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1.
Front Immunol ; 12: 702211, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34413854

RESUMO

BMP4 is a key growth factor well known in promoting bone regeneration and has been reported to be able to regulate T cell development in the thymus. Here, we showed that BMP4 downregulates the activation of naïve CD4+ T cells and the IFN-γ production of CD4+ T cells without increasing regulatory T cells. BMP4 could also moderate glycolysis of T cells and regulate Hif1α expression. Furthermore, BMP4 showed a suppressive function on the IFN-γ production of CD4+ T cells in vivo. These findings indicating a mechanism by which BMP-4 may regulate activation and IFN-γ production in CD4+ T cells via metabolism moderation and suggests that BMP4 may be a potential therapeutic supplement in autoinflammatory diseases.

2.
Medicine (Baltimore) ; 100(32): e26884, 2021 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-34397908

RESUMO

ABSTRACT: High tibial osteotomy (HTO) is a promising surgery that can treat osteoarthritis of the medial septum of the knee. However, the extensive release of soft tissue and the osteotomy gap may produce intraoperative and postoperative bone bleeding. Tranexamic acid (TXA) is an effective blood management strategy, as it competitively inhibits the activation process of plasminogen and prevents fibrinolytic enzymes from degrading fibrin. Therefore, we compared the operative bone bleeding of patients who underwent HTO who received either intravenous (IV) or topical TXA in this research.The medical records of a total of 191 patients (including 72 who received IV TXA, 64 who received topical TXA and 55 control patients) who received open-wedge HTO were retrospectively reviewed from January 2016 to August 2019. There were no obvious demographic differences between the groups. Here, we used independent parameters to assess the efficacy of topical and IV TXA in reducing blood loss.Compared with the IV TXA group, patients receiving topical TXA therapy had greater blood loss (622 ±â€Š231 ml versus 451 ±â€Š231 ml, mean difference 171 mL [95% CI, 87-254]; p < 0.001). The hemoglobin concentration of the IV TXA group was obviously higher than that of the topical medication group. No patients had thromboembolic complications during the entire study period.In our study, it seemed that either IV or topical use of TXA might reduce blood loss after open-wedge HTO, and the blood loss and amount of drainage in the IV TXA group showed huge decreases compared to those in the topical group.


Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Osteotomia/métodos , Hemorragia Pós-Operatória/prevenção & controle , Tíbia/cirurgia , Ácido Tranexâmico/administração & dosagem , Administração Tópica , Adulto , Idoso , Antifibrinolíticos/administração & dosagem , Feminino , Seguimentos , Humanos , Infusões Intravenosas , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
3.
Ann Palliat Med ; 10(4): 4799-4805, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33832319

RESUMO

Sphingosine 1-phosphate (S1P) regulates many cellular functions, such as differentiation, proliferation, migration, morphogenesis, cytoskeletal organization, adhesion, tight junction assembly, apoptosis and the localization of different cell types. S1P also controls the migration of osteoclast precursors between the blood and bone, and it keeps osteoclast precursors away from bone surfaces to reduce bone degradation, thus preventing bone decay. Osteoporosis is a systemic bone disease that predisposes patients to bone fracture due to decreased bone density and quality, disrupted bone microarchitecture, and increased bone fragility. As the global elderly population increases, the incidence of osteoporosis will greatly increase, and the associated adverse consequences will become more serious. S1P plays an important role in homeostasis, and disruption of the balance between osteoblasts and osteoclasts may induce osteoporosis. A high frequency of osteoporotic fracture is associated with increased plasma S1P levels. Studies have shown that S1P is an important therapeutic target in osteoporosis because it controls the migration of osteoclast precursors, vigorously maintains the bone mineralization process, and is a critical regulator of osteoclastogenesis. Improved understanding of the functional roles and molecular mechanisms of S1P in bone turnover could facilitate the discovery of novel targets for the treatment of osteoporosis. This review provides a critical discussion of the role of S1P in osteoporosis and treatments.


