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1.
Artigo em Inglês | MEDLINE | ID: mdl-32012486

RESUMO

Biomaterial-based therapy that can restore annulus fibrosus (AF) function in early stage and promote endogenous repair of AF tissues is a promising approach for AF tissue repair. In this study, we established a genipin-crosslinked decellularized AF hydrogels (g-DAF-G) that are injectable and could manifest better in situ formability than noncrosslinked decellularized AF hydrogel, while preserving the capacity of directing differentiation of human bone mesenchymal stem cells (hBMSCs) towards AF cells. Hematoxylin and eosin staining, 4',6-diamidino-2-phenylindole staining, and so forth showed that the majority of cellular components were removed, whereas extracellular matrix and microstructure were largely preserved. The storage modulus increased from 465.5 ± 9.4 Pa to 3.29 ± 0.24 MPa after 0.02% genipin crosslinking of decellularized AF hydrogels (DAF-G) to form g-DAF-G. AF-specific genes (COL1A1, COL5A1, TNMD, IBSP, FBLN1) were significantly higher in DAF-G and g-DAF-G groups than that in control group after 21 days of culturing. g-DAF-G significantly restored nucleus pulposus water content and preserved intervertebral structure in vivo. Summarily, we produced a novel AF regeneration biomaterial, g-DAF-G, which exhibited well biocompatibility, great bioactivity, and much higher mechanical strength than DAF-G. This study will provide an easy and fast therapeutic alternative to repair AF injuries or tears.

2.
ACS Appl Mater Interfaces ; 12(4): 4265-4275, 2020 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-31903741

RESUMO

Conventional therapeutic approaches to treat malignant tumors such as surgery, chemotherapy, or radiotherapy often lead to poor therapeutic results, great pain, economic burden, and risk of recurrence and may even increase the difficulty in treating the patient. Long-term drug administration and systemic drug delivery for cancer chemotherapy would be accompanied by drug resistance or unpredictable side effects. Thus, the use of photothermal therapy, a relatively rapid tumor elimination technique that regulates autophagy and exerts an antitumor effect, represents a novel solution to these problems. Heat shock protein 90 (HSP90), a protein that reduces photothermal or hypothermic efficacy, is closely related to AKT (protein kinase B) and autophagy. Therefore, it was hypothesized that autophagy could be controlled to eliminate tumors by combining exogenous light with a selective HSP90 inhibitor, for example, SNX-2112. In this study, an efficient tumor-killing strategy using graphene oxide loaded with SNX-2112 and folic acid for ultrafast low-temperature photothermal therapy (LTPTT) is reported. A unique mechanism that achieves remarkable therapeutic performance was discovered, where overactivated autophagy induced by ultrafast LTPTT led to direct apoptosis of tumors and enabled functional recovery of T cells to promote natural immunity for actively participating in the attack against tumors. This LTPTT approach resulted in residual tumor cells being rendered in an "injured" state, opening up the possibility of concurrent antitumor and antirecurrence treatment.

3.
J Surg Oncol ; 121(3): 570-577, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31902136

RESUMO

BACKGROUND: Joint-preserving intercalary tumor resection can result in better proprioception and a more normal joint function after reconstruction. However, most reported reconstruction techniques are usually associated with frequent complications. Therefore, the approach of reconstruction following joint-preserving tumor resection warrants further study. METHODS: Between September 2016 and October 2018, 12 patients with metaphyseal malignant bone tumors around the knee joint were treated by joint-preserving intercalary resections with the aid of three-dimensional (3D)-printed osteotomy guide plates and reconstructions using 3D-printed intercalary prostheses. We assessed the accuracy of the resection by comparing the cross sections at the resection plane with 3D-printed matching surface of the prostheses. The functional outcomes, complications and oncological status were also evaluated. RESULTS: All patients were observed for 7 to 32 months with an average follow-up of 22.5 months. The achieved resection was accurate, with accurate matching between the residual bone and prosthesis. The mean MSTS score was 28 (range, 26-30). Superficial infection occurred in two patients. Local recurrence was observed in one patient, while pulmonary metastasis was identified in one patient. CONCLUSIONS: The personalized osteotomy guide plate and prosthesis based on 3D printing technique facilitate joint-preserving tumor resection and functional reconstruction. However, longer follow-up and larger sample size are required to clarify its long-term outcomes. LEVEL OF EVIDENCE: Level IV, therapeutic study.


