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1.
Biochem J ; 2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32432317

RESUMO

Aberrant expression of microRNAs (miRNAs) has been associated with spinal ossification of the posterior longitudinal ligament (OPLL). Our initial bioinformatic analysis identified differentially expressed ADORA2A in OPLL and its regulatory miRNAs miR-497 and miR-195. Hence, this study was conducted to clarify the functional relevance of miR-497-195 cluster in OPLL, which may implicate in Adenosine A2A (ADORA2A). PLL tissues were collected from OPLL and non-OPLL patients, followed by quantification of miR-497, miR-195 and ADORA2A expression. The expression of miR-497, miR-195 and/or ADORA2A was altered in posterior longitudinal ligament (PLL) cells, which then were stimulated with cyclic mechanical stress (CMS). We validated that ADORA2A was expressed highly, while miR-497 and miR-195 were downregulated in PLL tissues of OPLL patients. miR-195 and miR-497 expression in CMS-treated PLL cells was restored by a demethylation reagent 5-aza-2'-deoxycytidine (AZA). Moreover, expression of miR-195 and miR-497 was decreased by promoting promoter CpG island methylation. ADORA2A was verified as the target of miR-195 and miR-497. Overexpression of miR-195 and miR-497 diminished expression of osteogenic factors in PLL cells by inactivating the cAMP/PKA signaling pathway via downregulation of ADORA2A. Collectively, miR-497-195 cluster augments osteogenic differentiation of PLL cells by inhibiting ADORA2A-dependent cAMP/PKA signaling pathway.

2.
Proc Inst Mech Eng H ; : 954411920921679, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32419625

RESUMO

The objective of this study was to design a novel dynamic fixation system with biodegradable components, apply it for lumbar fusion between articular processes and compare the fusion results and biomechanical changes to those of conventional rigid fixation. The novel dynamic fixation system was designed using a finite element model, stress distributions were compared and 24 mongrel dogs were randomly assigned to two groups and subjected to either posterior lumbar fusion surgery with a novel dynamic fixation system or titanium rods at the L5-L6 segments. Lumbar spines were assessed in both groups to detect radiographic, manual palpation and biomechanical changes. Histological examination was performed on organs and surrounding tissues. In the novel dynamic fixation system, stress was mainly distributed on the meshing teeth of the magnesium alloy spacer. The magnesium alloy components maintained their initial shape 8 weeks after the operation, but the meshing teeth were almost completely degraded at 16 weeks. The novel dynamic fixation system revealed an increased lateral bending range of motion at 8 weeks; however, both groups showed similar radiographic grades, fusion stiffness, manual palpation and histological results. The novel dynamic fixation system design is suitable, and its degradation in vivo is safe. The novel dynamic fixation system can be applied for posterior lumbar fusion between articular processes and complete the fusion like titanium rods.

3.
FASEB J ; 34(3): 4798-4811, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32039519

RESUMO

Recently, type H vessels were reported to couple angiogenesis and osteogenesis during osteoclastogenesis, and tartrate-resistant acid phosphatase (Trap)+ preosteoclasts were found to secrete increased PDGF-BB to promote type H vessel formation. Therefore, utilization of type H vessels may be a strategy to treat diseases involving bone loss. In the present study, we found that nuciferine, a natural bioactive compound, has various effects, including inhibiting osteoclastogenesis and promoting type H vessel formation. Nuciferine inhibited osteoclastogenesis and bone resorption but increased the relative number of Trap+ preosteoclasts. Nuciferine restrained the expression of osteoclast-specific genes and proteins, promoted PDGF-BB production and potentiated related angiogenic activities by inhibiting the MAPK and NF-κB signaling pathways in vitro. We confirmed the bone-protective effects of nuciferine in ovariectomized mice and found that nuciferine treatment increased the PDGF-BB concentration and the number of type H vessels in the femur. In conclusion, our results demonstrated that nuciferine can decrease multinucleated osteoclast formation and promote type H vessel formation through preservation of Trap+ preosteoclasts via inhibition of the MAPK and NF-κB signaling pathways and may be an excellent agent for the treatment of diseases involving bone loss.