Assuntos
Lisofosfolipídeos , Osteoporose , Idoso , Humanos , Osteoclastos , Esfingosina/análogos & derivados
4.
FEBS Open Bio ; 11(1): 289-299, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33146000

RESUMO

Arbutin, a glycoside extracted from the plant Arctostaphylos uva-ursi, has been previously reported to possess antioxidant, anti-inflammatory and anticancer effects. Here, we investigated whether arbutin affects the proliferation of the cells of the osteosarcoma (OS) cell lines MG-63 and SW1353. Arbutin suppressed OS cell viability in a dose- and time-dependent manner, as shown by Cell Counting Kit-8 assay. Furthermore, arbutin exposure decreased the protein levels of MTHFD1L, CCND1 and phosphorylated-protein kinase B (AKT)/phosphorylated-mammalian target of rapamycin (mTOR). Potential upstream miRNAs of MTHFD1L were predicted using TargetScan, PICTAR5, miRanda and miRWalk. We performed luciferase activity assays to show that miR-338-3p directly targets and negatively regulates the expression of MTHFD1L. Knockdown of miR-338-3p promoted cell invasion, migration and proliferation in arbutin-treated OS cells via MTHFD1L. In summary, our data suggest that arbutin inhibits OS cell proliferation, migration and invasion via miR-338-3p/MTHFD1L and by inactivating the AKT/mTOR pathway.

5.
Arch Phys Med Rehabil ; 101(11): 1991-2001, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32445847

RESUMO

OBJECTIVE: To evaluate the effects of respiratory muscle training in a population of stroke patients. DATA SOURCES: The following databases were searched for clinical trials through December 2019: PubMed, EMBASE, Cochrane Library, CINAHL, and China National Knowledge Infrastructure. STUDY SELECTION: Randomized controlled trials (N=9) published in English met the inclusion criteria. DATA EXTRACTION: Data were extracted and assessed for accuracy by 2 reviewers. Any disagreements were resolved after discussions with an independent third reviewer. The quality of the included randomized controlled trials was assessed using the Cochrane bias tool. DATA SYNTHESIS: The meta-analysis showed increased maximal inspiratory pressure (standardized mean difference [SMD], 0.88; 95% confidence interval [CI], 0.62-1.15; P<.001; 12-wk follow-up period: SMD, 0.94; 95% CI, 0.42-1.45; P<.001), maximal expiratory pressure (SMD, 0.83; 95% CI, 0.15-1.52; P=.017; 12-wk follow-up period: SMD, 0.99; 95% CI, 0.47-1.51; P<.001), forced expiratory volume in 1 second (SMD, 1.41; 95% CI, 0.57-2.24; P=.001), forced vital capacity (SMD, 1.36; 95% CI, 0.55-2.16; P<.001), peak expiratory flow (SMD, 0.74; 95% CI, 0.16-1.32; P=.013), 6-minute walk test (SMD, 0.67; 95% CI, 0.11-1.23; P=.020), and decreased respiratory complications (odds ratio, 0.55; 95% CI, 0.30-1.00; P=.050) compared with no respiratory intervention or a sham intervention. CONCLUSIONS: Respiratory muscle training improved poststroke muscle strength and the benefits were carried over for up to 12 weeks, including improved lung function, walking capacity, and a reduced risk of respiratory impediments.