Assuntos
Doenças Ósseas/cirurgia , Neoplasias Ósseas/cirurgia , Articulação do Joelho/cirurgia , Tratamentos com Preservação do Órgão/métodos , Impressão Tridimensional/instrumentação , Implantação de Prótese , Procedimentos Cirúrgicos Reconstrutivos/métodos , Adolescente , Adulto , Neoplasias Ósseas/patologia , Criança , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Osteotomia , Prognóstico , Desenho de Prótese , Estudos Retrospectivos
4.
Artigo em Inglês | MEDLINE | ID: mdl-31923126

RESUMO

STUDY DESIGN: Meta-analysis to collect relevant studies to assess the association between COL11A1 and GDF5 genetic variants and susceptibility to IDD. OBJECTIVE: To assess whether or not COL11A1 and GDF5 genetic variants were associated with susceptibility to IDD. SUMMARY OF BACKGROUND DATA: IDD or LDH is a major public health problem. There have been several studies evaluating the relationship between COL11A1 and GDF5 genetic variants with risk of IDD. However, the studies were limited in discrete outcome and sample size, and some of the results were contradictory. METHODS: We systematically searched the relevant publications in electronic databases. Eligible studies were included based on the defined criteria. The pooled ORs with its 95% CIs were received using STATA 15. Subgroup analysis, sensitivity analysis, publication bias and the "Trim and fill" method were performed in the meta-analysis. RESULTS: A total of 3287 IDD cases and 5115 controls were incorporated into the meta-analysis. Our results demonstrated that COL11A1 rs1676486 was significantly associated with increased IDD susceptibility under all genetic models (allele model T vs C: OR = 1.40, 95% CI 1.23-1.59, P = 0.000; homozygote model TT vs CC: OR = 1.89, 95%CI 1.40-2.56, P = 0.000; dominant model TT+TC vs CC: OR = 1.52, 95%CI 1.29-1.80, P = 0.000; recessive model TT vs TC+CC: OR = 1.58, 95%CI 1.18-2.12, P = 0.002). However, GDF5 rs143383 was not (allele model T vs C: OR = 1.15, 95%CI 0.91-1.44, P = 0.244; homozygote model TT vs CC: OR = 1.22, 95%CI 0.75-2.00, P = 0.429; dominant model TT vs CC+CT: OR = 1.22, 95%CI 0.95-1.57, P = 0.112; recessive model TC+TT vs CC: OR = 1.12, 95%CI 0.73-1.73, P = 0.594). Subgroup analysis indicated ethnicity was not the source of heterogeneity. Sensitivity analysis, publication bias and the "Trim and fill" method demonstrated the meta-analysis was of reliability. CONCLUSIONS: Our results suggested that COL11A1 rs1676486 was significantly associated with IDD and the T allele was a risky factor. However, GDF5 rs143383 was not. LEVEL OF EVIDENCE: 1.

5.
J Cell Biochem ; 121(2): 1834-1841, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31642106

RESUMO

Circular RNAs (circRNAs) have been extensively studied in many tumors. The aim of this study was to demonstrate the relationship between circRNAs and clinical features, prognosis, and diagnosis of osteosarcoma patients. We mainly included studies about circRNAs expression and osteosarcoma. The odds ratio (ORs) and 95% confidence intervals (CIs) were used for clinical features, sensitivity, and specificity, while the hazard ratios (HRs) and 95% CIs were used to assess overall survival (OS). A number of 13 articles were included in this study, including 9 about clinical features, 11 about prognosis, and 5 about diagnosis. The results showed that increased circRNAs expression was significantly correlated with adverse clinical characteristics. In terms of prognosis, oncogenic circRNAs had adverse effects on overall survival (OS: HR = 2.54; 95%Cl: 2.05-3.03), and increased expression of cancer-suppressor circRNAs prolonged survival (OS: HR = 0.42; 95%Cl: 0.210.64). Our study further showed an AUC of 0.85, with an 80% sensitivity and 77% specificity to distinguish osteosarcoma patients from healthy controls. In conclusion, circRNAs may be new promising indicators for prognostic evaluation and early diagnosis of osteosarcoma patients.

