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1.
Cell Death Dis ; 11(2): 103, 2020 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029706

RESUMO

N6 methyladenosine (m6A) is one of the most prevalent epitranscriptomic modifications of mRNAs, and plays a critical role in various bioprocesses. Bone-derived mesenchymal stem cells (BMSCs) can attenuate apoptosis of nucleus pulposus cells (NPCs) under compression; however, the underlying mechanisms are poorly understood. This study showed that the level of m6A mRNA modifications was decreased, and the autophagic flux was increased in NPCs under compression when they were cocultured with BMSCs. We report that under coculture conditions, RNA demethylase ALKBH5-mediated FIP200 mRNA demethylation enhanced autophagic flux and attenuated the apoptosis of NPCs under compression. Specific silencing of ALKBH5 results in impaired autophagic flux and a higher proportion of apoptotic NPCs under compression, even when cocultured with BMSCs. Mechanistically, we further identify that the m6A "reader" YTHDF2 is likely to be involved in the regulation of autophagy, and lower m6A levels in the coding region of FIP200 lead to a reduction in YTHDF2-mediated mRNA degradation of FIP200, a core molecular component of the ULK1 complex that participates in the initiating process of autophagy. Taken together, our study reveals the roles of ALKBH5-mediated FIP200 mRNA demethylation in enhancing autophagy and reducing apoptosis in NPCs when cocultured with BMSCs.

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 Cell Physiol ; 235(3): 2195-2208, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31478571

RESUMO

Intervertebral disc degeneration (IDD) is a complex and chronic disease that involves disc cell senescence, death, and extracellular matrix (ECM) degradation. HOTAIR, a long non-coding RNA (lncRNA) is reportedly associated with autophagy, whereas autophagy is shown to promote IDD. However, how it affects nucleus pulposus (NP) cells, the primary component of intervertebral discs is still unclear. We hypothesized that HOTAIR promotes NP cell apoptosis and senescence through upregulating autophagy. Thus, silencing HOTAIR should inhibit autophagy and exert a therapeutic effect on IDD. Our in vitro experiments in human NP cells revealed that HOTAIR expression positively correlated with IDD grade, and overexpression enhanced autophagy. Autophagy inhibition via 3-methyladenine reversed HOTAIR stimulatory effects on apoptosis, senescence, and ECM catabolism, while the AMP-activated protein kinase (AMPK) inhibitor Compound C suppressed HOTAIR-induced autophagy through regulating AMPK/mTOR/ULK1 pathways. Our in vivo experiment then illustrated that silencing HOTAIR ameliorates IDD in rats. Collectively, we demonstrated that HOTAIR stimulates autophagy to promote NP cell apoptosis, senescence, and ECM catabolism. Therefore, silencing HOTAIR has the potential to become a treatment option for IDD.

4.
Int J Med Sci ; 16(12): 1573-1582, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31839745

RESUMO

Colorectal cancer is one of the most common cancers worldwide with a high incidence rate. Therefore, the molecular basis of colorectal tumorigenesis and evolution must be clarified. Structure-specific recognition protein 1 (SSRP1) is involved in transcriptional regulation, DNA damage repair, and cell cycle regulation and has been confirmed to be highly expressed in various tumor tissues, including colorectal cancer. However, the role of SSRP1 in the development of colorectal cancer remains unclear. Therefore, this study explored the role of SSRP1 in the occurrence and development of colorectal cancer. Using bioinformatics databases, including samples from the Cancer Genome Atlas (TCGA), we confirmed high SSRP1 expression in human colorectal adenocarcinoma tissues. We demonstrated that SSRP1 knockdown via small interfering RNA significantly inhibited the proliferation of colorectal cancer cells and promoted apoptosis through the AKT signaling pathway, suppressing the invasion and migration of colorectal cancer cells in vitro and in vivo. In conclusion, this study demonstrated that SSRP1 silencing influenced the proliferation and apoptosis of colorectal cancer cells via the AKT signaling pathway.