4.
J Gene Med ; : e3174, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-32056303

RESUMO

BACKGROUND: MicroRNAs (miRs) hold critical implications in the modulation of osteogenesis. This work was designed to unravel the underlying regulatory mechanism of miR-22 during osteoblast differentiation. METHODS: Synthetic miR-22 mimics or inhibitors were transfected into preosteoblast MC3T3-E1 cells to regulate miR-22 expression. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] and flow cytometry analyses were employed to assess cell proliferation and apoptosis. A quantitative real-time polymerase chain reaction and western blot assays were applied to measure mRNA and protein expression. Alkaline phosphatase activity and alizarin red staining were tested to further analyze cell differentiation. In silico analysis and luciferase reporter assays were utilized to identify the direct binding between miR-22 and its potential target. RESULTS: MTT and flow cytometry analyses showed that miR-22 repressed MC3T3-E1 cell viability and promoted cell apoptosis. By detecting osteogenic-specific molecule expression, alkaline phosphatase activity and alizarin red staining, miR-22 was observed to suppress osteogenic differentiation of MC3T3-E1 cells. In silico analysis and luciferase reporter assays confirmed that ESR1 is a direct target gene of miR-22. In addition, miR-22 expression affected the phosphorylation of p38 mitogen-activated protein kinase and Jun N-terminal kinase expression in MC3T3-E1 cells. CONCLUSIONS: The findings of the present study highlight the functional significance of miR-22 in osteoblast differentiation and suggest its role as a possible therapeutic target in metabolic bone disorders.

5.
Artigo em Inglês | MEDLINE | ID: mdl-31983200

RESUMO

In recent years, many different kinds of nonlinear optical materials have been applied to passively Q-switched solid-state lasers. However, the average output powers of these lasers are typically limited to 1 W due to the low damage threshold of the materials. In this study, a molybdenum-disulfide-doped glass-composite absorber was synthesized using the sol-gel method and spin-coating technique. The optical damage threshold of the absorber reached 3.17 J/cm2. Saturation intensity, modulation depth, and nonsaturable loss are 9.35 MW/cm2, 8.41%, and 9.14%, respectively. After inserting the absorber into a linear Nd:YAG laser cavity, the maximum average output power (3.22 W) and stable Q-switched laser pulses duration (132 ns) were obtained.

6.
Medicine (Baltimore) ; 99(4): e18974, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977914

RESUMO

We aimed to develop a nomogram based on a population-based cohort to estimate the individualized overall survival (OS) for patients with nasopharyngeal carcinoma (NPC) and compare its predictive value with that of the traditional staging system.Data for 3693 patients with NPC were extracted from the Surveillance, Epidemiology, and End Results dataset and randomly divided into two sets: training (n = 2585) and validation (n = 1108). On the basis of multivariate Cox regression analysis, a nomogram was constructed to predict the 3-, 5-, and 10-year survival probability for a patient. The performance of the nomogram was quantified with respect to discrimination, calibration, and clinical utility.In the training set, age, sex, race, marital status, histological type, T stage, N stage, M stage, radiotherapy, and chemotherapy were selected to develop a nomogram for predicting the OS probability based on the multivariate Cox regression model. The nomogram was generally more discriminative compared with the American Joint Committee on Cancer 7th staging system. Calibration plots exhibited an excellent consistency between the observed probability and the nomogram's prediction. Categorical net classification improvement and integrated discrimination improvement suggested that the predictive accuracy of the nomogram exceeded that of the classic staging system. With respect to decision curve analyses, the nomogram exhibited preferable net benefit gains than the staging system across a wide range of threshold probabilities.This proposed nomogram exhibits an excellent performance with regard to its predictive accuracy, discrimination capability, and clinical utility, and thus can be used as a convenient and reliable tool for prognosis prediction in patients with NPC.


Assuntos
Carcinoma Nasofaríngeo/mortalidade , Nomogramas , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Modelos de Riscos Proporcionais , Melhoria de Qualidade , Programa de SEER/estatística & dados numéricos , Adulto Jovem
8.
J Mater Chem B ; 7(44): 7052-7064, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31641711

