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1.
IUBMB Life ; 70(7): 625-632, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29774985

RESUMO

In this work, we explored the aberrant expression pattern, clinical association, and functional regulations of microRNA-1270 (miR-1270) in osteosarcoma. Among in vitro osteosarcoma cell lines and in situ tissues of osteosarcoma patients, quantitative real time-PCR was used to examine their endogenous miR-1270 expression. Clinical correlation between endogenous miR-1270 expression and clinicopathological features of osteosarcoma patients, as well as cancer patients' overall survival, was statistically examined. MiR-1270 was downregulated in 143B and MG-63 cells by lentiviral transduction. The mechanistic effects of miR-1270 downregulation on osteosarcoma in vitro proliferation and migration, as well as in vivo tumorigenesis, were further examined. MiR-1270 was aberrantly upregulated in both in vitro osteosarcoma cell lines and in situ human tumors. Statistical analysis demonstrated endogenous miR-1270 was associated with poor clinical outcomes and shorter overall survival of osteosarcoma patients. Lentivirus-induced miR-1270 downregulation inhibited cancer in vitro proliferation and migration, as well as in vivo tumorigenesis. Aberrant upregulation miR-1270 may be a prognostic biomarker for osteosarcoma patients with poor clinical outcomes and shorter survival. Inhibition of miR-1270 may also be a potential therapeutic target for anticancer treatment in osteosarcoma. © 2018 IUBMB Life, 70(7):625-632, 2018.


Assuntos
MicroRNAs/genética , Osteossarcoma/genética , Osteossarcoma/mortalidade , Adolescente , Adulto , Animais , Biomarcadores Tumorais/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Estimativa de Kaplan-Meier , Lentivirus/genética , Masculino , Camundongos Nus , Osteossarcoma/patologia , Prognóstico , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Tumour Biol ; 39(7): 1010428317703841, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28705117

RESUMO

Altered expression of the miR-25 has been implicated in many human malignant progression as oncogene or tumor suppressor. However, the precise role of miR-25 in osteosarcoma progression remains largely unclear. This study aimed to investigate the role and underlying mechanism of miR-25 in osteosarcoma. In this study, we demonstrated that miR-25 was significantly downregulated in osteosarcoma cell lines and tissues and that lower miR-25 was associated with advanced tumor-node-metastasis stage and lymph node metastasis. Then, we found that introduction of miR-25 significantly suppressed the proliferation, colony formation, migration, and invasion of osteosarcoma cells in vitro and retarded tumor growth in vivo. Further studies indicated that the epithelial-mesenchymal transition-related transcription factor, SOX4 (SRY-related high-mobility group box 4), was a direct target gene of miR-25, evidenced by bioinformatics analysis predicted and luciferase reporter assay. Furthermore, miR-25 could decrease the expression of SOX4 levels and inhibited epithelial-mesenchymal transition process. The levels of miR-25 were inversely correlated with those of SOX4 expression in osteosarcoma tissues. SOX4 overexpression rescued miR-25-induced suppression of proliferation, migration, and invasion of osteosarcoma cells. Taken together, these results suggest that miR-25 functions as a tumor suppressor in the progression of osteosarcoma by repressing SOX4.


Assuntos
MicroRNAs/genética , Osteossarcoma/genética , Fatores de Transcrição SOXC/genética , Adolescente , Adulto , Animais , Movimento Celular/genética , Proliferação de Células/genética , Criança , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Invasividade Neoplásica/genética , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Osteossarcoma/patologia , Fatores de Transcrição SOXC/biossíntese , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Mol Med Rep ; 27(2)2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36484386