5.
ACS Appl Mater Interfaces ; 11(44): 41758-41769, 2019 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-31610117

RESUMO

Bone repair and regeneration are greatly influenced by the local immune microenvironment. In this regard, the immunomodulatory capability of biomaterials should be considered when evaluating their osteogenic effects. In this study, we investigated the modulatory effects of gold nanoparticle (AuNP)-loaded mesoporous silica nanoparticles (Au-MSNs) on macrophages and the subsequent effects on the behavior of osteoblastic lineage cells. The results demonstrate that Au-MSNs could generate a favorable immune microenvironment by stimulating an anti-inflammatory response and promoting the secretion of osteogenic cytokines by macrophages. As a result, there is an enhancement of osteogenic differentiation in preosteoblastic MC3T3 cells as assessed by the increased expression of osteogenic markers, alkaline phosphatase (ALP) production, and calcium deposition. The immunomodulatory effects and direct osteogenic stimulation by Au-MSNs synergistically increased the osteogenic differentiation capability of MC3T3 cells as a result of crosstalk between Au-MSN-conditioned macrophages and Au-MSN-treated osteoblasts in a coculture system. An in vivo study further revealed that Au-MSNs could accelerate new bone formation in a critical-sized cranial defect site in rats based on computed tomography analysis and histological examination. Together, this novel Au-MSNs could significantly promote osteogenic activity by modulating the immune microenvironment, showing its therapeutic potential for bone tissue repair and regeneration.

6.
Int J Oncol ; 55(4): 879-895, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31485609

RESUMO

Bromodomain and extraterminal domain proteins, especially bromodomain­containing protein 4 (Brd4), have recently emerged as therapeutic targets for several cancers, although the role and mechanism of Brd4 in glioblastoma multiforme (GBM) are unclear. In this study, we aimed to explore the underlying mechanisms of the anti­tumor effects of Brd4 and the bromodomain inhibitor JQ1 on glioma stem cells (GSCs). In vitro, JQ1 and small interfering RNAs targeting Brd4 (siBrd4) inhibited the proliferation and self­renewal of GSCs. In vivo, JQ1 significantly inhibited the growth of xenograft GSCs tumors. The RNA­seq analysis revealed that the PI3K­AKT pathway played an important role in GBM. Vascular endothelial growth factor (VEGF) and VEGF receptor 2 phosphorylation was downregulated by exposure to JQ1 in GSCs, thereby reducing PI3K and AKT activity. In addition, treatment with JQ1 inhibited MMP expression, thereby inhibiting degradation of the extracellular matrix by MMP and angiogenesis in GBM tumors. Suppression of AKT phosphorylation inhibited the expression of the retinoblastoma/E2F1 complex, resulting in cell cycle arrest. In addition, treatment with siBrd4 or JQ1 induced apoptosis by activating AKT downstream target genes involved in apoptosis. In conclusion, these results suggest that Brd4 has great potential as a therapeutic target, and JQ1 has notable anti­tumor effects against GBM which may be mediated via the VEGF/PI3K/AKT signaling pathway.


Assuntos
Azepinas/administração & dosagem , Neoplasias Encefálicas/tratamento farmacológico , Proteínas de Ciclo Celular/metabolismo , Glioma/tratamento farmacológico , Células-Tronco Neoplásicas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Triazóis/administração & dosagem , Animais , Azepinas/farmacologia , Neoplasias Encefálicas/metabolismo , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioma/metabolismo , Humanos , Masculino , Camundongos , Células-Tronco Neoplásicas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Triazóis/farmacologia , Fator A de Crescimento do Endotélio Vascular/metabolismo , Ensaios Antitumorais Modelo de Xenoenxerto
7.
Int J Nanomedicine ; 14: 6151-6163, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447557

