematoxylin and eosin (H&E) staining and immunohistochemistry to evaluate cartilage regeneration. Results: The results showed that there were 28 genes potentially interacting in the TIIA-chondrocyte dedifferentiation network, and nine hub genes were identified. In vitro experiments showed an inhibitory effect of TIIA on chondrocyte dedifferentiation. The proliferation and viability of chondrocytes were promoted by TIIA at a concentration of 100-200 µg/mL, but inhibited by TIIA at 400 µg/mL. Furthermore, the histology results showed that chondrocyte/hydrogel spheres pre-treated with TIIA had better cartilage repair. Conclusions: This study revealed a systematic network pharmacology approach and provided a basis for the future study of TIIA as an effective treatment for cartilage regeneration. Moreover, in vitro and in vivo results confirmed the protective effects of TIIA against chondrocyte dedifferentiation.

3.
Stem Cell Res Ther ; 12(1): 118, 2021 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-33579354

RESUMO

BACKGROUND: Oligovascular niche mediates interactions between cerebral endothelial cells and oligodendrocyte precursor cells (OPCs). Disruption of OPC-endothelium trophic coupling may aggravate the progress of cerebral white matter injury (WMI) because endothelial cells could not provide sufficient support under diseased conditions. Endothelial progenitor cells (EPCs) have been reported to ameliorate WMI in the adult brain by boosting oligovascular remodeling. It is necessary to clarify the role of the conditioned medium from hypoxic endothelial cells preconditioned EPCs (EC-pEPCs) in WMI since EPCs usually were recruited and play important roles under blood-brain barrier disruption. Here, we investigated the effects of EC-pEPCs on oligovascular remodeling in a neonatal rat model of WMI. METHODS: In vitro, OPC apoptosis induced by the conditioned medium from oxygen-glucose deprivation-injured brain microvascular endothelial cells (OGD-EC-CM) was analyzed by TUNEL and FACS. The effects of EPCs on EC damage and the expression of cytomokine C-X-C motif ligand 12 (CXCL12) were examined by western blot and FACS. The effect of the CM from EC-pEPCs against OPC apoptosis was also verified by western blot and silencing RNA. In vivo, P3 rat pups were subjected to right common carotid artery ligation and hypoxia and treated with EPCs or EC-pEPCs at P7, and then angiogenesis and myelination together with cognitive outcome were evaluated at the 6th week. RESULTS: In vitro, EPCs enhanced endothelial function and decreased OPC apoptosis. Meanwhile, it was confirmed that OGD-EC-CM induced an increase of CXCL12 in EPCs, and CXCL12-CXCR4 axis is a key signaling since CXCR4 knockdown alleviated the anti-apoptosis effect of EPCs on OPCs. In vivo, the number of EPCs and CXCL12 protein level markedly increased in the WMI rats. Compared to the EPCs, EC-pEPCs significantly decreased OPC apoptosis, increased vascular density and myelination in the corpus callosum, and improved learning and memory deficits in the neonatal rat WMI model. CONCLUSIONS: EC-pEPCs more effectively promote oligovascular remodeling and myelination via CXCL12-CXCR4 axis in the neonatal rat WMI model.


Assuntos
Isquemia Encefálica , Células Progenitoras Endoteliais , Animais , Animais Recém-Nascidos , Meios de Cultivo Condicionados/farmacologia , Neovascularização Patológica , Ratos
4.
Exp Neurol ; 337: 113593, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33387462

RESUMO

Increasing evidence has demonstrated that the Nod-like receptor pyrin domain containing 3 (Nlrp3) inflammasome overactivated during demyelinating disorders. It has been implicated that transient receptor potential type 4 (Trpv4) is regarded as a polymodal ionotropic receptor that plays an important role in a multitude of pathological conditions, including inflammation. The aim of this study was to investigate whether the Trpv4 channel regulates Nlrp3 inflammasome in the corpus callosum of mice with demyelination. Our results showed that CPZ treatment significantly increased the expression of Trpv4, activated Nlrp3 inflammasome, reduced peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) and decreased mitochondrial function. siRNA-mediated Nlrp3 knockdown inhibited glial activation and alleviated demyelination. Whereas knockdown of Trpv4 by siRNA markedly ameliorated Nlrp3 inflammasome activation and restored mitochondrial function as well as reducing the level of reactive oxygen species (ROS). Meanwhile, glial activation, demyelination and behavioral impairment induced by CPZ were also alleviated by siRNA-mediated Trpv4 knockdown. Furthermore, immunoprecipitation and use of a lysine acetylation assay showed that Sirtuin1 (SIRT1) mediated the PGC-1α deacetylation, which is involved in Nlrp3 inflammasome activation. These findings suggest that Trpv4 regulates mitochondrial function through the SIRT1/PGC-1α pathway, which further trigger Nlrp3 inflammasome activation in the CPZ-induced demyelination in mice.