RESUMO

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, on p. 2174 in the Materials and methods section (subsection "Lentivirus production and lentiviral transduction"), the sequence presented for the shRNA targeting the gene NOB1 appeared to conform with the sequence that would have been predicted to target PNO1, according to a blastn search. The authors have checked their original paper, and realize that the sequence of this shRNA was written incorrectly in the paper; the sequence for the shRNA targeting the gene NOB1 should have been written as: GCTTGCACTCACATACCAGTTCTCGAG- AACTGGTATGTGAGTGCAAGC. Furthermore, the published version of Fig. 5A on p. 2178 contained a pair of overlapping panels, such that data were apparently derived from the same original source even though they were intended to show the results from differently performed experiments. After having re­examined their original data, the authors have realized that a pair of data panels were inadvertently incorporated into this figure incorrectly; specifically, the centre panel of the Lv­shCon group and the right­hand panel of the Lv­shNOB1 group. The revised version of Fig. 5, showing the correct images for the abovementioned pair of data panels in Fig. 5A, is shown opposite. Note that these errors did not significantly affect either the results or the conclusions reported in this paper, and all the authors agree to this corrigendum. Furthermore, the authors thank the Editor of Molecular Medicine Reports for allowing them the opportunity to publish this corrigendum, and apologize to the readership for any inconvenience caused. [Molecular Medicine Reports 9: 2173­2179, 2014; DOI: 10.3892/mmr.2014.2119].

4.
Biomech Model Mechanobiol ; 22(3): 961-970, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36696049

RESUMO

Metal block augmentations are common solutions in treating bone defects of total knee revision. However, the stress shielding and poor osteointegration resulted from metal block application could not be neglected in bone defects restoration. In this study, a novel porous metal block was designed with topology optimization to improve biomechanical performance. The biomechanical difference of the topologically optimized block, solid Ti6Al4V block, and porous Ti6Al4V block in treating bone defects of total knee revision was compared by finite element analysis. The inhomogeneous femoral model was created according to the computed tomography data. Combined with porous structures, minimum compliance topology optimization subjected to the volume fraction constraint was utilized for the redesign of the metal block. The region of interest was defined as a 10 mm area of the distal femur beneath the contacting surface. The biomechanical performance of daily motions was investigated. The von Mises stress, the strain energy density of the region of interest, and the von Mises stress of metal blocks were recorded. The results were analyzed in SPSS. In terms of the region of interest, the maximum von Mises stress of the topological optimized group increased obviously, and its average stress was significantly higher than that of the other groups (p < 0.05). Moreover, the topologically optimized block group had the highest maximum strain energy density of the three groups, and the lowest maximum stress of block was also found in this group. In this study, the stress shielding reduction and stress transfer capability were found obviously improved through topology optimization. Therefore, the topological optimized porous block is recommended in treating bone defects of total knee revision. Meanwhile, this study also provided a novel approach for mechanical optimization in block designing.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Humanos , Masculino , Pessoa de Meia-Idade , Artroplastia do Joelho/métodos , Fêmur/cirurgia , Articulação do Joelho/cirurgia , Metais , Fenômenos Biomecânicos
5.
Front Bioeng Biotechnol ; 10: 939371, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35866028

RESUMO

Purpose: The management of bone defects is a crucial content of total knee revision. This study compared the biomechanical performance of porous Ti6Al4V block and tumor prosthesis UHMWPE block in treating distal femoral bone defects. Methods: The finite element models of AORI type 3 distal femoral bone defect treated with porous Ti6Al4V block and UHMWPE block were established. Sensitivity analysis was performed to obtain the appropriate mesh size. The biomechanical performance of treatment methods in bone defects were evaluated according to the peak stress, the Von Mises stress distribution, and the average stresses of regions of interest under the condition of standing on one foot and flexion of the knee. Statistical analysis was conducted by independent samples t-test in SPSS (p < 0.05). Results: In the standing on one-foot state, the peak stress of the porous Ti6Al4V block was 12.42 MPa and that of the UHMWPE block was 19.97 MPa, which is close to its yield stress (21 MPa). Meanwhile, the stress distribution of the UHMWPE block was uneven. In the flexion state, the peak stress of the porous Ti6Al4V block was 16.28 MPa, while that of the UHMWPE block was 14.82 MPa. Compared with the porous Ti6Al4V block group, the average stress of the region of interest in UHMWPE block group was higher in the standing on one foot state and lower in the flexion state (p < 0.05). Conclusion: More uniform stress distribution was identified in the porous Ti6Al4V block application which could reserve more bone. On the contrary, uneven stress distribution and a larger high-stress concentration area were found in the UHMWPE block. Hence, the porous Ti6Al4V block is recommended for the treatment of AORI type 3 distal femoral bone defect.