RESUMO

Background: Precise control and induction of the differentiation of stem cells to osteoblasts by artificial biomaterials are a promising strategy for rapid bone regeneration and reconstruction. Purpose: In this study, gold nanoparticles (AuNPs)-loaded hydroxyapatite (HA-Au) nanocomposites were designed to guide the osteogenic differentiation of human bone marrow-derived mesenchymal stem cells (hMSCs) through the synergistic effects of both AuNPs and HA. Materials and methods: The HA-Au nanoparticles were synthesized and characterized by several analytical techniques. Cell viability and proliferation of hMSCs were characterized by CCK-8 test. Cellular uptake of nanoparticles was observed by transmission electron microscope. For the evaluation of osteogenic differentiation, alkaline phosphatase (ALP) activity and staining, Alizarin red staining, and a quantitative real-time polymerase chain reaction (RT-PCR) analysis were performed. In order to examine specific signaling pathways, RT-PCR and Western blotting assay were performed. Results: The results confirmed the successful synthesis of HA-Au nanocomposites. The HA-Au nanoparticles showed good cytocompatibility and internalized into hMSCs at the studied concentrations. The increased level of ALP production, deposition of calcium mineralization, as well as the expression of typical osteogenic genes, indicated the enhancement of osteogenic differentiation of hMSCs. Moreover, the incorporation of Au could activate the Wnt/ß-catenin signaling pathway, which seemed to be the molecular mechanism underlying the osteoinductive capability of HA-Au nanoparticles. Conclusion: The HA-Au nanoparticles exerted a synergistic effect on accelerating osteogenic differentiation of hMSCs, suggesting they may be potential candidates for bone repair and regeneration.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Durapatita/farmacologia , Ouro/química , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Nanopartículas Metálicas/química , Osteogênese , Via de Sinalização Wnt/efeitos dos fármacos , Fosfatase Alcalina/metabolismo , Cálcio/metabolismo , Diferenciação Celular/genética , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/enzimologia , Nanopartículas Metálicas/ultraestrutura , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Osteogênese/genética
8.
Med Sci Monit ; 25: 5613-5620, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31353362

RESUMO

BACKGROUND The number of patients with spinal cord injury caused by motor vehicle accidents, violent injuries, and other types of trauma increases year by year, and bone marrow mesenchymal stem cell (BMSC) transplants are being widely investigated to treat this condition. However, the success rate of BMSCs transplants is relatively low due to the presence of oxidative stress in the new microenvironment. Our main goals in the present study were to evaluate the damaging effects of H2O2 on BMSCs and to develop a model of "stemness loss" using rat BMSCs. MATERIAL AND METHODS Bone marrow-derived mesenchymal stem cells were obtained from the bone marrow of young rats reared under sterile conditions. The stem cells were used after 2 passages following phenotypic identification. BMSCs were divided into 4 groups to evaluate the damaging effects of H2O2: A. blank control; B. 100 uM H2O2; C. 200 uM H2O2 and D. 300 uM H2O2. The ability of the BMSCs to differentiate into 3 cell lineages and their colony formation and migration capacities were analyzed by gene expression, colony formation, and scratch assays. RESULTS The cells we obtained complied with international stem cell standards demonstrated by their ability to differentiate into 3 cell lineages. We found that 200-300 uM H2O2 had a significant effect on the biological behavior of BMSCs, including their ability to differentiate into 3 cell lineages, the expression of stemness-related proteins, and their migration and colony formation capacities. CONCLUSIONS H2O2 can damage the stemness ability of BMSCs at a concentration of 200-300 uM.


Assuntos
Peróxido de Hidrogênio/efeitos adversos , Transplante de Células-Tronco Mesenquimais/métodos , Células-Tronco Mesenquimais/efeitos dos fármacos , Animais , Medula Óssea/metabolismo , Células da Medula Óssea/metabolismo , Técnicas de Cultura de Células/métodos , Diferenciação Celular/efeitos dos fármacos , Células Cultivadas , Feminino , Peróxido de Hidrogênio/metabolismo , Masculino , Células-Tronco Mesenquimais/metabolismo , Ratos , Ratos Sprague-Dawley
9.
Insect Sci ; 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30919568

RESUMO

The Hedgehog (Hh) signaling pathway is one of the major regulators of embryonic development and tissue homeostasis in multicellular organisms. However, the role of this pathway in the silkworm, especially in the silkworm midgut, remains poorly understood. Here, we report that Bombyx mori Hedgehog (BmHh) is expressed in most tissues of silkworm larvae and that its functions are well-conserved throughout evolution. We further demonstrate that the messenger RNA of four Hh signaling components, BmHh ligand, BmPtch receptor, signal transducer BmSmo and transcription factor BmCi, are all upregulated following Escherichia coli or Bacillus thuringiensis infection, indicating the activation of the Hh pathway. Simultaneously, midgut cell proliferation is strongly promoted. Conversely, the repression of Hh signal transduction with double-stranded RNA or cyclopamine inhibits the expression of BmHh and BmCi and reduces cell proliferation. Overall, these findings provide new insights into the Hh signaling pathway in the silkworm, B. mori.