Assuntos
Exercícios Respiratórios/métodos , Transtornos Respiratórios/prevenção & controle , Reabilitação do Acidente Vascular Cerebral/métodos , Acidente Vascular Cerebral/fisiopatologia , Idoso , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Força Muscular , Transtornos Respiratórios/etiologia , Músculos Respiratórios/fisiopatologia , Resultado do Tratamento , Capacidade Vital , Teste de Caminhada , Caminhada
6.
J Recept Signal Transduct Res ; 40(6): 584-590, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32456526

RESUMO

Osteosarcoma (OS) is the most frequent primary malignancy initially in bone with multiple genomic aberrations. Methylenetetrahydrofolate dehydrogenase 1-like (MTHFD1L) is linked with the progression of diverse tumors. However, its function in OS is not understood completely. The expression pattern and prognostic significance of MTHFD1L in OS tissues were analyzed based on GEO database. The expression level of MTHFD1L in OS cell lines was explored by qRT-PCR. The cell proliferation, colony formation ability, invasion as well as migration in OS cells after MTHFD1L knockdown were determined using cell counting kit 8 (CCK-8) assay, colony formation and transwell methods. GSEA analysis was performed to predict the underlying mechanisms of MTHFD1L in OS development. Furthermore, the western blot was utilized to study the influence of MTHFD1L on AKT/mTOR pathway. Our results indicated that MTHFD1L expression was significantly up-regulated in OS tissues and cells compared with normal tissues and cells. High expression of MTHFD1L could lead to poor prognosis of OS patients. Cell proliferation, colony formation ability, migration and invasion were blocked because of reduced MTHFD1L in vitro. Moreover, cell cycle and AKT/mTOR pathway were all associated with MTHFD1L expression. In conclusion, the findings revealed that MTHFD1L might promote the development of OS via mediating cell cycle and AKT/mTOR pathway, indicating that MTHFD1L might act as a promising therapeutic target for OS treatment.

7.
Aging (Albany NY) ; 12(5): 4111-4123, 2020 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-32155130

RESUMO

Mounting studies have shown that long noncoding RNAs (lncRNAs) play important roles in the development and occurrence of several human diseases. However, the role of LINC00461 in osteoarthritis (OA) remains obscure. A CCK-8 assay was performed to detect cell viability, and qRT-PCR analysis was used to measure mRNA expression. The targeting by miR-30a-5p of the LINC00461 3'UTR was detected using a luciferase reporter assay. Our data indicated that the inflammatory mediators IL-6 and TNF-α induced LINC00461 expression in chondrocytes and that the expression of LINC00461 was upregulated in OA tissues. Furthermore, we showed that TNF-α and IL-6 suppressed the expression of miR-30a-5p and that miR-30a-5p expression was lower in OA tissues than in normal samples. The expression level of miR-30a-5p in OA tissues was negatively related to LINC00461 expression. In addition, we showed that LINC00461 directly interacted with miR-30a-5p in chondrocytes. Elevated expression of LINC00461 induced chondrocyte proliferation, cell cycle progression, inflammation, and extracellular matrix (ECM) degradation. However, we demonstrated that ectopic expression of miR-30a-5p suppressed cell growth, cell cycle progression, inflammation and ECM degradation. Finally, we found that overexpression of LINC00461 enhanced chondrocyte proliferation, cell cycle progression, inflammation, and ECM degradation by downregulating miR-30a-5p. These data demonstrated that LINC00461 may modulate the development of OA by suppressing miR-30a-5p expression in chondrocytes. We propose that LINC00461 and miR-30a-5p may be potential therapeutic and diagnostic targets for OA.


Assuntos
Cartilagem Articular/metabolismo , Condrócitos/metabolismo , MicroRNAs/metabolismo , Osteoartrite do Joelho/metabolismo , RNA Longo não Codificante/metabolismo , Adulto , Idoso , Ciclo Celular/fisiologia , Proliferação de Células/fisiologia , Progressão da Doença , Feminino , Humanos , Inflamassomos/genética , Inflamassomos/metabolismo , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Osteoartrite do Joelho/genética , RNA Longo não Codificante/genética , Regulação para Cima
8.
Am J Transl Res ; 11(11): 7027-7034, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31814906