Assuntos
Doenças Desmielinizantes/genética , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Sirtuína 1/genética , Canais de Cátion TRPV/fisiologia , Animais , Quelantes , Transtornos Cognitivos/genética , Transtornos Cognitivos/psicologia , Corpo Caloso/patologia , Cuprizona , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/psicologia , Técnicas de Silenciamento de Genes , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Neuroglia , RNA Interferente Pequeno/genética , Espécies Reativas de Oxigênio
5.
Neurosci Bull ; 37(1): 15-30, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33015737

RESUMO

The massive loss of oligodendrocytes caused by various pathological factors is a basic feature of many demyelinating diseases of the central nervous system (CNS). Based on a variety of studies, it is now well established that impairment of oligodendrocyte precursor cells (OPCs) to differentiate and remyelinate axons is a vital event in the failed treatment of demyelinating diseases. Recent evidence suggests that Foxg1 is essential for the proliferation of certain precursors and inhibits premature neurogenesis during brain development. To date, very little attention has been paid to the role of Foxg1 in the proliferation and differentiation of OPCs in demyelinating diseases of the CNS. Here, for the first time, we examined the effects of Foxg1 on demyelination and remyelination in the brain using a cuprizone (CPZ)-induced mouse model. In this work, 7-week-old Foxg1 conditional knockout and wild-type (WT) mice were fed a diet containing 0.2% CPZ w/w for 5 weeks, after which CPZ was withdrawn to enable remyelination. Our results demonstrated that, compared with WT mice, Foxg1-knockout mice exhibited not only alleviated demyelination but also accelerated remyelination of the demyelinated corpus callosum. Furthermore, we found that Foxg1 knockout decreased the proliferation of OPCs and accelerated their differentiation into mature oligodendrocytes both in vivo and in vitro. Wnt signaling plays a critical role in development and in a variety of diseases. GSK-3ß, a key regulatory kinase in the Wnt pathway, regulates the ability of ß-catenin to enter nuclei, where it activates the expression of Wnt target genes. We then used SB216763, a selective inhibitor of GSK-3ß activity, to further demonstrate the regulatory mechanism by which Foxg1 affects OPCs in vitro. The results showed that SB216763 clearly inhibited the expression of GSK-3ß, which abolished the effect of the proliferation and differentiation of OPCs caused by the knockdown of Foxg1. These results suggest that Foxg1 is involved in the proliferation and differentiation of OPCs through the Wnt signaling pathway. The present experimental results are some of the first to suggest that Foxg1 is a new therapeutic target for the treatment of demyelinating diseases of the CNS.


Assuntos
Doenças Desmielinizantes , Remielinização , Animais , Diferenciação Celular , Cuprizona/toxicidade , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/genética , Fatores de Transcrição Forkhead/genética , Quinase 3 da Glicogênio Sintase , Camundongos , Camundongos Endogâmicos C57BL , Bainha de Mielina , Proteínas do Tecido Nervoso , Oligodendroglia , Via de Sinalização Wnt
6.
Eur Radiol ; 31(5): 3518-3529, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33146792