6.
J Cell Physiol ; 235(2): 1780-1794, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31317559

RESUMO

To investigate whether TP53-induced glycolysis and apoptosis regulator (TIGAR) participates in compression-induced intervertebral disc (IVD) degeneration, and to determine the regulatory effect of TIGAR on nucleus pulposus (NP) cell autophagy and apoptosis following compression-induced injuries. IVD tissues were collected from human patients undergoing surgery (n = 20) and skeletally mature Sprague-Dawley rats (n = 15). Initially, the effect of compression on the expression of TIGAR was evaluated with in vivo and in vitro models. In addition, TIGAR was silenced to investigate the regulatory effect of TIGAR on compression-induced intracellular reactive oxygen species (ROS) levels, autophagy, and apoptosis in rat NP cells. Furthermore, the P53 inhibitor pifithrin-α (PFTα) and SP1 inhibitor mithramycin A were employed to detect expression level changes of TIGAR and autophagy-associated target molecules. TIGAR expression of NP cells increased gradually in human degenerative IVDs and in rat NP cells under compression both in vivo and in vitro. TIGAR knockdown enhanced compression-induced intracellular ROS generation and the NADPH/NADP+ and GSH/GSSG ratios. Moreover, TIGAR knockdown amplified the compression-induced caspase-3 activation and the apoptosis rate of rat NP cells. Likewise, knockdown of TIGAR significantly accelerated LC3B expression and autophagosome formation in rat NP cells during compression-induced injuries. The results also established that mithramycin A could inhibit TIGAR expression and autophagy levels in NP cells under compression conditions, while PFTα had no similar effect. Our data demonstrated that TIGAR acted as an important endogenous negative regulator of ROS levels, which might inhibit compression-induced apoptosis and autophagy through SP1-dependent mechanisms.

7.
Gene Ther ; 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784675

RESUMO

Circular RNA (circRNA) is important in the pathogenesis of many diseases. By analyzing the GSE96964 microarray, hsa_circ_0000285 (circ-0000285) was found to be highly expressed in osteosarcoma. Recent studies have shown that circ-0000285 is capable of regulating proliferative and migratory potentials. Here, we investigated the potential functions in regulating osteosarcoma cells to proliferate and migrate. First of all, qRT-PCR data revealed a higher level of circ-0000285 in osteosarcoma cell lines relative to normal osteoblasts. Through dual-luciferase reporter gene assay and RIP assay, we confirmed that both circ-0000285 and TGFB2 could directly bind to miRNA-599. Regulatory effects of circ-0000285 and miRNA-599 on proliferative and migratory potentials were evaluated by EdU assay and transwell migration assay. It is indicated that circ-0000285 overexpression enhanced the proliferative and migratory potentials of osteosarcoma, which could be reversed by miRNA-599 overexpression. This study revealed a vital role of circ-0000285/miRNA-599/TGFB2 axis in regulating the progression of osteosarcoma, providing a novel perspective for clarifying its pathogenesis.

8.
Aging (Albany NY) ; 11(24): 12476-12496, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31825894

RESUMO

Understanding the bone and musculoskeletal system is essential to maintain the health and quality of life of our aging society. Mesenchymal stem cells (MSCs) can undergo self-renewal and differentiate into multiple tissue types including bone. We demonstrated that BMP9 is the most potent osteogenic factors although molecular mechanism underlying BMP9 action is not fully understood. Long noncoding RNAs (lncRNAs) play important regulatory roles in many physiological and/or pathologic processes. Here, we investigated the role of lncRNA Rmst in BMP9-induced osteogenic differentiation of MSCs. We found that Rmst was induced by BMP9 through Smad signaling in MSCs. Rmst knockdown diminished BMP9-induced osteogenic, chondrogenic and adipogenic differentiation in vitro, and attenuated BMP9-induced ectopic bone formation. Silencing Rmst decreased the expression of Notch receptors and ligands. Bioinformatic analysis predicted Rmst could directly bind to eight Notch-targeting miRNAs, six of which were downregulated by BMP9. Silencing Rmst restored the expression of four microRNAs (miRNAs). Furthermore, an activating Notch mutant NICD1 effectively rescued the decreased ALP activity caused by Rmst silencing. Collectively, our results strongly suggest that the Rmst-miRNA-Notch regulatory axis may play an important role in mediating BMP9-induced osteogenic differentiation of MSCs.