RESUMO

Micro-nano based fibrous scaffolds have been extensively studied in regenerative medicine. Bone marrow stem cells (BMSCs) and BMP2-derived peptides, two other important components for tissue engineering, have been successfully used for bone regeneration. However, a scaffold that specifically captures BMSCs and delivers BMP2-derived peptides to promote osteogenic differentiation of enriched BMSCs has not been reported. In this study, a microfiber scaffold was constructed by coaxial electrospinning technology using a polyvinylpyrrolidone/bovine serum albumin/BMP2-derived peptide compound as the core solution and a polycaprolactone/collagen I compound as the shell solution. The scaffolds were further functionalized by covalent grafting of a BMSC affinity peptide (E7) to develop a dual drug release system for the delivery of the BMP2-derived peptide and E7. Structural analysis indicated that the microfibers had a uniform diameter and homogeneous core-shell structure. Fourier transform infrared spectroscopy (FTIR) revealed that E7 was covalently bonded onto the surface of the fibers. In vitro, the E7-modified scaffolds promoted the initial adhesion of BMSCs and were more favorable for BMSC survival. Furthermore, the BMP2-derived peptide loaded in the E7-modified scaffolds was released in a sustained manner and retained bioactivity, significantly improving the osteogenic differentiation of BMSCs. In vivo, scaffolds loaded with the BMP2-derived peptide and E7 (PCME scaffolds) led to enhanced new bone formation and defect closure in a rat calvarial defect model. Overall, the PCME scaffold simultaneously facilitated all three of the essential elements needed for bone tissue engineering, providing a promising method for bone regeneration.

9.
Mater Sci Eng C Mater Biol Appl ; 104: 109842, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31500042

RESUMO

Hydroxyapatite (HA) ceramics are well known for their biocompatibility, bioactivity, and osteoconductive nature. However, limited hierarchical structure and lack of ease in modularity hinder the widespread application of conventional HA ceramics. By using three-dimensional printing (3DP) techniques with multiple materials, including HA, complex biological and mechanical architecture of natural organisms can be achieved through biomimetics. In this study, we designed an osteoid, biomimetic, hierarchical, porous HA ceramic 3D printed scaffold (3DPs). Further incorporation of a covalent, modular, controlled release system (CMR), based on Watson-Crick's complementary oligonucleotides, and was added to carry a bone morphogenetic protein-2 (BMP2) peptide. The choice of a HA biomimetic scaffold housing BMP2 protein fragments was selected to successfully promote osteogenesis both in vitro and in vivo. Scanning electron microscopy, micro-computed tomography analysis and computer fluid dynamics simulations of the 3DPs showed a uniform biomimetic hierarchical structure and an effective interior permeability. Active molecules were found bound with high stability and modular to the scaffold surface via the CMR system. After 7 days of incubation under physiological conditions, approximately 90% of active factors remained bound. Compared to control groups, the 3DPs-CMR-BMP2 group significantly enhanced cell proliferation and adhesion. Moreover, the 3DPs-CMR-BMP2 group exhibited more extensive and sustained osteogenic effects through upregulated expression of osteogenic factors and enhanced calcium deposition, as compared to study and control groups. Furthermore, ectopic osteogenesis and a critical calvarial defect model confirmed that the 3DPs-CMR-BMP2 group significantly promoted in vivo bone healing versus control. Thus, our results showed that biomimetic hierarchical 3DPs with a CMR system successfully promote cell proliferation, adhesion, differentiation and osteogenesis, on a continuous cycle. The biomimetic hierarchical 3DPs with a CMR system offers a promising multi-functional, bone substitute material for treatment of patients with bone defects.


Assuntos
Biomimética , Sistemas de Liberação de Medicamentos , Osteogênese , Impressão Tridimensional , Tecidos Suporte/química , Fosfatase Alcalina/metabolismo , Animais , Adesão Celular , Proliferação de Células , Sobrevivência Celular , Cerâmica/química , Durapatita/química , Fluorescência , Regulação da Expressão Gênica , Hidrodinâmica , Masculino , Minerais/metabolismo , Oligonucleotídeos/química , Osteogênese/genética , Permeabilidade , Porosidade , Ratos Sprague-Dawley , Microtomografia por Raio-X
10.
Asian J Androl ; 2019 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-31417010