RESUMO

Osteoarthritis (OA) is the most common degenerative joint disease. microRNAs (miRNAs) have been showen to act critical roles in several diseases including OA. However, the involvement and underlying mechanism of miR-137 in development of OA remains unkown. In our study, we firstly showed that IL-1ß decreased the expression of miR-137 in the chondrocytes and we demonstrated that the miR-37 expression level was lower in the OA cases than in the control patients. Dual-luciferase reporter analysis was performed to confirm that ADAMTS-5 was a direct target gene of miR-137. Furthermore, we indicated that elevated expression of miR-137 decreased the protein expression of ADAMTS-5 in the chondrocytes. In additional, we showed that IL-1ß induces the ADAMTS-5 expression in the chondrocytes. The ADAMTS-5 expression level was higher in the OA cases than in the control patients. We showed that the expression of ADAMTS-5 was negatively correlated with the miR-137 expression level in OA tissues. Overexpression of miR-137 suppressed cell growth, extracellular matrix (ECM) degradation and inflammation in chondrocytes. These preliminary data elucidated that miR-137 suppressed OA progression via inhibiting cell growth, inflammation and ECM degradation.

9.
Complement Ther Clin Pract ; 35: 121-125, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31003647

RESUMO

BACKGROUND AND PURPOSE: Postoperative rehabilitation plays an indispensable role for a successful total knee arthroplasty (TKA) and the optimal exercises programs are not known. A single-centre, single-blind, randomised controlled trial was designed to explore whether tai chi chuan (TCC) exercises can improve the functional outcomes and the quality of life (QOL) in patients with primary TKA due to knee osteoarthritis (OA). MATERIALS AND METHODS: One hundred seven participants with primary TKA for end-stage knee OA were enrolled from January 2014 to January 2017. Patients were treated for 12 weeks either with TCC exercises (intervention) or traditional physical exercises (control). Outcomes including western ontario and mcMaster universities arthritis index (WOMAC), 6-min walk test (6 MWT), knee range of motion (ROM), and short form (36) health survey (SF-36) were assessed. The adverse events related to TCC exercises or TKA were recorded. RESULTS: Before the intervention, the two groups were comparable after examining the general descriptions of patients. Compared with the control group (CG), the TCC group (TG) had significantly better scores in the WOMAC physical function score, 6 MWT, SF-36 physical component score (PCS), and the mental component score (MCS) (P < 0.05) after the 12-week intervention. Nevertheless, there were no significant differences in WOMAC pain score and knee ROM. There were no adverse events related to the TCC exercise program. In the CG, three patients reported one fall each, but those falls did not lead to a further problem. CONCLUSION: The TCC exercises improve the physical function and the QOL in patients with primary TKA without additional risks.


Assuntos
Artroplastia do Joelho , Osteoartrite do Joelho/reabilitação , Cuidados Pós-Operatórios/métodos , Qualidade de Vida , Tai Ji , Idoso , Feminino , Indicadores Básicos de Saúde , Humanos , Articulação do Joelho/fisiopatologia , Masculino , Osteoartrite do Joelho/fisiopatologia , Osteoartrite do Joelho/cirurgia , Estudos Prospectivos , Amplitude de Movimento Articular , Método Simples-Cego , Resultado do Tratamento
10.
Exp Ther Med ; 17(4): 2694-2702, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30906459