6.
Med Biol Eng Comput ; 59(9): 1673-1689, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34363576

RESUMO

Metal implants are widely used in the treatment of orthopedic diseases. However, owing to the mismatched elastic modulus of the bone and implants, stress shielding often occurs clinically which can result in failure of the implant or fractures around the implant. Topology optimization (TO) is a technique that can provide more efficient material distribution according to the objective function under the special load and boundary conditions. Several researchers have paid close attention to TO for optimal design of orthopedic implants. Thanks to the development of additive manufacturing (AM), the complex structure of the TO design can be fabricated. This article mainly focuses on the current stage of TO technique with respect to the global layout and hierarchical structure in orthopedic implants. In each aspect, diverse implants in different orthopedic fields related to TO design are discussed. The characteristics of implants, methods of TO, validation methods of the newly designed implants, and limitations of current research have been summarized. The review concludes with future challenges and directions for research. Wang TO design of global layout and local structure of implants in diverse fields of orthopedic.


Assuntos
Próteses e Implantes , Módulo de Elasticidade , Análise de Elementos Finitos , Estresse Mecânico
7.
Comput Biol Med ; 130: 104241, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33529844

RESUMO

The treatment of sizeable segmental bone defects remains a challenge encountered by surgeons. In addition to bone transplantation, porous scaffolds have become a common option. Although the mechanical and biological properties of porous scaffold have recently been the subject of intense research, pore irregularity as a critical characteristic has been poorly explored. Therefore, this study aimed to design an irregular biomimetic scaffold for use in bone tissue engineering applications. The irregular scaffold was based on the Voronoi tessellation method for similarity with the primary histomorphological indexes of bone (porosity, trabecular thickness, cortical bone thickness, and surface to volume ratio). Moreover, a new gradient method was adopted, in which porosity was maintained constant, and the strut diameter was changed to generate a gradient in the irregular scaffold. The permeability and stress concentration characteristics of the irregular scaffold were compared against three conventional scaffolds (the octet, body-centered cubic, pillar body-centered cubic). The results illustrated that the microstructure of the irregular scaffold could be controlled similarly to that of the cortical/cancellous bone unit. Simultaneously, a broad range of permeability was identified for the irregular scaffold, and gradient irregular scaffolds performed better in terms of both permeability and stress distribution than regular scaffolds. This study describes a novel method for the design of irregular scaffolds, which have good controllability and excellent permeability.


Assuntos
Biomimética , Engenharia Tecidual , Osso e Ossos , Porosidade , Alicerces Teciduais
8.
Front Bioeng Biotechnol ; 9: 765438, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34820364

RESUMO

Metal block augmentation, which is used for the treatment of tibial bone defects in total knee arthroplasty, with high stiffness will cause significant alteration in stress distribution, and its solid structure is not suitable for osseointegration. This study aimed to design a porous block to reduce weight, promote bone ingrowth, and improve its biomechanical performance. The metal block augmentation technique was applied to finite element models of tibial bone defects. Minimum compliance topology optimization subject to volume fraction combined with the porous architecture was adopted to redesign the block. Biomechanical changes compared with the original block were analyzed by finite element analysis. The stress distribution of the block and proximal tibia was recorded. The strain energy density of the proximal tibia was obtained. The newly designed block realized 40% weight reduction. The maximum stress in the optimized block decreased by 11.6% when compared with the solid one. The maximum stress of the proximal tibia in the optimized group increased by 18.6%. The stress of the anterior, medial, and posterior parts of the proximal medial tibia in the optimized group was significantly greater than that in the original group (all p < 0.05). The optimized block could effectively improve the biomechanical performance between the block and the bone. The presented method might provide a reference for the design of customized three-dimensional printed prostheses.