RESUMO

OBJECTIVES: To evaluate parameters of diffusion-weighted imaging (DWI) and dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) as early imaging indicators of tumor histologic response to pre-operative neoadjuvant chemotherapy and as probable prognostic factors for event-free survival (EFS) and overall survival in osteosarcoma (OS) in both tumoral and peritumoral areas. METHODS: Thirty-four OS patients who received three courses of neoadjuvant chemotherapy followed by surgery during 2014-2018 were enrolled in this study. All patients underwent baseline and post-chemotherapy DWI and DCE-MRI. Lesion region was defined as the tumoral area and peritumoral area. Parameters of apparent diffusion coefficient, capacity transfer constant (Ktrans), elimination rate constant, extravascular extracellular space volume ratio (Ve), and initial area under the curve as well as corresponding differences between pre- and post-chemotherapy in lesion regions were evaluated. Receiver operating characteristic analysis was used to evaluate the diagnostic performance of these parameters. The associations of all parameters with tumor histologic response, EFS, and overall survival were also calculated. RESULTS: In the tumor area, moderate evidence was found that post-Ktrans was lower in responders as compared with that in poor responders (p = 0.04, false discovery rate [FDR] corrected), and ΔKtrans exhibited significant between-groups differences (p = 0.04, Bonferroni corrected; or p = 0.006, FDR corrected). Weak evidence for the between-groups difference was found in the Ve in the peritumoral area (p = 0.025 before treatment and p = 0.021 after treatment, uncorrected). Furthermore, lower post-Ktrans in the tumoral area and lower pre-Ve in the peritumoral area were significant prognostic indicators for longer EFS (p = 0.002, p = 0.026) and overall survival (p = 0.003, p = 0.023). CONCLUSIONS: In OS, DWI and DCE-MRI parameters in both tumoral and peritumoral areas can reflect the chemotherapy response and prognosticate EFS and overall survival. KEY POINTS: • Peritumoral MRI parameters can reflect the chemotherapy response in OS patients. • Peritumoral MRI parameters can predict EFS and overall survival in OS patients. • MRI parameters may be predictive factors for evaluating chemotherapy efficacy and EFS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Neoplasias Ósseas/diagnóstico por imagem , Meios de Contraste , Imagem de Difusão por Ressonância Magnética , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Osteossarcoma/diagnóstico por imagem , Osteossarcoma/tratamento farmacológico , Prognóstico
7.
Aerosp Med Hum Perform ; 91(11): 901-903, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-33334412

RESUMO

BACKGROUND: Rhabdomyolysis is a potentially fatal disease caused by trauma, infections, and toxins. Rhabdomyolysis has not been reported in Chinese civil aircrew, but in our case report a male civil copilot contracted rhabdomyolysis after excessive exercise, showing potential for morbidity in pilots.CASE REPORT: After excessive exercise, a 29-yr-old male civil aviation copilot complained of serious myalgia and weakness in lower limb muscles and gross hematuria, whose values of alanine transaminase (ALT), aspartate transaminase (AST), myohemoglobin (Mb), creatine kinase (CK), CK-MB, lactate dehydrogenase (LDH), and -hydroxybutyrate dehydrogenase (-HBDH) were conspicuously increased. Magnetic resonance imaging showed abnormal signal intensities in the lower limbs. The patient was diagnosed with rhabdomyolysis. He was treated with hydration and urine alkalinization. When his condition was stabilized, the patient was discharged. After remaining asymptomatic for 3 mo and getting documentation of normalized lab results, he was granted a first-class medical certificate and returned to work.DISCUSSION: This was the first case of rhabdomyolysis reported in Chinese civil aircrew. Excessive exercise in an overweight pilot may induce rhabdomyolysis. This condition can be controlled and cured by early and effective treatment. Rhabdomyolysis could occur in a population suffering from overweight, obesity, or hyperlipidemia. This case fits in with several other cases of military pilots exercising excessively. The progression could lead to acute kidney injury without prompt and effective intervention. And common symptoms like muscular weakness or myalgia may induce sudden in-flight incapacitation, so early medical intervention should be adopted. Moreover, recurrence of rhabdomyolysis should be considered when resuming flying duties.Liu X, Meng X, Zhang C, Chen J, Li P, Wu X, Fan H. Rhabdomyolysis in a civil aviation pilot. Aerosp Med Hum Res. 2020; 91(11):901903.