9.
Spine (Phila Pa 1976) ; 44(24): 1697-1704, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31794507

RESUMO

MINI: The surgical results of modified and traditional open-door laminoplasties were retrospectively compared. There were no differences in neurological outcomes and postoperative complications. However, compared with traditional laminoplasty, modified laminoplasty was associated with better maintenance of cervical curvature and ROM, as well as a lower incidence of postoperative axial symptoms. STUDY DESIGN: A retrospective comparative study. OBJECTIVE: The aim of this study was to evaluate the efficacy of modified unilateral open-door laminoplasty with posterior muscle-ligament complex preservation in treating cervical spondylotic myelopathy (CSM). SUMMARY OF BACKGROUND DATA: The prevalence of axial symptoms after open-door laminoplasty ranges from 5% to 86%. Current modified laminoplasty techniques cannot satisfactorily reduce postoperative axial symptoms. METHODS: From June 2014 to July 2016, 36 patients with CSM underwent modified laminoplasty with posterior muscle-ligament complex preservation (modified group) and 27 patients underwent traditional laminoplasty (control group). The demographics, operation duration, blood loss volume, cervical curvature, cervical curvature index (CCI), range of motion (ROM), cervical posterior muscle volume on magnetic resonance imaging (MRI), axial symptoms, visual analog scale (VAS) score, Japanese Orthopedic Association (JOA) score, neck disability index (NDI), and complications were recorded and analyzed before operation, after operation, and at the final follow-up. RESULTS: Cervical flexion curvature, cervical curvature, ROM, and CCI were better in the modified group than in controls at the final follow-up (P < 0.01). Postoperative VAS and NDI scores were significantly reduced in the modified group compared with controls (1.15 ±â€Š0.76 vs. 2.63 ±â€Š1.06, 5.67 ±â€Š2.57 vs. 8.89 ±â€Š5.37, respectively) (P < 0.01). Posterior muscle volume at the hinge side in the modified group was not different at final follow-up relative to that before the operation, whereas it was reduced in controls (P < 0.01). Finally, the incidence of axial symptoms was significantly lower in the modified group than in controls (6% vs. 22%) (P = 0.03). CONCLUSION: Modified unilateral open-door laminoplasty with posterior muscle-ligament complex preservation is effective for treating CSM with good recovery of neurological functions and satisfactory maintenance of cervical curvature and ROM. Furthermore, it reduces the incidence of postoperative axial symptoms compared with conventional open-door laminoplasty. LEVEL OF EVIDENCE: 3.

10.
Oxid Med Cell Longev ; 2019: 4764071, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885796

RESUMO

Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor γ, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.

11.
World Neurosurg ; 2019 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-31778833

RESUMO

BACKGROUND: Schwannomas are the most common benign tumors in the intraspinal location with slow growing and non-aggressive features. Calcification is not a common histopathological and radiological feature in schwannoma. CASE DESCRIPTION: We report a case of 43-year-old male with soreness in the lower back, left buttock and lower limb for one month. In MRI and CT scan, an intradural mass with extensive calcification was found in L1-L2 level. The tumor was completely removed in the surgery with the sacrifice of one nerve root. After the surgery, the symptoms were relieved, and no dysfunction of lower limbs and sphincter was observed. Pathologically, the tumor was diagnosed as schwannoma with extensive calcification. At 7 months follow-up, no complaints were found. CONCLUSION: Although intraspinal schwannoma with extensive calcification is rare, which obstructs the accuracy of preoperative diagnosis, the tumor can be completely removed with or without excision of the nonfunctional nerve roots.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31767195