9.
Neural Regen Res ; 16(1): 93-98, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-32788452

RESUMO

Peripheral nerve injury (PNI) is common and, unlike damage to the central nervous system injured nerves can effectively regenerate depending on the location and severity of injury. Peripheral myelinating glia, Schwann cells (SCs), interact with various cells in and around the injury site and are important for debris elimination, repair, and nerve regeneration. Following PNI, Wallerian degeneration of the distal stump is rapidly initiated by degeneration of damaged axons followed by morphologic changes in SCs and the recruitment of circulating macrophages. Interaction with fibroblasts from the injured nerve microenvironment also plays a role in nerve repair. The replication and migration of injury-induced dedifferentiated SCs are also important in repairing the nerve. In particular, SC migration stimulates axonal regeneration and subsequent myelination of regenerated nerve fibers. This mobility increases SC interactions with other cells in the nerve and the exogenous environment, which influence SC behavior post-injury. Following PNI, SCs directly and indirectly interact with other SCs, fibroblasts, and macrophages. In addition, the inter- and intracellular mechanisms that underlie morphological and functional changes in SCs following PNI still require further research to explain known phenomena and less understood cell-specific roles in the repair of the injured peripheral nerve. This review provides a basic assessment of SC function post-PNI, as well as a more comprehensive evaluation of the literature concerning the SC interactions with macrophages and fibroblasts that can influence SC behavior and, ultimately, repair of the injured nerve.

10.
Biomed Res Int ; 2020: 2049306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32566666

RESUMO

METHODS: Bilateral VCA of 50 DDH patients and 56 normal volunteers were measured by Mimics software in the 3D method and X-ray in 2D. Two VCA (the upper VCA and the lower VCA) were measured in both two methods. Every VCA was measured by observer A and observer B for twice separately. The statistical analyses of the differences were calculated among the measurements of the VCA. RESULTS: The mean value of the upper VCA measured in 3D was 4.95° ± 0.76° in DDH group and 5.56° ± 0.62° in the normal group with significant difference (t = -6.457, p < 0.01). The VCA of DDH group and normal group measured by 3D was larger than 2D, both the upper VCA and the lower VCA. The differences indicated statistically significant. The mean value of lower VCA was 0.60° smaller than the mean value of upper VCA in normal volunteers. The mean value of the lower VCA was 0.58° larger than the mean value of the upper VCA in DDH patients. CONCLUSIONS: Compared to X-ray, 3D reconstruction technology is more accurate without conventional limitations. The lower VCA of DDH patients should be regarded as the femoral intramedullary guide angle in TKA, especially for patients with femoral deformities.


Assuntos
Displasia do Desenvolvimento do Quadril , Fêmur , Articulação do Quadril , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho , Displasia do Desenvolvimento do Quadril/diagnóstico por imagem , Displasia do Desenvolvimento do Quadril/fisiopatologia , Fêmur/diagnóstico por imagem , Fêmur/fisiologia , Articulação do Quadril/diagnóstico por imagem , Articulação do Quadril/fisiologia , Humanos , Imageamento Tridimensional , Articulação do Joelho/diagnóstico por imagem , Articulação do Joelho/fisiologia , Articulação do Joelho/cirurgia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Adulto Jovem
11.
Artigo em Inglês | MEDLINE | ID: mdl-32626698

RESUMO

With the increasing application of orthopedic scaffolds, a dramatically increasing number of requirements for scaffolds are precise. The porous structure has been a fundamental design in the bone tissue engineering or orthopedic clinics because of its low Young's modulus, high compressive strength, and abundant cell accommodation space. The porous structure manufactured by additive manufacturing (AM) technology has controllable pore size, pore shape, and porosity. The single unit can be designed and arrayed with AM, which brings controllable pore characteristics and mechanical properties. This paper presents the current status of porous designs in AM technology. The porous structures are stated from the cellular structure and the whole structure. In the aspect of the cellular structure, non-parametric design and parametric design are discussed here according to whether the algorithm generates the structure or not. The non-parametric design comprises the diamond, the body-centered cubic, and the polyhedral structure, etc. The Voronoi, the Triply Periodic Minimal Surface, and other parametric designs are mainly discussed in parametric design. In the discussion of cellular structures, we emphasize the design, and the resulting biomechanical and biological effects caused by designs. In the aspect of the whole structure, the recent experimental researches are reviewed on uniform design, layered gradient design, and layered gradient design based on topological optimization, etc. These parts are summarized because of the development of technology and the demand for mechanics or bone growth. Finally, the challenges faced by the porous designs and prospects of porous structure in orthopedics are proposed in this paper.