Assuntos
Aviação , Militares , Pilotos , Rabdomiólise , Exercício Físico , Humanos , Masculino , Rabdomiólise/etiologia
8.
Sensors (Basel) ; 20(18)2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32942782

RESUMO

As a next-generation power system, the smart grid can implement fine-grained smart metering data collection to optimize energy utilization. Smart meters face serious security challenges, such as a trusted third party or a trusted authority being attacked, which leads to the disclosure of user privacy. Blockchain provides a viable solution that can use its key technologies to solve this problem. Blockchain is a new type of decentralized protocol that does not require a trusted third party or a central authority. Therefore, this paper proposes a decentralized privacy-preserving data aggregation (DPPDA) scheme for smart grid based on blockchain. In this scheme, the leader election algorithm is used to select a smart meter in the residential area as a mining node to build a block. The node adopts Paillier cryptosystem algorithm to aggregate the user's power consumption data. Boneh-Lynn-Shacham short signature and SHA-256 function are applied to ensure the confidentiality and integrity of user data, which is convenient for billing and power regulation. The scheme protects user privacy data while achieving decentralization, without relying on TTP or CA. Security analysis shows that our scheme meets the security and privacy requirements of smart grid data aggregation. The experimental results show that this scheme is more efficient than existing competing schemes in terms of computation and communication overhead.

9.
J Neuroinflammation ; 16(1): 183, 2019 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-31561751

RESUMO

BACKGROUND: Toll-like receptor 4 (TLR4) is well known for activating the innate immune system; however, it is also highly expressed in adaptive immune cells, such as CD4+ T-helper 17 (Th17) cells, which play a key role in multiple sclerosis (MS) pathology. However, the function and governing mechanism of TLR4 in Th17 remain unclear. METHODS: The changes of TLR4 in CD4+ T cells from MS patients and experimental autoimmune encephalomyelitis (EAE) mice were tested. TLR4-deficient (TLR4-/-) naïve T cells were induced in vitro and transferred into Rag1-/- mice to measure Th17 differentiation and EAE pathology. DNA sequence analyses combining with deletion fragments and mutation analyses, chromatin immunoprecipitation (ChIP), and electrophoretic mobility shift assay (EMSA) were used to explore the mechanism of TLR4 signaling pathway in regulating Th17 differentiation. RESULTS: The levels of TLR4 were increased in CD4+ Th17 cells both from MS patients and EAE mice, as well as during Th17 differentiation in vitro. TLR4-/- CD4+ naïve T cells inhibited their differentiation into Th17, and transfer of TLR4-/- CD4+ naïve T cells into Rag1-/- mice was defective in promoting EAE, characterized by less demyelination and Th17 infiltration in the spinal cord. TLR4 signal enhanced Th17 differentiation by activating RelA, downregulating the expression of miR-30a, a negative regulator of Th17 differentiation. Inhibition of RelA activity increased miR-30a level, but decreased Th17 differentiation rate. Furthermore, RelA directly regulated the expression of miR-30a via specific binding to a conserved element of miR-30a gene. CONCLUSIONS: TLR4-/- CD4+ naïve T cells are inadequate in differentiating to Th17 cells both in vitro and in vivo. TLR4-RelA-miR-30a signal pathway regulates Th17 differentiation via direct binding of RelA to the regulatory element of miR-30a gene. Our results indicate modulating TLR4-RelA-miR-30a signal in Th17 may be a therapeutic target for Th17-mediated neurodegeneration in neuroinflammatory diseases.


Assuntos
Encefalomielite Autoimune Experimental/imunologia , Esclerose Múltipla/imunologia , Transdução de Sinais/fisiologia , Células Th17/imunologia , Animais , Diferenciação Celular/imunologia , Humanos , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/imunologia , MicroRNAs/metabolismo , Receptor 4 Toll-Like/imunologia , Receptor 4 Toll-Like/metabolismo , Fator de Transcrição RelA/imunologia , Fator de Transcrição RelA/metabolismo
10.
Med Eng Phys ; 69: 8-16, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31229384

RESUMO

In this study, a multi-objective topology optimization method has been formulated and carried out for various resection types, with minimization of a weighted sum of the compliance (maximized stiffness) under six routine activities of daily life as the objective function and volume reduction as a constraint. Unique prosthetic geometries with low weight and remarkable strength closely matching the pelvic bone shape were obtained. The strength of the optimized implants was investigated through finite element analysis and it has been found that the initial geometries of the optimized implants could withstand the static loading conditions of various routine activities having less stress concentration areas. A 3D printed patient-specific topology optimized hemi-pelvic prosthesis has been designed based on the proposed method and implanted successfully in a patient with pelvic sarcoma. Therefore, pelvic prostheses can be designed and then manufactured via additive manufacturing technologies with the minimum material in less time and having robust mechanical fixation responses. Conclusively, the topology optimization method used for the design of pelvic prostheses improves the biomechanical performance of the implants with reduced weight and higher stiffness than the traditional implants. Including the topology optimization procedure in the phase of designing patient-specific pelvic implants is therefore, highly recommended.