RESUMO

An assessment of Levofloxacin by high-performance liquid chromatography (HPLC) or ultraviolet-visible spectrophotometry (UV-Vis) and its pharmacokinetics in serum or plasma was made in a previous study by the present authors. Levofloxacin-loaded mesoporous silica microspheres/nano-hydroxyapatite (n-HA) composite scaffolds comprise a novel synthetic composite scaffold that may be utilized as a drug-delivery system for clinical usage. However, few studies have been published concerning a comparison of HPLC with UV-Vis, which is the preferred method for determination of Levofloxacin. In the present study, an HPLC method was first established, and subsequently a comparison of HPLC with the UV-Vis method was performed. The standard curve was established, and recovery rate from simulated body fluid was calculated. The linear concentration range for Levofloxacin was 0.05-300 µg/ml. The regression equation for HPLC was y=0.033x+0.010, with R 2=0.9991, whereas that for UV-Vis was y=0.065x+0.017, with R 2=0.9999. The recovery rates of low, medium and high (5, 25 and 50 µg/ml) concentrations of Levofloxacin determined by HPLC were 96.37±0.50, 110.96±0.23 and 104.79±0.06%, respectively, whereas those for low, medium and high concentrations according to UV-Vis were 96.00±2.00, 99.50±0.00 and 98.67±0.06%, respectively. Taken together, these findings demonstrated that it is not accurate to measure the concentration of drugs loaded on the biodegradable composite composites by UV-Vis. HPLC is the preferred method to evaluate sustained release characteristics of Levofloxacin released from mesoporous silica microspheres/n-HA composite scaffolds. The present study also provides guidance on which methods should be selected for investigating the sustained release properties of drugs in tissue engineering. The accurate determination of drug concentration in the drug delivery system provides guidance for the treatment of infectious diseases.

11.
Oncotarget ; 8(53): 91281-91290, 2017 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-29207643

RESUMO

Osteoarthritis (OA) is a common degenerative disease characterized by degeneration of articular cartilage. Increasing studies showed that long noncoding RNAs (lncRNAs) play important roles in the cartilage damage. However, little is known about the role of UCA1 in the osteoarthritis. The expression level of UCA1 was upregulated in the OA cartilage. Overexpression of UCA1 suppressed the miR-204-5p expression in the chondrocytes. The expression of miR-204-5p was downregulated in the OA cartilage. Moreover, the expression of miR-204-5p was negatively correlated with the UCA1 expression in the OA cartilage. Elevated expression of UCA1 promoted the chondrocytes cell proliferation and overexpression of miR-204-5p suppressed chondrocytes cell proliferation. In addition, overexpression of UCA1 decreased the expression of the type II collagen and type IV collagen expression in the chondrocytes. Elevated expression of miR-204-5p promoted the type II collagen and type IV collagen expression in the chondrocytes. We idetified MMP-13 was a direct target gene of miR-204-5p in the chondrocytes. Overexpression of UCA1 enhanced the MMP-13 expression in the chondrocytes. Elevated expression of UCA1 regulated the chondrocytes cell proliferation and collagen expression through inhibiting the miR-204-5p expression.These results suggested that UCA1 played as an important regulator of survival and matrix synthesis of chondrocytes partly through suppressing the miR-204-5p expression.

12.
Exp Ther Med ; 14(6): 5641-5646, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29285104

RESUMO

Osteoarthritis (OA) is a common age-related degenerative joint disease, which is caused by the breakdown of joint cartilage and the underlying bone. Carboxymethyl (CM)-chitosan is a soluble derivative of chitosan that has similar physicochemical properties to the extracellular proteoglycans identified in hyaline cartilage. Previous studies have demonstrated that CM-chitosan serves a protective role in a rabbit OA model. The aim of the present study was to investigate the effect of CM-chitosan on NO production and inflammation through its upregulation of interleukin (IL)-10, and the activation of the janus kinase (JAK)/signal transducer and activator of transcription (STAT)/suppressor of cytokine signaling (SOCS) signaling pathway. In the present study primary rat chondrocytes were induced to inflammation with 2 µg/ml lipopolysaccharide. The cells were subsequently subjected to increasing concentrations of CM-chitosan (50, 100 and 200 µg/ml) and the relative mRNA and protein expression of inducible nitric oxide synthase (iNOS), IL-10, JAK1, STAT3 and SOCS3 were measured by RT-qPCR and western blot analysis respectively. The results revealed that CM-chitosan attenuated inflammation by significantly reducing iNOS expression and upregulating the anti-inflammatory cytokine IL-10 in a dose-dependent manner (P<0.05). The expression of JAK1, STAT3 and SOCS3 were also significantly upregulated by CM-chitosan (all P<0.05). The protective role of CM-chitosan against NO production was due to its upregulation of IL-10 and its activation of the JAK/STAT/SOCS signaling pathway.