RESUMO

Hypoxia-induced erythropoietin signaling plays an important role in tumor growth and invasion. In the present study, we investigated the contribution of erythropoietin signaling pathway to castration-resistant prostate cancer and the development of a neuroendocrine phenotype. Immunohistochemical staining showed that the erythropoietin and erythropoietin receptor scores in castration-resistant prostate cancer and androgen-dependent prostate cancer were 7.55 versus 4.5 and 7.45 versus 5.9,respectively (P < 0.001). Furthermore, a cell proliferation assay was conducted, and the differential expression of erythropoietin and erythropoietin receptor in LNCaP cells and hypoxia-induced LNCaP cells was evaluated using western blot and quantitative real-time PCR. The proliferation capacity of hypoxia-induced LNCaP cells was similar in cultures of both fetal bovine serum and charcoal-stripped fetal bovine serum, suggesting that LNCaP cells acquired hypoxia-induced androgen-independent growth. After 2 weeks of hypoxic culture, LNCaP cells showed a neuroendocrine cell change and increased expression of neuron-specific enolase, erythropoietin, and erythropoietin receptor; knockdown of erythropoietin receptor reversed the hypoxia-induced upregulation of neuron-specific enolase in the LNCaP cells. In conclusion, the concurrent upregulation of erythropoietin and erythropoietin receptor in castration-resistant prostate cancer suggests that the erythropoietin/erythropoietin receptor autocrine loop plays an important role in the progression of castration resistance and is responsible for the development of a neuroendocrine phenotype.

11.
ACS Omega ; 4(5): 8087-8093, 2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-31459899

RESUMO

Using density functional theory calculations and photoemission measurements, we have studied the interaction between the non-fullerene small-molecule acceptor ITIC and K atoms (a representative of reactive metals). It is found that the acceptor-donor-acceptor-type geometric structure and the electronic structure of ITIC largely decide the interaction process. One ITIC molecule can combine with more than 20 K atoms. For stoichiometries K x≤6ITIC, the K atoms are attracted to the acceptor units of the molecule and donate their 4s electrons to the unoccupied molecular orbitals. K-ITIC organometallic complexes, characterized by the breaking of some S-C bonds in the donor unit of ITIC and the formation of K-S bonds, are formed for stoichiometries K x≥7ITIC. The complexes are still conjugated despite the breaking of some S-C bonds.

12.
Yonsei Med J ; 60(6): 585-591, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31124343

RESUMO

PURPOSE: The aim of this study was to explore the function of microRNA-27b (miR-27b) in fibroblast-like synoviocytes (FLSs) stimulated by tumor necrosis factor α (TNF-α). MATERIALS AND METHODS: mRNA expression of miR-27b in FLS cells (MH7A) treated with or without TNF-α was determined by q-PCR. MiR-27b mimics was transfected into MH7A cells to upregulate miR-27b expression. MTT assay and flow cytometry analysis were performed to investigate the effect of miR-27b on MH7A cell viability and apoptosis. The targets of miR-27b were predicted by TargetScan. The direct regulation of miR-27b on IL-1ß expression was verified by luciferase assay. The protein expression levels of apoptosis-related proteins, IL-1ß, and NF-κB signaling-related proteins were detected by Western blot. RESULTS: We discovered that miR-27b expression was decreased in MH7A cells stimulated by TNF-α. Upregulation of miR-27b by miR-27b mimics significantly inhibited the proliferation and promoted the apoptosis of TNF-α-stimulated MH7A cells. Consistently, upregulation of miR-27 decreased the level of Bcl-2 and increased Bax and caspase-3 expression in MH7A cells stimulated by TNF-α. Luciferase assay revealed that IL-1ß was indeed a target of miR-27b. By quantitative real-time PCR and Western blot, we found that the expression of IL-1ß is negatively regulated by miR-27b. Moreover, the NF-κB signaling pathway was significantly inhibited by miR-27b. CONCLUSION: Taken together, our results illustrated that enhanced miR-27b expression results in the suppression of proliferation and the promotion of apoptosis in FLSs stimulated by TNF-α, partially by regulating IL-1ß expression and NF-κB signaling.


Assuntos
Apoptose , Fibroblastos/patologia , MicroRNAs/genética , Sinoviócitos/patologia , Fator de Necrose Tumoral alfa/farmacologia , Regulação para Cima/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Sequência de Bases , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , MicroRNAs/metabolismo , NF-kappa B/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sinoviócitos/efeitos dos fármacos , Sinoviócitos/metabolismo , Regulação para Cima/efeitos dos fármacos
13.
Prion ; 13(1): 106-115, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-31050590