RESUMO

BACKGROUND: Trauma- or osteoarthritis-related cartilage damage resulted in functional decline of joints and heavy burden of public health. Recently, the reparative role of mesenchymal stem/progenitor cells (MSCs) in articular cartilage (AC) reconstruction is drawing more and more attention. OBJECTIVE: To provide a review on (1) the locations and categories of joint-resident MSCs, (2) the regulation of chondrogenic capacities of MSCs, (3) the migratory approaches of MSCs to diseased AC and regulatory mechanisms. METHODS: PubMed and Web of Science were searched for English-language articles related to MSC recruitment and migration for AC repair until June 2019. The presence of various MSCs in or around joints, the potential approaches to diseased AC` and the regenerative capacities of MSCs were reviewed. RESULTS: Various intra- and peri-articular MSCs, with inherent migratory potentials, are present in multiple stem cell niches in or around joints. The recruitment and migration of joint-resident MSCs play crucial roles in endogenous AC repair. Multiple recruiting signals, such as chemokines, growth factors, etc., emerge during the development of AC diseases and participate in the regulation of MSC mobilization. Motivated MSCs could migrate into cartilage lesions and then exert multiple reparative potentials, including extracellular matrix (ECM) reconstruction and microenvironment modulation. CONCLUSION: In general, AC repair based on endogenous MSC recruitment and migration is a feasible strategy, and a promising research field. Furthermore, endogenous AC repair mediated by native MSCs would provide new opportunities to efficient preventative or therapeutic options for AC diseases.

13.
Oncol Lett ; 18(5): 5294-5300, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31612039

RESUMO

T-cell immunoglobulin and mucin domain-containing-3 (TIM-3) performs a critical function in immune tolerance by suppressing the activation and proliferation of T cells. TIM-3 serves an important role in tumor progression in a number of carcinomas, including non-small cell lung cancer, hepatitis B virus-associated hepatocellular carcinoma, Langerhans cell sarcoma, head and neck cancer and follicular B cell non-Hodgkin lymphoma. The aim of the present study was to evaluate the possible association of TIM-3 with the prognosis of osteosarcoma. TIM-3 expression was assessed by immunohistochemical analysis in osteosarcoma tissues. The association between TIM-3 expression and prognosis was examined. To assess the association between TIM-3 expression levels and clinicopathological features, a Fisher's exact test was used. TIM-3 overexpression was indicated to be associated with surgical treatment and survival. Kaplan-Meier analysis indicated that TIM-3 is an independent predictor of overall survival, and its overexpression was indicated to be associated with poor prognosis in patients with osteosarcoma. Additionally, reverse transcription-quantitative polymerase chain reaction and western blot analysis were carried out to evaluate TIM-3 expression levels in fresh tumor tissue samples, adjacent-tissue samples, osteosarcoma cell lines, and in an osteoblastic cell line. TIM-3 was indicated to be overexpressed in fresh osteosarcoma tissue samples and in osteosarcoma cell lines. In conclusion, TIM-3 overexpression is associated with poor survival among patients with osteosarcoma and may be a possible therapeutic target in these types of tumors.

14.
Proc Inst Mech Eng H ; 233(12): 1310-1317, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617820

RESUMO

This study aimed to evaluate the safety and accuracy of mixed reality-based intraoperative three-dimensional navigated pedicle screws in three-dimensional printed model of fractured upper cervical spine. A total of 27 cervical model from patients of upper cervical spine fractures formed the study group. All the C1 and C2 pedicle screws were inserted under mixed reality-based intraoperative three-dimensional image-guided navigation system. The accuracy and safety of the pedicle screw placement were evaluated on the basis of postoperative computerized tomography scans. A total of 108 pedicle screws were properly inserted into the cervical three-dimensional models under mixed reality-based navigation, including 54 C1 pedicle screws and 54 C2 pedicle screws. Analysis of the dimensional parameters of each pedicle at C1/C2 level showed no statistically significant differences in the ideal and the actual entry points, inclined angles, and tailed angles. No screw was misplaced outside the pedicle of the three-dimensional printed model, and no ionizing X-ray radiation was used during screw placement under navigation. It is easy and safe to place C1/C2 pedicle screws under MR surgical navigation. Mixed reality-based navigation is feasible within upper cervical spinal fractures with improved safety and accuracy of C1/C2 pedicle screw insertion.