13.
Mol Med Rep ; 15(1): 75-80, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-27922673

RESUMO

Osteoarthritis (OA) is a common cause of functional deterioration in older adults, and altered chondrogenesis is the most common pathophysiological process involved in the development of OA. MicroRNA­145 (miR­145) has been shown to regulate chondrocyte homeostasis. However, the function of miR­145 in OA remains to be elucidated. In the present study, the expression levels of miR­145 were examined in cartilage specimens from 25 patients with knee OA using reverse transcription­quantitative polymerase chain reaction analysis. The effects of miR­145 on the proliferation and fibrosis of the C­20/A4 and CH8 cell lines were also investigated using 3-(4,5-dimethylth-iazol-2-yl)-2,5-diphenyltetrazolium bromide and western blot assays in vitro. The results revealed that the expression of miR-145 was decreased in the OA cartilage tissues, compared with normal cartilage tissues. The overexpression of miR­145 by transfection of cells with miR­145 mimics significantly inhibited C­20/A4 and CH8 cell proliferation and fibrosis. Furthermore, tumor necrosis factor receptor superfamily, member 11b (TNFRSF11B) was identified as a direct target of miR­145 in chondrocytes, which was confirmed using a dual­luciferase reporter assay. The expression level of TNFRSF11B was markedly upregulated in the patients with OA, and the ectopic expression of miR­145 was capable of suppressing the expression of TNFRSF11B. In addition, the knock down of TNFRSF11B using specific small interfering RNA also inhibited the proliferation and fibrosis of C­20/A4 and CH8 cells in vitro. These data provide the first evidence, to the best of our knowledge, to suggest the critical function of miR­145 in regulating the expression of TNFRSF11B, which may have important implications on the regulation of chondrocyte proliferation and fibrosis in OA.


Assuntos
Proliferação de Células , Condrócitos/patologia , Regulação da Expressão Gênica , MicroRNAs/genética , Osteoartrite do Joelho/genética , Osteoartrite do Joelho/patologia , Osteoprotegerina/genética , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Linhagem Celular , Fibrose , Humanos
14.
Int J Syst Evol Microbiol ; 66(2): 530-535, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26552810

RESUMO

A novel Gram-stain-positive, non-motile, moderately halophilic and alkalitolerant actinobacterium, designated EGI 80432T, was isolated from a saline-alkaline soil of Xinjiang province, north-west China. Cells were non-endospore-forming cocci with a diameter of 0.5-0.8 µm. Strain EGI 80432T grew in the presence of 0-9 % (w/v) NaCl (optimum at 3-5 %), and also grew within the pH range 6.0-10.0 (optimum at pH 8.0-9.0) on marine 2216E medium. The peptidoglycan type was A1γ. The whole-cell hydrolysates contained glucose, galactose, mannose and three unknown sugars as major sugars. The predominant menaquinone was MK-9(H4). The major fatty acids were C17 : 1ω8c, summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), C18 : 1ω9c and iso-C15 : 0 The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, one unknown phosphoglycolipid, three unknown phospholipids and four unknown polar lipids. The genomic DNA G+C content was 75.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain EGI 80432T clustered within the radius of the class Nitriliruptoria. Levels of sequence similarity between strain EGI 80432T and its phylogenetic neighbours Nitriliruptor alkaliphilus ANL-iso2T and Euzebya tangerina F10T were 94.1 and 88.1 %, respectively. Based on morphological, physiological and chemotaxonomic characteristics and phylogenetic analysis, a novel species of a new genus, Egicoccus halophilus gen. nov., sp. nov., is proposed, within the new family and new order Egicoccaceae fam. nov. and Egicoccales ord. nov. in the class Nitriliruptoria. The type strain of Egicoccus halophilus is EGI 80432T ( = CGMCC 1.14988T = KCTC 33612T).