12.
Medicine (Baltimore) ; 99(31): e21481, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32756174

RESUMO

RATIONALE: Severe bone defect could often occur after removing the fractured fixation plates of comminuted fracture in the distal humerus. The reoperation of internal fixation or conventional total elbow arthroplasty could hardly restore the anatomy structure and function of the elbow. However, a novel exploration of 3-dimensional (3D) printed personalized elbow prosthesis was presented in this work. This is a rare and successful treatment for the severe bone defect after removing the fractured fixation plates of comminuted distal humerus fracture. PATIENT CONCERNS: A 60-year-old male patient was admitted to the hospital with the chief complaint of right elbow joint pain and limitation of motion for 10 years. He suffered from an open reduction with internal fixation surgery 10 years ago due to a fall injury-induced right distal humerus fracture. DIAGNOSES: Plain radiographs and computed tomography scan revealed fracture lines, fracture displacement, and fixator breakage in the right distal humerus. Pain, swelling, and limitation of motion could be found in the physical examination. Fixation failure and nonunion after internal fixation of comminuted distal humerus fracture were considered. INTERVENTIONS: The patient was treated with 3D printed personalized TEA and functional rehabilitation exercises. OUTCOMES: No severe complications were observed during the 36 months follow-up. The patient could complete the daily activities without pain. The hospital for special surgery score increased from 15 points before surgery to 90 points 36 months after surgery. LESSONS: The 3D printed personalized prosthesis could successfully reconstruct the anatomical structures and function of the elbow joint with a severe bone defect. The 3D printed personalized total elbow arthroplasty might provide a feasible method for treating the complex elbow joint diseases in the elderly.


Assuntos
Artroplastia de Substituição do Cotovelo/instrumentação , Prótese de Cotovelo , Fraturas Cominutivas/cirurgia , Fraturas do Úmero/cirurgia , Impressão Tridimensional , Reoperação/instrumentação , Artroplastia de Substituição do Cotovelo/métodos , Placas Ósseas/efeitos adversos , Cotovelo/cirurgia , Fixação Interna de Fraturas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Redução Aberta/efeitos adversos , Reoperação/métodos , Resultado do Tratamento
13.
Medicine (Baltimore) ; 99(11): e19268, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32176050

RESUMO

The purpose of this study was to investigate metal artifact reduction effect of orthopedics metal artifact reduction (O-Mar) algorithm in computer tomography (CT) image of patients who have undergone total hip arthroplasty (THA) or total knee arthroplasty (TKA).35 cases of patients who underwent TKA or THA have been recruited in this study. CT image of hip or knee joint was obtained with Philips 256-row CT scanner. Tube voltages of 120 and 140 kilovolt peak (KVP) were set. Afterwards, CT image was reconstructed by O-Mar algorithm to reduce metal artifact. Grade of image quality and severity of metal artifact would be taken into qualitative evaluation. While, quantitative evaluation mainly included measurement of metal artifact volume and 2D measurement of average CT value in region of interest (ROI). The visibility of interface between bone-prostheses was also estimated.Result of qualitative analysis indicated that score of CT quality was improved and grade of metal artifact was decreased significantly with O-Mar. Quantitative analysis illustrated that volume of beam-hardening (B-H) metal artifact decreased remarkably after reconstruction of O-Mar (P < .001). In addition, O-Mar algorithm reduced 83.3% to 83.7% volume of photon-starvation (P-S) metal artifact. As for result of 2D measurement, CT value in ROI was closer to standard value in O-Mar group CT image (P < .001). Meanwhile, error of CT value also decreased significantly after reconstruction of O-Mar algorithm. Visibility rate of bone-prosthesis interface improved from 34.3% (Non-O-Mar) to 66.7% (O-Mar).O-Mar algorithm could significantly reduce metal artifact in CT image of THA and TKA in both 2D and three-dimensional (3D) level. Therefore, better image quality and visibility of bone-prostheses interface could be presented. In this study, O-Mar was proved as an efficient metal artifact reduction method in CT image of THA and TKA.