Assuntos
Análise de Elementos Finitos , Ossos Pélvicos , Desenho de Prótese/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Ossos Pélvicos/cirurgia , Resistência ao Cisalhamento , Estresse Mecânico
11.
J Neuroimmune Pharmacol ; 14(3): 493-502, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31065973

RESUMO

Toll-like receptor 4 (TLR4) is a key component in innate immunity and has been linked to central nervous system (CNS) inflammation diseases, such as multiple sclerosis (MS), an inflammatory disorder induced by autoreactive Th17 cells. In our study, we found that TLR4 deficient (TLR4-/-) mice were inadequate to induce experimental autoimmune encephalomyelitis (EAE), characterized by low clinic score and weight loss, alleviative demyelinating, as well as decreased inflammatory cell infiltration in the spinal cord. In the lesion area of EAE mice, loss of TLR4 down-regulated the secretion of inflammatory cytokines and chemokine CCL25. Furthermore, the expression of CCR9 was decreased and chemotactic migration was attenuated in TLR4-/- Th17 cells. Our results demonstrate that TLR4 may mediate Th17 infiltration through CCL25/CCR9 signal during pathogenesis of EAE. Graphical Abstract Immunofluorescent staining of RORγt (green) and CCR9 (red) in spinal cords. TLR4 deficiency down-regulates CCR9 expression in infiltrating lymphocytes.


Assuntos
Quimiocinas CC/fisiologia , Encefalomielite Autoimune Experimental/imunologia , Receptores CCR/fisiologia , Células Th17/metabolismo , Receptor 4 Toll-Like/fisiologia , Animais , Células Cultivadas , Quimiotaxia de Leucócito , Encefalomielite Autoimune Experimental/etiologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Regulação da Expressão Gênica/fisiologia , Linfopoese , Camundongos Endogâmicos C57BL , Camundongos Knockout , Glicoproteína Mielina-Oligodendrócito/imunologia , Glicoproteína Mielina-Oligodendrócito/toxicidade , Fragmentos de Peptídeos/imunologia , Fragmentos de Peptídeos/toxicidade , Receptores CCR/biossíntese , Transdução de Sinais/fisiologia , Medula Espinal/patologia , Baço/imunologia , Baço/patologia , Receptor 4 Toll-Like/deficiência , Receptor 4 Toll-Like/genética
12.
Neuroreport ; 30(3): 232-240, 2019 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-30614910

RESUMO

According to the previous research, metformin, a medication utilized for type 2 diabetes management, inhibits neural aging and reduces infarct size by enhancing angiogenesis in a mouse stroke model. What is more, metformin administration also promotes neural precursor cells proliferation, migration, as well as differentiation for newborn mice with hypoxia-ischemia brain injury. However, whether metformin regulates neurogenesis in an adult rat ischemia/reperfusion (I/R) model remains unclear. The current research found that metformin administration reduced neuronal damage in the CA1 area of hippocampus in a rat model of I/R. The number of neuronal nuclei positive neuron was significantly increased and glial fibrillary acidic protein positive astrocyte became obviously declined in the CA1 region in I/R rats treated with metformin. It was further demonstrated that metformin promoted neuroblasts proliferation and neuronal differentiation in the subgranular zone of the dentate gyrus and inhibited the formation of astrocyte. Our study indicates that activation of endogenous neuroblasts using metformin will become a favorable target in therapeutic intervention of cerebral ischemia injury models.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Metformina/farmacologia , Neurônios/efeitos dos fármacos , Animais , Astrócitos/citologia , Astrócitos/efeitos dos fármacos , Isquemia Encefálica/metabolismo , Diferenciação Celular/fisiologia , Modelos Animais de Doenças , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Células-Tronco Neurais/citologia , Células-Tronco Neurais/enzimologia , Neurogênese/efeitos dos fármacos , Neurogênese/fisiologia , Neurônios/citologia , Neurônios/metabolismo , Ratos Sprague-Dawley , Reperfusão/métodos
13.
Front Cell Neurosci ; 12: 392, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30455633