Assuntos
Actinobacteria/classificação , Filogenia , Microbiologia do Solo , Actinobacteria/genética , Actinobacteria/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , China , DNA Bacteriano/genética , Ácidos Graxos/química , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Vitamina K 2/análogos & derivados , Vitamina K 2/química
15.
Am J Transl Res ; 7(10): 2000-6, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26692943

RESUMO

Osteoarthritis (OA) is the most common joint degenerative disease affecting the joint structure, leading to loss of joint function and tissue destruction. Recent studies have demonstrated that miRNAs are involved in many pathological conditions, including OA. The study was to investigate the role of miR-411 in the pathogenesis of OA. The expression of miR-411 was downregulated in OA cartilage compared with in normal cartilage. Conversely, the expression of MMP-13 was upregulated in OA cartilage compared with in normal cartilage. IL-1ß treatment repressed miR-411 expression in chondrocytes. Moreover, we identified MMP-13 as a direct target gene of miR-411 in chondrocytes and overexpression of miR-411 inhibited the MMP-13 expression. Furthermore, overexpression of miR-411 increased the expression of type II collagen and type IV collagen expression in chondrocytes. MiR-411 is a crucial regulator of MMP-13 in chondrocytes and may response to the development of OA.

16.
Chem Biol Interact ; 242: 255-61, 2015 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-26482937

RESUMO

Extensive evidence indicates that oxidative stress plays a pivotal role in the development of osteoporosis. We show that naringin, a natural antioxidant and anti-inflammatory compound, effectively protects human adipose-derived mesenchymal stem cells (hADMSCs) against hydrogen peroxide (H2O2)-induced inhibition of osteogenic differentiation. Naringin increased viability of hAMDSCs and attenuated H2O2-induced cytotoxicity. Naringin also reversed H2O2-induced oxidative stress. Oxidative stress induced by H2O2 inhibits osteogenic differentiation by decreasing alkaline phosphatase (ALP) activity, calcium content and mRNA expression levels of osteogenesis marker genes RUNX2 and OSX in hADMSCs. However, addition of naringin leads to a significant recovery, suggesting the protective effects of naringin against H2O2-induced inhibition of osteogenic differentiation. Furthermore, the H2O2-induced decrease of protein expressions of ß-catenin and clyclin D1, two important transcriptional regulators of Wnt-signaling, was successfully rescued by naringin treatment. Also, in the presence of Wnt inhibitor DKK-1, naringin is no longer effective in stimulating ALP activity, increasing calcium content and mRNA expression levels of RUNX2 and OSX in H2O2-exposed hADMSCs. These data clearly demonstrates that naringin protects hADMSCs against oxidative stress-induced inhibition of osteogenic differentiation, which may involve Wnt signaling pathway. Our work suggests that naringin may be a useful addition to the treatment armamentarium for osteoporosis and activation of Wnt signaling may represent attractive therapeutic strategy for the treatment of degenerative disease of bone tissue.


Assuntos
Tecido Adiposo/citologia , Diferenciação Celular/efeitos dos fármacos , Flavanonas/farmacologia , Peróxido de Hidrogênio/efeitos adversos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteogênese/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Citoproteção/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/metabolismo , Osteoblastos/citologia , Osteoblastos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Via de Sinalização Wnt/efeitos dos fármacos
17.
Tumour Biol ; 36(8): 6201-9, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25761878