RESUMO

OBJECTIVE: To evaluate whether EPC-MVs could promote bone regeneration by directly regulating osteoblast through miR-126. The underlying mechanisms were also explored. METHODS: EPCs were isolated from bone marrow mononuclear cells. EPC-MVs were collected from EPCs cultured medium. The lentivirus was used to induce miR-126 over-expression in EPCs and EPC-MVs. miR-126 expression was detected by qRT-PCR. The proliferation, migration, apoptosis and differentiation abilities of osteoblast cells MC3T3-E1 were analysed in the presence or absence of EPC-MVs or miR-126 overexpressed EPC-MVs (EPC-MVs-miR126). The proteins of Erk1/2 and Bcl-2 were analysed by western blot. Erk1/2 inhibitor was used for pathway exploration. RESULTS: EPC-MVs reduced apoptosis and promoted proliferation and migration of MC3T3-E1 cells, which could be enhanced by miR-126 enrichment (p< 0.05). Neither EPC-MVs nor EPC-MVs-miR126 had an effect on MC3T3-E1 cell osteogenic differentiation (p> 0.05). EPC-MVs-miR126 had better effects than EPC-MVs on upregulating the expressions of p-Erk1/2 and Bcl-2, which were abolished by Erk1/2 inhibitor. ERK1/2-Bcl-2 activity plays a crucial role in the regulation of EPC-MVs/EPC-MVs-miR126 on the effect of MC3T3-E1 cells. CONCLUSION: EPC-MVs promote proliferation and migration of MC3T3-E1 cell while reduced apoptosis via the miR-126/Erk1/2-Bcl-2 pathway. A combination of EPC-MVs and miR-126 might provide novel therapeutic targets for bone regeneration and fracture healing through regulating osteoblast.

14.
Rev Sci Instrum ; 90(3): 033108, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30927815

RESUMO

Broadband laser ranging (BLR) is an appropriate method to obtain absolute distance in dynamic experiments. In this article, we first analyze the performance limit for BLR and indicate that the measuring range can be hardly increased while keeping the distance or time resolution unchanged. Then, multi-reference BLR is proposed, which can break this limit and greatly increase the measuring range. Its validity is demonstrated by an experiment with an explosively driven aluminum surface flying over 100 mm. This method would improve the capability of BLR.

15.
Molecules ; 24(7)2019 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987158

RESUMO

Flavonoids from plants are particularly important in our diet. Buckwheat is a special crop that is rich in flavonoids. In this study, four important buckwheat varieties, including one tartary buckwheat and three common buckwheat varieties, were selected as experimental materials. The total flavonoid content of leaves from red-flowered common buckwheat was the highest, followed by tartary buckwheat leaves. A total of 182 flavonoid metabolites (including 53 flavone, 37 flavonol, 32 flavone C-glycosides, 24 flavanone, 18 anthocyanins, 7 isoflavone, 6 flavonolignan, and 5 proanthocyanidins) were identified based on Ultra Performance Liquid Chromatography-Electrospray Ionization-Tandem Mass Spectrometry (UPLC-ESI-MS/MS) system. Through clustering analysis, principal component analysis (PCA), and orthogonal signal correction and partial least squares-discriminant analysis (OPLS-DA), different samples were clearly separated. Considerable differences were observed in the flavonoid metabolites between tartary buckwheat leaves and common buckwheat leaves, and both displayed unique metabolites with important biological functions. This study provides new insights into the differences of flavonoid metabolites between tartary buckwheat and common buckwheat leaves and provides theoretical basis for the sufficient utilization of buckwheat.


Assuntos
Fagopyrum/química , Flavonoides/química , Metaboloma , Metabolômica , Folhas de Planta/química , Cromatografia Líquida de Alta Pressão , Biologia Computacional/métodos , Fagopyrum/metabolismo , Flavonoides/metabolismo , Metabolômica/métodos , Anotação de Sequência Molecular , Folhas de Planta/metabolismo , Espectrometria de Massas por Ionização por Electrospray
16.
FEBS Open Bio ; 9(4): 781-790, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30984551

RESUMO

Although the long non-coding RNA THOR has been reported to promote cancer stem cell expansion in liver cancer and gastric cancer, its effects on osteosarcoma (OS) cells remain unclear. Here, we investigated the roles of THOR in the stemness and migration of OS cells. We report that the level of THOR is remarkably upregulated in OS cell spheroids compared to that in OS adherent cells. THOR overexpression increased spheroid formation ability and aldehyde dehydrogenase 1 (ALDH1) activity in OS adherent cells, and the opposite effect was observed in spheroids with THOR knockdown. Additionally, the spheroids formed by OS adherent cells exhibited a stronger migration ability, which was attenuated by THOR knockdown, and THOR overexpression increased OS cell migration. Mechanistically, mRNA stability, luciferase reporter, and RNA-RNA in vitro interaction assays indicated that THOR can directly bind to the middle region of the SOX9 3'-untranslated region (UTR), and enhances its mRNA stability, thereby increasing its expression. Notably, SOX9 knockdown reduced the ability of THOR overexpression to promote the stemness of OS cells. These findings indicate that the lncRNA THOR can promote the stemness and migration of OS cells by directly binding to the middle region of SOX9 3'UTR, thereby enhancing SOX9 mRNA stability and increasing its expression; thus, we provide information that may be of use in identifying potential targets for OS treatment.