RESUMO

The inhibition of demyelination and the promotion of remyelination are both considerable challenges in the therapeutic process for many central nervous system (CNS) diseases. Increasing evidence has demonstrated that neuroglial activation and neuroinflammation are responsible for myelin sheath damage during demyelinating disorders. It has been revealed that the nonselective cation channel transient receptor potential vanilloid 4 (TRPV4) profoundly affects a variety of physiological processes, including inflammation. However, its roles and mechanisms in demyelination have remained unclear. Here, for the first time, we found that there was a significant increase in TRPV4 in the corpus callosum in a demyelinated mouse model induced by cuprizone (CPZ). RN-1734, a TRPV4-antagonist, clearly alleviated demyelination and inhibited glial activation and the production of tumor necrosis factor α (TNF-α) and interleukin 1ß (IL-1ß) without altering the number of olig2-positive cells. In vitro, RN-1734 treatment clearly inhibited the influx of calcium and decreased the levels of IL-1ß and TNF-α in lipopolysaccharide (LPS)-activated microglial cells by suppressing NF-κB P65 phosphorylation. Apoptosis of oligodendrocyte induced by LPS-activated microglia was also alleviated by RN-1734. The results suggest that activation of TRPV4 in microglia is involved in oligodendrocyte apoptosis through the activation of the NF-κB signaling pathway, thus revealing a new mechanism of CNS demyelination.

14.
Sci Rep ; 8(1): 15848, 2018 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-30374121

RESUMO

A correction has been published and is appended to both the HTML and PDF versions of this paper. The error has not been fixed in the paper.

15.
Brain Res Bull ; 143: 234-245, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30266587

RESUMO

S100A8/A9, a heterodimer complex composed of calcium-binding proteins S100A8 and S100A9, is significantly increased in the serum of multiple sclerosis (MS) patients. Relevant reports have revealed that MS pathology is commonly associated with the activation of microglial cells and the damage of oligodendrocyte precursor cells (OPCs). Moreover, microglia activation following stimulation increases the expression of pro-inflammatory cytokines, such as interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), which further exacerbate the damage to OPCs. In this study, we were the first to confirm that S100A8/A9 treatment induced the activation, proliferation and migration of the murine microglia cell line BV-2; moreover, this treatment caused the cells to switch from an anti-inflammatory activated (M2) phenotype to a pro-inflammatory activated (M1) phenotype. Meanwhile, the level of the phosphorylated nuclear factor-κB (p-NF-κB) P65 protein was remarkably elevated, and the production of pro-inflammatory factors (IL-1ß, TNF-α, MMP-9) and chemokines (CCL2, CCL3, CXCL10) was also increased in the S100A8/A9-treated BV-2 microglial cells. Inhibition of NF-κB P65 phosphorylation reversed the effects of S100A8/A9 on the production of pro-inflammatory factors and chemokines. We also explored the effects of S100A8/A9 and S100A8/A9-activated BV-2 microglial cells on the viability of OPCs. The results showed that both the S100A8/A9 complex and the conditioned medium (CM) of the S100A8/A9-activated BV-2 microglial cells resulted in OPC apoptosis, which was more pronounced in the case of the CM treatment. However, OPC apoptosis in the CM group was obviously decreased through the inhibition of NF-κB p65 phosphorylation. This study indicates that S100A8/A9 induces the activation of BV-2 microglial cells and promotes the production of pro-inflammatory factors by activating the NF-κB signaling pathway, which further exacerbates OPC damage.


Assuntos
Calgranulina A/fisiologia , Calgranulina B/fisiologia , Microglia/fisiologia , Animais , Apoptose , Calgranulina A/metabolismo , Calgranulina B/metabolismo , Citocinas/metabolismo , Feminino , Inflamação , Interleucina-1beta/metabolismo , Ativação de Macrófagos , Macrófagos/patologia , Masculino , NF-kappa B/metabolismo , Células Precursoras de Oligodendrócitos/efeitos dos fármacos , Células Precursoras de Oligodendrócitos/metabolismo , Fosforilação , Cultura Primária de Células , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Fator de Necrose Tumoral alfa/metabolismo
16.
J Bone Oncol ; 12: 78-82, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30123734