Assuntos
Algoritmos , Artroplastia de Quadril/métodos , Artroplastia do Joelho/métodos , Artefatos , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Prótese do Joelho , Masculino , Metais , Pessoa de Meia-Idade , Ortopedia , Estudos Retrospectivos
14.
Front Bioeng Biotechnol ; 8: 590549, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33117788

RESUMO

The injury to the spinal cord is among the most complex fields of medical development. Spinal cord injury (SCI) leads to acute loss of motor and sensory function beneath the injury level and is linked to a dismal prognosis. Currently, while a strategy that could heal the injured spinal cord remains unforeseen, the latest advancements in polymer-mediated approaches demonstrate promising treatment forms to remyelinate or regenerate the axons and to integrate new neural cells in the SCI. Moreover, they possess the capacity to locally deliver synergistic cells, growth factors (GFs) therapies and bioactive substances, which play a critical role in neuroprotection and neuroregeneration. Here, we provide an extensive overview of the SCI characteristics, the pathophysiology of SCI, and strategies and challenges for the treatment of SCI in a review. This review highlights the recent encouraging applications of polymer-based scaffolds in developing the novel SCI therapy.

15.
Comput Biol Med ; 125: 104006, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32971324

RESUMO

BACKGROUND: Managing bone defects is a critical aspect of total knee arthroplasty. In this study, we compared the metal block and cement-screw techniques for the treatment of Anderson Orthopaedic Research Institute type 2A tibial bone defects from the biomechanical standpoint. METHOD: The metal block and cement-screw techniques were applied to finite element models of 5- and 10-mm tibial bone defects. Biomechanical compatibility was evaluated based on the stress distributions of the proximal tibia and tibial tray. The displacement of the tibial tray and maximum relative micromotion between the tibial stem and tibia were analyzed to assess the stability of the implant. RESULTS: The maximum stress in both the proximal tibia and tibial tray was greater with the cement-screw technique than with the metal block technique. The stress of the proximal lateral tibia with the cement-screw technique was significantly larger than with the metal block technique (p < 0.05). For the 5-mm bone defect, the maximum relative micromotion was lower than the critical value of 150 µm. For the 10-mm defect, the maximum relative micromotion was 128 µm with the metal block technique and 155 µm with the cement-screw technique, with the latter exceeding the critical value. CONCLUSIONS: The cement-screw technique showed superior biomechanical compatibility to the metal block technique and is more suitable for 5-mm bone defects. However, as it may reduce the fixation strength in 10-mm bone defects, the metal block technique is more appropriate in this case.


Assuntos
Artroplastia do Joelho , Prótese do Joelho , Fenômenos Biomecânicos , Cimentos Ósseos , Parafusos Ósseos , Análise de Elementos Finitos , Tíbia/cirurgia
16.
Aging (Albany NY) ; 13(2): 2330-2347, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33318303

RESUMO

In the mammalian brain, alternative pre-mRNA splicing is a fundamental mechanism that modifies neuronal function dynamically where secretion of different splice variants regulates neurogenesis, development, pathfinding, maintenance, migration, and synaptogenesis. Sequence-specific RNA-Binding Protein CPEB3 has distinctive isoform-distinct biochemical interactions and neuronal development assembly roles. Nonetheless, the mechanisms moderating splice isoform options remain unclear. To establish the modulatory trend of CPEB3, we cloned and excessively expressed CPEB3 in HT22 cells. We used RNA-seq to analyze CPEB3-regulated alternative splicing on control and CPEB3-overexpressing cells. Consequently, we used iRIP-seq to identify CPEB-binding targets. We additionally validated CPEB3-modulated genes using RT-qPCR. CPEB3 overexpression had insignificant effects on gene expression in HT22 cells. Notably, CPEB3 partially modulated differential gene splicing enhanced in the modulation of neural development, neuron cycle, neurotrophin, synapse, and specific development pathway, implying an alternative splicing regulatory mechanism associated with neurogenesis. Moreover, qRT-PCR verified the CPEB3-modulated transcription of neurogenesis genes LCN2 and NAV2, synaptogenesis gene CYLD, as well as neural development gene JADE1. Herein, we established that CPEB3 is a critical modulator of alternative splicing in neurogenesis, which remarkably enhances the current understanding of the CPEB3 mediated alternative pre-mRNA splicing.