Assuntos
Transformação Celular Neoplásica/genética , Células-Tronco Neoplásicas/metabolismo , Osteossarcoma/genética , RNA Longo não Codificante/genética , Fatores de Transcrição SOX9/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Estabilidade de RNA/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fatores de Transcrição SOX9/metabolismo , Esferoides Celulares/metabolismo
18.
Biomaterials ; 196: 109-121, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-29655516

RESUMO

Spinal disorders often require surgical treatment called spinal fusion to restore a stabilized spine where bone grafts are implanted for the fusion of adjacent vertebras. In this study, we developed a bioactive composite scaffold incorporated with salvianolic acid B (SB), an active component extracted from Danshen. This study aimed to evaluate the effects of SB-incorporated porous scaffold on spinal fusion models. The composite scaffolds composed of poly (lactic-co-glycolic acid) and tricalcium phosphate (PLGA/ß-TCP) were fabricated with low-temperature rapid prototyping technique, which incorporated SB at low (SB-L), middle (SB-M), high (SB-H) doses, and pure PLGA/ß-TCP as blank control (Con). The release profile of SB from the scaffolds was determined by high performance liquid chromatography. Osteoconductive and osteoinductive properties of the scaffolds were reflected by the osteogenic differentiation ability of rat primary mesenchymal stem cells. The angiogenesis was determined by the forming of tube-like structures resembling capillaries using endothelial cell line (EA hy9.26). A well-established spinal fusion model was used to evaluate the in vivo bony fusion. Animals were transplanted with scaffolds, or autografts from iliac crest as positive controls. Micro-computed tomography (CT) analysis, CT-based angiography, manual palpation test, histomorphometry, and histology were performed after 8 weeks of transplantation. Results revealed that incorporated SB was steadily released from the scaffolds. The aliquot of released SB promoted osteogenesis and angiogenesis in vitro in a dose-dependent manner. In animal study, a dose-dependent effect of SB on new bone formation, mineral apposition rate, and vessel density within the scaffold were demonstrated. Manual palpation test showed little numerical improvement in fusion rate when compared with the blank controls. In summary, our results suggested that SB-incorporated PLGA/ß-TCP composite scaffold could enhance bony fusion through the promotion of osteogenesis and angiogenesis.

20.
Ann Hematol ; 97(11): 2185-2194, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30039296

RESUMO

Newly diagnosed acute myeloid leukemia (AML) failed to achieve complete remission after two courses of intensive chemotherapy. This was considered as primary refractory AML (PRR-AML), and still has a dismal prognosis. Allogeneic hematopoietic stem cell transplantation could be the only cure for these patients. However, the role of haploidentical hematopoietic stem cell transplantation (HID-HCT) for PRR-AML is still undetermined. We retrospectively analyzed the outcomes of 45 adult patients with PRR-AML who underwent HID-HCT, and compared it with the result of 53 patients who received HLA-matched related or unrelated donor transplantation (MD-HCT) during the same treatment period. The 3-year overall survival (OS), leukemia-free survival (LFS), cumulative incidence of relapse (CIR), and non-relapse mortality (NRM) rates in the HID-HCT group were 19.0, 16.5, 70.0, and 35.2%, respectively, but showed no significant differences from the results of MD-HCT. Multivariate analysis showed that complex karyotype with del(7) and time > 6 months from diagnosis to transplantation were associated with lower OS and LFS, and chronic GVHD demonstrated better OS and LFS in the entire cohort. Complex karyotype with del(7) was related with higher CIR and chronic GVHD with lower CIR. In conclusion, HID-HCT could be an alternative treatment strategy to improve the long-term survival in PRR-AML adult patients who have no HLA-matched donors.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Teste de Histocompatibilidade , Leucemia Mieloide Aguda , Doadores não Relacionados , Adolescente , Adulto , Aloenxertos , Intervalo Livre de Doença , Feminino , Humanos , Leucemia Mieloide Aguda/mortalidade , Leucemia Mieloide Aguda/terapia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Taxa de Sobrevida
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