RESUMO

Background: Bone benign fibrous histiocytoma (BFH) is an invasive primary bone tumor. When the local excision is not complete, the risk of recurrence is high, and hence, one-piece resection is necessary. The major challenge for clinicians is to reconstruct the bone after resection of the tumor. The present study investigated the efficacy of 3-dimensional (3D) printing technique in the treatment of benign fibrous histiocytoma of the scapula. Methods: The patient with benign fibrous histiocytoma of scapular bone was treated with PEEK (polyetheretherketone) prosthesis replacement using the 3D printing technique. X-ray and computed tomography (CT) scans evaluated the relationship between the position of the prosthesis and that of the shoulder joint. Also, the constant score of the shoulder joint was calculated. Results: The anteroposterior radiograph showed that the position of the left scapula prosthesis is satisfactory and that of the shoulder joint is normal. Three months after the operation, the X-ray examination indicated the lack of flexibility and shift, as well as, dislocation and disjunction of PEEK prosthesis. The constant score of the left shoulder function was 68 points. Active shoulder joint activity: 120° on the lift, 90° on abduction, 50° on the external rotation, and 70° on internal rotation. Conclusions: The application of 3D-printed PEEK scapula prosthesis with total shoulder replacement offers the possibility of accurate reconstruction, improves the operability of surgery, shortens the operation time, and allows early functional recovery of the patients.

17.
J Neurosci Res ; 96(1): 138-150, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28609588

RESUMO

Diabetic encephalopathy (DE), one of the most prevalent chronic complications of diabetes mellitus, is short of effective prevention and formidable therapeutic strategies. The aim of the present study is to reveal the imbalance of tryptophan (Trp) and its metabolites in streptozotocin (STZ)-induced experimental DE rats to underscore their critical values in clinical diagnosis of the disease. For this purpose, we first developed an accurate and appropriate simultaneous method for measuring Trp and its metabolites using liquid chromatography-tandem mass spectrometry, which was in accordance with the requirements of biological sample analysis. Secondly, a single STZ intraperitoneal injection was administered to male Sprague-Dawley rats, and their cognitive function was detected by Morris water maze tests. Cerebrospinal fluid (CSF), serum, and brain tissue were then collected for the determination of Trp and its metabolites. Compared with age-matched control rats, the levels of neuroprotective serotonin decreased significantly in the samples of cortices, hippocampi, striatum, CSF, and serums in the STZ-induced DE rats, while the levels of neurotoxic 3-hydroxykynurenine increased significantly. Moreover, analogous changes of both compounds were found in the central nervous system and peripheral blood of the STZ-induced DE rats. In conclusion, we established a quantitative method for the simultaneous detection of Trp and its metabolites, and we also present a critical elucidation of the nervous system dysfunction in DE.


Assuntos
Encefalopatias/metabolismo , Encéfalo/metabolismo , Diabetes Mellitus Experimental/metabolismo , Neurotransmissores/metabolismo , Triptofano/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/líquido cefalorraquidiano , Biomarcadores/metabolismo , Encéfalo/patologia , Encefalopatias/patologia , Diabetes Mellitus Experimental/patologia , Masculino , Neurotransmissores/análise , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem/métodos , Triptofano/análise
18.
Brain Res ; 1678: 75-84, 2018 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-29038005

RESUMO

Myelin abnormalities, oligodendrocyte damage, and concomitant glia activation are common in demyelinating diseases of the central nervous system (CNS). Increasing evidence has demonstrated that the inflammatory response triggers demyelination and gliosis in demyelinating disorders. Numerous clinical interventions, including those used to treat multiple sclerosis (MS), have confirmed prednisone (PDN) as a powerful anti-inflammatory drug that reduces the inflammatory response and promotes tissue repair in multiple inflammation sites. However, the underlying mechanism of PDN in ameliorating myelin damage is not well understood. In our study, a cuprizone (CPZ)-induced demyelinated mouse model was used to explore the mechanism of the protection provided by PDN. Open-field tests showed that CPZ-treated mice exhibited significantly increased anxiety and decreased exploration. However, PDN improved emotional behavior, as evidenced by an increase in the total distance traveled, and central distance traveled as well as the mean amount of time spent in the central area. CPZ-induced demyelination was observed to be alleviated in PDN-treated mice based on luxol fast blue (LFB) staining and myelin basic protein (MBP) expression analyses. In addition, PDN reduced astrocyte and microglia activation in the corpus callosum. Furthermore, we demonstrated that PDN inhibited the Nod-like receptor pyrin domain containing 3 (NLRP3) inflammasome signaling pathway and related inflammatory cytokines and chemokines, including TNF-α, CCL8, CXCL10 and CXCL16. PDN also reduced the serum corticosterone levels in the CPZ-treated mice. Taken together, these results suggest that inhibition of the NLRP3 signaling pathway may be a novel mechanism by which PDN exerts its protective actions in demyelinating diseases.