Assuntos
Processamento Alternativo/genética , Neurogênese/genética , Neurônios/metabolismo , Proteínas de Ligação a RNA/metabolismo , Animais , Linhagem Celular , Hipocampo/metabolismo , Camundongos , Splicing de RNA , Proteínas de Ligação a RNA/genética
17.
Medicine (Baltimore) ; 98(37): e17142, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31517856

RESUMO

Morphological data of talus are important for the design of talar prostheses. The talar morphology of Chinese population has been rarely reported. This study adopted a three-dimensional (3D) measurement approach to provide accurate data for the anatomical morphology of talus in Northeast Chinese population and compared it with that of foreigners.One hundred forty-six healthy subjects form Northeast China underwent computed tomography (CT) arthrography. 3D digital talar model was reconstructed and thirteen morphological parameters were measured through Mimics and Magics software. Length and breadth indexes of total talus, trochlea, medial and lateral malleolus articular surface were mainly selected. Statistical analysis was conducted by independent-samples and paired-samples t test through SPSS software.All the indexes were normally distributed. No significant difference between left and right talus was identified in either males or females (P > .05). Most of the indexes showed significant sexual differences except the radian of lateral malleolus articular surface and the posterior breadth of trochlea (P < .05). The talar anatomy of Chinese subjects is different from the published data in other populations.The promising approach adopted in this study addresses some inconvenience with previous conventional methods on cadaver specimens. The geometric parameters of talus in Chinese population differ from those in other populations. The talar measurements and morphology analysis in this study suggest that population characteristics should be taken into account. This study will provide references for the design of talar prostheses in Chinese population.


Assuntos
Imageamento Tridimensional , Ossos do Tarso/anatomia & histologia , Ossos do Tarso/diagnóstico por imagem , Tomografia Computadorizada por Raios X , Adulto , China , Feminino , Humanos , Imageamento Tridimensional/métodos , Masculino , Pessoa de Meia-Idade , Variações Dependentes do Observador , Tamanho do Órgão , Reprodutibilidade dos Testes , Caracteres Sexuais , Software , Tomografia Computadorizada por Raios X/métodos , Adulto Jovem
18.
DNA Cell Biol ; 38(7): 734-746, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31149839

RESUMO

Multiple gene polymorphisms have been demonstrated to correlate with the susceptibility to osteonecrosis of the femoral head (ONFH). However, as a complex disease induced by multiple genes, the development of ONFH has rarely been reported to involve in gene interaction. In this study, we first explored the association of 10 variants interactions in receptor activator of nuclear factor-kappa B (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), tumor necrosis factor receptor-associated factor 6 (TRAF6), and nuclear factor of activated T cells cytoplasmic 1 (NFATC1) genes with the development and clinical phenotypes of ONFH in a 377 ONFH case-control study with using Mass ARRAY® platform. Our results showed that not only a total of 6 interactional variants in the paired 10 variants interactions were significantly associated with the development of ONFH (OPG rs2073617 and NFATC1 rs754093, p < 0.019; OPG rs2073618 and NFATC1 rs754093, p < 0.008; OPG rs2073617 and RANKL rs1054016, p < 0.039, respectively) but also a total of 4 paired interactional variants were found to involve significantly in the increased risk of bilateral hip lesions in ONFH (OPG rs2073617 and TRAF6 rs5030411, p = 0.044; RANK rs884205 and TRAF6 rs5030411, p = 0.045, respectively). Moreover, the results from generalized multifactor dimensionality reduction also showed that the five best models were identified and associated significantly with ONFH risk, p = 0.001, 0.01, 0.01, 0.01, and 0.01, respectively. Our results first suggest that the variants in RANK/RANKL/OPG pathway genes affected the development of ONFH in gene interaction manner through the interaction of the paired variants and multiple variants.