10.
BMC Gastroenterol ; 19(1): 231, 2019 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-31888534

RESUMO

BACKGROUND: Statin has been more and more widely used in chronic liver disease, however, existed studies have attained contradictory results. According to the present study, we aimed to test the efficacy and safety of statin via a meta-analysis. METHODS: Different databases were searched for full-text publication based on inclusion and exclusion criteria. For data-pooling, fixed-effect model was applied if heterogeneity wasn't detected. Otherwise, random-effect model was adopted. Heterogeneity was detected by I squire (I2) test. All results of analysis were illustrated as forest plots. Publication bias was assessed using the Begg's adjusted rank correlation test. Standard mean difference (SMD) was calculated in continuous variables. Pooled hazard ratio or odds ratio was calculated in catergorical variables. RESULTS: Seventeen clinical studies were finally included. Hepatic portal hemodynamic parameters were improved in statin users for a short-term response. For a long-term follow-up, statin treatment surprisingly decreased mortality rate (HR = 0.782, 95% CI: 0.718-0.846, I2 > 50%) and lower the occurrence of hepatocellular carcinoma (HR = 0.75, 95% CI: 0.64-0.86, I2 > 50%) in liver cirrhosis. Statin seemed not to decrease the risk of esophageal variceal bleeding and spontaneous bacterial peritonitis. However, statin was proved to decrease the risk of hepatic encephalopathy and ascites. Incidence of drug related adverse events didn't increase in statin users. Dose-dependent effects of statin on hepatocellular carcinoma development, decompensated cirrhosis events occurrence, and liver cirrhosis progression. CONCLUSION: Statin influenced parameters of hepatic portal vessel pressure in short-term treatment. Prognosis of liver cirrhosis benefited from statin treatment in long term follow-up. The efficacy and safety of statin in liver cirrhosis treatment is confirmed. To date, similar study is hardly seen before.

11.
Stem Cells Int ; 2018: 1481243, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30402107

RESUMO

Purpose: Mechanical loading plays a vital role in the progression of intervertebral disc (IVD) degeneration, but little is known about the effect of compression loading on human nucleus pulposus-derived mesenchymal stem cells (NP-MSCs). Thus, this study is aimed at investigating the effect of compression on the biological behavior of NP-MSCs in vitro. Methods: Human NP-MSCs were isolated from patients undergoing lumbar discectomy for IVD degeneration and were identified by immunophenotypes and multilineage differentiation. Then, cells were cultured in the compression apparatus at 1.0 MPa for different times (0 h, 24 h, 36 h, and 48 h). The viability-, differentiation-, and differentiation-related genes (Runx2, APP, and Col2) and colony formation-, migration-, and stem cell-related proteins (Sox2 and Oct4) were evaluated. Results: The results showed that the isolated cells fulfilled the criteria of MSC stated by the International Society for Cellular Therapy (ISCT). And our results also indicated that compression loading significantly inhibited cell viability, differentiation, colony formation, and migration. Furthermore, gene expression suggested that compression loading could downregulate the expression of stem cell-related proteins and lead to NP-MSC stemness losses. Conclusions: Our results suggested that the biological behavior of NP-MSCs could be inhibited by compression loading and therefore enhanced our understanding on the compression-induced endogenous repair failure of NP-MSCs during IVDD.

12.
BMC Musculoskelet Disord ; 19(1): 381, 2018 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-30342505

RESUMO

BACKGROUND: Intervertebral disk degeneration (IDD) is a common musculoskeletal disease associated with genetic factors. COL9A3 gene encodes the α3 (IX) chain of type IX collagen that is part of the interior structure of the disc. Mutations in COL9A3 gene sequence, leading to an Arg103Trp substitution in its 3 chain (the Trp3 allele at rs61734651 site), respectively, have been found to be connected with IDD occurrence in several studies. However, those studies have showed conflict results. Thus, a meta-analysis has been performed to assess the associations between the COL9A3 trp3 polymorphism and IDD. METHODS: Data were gathered from the following four electronic databases: PubMed, Web of Science (WOS), Embase and Cochrane library up to January 01, 2018. The pooled odds ratio (polled ORs) and 95% confidence interval (CI) were calculated to evaluate the strength of relationship between the COL9A3 trp3 polymorphism and IDD. RESULTS: Eleven eligible studies with 1631 cases of IDD and 1366 controls were included in this meta-analysis. The results indicated that the COL9A3 trp3 polymorphism was not associated with IDD (trp3 positive versus trp3 negative: OR = 1.31, 95%CI = 0.78-2.21, P = 0.309). Furthermore, the Egger's test and the Begg funnel plot did not show any evidence of publication bias. CONCLUSIONS: Our results suggest that the COL9A3 trp3 polymorphism might not be associated with IDD. Nor did we find any relationship in subgroup analyses stratified by gender and ethnicity. Future researches with larger samples are required to verify this outcome.