15.
BMC Cancer ; 19(1): 997, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31651287

RESUMO

BACKGROUND: High level of reactive oxygen species (ROS) has been detected in almost all cancers, which make it become one of the best-characterized phenotypes in cancers. Though ROS plays an important role in tumors, the degree of oxidative stress can be better evaluated by assessing stable metabolites of oxidative reactions because of its high instability. 8-hydroxy-2'-deoxyguanosine (8-OHdG), a product of oxidative damage to 2'-deoxyguanosine, is known as a useful marker for assessing oxidative DNA damage and has been a feature of carcinogenesis in several researches. But the exact prognostic value of 8-OHdG expression in patients with cancer is still unclear. METHODS: A comprehensive search was performed in PubMed, Web of Science, EMBASE. Eligible studies were included based on defined exclusion and inclusion criteria to perform a meta-analysis. STATA 14.0 was used to estimate pooled hazard ratios (HRs) with 95% confidence interval (95% CI), the heterogeneity among studies and publication bias to judge the prognostic value. RESULTS: A total of 2121 patients from 21 eligible studies were included in the meta-analysis. A significant association was found between elevated 8-OHdG expression and poor OS (overall survival) in cancer patients (pooled HR 1.921, 95% CI: 1.437-2.570); In the subgroup analysis, race of sample, cancer types, detection method of 8-OHdG, sample classification, detection location of 8-OHdG and paper quality (score more or less than 7) did not alter the association between 8-OHdG expression and cancer prognosis. Furthermore, 8-OHdG expression was an independent prognostic marker for overall survival in patients with cancer (pooled HR 2.110, 95% CI: 1.482-3.005) using Cox multivariate analyses. CONCLUSIONS: This meta-analysis found that highly expressed 8-OHdG in tumor tissues may be a predictor of prognosis in most solid tumors. However, especially in breast cancer, low 8-OHdG expression is associated with poor prognosis, which is partly because of the increased antioxidant mechanisms in breast cancer tissues. This study demonstrates for the first time that 8-OHdG expression is associated with the prognosis of cancer patients. In the future, whether the expression level of 8-OHdG can be used as a biomarker for the prognosis of all human cancers requires more research.

16.
Cell Commun Signal ; 17(1): 138, 2019 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-31665012

RESUMO

Following publication of the original article [1], it was reported that Figs. 4 and 5 were not updated during the production process.

17.
Exp Ther Med ; 18(4): 2933-2941, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31572536

RESUMO

Traumatic soft tissue defects such as bedsores, chronic skin ulcers, limb necrosis, osteonecrosis and other ischemic orthopedic diseases are the most clinically intractable and common problems in orthopedics due to unsatisfactory conventional treatments. The present study designed poly(ethylene glycol; PEG) hydrogels with covalently binded arginylglycylaspartic acid (RGD). Endothelial progenitor cells (EPCs) were encapsulated in the modified hydrogel along with vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Results demonstrated that the modified hydrogel displayed good mechanical properties appropriate for a sustained release carrier. RGD modification significantly promoted EPC biocompatibility. VEGF and bFGF encapsulation enhanced the adhesion of EPCs, promoted the production of extracellular matrix and facilitated EPC proliferation. In addition, bFGF and VEGF induced angiogenesis. The combination of growth factors and EPCs in the hydrogel displayed a strong synergy to improve biocompatibility. The present results provided a potential novel treatment approach for soft tissue defects such as bone exposure, chronic skin ulcers, bedsores, limb necrosis, osteonecrosis and other ischemic diseases.