Assuntos
Necrose da Cabeça do Fêmur/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Pessoa de Meia-Idade , Fatores de Transcrição NFATC/genética , Osteoprotegerina/genética , Ligante RANK/genética , Receptor Ativador de Fator Nuclear kappa-B/genética , Fator 6 Associado a Receptor de TNF/genética
19.
Leg Med (Tokyo) ; 44: 101647, 2019 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-32217444

RESUMO

OBJECTIVE: The determination of sex is an essential part of building the biological profile for unknown human remains. Sex determination from talus in Chinese population has been rarely reported. The aim of this study was to determine sex by discriminant function analysis through talus measurement in Chinese population. METHODS: 48 male and 47 female Chinese northeast subjects were taken in this research. The ankle joints of these subjects were scanned by CT. In total, thirteen indexes were measured through Mimics and Magics software. Length and breadth indexes of total talus, trochlea, talar head, medial and lateral malleolus articular surface were mainly selected. Nine of them were measured through Mimics software. The other four indexes were measured through Magics software. All data were analyzed by independent-samples t-test in SPSS and Stata software. Discriminant function equations were generated for sex determination. RESULTS: All the indexes were normally distributed. No significant difference between left and right talus in either males or females was identified (P > 0.05). All results showed significant sexual difference (P < 0.05) except posterior breadth of trochlea. The average accuracy of sex determination ranged from 95.85% to 98.45% in the direct method and 98.95% in the stepwise method. CONCLUSIONS: Length indexes showed higher accuracy rate than breadth ones. Length of lateral malleolus articular surface was the best discriminator of sexual dimorphism. Talus was proved effective for sex determination in Chinese population. This study provided a remarkable reference for sex determination in forensic science.

20.
Medicine (Baltimore) ; 98(45): e17508, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31702611

RESUMO

Tibial component of total knee arthroplasty (TKA) is designed according to morphology of proximal tibia to a large extent. Owing to racial difference, current design of tibial component based on Caucasian may not be suitable for Chinese patients. Meanwhile, data of proximal tibial morphology in Chinese population is lacking. The objective of this research was to investigate proximal tibial morphology of northeast Chinese population.Computer tomography (CT) image of 164 northeast Chinese participants was collected. After three-dimensional (3D) reconstruction, size of tibia plateau and TKA resected surface were gauged to guide the design of TKA tibia prothesis in northeast Chinese population. Measurement of tibial size mainly includes tibial mediolateral length (tML), tibial medial/lateral anteroposterior length (tMAP and tLAP). Afterwards, tML/tAP ratio of tibia plateau and TKA resected surface were calculated as feature point of tibia prothesis. tMAP/tLAP ratio of TKA resected surface was calculated to represent tibial asymmetry degree. Medial and lateral posterior tibial slope (MPTS and LPTS) were also measured to give reference to posterior angle of tibia prothesis and angle of tibia osteotomy in TKA. Independent sample t test was performed to conduct statistical analysis, P < .05 was regarded as statistically significance.Northeast Chinese male has larger knee size than female. Significant difference of tML/tAP ratio was also observed between male and female on tibia plateau (1.71 ±â€Š0.07 vs 1.77 ±â€Š0.09) but not on TKA resected surface (1.60 ±â€Š0.05 versus 1.61 ±â€Š0.06). Significant difference of tMAP/tLAP ratio between male and female was also found and they were 1.31 ±â€Š1.03 and 1.11 ±â€Š0.05 respectively. Northeast Chinese female has higher PTS than male (MPTS: 9.56 ±â€Š2.96° vs 8.81 ±â€Š2.87° and LPTS: 8.57 ±â€Š3.19° vs 8.44 ±â€Š2.76°).Significant gender-difference of tibial size and asymmetry degree of tibial resected surface were found between northeast Chinese male and female. Meanwhile, northeast Chinese population has smaller knee size, larger PTS and tML/tAP ratio than that of Caucasian population. Therefore, Chinese-specific and gender-specific tibial prostheses were strongly recommended to be designed.


Assuntos
Artroplastia do Joelho/métodos , Interpretação de Imagem Assistida por Computador/métodos , Tíbia/diagnóstico por imagem , Tíbia/cirurgia , Adulto , China , Feminino , Humanos , Imageamento Tridimensional , Masculino , Osteotomia , Tomografia Computadorizada por Raios X , Adulto Jovem
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