Assuntos
Colágeno Tipo IX/genética , Predisposição Genética para Doença , Degeneração do Disco Intervertebral/genética , Alelos , Humanos , Degeneração do Disco Intervertebral/epidemiologia , Mutação , Polimorfismo de Nucleotídeo Único
13.
Medicine (Baltimore) ; 97(37): e12147, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30212940

RESUMO

RATIONALE: Bronchial foreign body aspiration is a critical condition that jeopardizes the respiratory function of children. Prompt diagnosis and removal of the foreign body can reduce occurrence of foreign body complications and mortality. Aspiration of spherical plastic beads is rare, and the bead is difficult to retrieve. PATIENT CONCERNS: An 8-year-old girl developed cough, transient throat wheezing, and intermittent cough after she accidentally inhaled a plastic bead 7 hours ago. Chest computed tomography scan revealed a round shadow 1.2 cm in diameter in the right main bronchus. DIAGNOSES: Foreign body in the right main bronchus. INTERVENTIONS: Retrieval by balloon-tipped catheter via flexible bronchoscopy was undertaken. OUTCOMES: The bead was successfully retrieved and the child recovered uneventfully. LESSONS: Foreign body aspiration in children constitutes a medical emergency in severe cases. Flexible bronchoscopy and balloon-tipped catheter retrieval can be used as an effective noninvasive treatment for aspiration of plastic beads.


Assuntos
Brônquios/cirurgia , Broncoscopia/métodos , Cateterismo/métodos , Corpos Estranhos/cirurgia , Criança , Feminino , Humanos , Tomografia Computadorizada por Raios X
14.
BMC Musculoskelet Disord ; 19(1): 137, 2018 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-29734947

RESUMO

BACKGROUND: It was reported that Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) gene polymorphism might be related to the risk of musculoskeletal degenerative diseases (MSDD), such as osteoarthritis (OA), intervertebral disc degeneration (IVDD) and rheumatoid arthritis (RA). However, data from different studies was inconsistent. Here we aim to elaborately summarize and explore the association between the Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) and MSDD. METHODS: Literatures were selected from PubMed, Web of Science, Embase, Scopus and Medline in English and VIP, SinoMed, Wanfang and the China National Knowledge Infrastructure (CNKI) in Chinese up to August 21, 2017. All the researches included are case-control studies about human. We calculated the pooled odds ratios (ORs) with 95% confidence intervals (95% CI) to evaluate the strengths of the associations of Fas (rs1800682, rs2234767) and FasL (rs5030772, rs763110) polymorphisms with MSDD risk. RESULTS: Eleven eligible studies for rs1800682 with 1930 cases and 1720 controls, 6 eligible studies for rs2234767 with 1794 cases and 1909 controls, 3 eligible studies for rs5030772 with 367 cases and 313 controls and 8 eligible studies for rs763110 with 2010 cases and 2105 controls were included in this analysis. The results showed that the G allele of Fas (rs1800682) is associated with an increased risk of IVDD in homozygote and recessive models. The G allele of Fas (rs2234767) is linked to a decreased risk of RA but an enhanced risk of OA in allele and recessive models. In addition, the T allele of FasL (rs763110) is correlated with a reduced risk of IVDD in all of models. However, no relationship was found between FasL (rs5030772) and these three types of MSDD in any models. CONCLUSIONS: Fas (rs1800682) and FasL (rs763110) polymorphism were associated with the risk of IVDD and Fas (rs2234767) was correlated to the susceptibility of OA and RA. Fas (rs1800682) and Fas (rs2234767) are more likely to be associated with MSDD for Chinese people. FasL (rs763110) is related to the progression of MSDD for both Caucasoid and Chinese race groups. But FasL (rs5030772) might not be associated with any types of MSDD or any race groups statistically.