18.
Cancer Med ; 8(17): 7345-7358, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31631559

RESUMO

Patients with osteosarcoma exhibiting resistance to chemotherapy or presenting with metastasis usually have a poor prognosis. Osteosarcoma stem cells (OSCs) are a potential cause of tumor metastasis, relapse, and chemotherapy resistance. Therefore, it is necessary to develop novel therapeutic drugs, which not only kill osteosarcoma cells but also target OSCs. This study aims to explore the anti-osteosarcoma effects of Bruceine D (BD), a natural compound derived from Brucea javanica, and investigate its underlying mechanisms. Results demonstrated that BD could significantly inhibit cell proliferation and migration, induce cell cycle arrest, and promote apoptosis in osteosarcoma cells. Besides, BD could also suppress the sphere-forming and self-renewal ability of OSCs. Mechanistically, the inhibitory role of BD on osteosarcoma cell growth and migration including OSC stemness was partially executed through the inhibition of STAT3 signaling pathway. More importantly, BD showed significant anti-osteosarcoma activity without obvious side effects in vivo. Collectively, the results of this study demonstrated that BD exerts a strong inhibitory effect on tumor growth and stem cell like traits of osteosarcoma which may be partially due to STAT3 inhibition, suggesting that BD maybe a promising therapeutic candidate against osteosarcoma.

19.
Cell Commun Signal ; 17(1): 125, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31610798

RESUMO

BACKGROUND: Aberrant expression of cyclin-dependent protein kinases (CDK) is a hallmark of cancer. CDK11 plays a crucial role in cancer cell growth and proliferation. However, the molecular mechanisms of CDK11 and CDK11 transcriptionally regulated genes are largely unknown. METHODS: In this study, we performed a global transcriptional analysis using gene array technology to investigate the transcriptional role of CDK11 in osteosarcoma. The promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay were used to identify direct transcriptional targets of CDK11. Clinical relevance and function of core-binding factor subunit beta (CBFß) were further accessed in osteosarcoma. RESULTS: We identified a transcriptional role of protein-DNA interaction for CDK11p110, but not CDK11p58, in the regulation of CBFß expression in osteosarcoma cells. The CBFß promoter luciferase assay, chromatin immunoprecipitation assay, and Gel Shift assay confirmed that CBFß is a direct transcriptional target of CDK11. High expression of CBFß is associated with poor outcome in osteosarcoma patients. Expression of CBFß contributes to the proliferation and metastatic behavior of osteosarcoma cells. CONCLUSIONS: These data establish CBFß as a mediator of CDK11p110 dependent oncogenesis and suggest that targeting the CDK11- CBFß pathway may be a promising therapeutic strategy for osteosarcoma treatment.

20.
Cell Death Dis ; 10(10): 687, 2019 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-31534119

RESUMO

Osteosarcoma (OS) is the most common malignant bone tumor. The prognosis of metastatic and recurrent OS patients still remains unsatisfactory. Cisplatin reveals undeniable anti-tumor effect while induces severe side effects that threatening patients' health. Dynasore, a cell-permeable small molecule that inhibits dynamin activity, has been widely studied in endocytosis and phagocytosis. However, the anti-tumor effect of dynasore on OS has not yet been ascertained. In the present study, we suggested that dynasore inhibited cell proliferation, migration, invasion, and induced G0/G1 arrest of OS cells. Besides, dynasore repressed tumorigenesis of OS in xenograft mouse model. In addition, we demonstrated that dynasore improved the anti-tumor effect of cisplatin in vitro and in vivo without inducing nephrotoxicity and hepatotoxicity. Mechanistically, dynasore repressed the expression of CCND1, CDK4, p-Rb, and MMP-2. Furthermore, we found that dynasore exerts anti-tumor effects in OS partially via inhibiting STAT3 signaling pathway but not ERK-MAPK, PI3K-Akt or SAPK/JNK pathways. P38 MAPK pathway served as a negative regulatory mechanism in dynasore induced anti-OS effects. Taken together, our study indicated that dynasore does suppress cell proliferation, migration, and invasion via STAT3 signaling pathway, and enhances the antitumor capacity of cisplatin in OS. Our results suggest that dynasore is a novel candidate drug to inhibit the tumor growth of OS and enhance the anti-tumor effects of cisplatin.

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