Assuntos
Proteína 3 que Contém Domínio de Pirina da Família NLR/efeitos dos fármacos , Prednisona/metabolismo , Prednisona/farmacologia , Animais , Astrócitos/metabolismo , Corpo Caloso/metabolismo , Cuprizona/farmacologia , Citocinas/metabolismo , Doenças Desmielinizantes/induzido quimicamente , Modelos Animais de Doenças , Inflamassomos/antagonistas & inibidores , Inflamassomos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Esclerose Múltipla/metabolismo , Proteína Básica da Mielina/metabolismo , Bainha de Mielina/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Oligodendroglia/metabolismo , Transdução de Sinais
19.
Med Eng Phys ; 51: 17-23, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29239747

RESUMO

Compressive loading is crucial for tissue regeneration in cartilage; however, the role played by shearing induced from translational or rotational motion of the knee joint has yet to be identified. This study aims at investigating the effects of in vivo like dynamic load-compression integrated with shearing on tissue regeneration, particularly to identify the role played by shearing induced from rotational motion. Tissue samples fabricated from a calcium alginate hydrogel embedded with chondrocytes were subjected to a dynamic tissue culture. Three culturing regimes were included: a static culture control (CON), compression combined with shearing induced from translational motion (CS), and compression combined with shearing induced from both translational and rotational motion (CSR). The results indicate that the CS group has a significantly larger chondrocyte proliferation rate (p < .01), and that the CSR group has no advantages over the CS group. However, the CSR group was found to have a marked influence on the matrix synthesis compared to that of the CS group (p < .01). It can be concluded that shearing from individual joint motions offers a different contribution to the chondrocyte proliferation, matrix synthesis, and phenotype maintenance, and better insight into these individual roles will be necessary for determining the efficacy of in vivo/vitro cartilageous tissue functionalization.


Assuntos
Cartilagem Articular/citologia , Teste de Materiais , Fenômenos Mecânicos , Engenharia Tecidual , Animais , Fenômenos Biomecânicos , Proliferação de Células , Condrócitos/citologia , Condrócitos/metabolismo , Colágeno/metabolismo , Análise de Elementos Finitos , Glicosaminoglicanos/metabolismo , Articulação do Joelho/citologia , Coelhos , Resistência ao Cisalhamento , Estresse Mecânico
20.
Front Mol Neurosci ; 10: 376, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29184483

RESUMO

Recently, it is reported that monocarboxylate transporter 1 (MCT1) plays crucial role in oligodendrocyte differentiation and myelination. We found that MCT1 is strongly expressed in oligodendrocyte but weakly expressed in oligodendrocyte precursors (OPCs), and the underlying mechanisms remain elusive. Histone deacetylases (HDACs) activity is required for induction of oligodendrocyte differentiation and maturation. We asked whether HDACs are involved in the regulation of MCT1 expression. This work revealed that the acetylation level of histone H3K9 (H3K9ac) was much higher in mct1 gene (Slc16a1) promoter in OPCs than that in oligodendrocyte. H3K9ac regulates MCT1 expression was confirmed by HDAC acetyltransferase inhibitors trichostatin A and curcumin. Of note, there was a negative correlation between H3K9ac and MCT1 expression in oligodendrocyte. Further, we found that the levels of HDAC1, 2, and 3 protein in oligodendrocyte were obviously higher than those in OPCs. However, specific knockdown of HDAC2 but not HDAC1 and HDAC3 significantly decreased the expression of MCT1 in oligodendrocyte. Conversely, overexpression of HDAC2 remarkably enhanced the expression of MCT1. The results imply that HDAC2 is involved in H3K9ac modification which regulates the expression of MCT1 during the development of oligodendrocyte.

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