Assuntos
Proteína Ligante Fas/genética , Estudos de Associação Genética/métodos , Doenças Musculoesqueléticas/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor fas/genética , Grupo com Ancestrais do Continente Asiático/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Humanos , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/epidemiologia
15.
Artigo em Inglês | MEDLINE | ID: mdl-29259641

RESUMO

Purpose: To explore the effect and possible mechanism of icariin, a prenylated flavonol glycoside derived from the Chinese herb Epimedium sagittatum that was applied to IL-1ß pretreated human nucleus pulposus (NP) cells. Methods: Human NP cells were isolated from intervertebral discs of patients with scoliosis and lumbar spondylolisthesis. The cells were divided into five groups: A (blank control); B (20 ng/ml IL-1ß); C (20 ng/ml IL-1ß + 20 µM icariin); D (20 µM icariin + 20 ng/ml IL-1ß + 25 µM LY294002); E (20 ng/ml IL-1ß + 25 µM LY294002). For each of the five groups, the CCK8, apoptosis rates, ROS rates, and JC-1 rates were determined and an electron micrograph was performed. Different expression levels of apoptosis proteins and proteins in the PI3K/AKT pathway were detected via western blot. Results: We found that the damage effects on human nucleus pulposus cells from 20 ng/ml of IL-1ß exposure were attenuated by icariin. When the PI3K/AKT pathway was blocked by LY294002, a specific inhibitor of this pathway, the protective effect of icariin was impaired. In summary, icariin might be a protective traditional Chinese medicine, which prevents inflammation-induced degeneration of intervertebral discs partly through the PI3K/AKT pathway.

16.
Oncol Lett ; 13(5): 3760-3766, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28529590

RESUMO

Choroidal melanoma is the most common primary intraocular tumor in adults. Cepharanthine (CEP), a natural alkaloid extracted from the roots of Stephania cepharantha Hayata, has been demonstrated to inhibit the proliferation of various cancer cells. However, its potential anticancer effect in choroidal melanoma has not been clarified yet. In the present study, it was identified that CEP may potently inhibit the proliferation of human choroidal melanoma cells, induce cell death and cell cycle arrest, and activate cellular apoptotic proteins, including Bcl-2-associated X protein, caspase and poly(ADP-ribose) polymerase. Results also revealed that CEP induced the cellular production of reactive oxygen species (ROS) and led to cytochrome c release, whereas concurrent treatment with N-acetyl-L-cysteine (a ROS scavenger) attenuated the situation. In addition, CEP was also revealed to activate c-Jun N-terminal kinase (JNK) 1 and 2, whereas inhibition of JNK1/2 partially abrogated the proliferation inhibitory effect of CEP, indicating that JNK1 and JNK2 were involved in CEP-triggered cellular apoptosis. In addition, the anticancer effects of CEP were also observed in a choroidal melanoma xenograft model. In summary, the results of the present study demonstrated that CEP is effective in suppressing human choroidal melanoma cell and tumor cell proliferation, and that CEP may therefore represent a potentially novel therapeutic agent for the treatment of choroidal melanoma.

17.
Artigo em Inglês | MEDLINE | ID: mdl-28536643

RESUMO

Icariin is a prenylated flavonol glycoside derived from the Chinese herb Epimedium sagittatum. This study investigated the mechanism by which icariin prevents H2O2-induced apoptosis in rat nucleus pulposus (NP) cells. NP cells were isolated from the rat intervertebral disc and they were divided into five groups after 3 passages: (A) blank control; (B) 200 µM H2O2; (C) 200 µM H2O2 + 20 µM icariin; (D) 20 µM icariin + 200 µM H2O2 + 25 µM LY294002; (E) 200 µM H2O2 + 25 µM LY294002. LY294002 is a selective inhibitor of the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. NP cell viability, apoptosis rate, intracellular reactive oxygen species levels, and the expression of AKT, p-AKT, p53, Bcl-2, Bax, caspase-3 were estimated. The results show that, compared with the control group, H2O2 significantly increased NP cell apoptosis and the level of intracellular ROS. Icariin pretreatment significantly decreased H2O2-induced apoptosis and intracellular ROS and upregulated p-Akt and BCL-2 and downregulated caspase-3 and Bax. LY294002 abolished the protective effects of icariin. Our results show that icariin can attenuate H2O2-induced apoptosis in rat nucleus pulposus cells and PI3K/AKT pathway is at least partly included in this protection effect.

18.
Comput Methods Biomech Biomed Engin ; 20(4): 355-364, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-27626889

RESUMO

Spinal cages are used to create a suitable mechanical environment for interbody fusion in cases of degenerative spinal instability. Due to individual variations in bone structures and pathological conditions, patient-specific cages can provide optimal biomechanical conditions for fusion, strengthening patient recovery. Finite element analysis (FEA) is a valuable tool in the biomechanical evaluation of patient-specific cage designs, but the time- and labor-intensive process of modeling limits its clinical application. In an effort to facilitate the design and analysis of patient-specific spinal cages, an integrated CAD-FEA system (CASCaDeS, comprehensive analytical spinal cage design system) was developed. This system produces a biomechanical-based patient-specific design of spinal cages and is capable of rapid implementation of finite element modeling. By comparison with commercial software, this system was validated and proven to be both accurate and efficient. CASCaDeS can be used to design patient-specific cages with a superior biomechanical performance to commercial spinal cages.


Assuntos
Projeto Auxiliado por Computador , Análise de Elementos Finitos , Modelagem Computacional Específica para o Paciente , Próteses e Implantes , Desenho de Prótese , Adulto , Fenômenos Biomecânicos , Humanos , Processamento de Imagem Assistida por Computador , Vértebras Lombares/patologia , Fusão Vertebral , Estresse Mecânico
19.
Stem Cells Int ; 2017: 9843120, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-29387092

RESUMO

Objective: Excessive apoptosis of nucleus pulposus cells (NPCs) induced by various stresses, including compression, contributes to the development of intervertebral disc degeneration (IVDD). Mesenchymal stem cells (MSCs) can benefit the regeneration of NPCs and delay IVDD, but the underlying molecular mechanism is poorly understood. This study aimed to evaluate the antiapoptosis effects of bone marrow-derived MSC (BMSC) on rat NPCs exposed to compression and investigate whether the mitochondrial pathway was involved. Methods: BMSCs and NPCs were cocultured in the compression apparatus at 1.0 MPa for 36 h. Cell viability, apoptosis, mitochondrial function, and the expression of apoptosis-related proteins were evaluated. Results: The results showed that coculturing with BMSCs increased the cell viability and reduced apoptosis of NPCs exposed to compression. Meanwhile, BMSCs could relieve the compression-induced mitochondrial damage of NPCs by decreasing reactive oxygen species level and maintaining mitochondrial membrane potential as well as mitochondrial integrity. Furthermore, coculturing with BMSCs suppressed the activated caspase-3 and activated caspase-9, decreased the expressions of cytosolic cytochrome c and Bax, and increased the expression of Bcl-2. Conclusions: Our results suggest that BMSCs can protect against compression-induced apoptosis of NPCs by inhibiting the mitochondrial pathway and thus enhance our understanding on the MSC-based therapy for IVDD.

20.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 31(10): 1267-1272, 2017 10 15.
Artigo em Chinês | MEDLINE | ID: mdl-29806333

RESUMO

Objective: To summarize the research progress of intervertebral disc endogenous stem cells for intervertebral disc regeneration and deduce the therapeutic potential of endogenous repair for intervertebral disc degeneration. Methods: The original articles about intervertebral disc endogenous stem cells for intervertebral disc regeneration were extensively reviewed; the reparative potential in vivo and the extraction and identification in vitro of intervertebral disc endogenous stem cells were analyzed; the prospect of endogenous stem cells for intervertebral disc regeneration was predicted. Results: Stem cell niche present in the intervertebral discs, from which stem cells migrate to injured tissues and contribute to tissues regeneration under certain specific microenvironment. Moreover, the migration of stem cells is regulated by chemokines system. Tissue specific progenitor cells have been identified and successfully extracted and isolated. The findings provide the basis for biological therapy of intervertebral disc endogenous stem cells. Conclusion: Intervertebral disc endogenous stem cells play a crucial role in intervertebral disc regeneration. Therapeutic strategy of intervertebral disc endogenous stem cells is proven to be a promising biological approach for intervertebral disc regeneration.


Assuntos
Degeneração do Disco Intervertebral/terapia , Disco Intervertebral/crescimento & desenvolvimento , Regeneração , Humanos , Células-Tronco
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