RESUMO

Downregulation of miR-26b has been found in various cancers, but it has never been investigated in osteosarcoma. In this study, we demonstrated downregulation of miR-26b in osteosarcoma tissues, negatively correlated with the expression of connective tissue growth factor (CTGF) and Smad1. Luciferase reporter assay confirmed the interaction of miR-26b with the 3' untranslated regions (UTRs) of CTGF and Smad1. Transfection of miR-26b in osteosarcoma cells suppressed the expression of CTGF and Smad1, suggesting CTGF and Smad1 as direct targets of miR-26b. Overexpression of miR-26b inhibited the migration of osteosarcoma cells, which was reversed by overexpression of CTGF or Smad1. Knockdown of CTGF by small interfering RNA (siRNA) interference blocked the activation of Smad1, ERK1/2, and MMP2, which was opposite to the overexpression of CTGF. Differently, Smad1 did not significantly affect CTGF level, but mediated ERK1/2 phosphorylation and MMP2 activation. Furthermore, miR-26b inhibited lung metastasis of osteosarcoma in vivo. Our data indicated that downregulation of miR-26b in osteosarcoma elevated the levels of CTGF and Smad1, facilitating osteosarcoma metastasis.


Assuntos
Fator de Crescimento do Tecido Conjuntivo/genética , Neoplasias Pulmonares/genética , MicroRNAs/genética , Osteossarcoma/genética , Proteína Smad1/genética , Animais , Linhagem Celular Tumoral , Fator de Crescimento do Tecido Conjuntivo/biossíntese , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Metaloproteinase 2 da Matriz/genética , Camundongos , MicroRNAs/biossíntese , MicroRNAs/metabolismo , Metástase Neoplásica , Osteossarcoma/patologia , RNA Interferente Pequeno , Proteína Smad1/biossíntese , Proteína Smad1/metabolismo
18.
Biochem Biophys Res Commun ; 459(3): 367-73, 2015 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-25727016

RESUMO

MicroRNAs have been implicated in drug resistance of osteosarcoma (OS). MicroRNA-301a (miR-301a) is up-regulated and functions as an oncogene in various cancers. However, little is known about the role of miR-301a in drug resistance of OS cells. In this study, we found that doxorubicin induced time-dependent expression of miR-301a in OS cells. Meantime, doxorubicin promoted HMGCR expression and inhibited AMPKα1 expression, which was further facilitated by miR-301a overexpression. Luciferase reporter assay identified AMPKα1 as direct target gene of miR-301a. Notably, miR-301a reduced doxorubicin-induced cell apoptosis whereas anti-miR-301a enhanced apoptosis in OS cells, suggesting that up-regulation of miR-301a contributed to chemoresistance of OS cells. Consistently, our data showed that miR-301a and HMGCR were up-regulated in chemotherapy-resistant OS compared to those in control OS. Our findings suggested that miR-301a might be a potential biomarker for chemotherapy-resistant OS and a promising therapeutic target for overcoming drug resistance of OS.


Assuntos
Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Proteínas Quinases Ativadas por AMP/genética , Antineoplásicos/farmacologia , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/genética , Doxorrubicina/farmacologia , MicroRNAs/genética , Osteossarcoma/tratamento farmacológico , Osteossarcoma/genética , Apoptose/efeitos dos fármacos , Apoptose/genética , Neoplasias Ósseas/metabolismo , Estudos de Casos e Controles , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Hidroximetilglutaril-CoA Redutases/genética , Hidroximetilglutaril-CoA Redutases/metabolismo , MicroRNAs/metabolismo , Osteossarcoma/metabolismo , Regulação para Cima/efeitos dos fármacos
19.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 27(9): 1037-40, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24279009

RESUMO

OBJECTIVE: To investigate the effectiveness of posterior cruciate ligament (PCL) reconstruction with remnant preservation and autogenous quadrupled hamstring tendons under arthroscopy. METHODS: Between October 2007 and August 2012, 32 patients with PCL rupture were treated and followed up for more than 1 year. There were 24 males and 8 females, aged 20-53 years (mean, 35.6 years). The causes of injury included traffic accident injury in 21 cases, sports injury in 8 cases, and falling injury from height in 3 cases. The disease duration ranged 1 week to 2 years (median, 6.3 weeks). Nine patients had simple PCL rupture, 23 patients complicated by ligament injury, including 10 cases of anterior cruciate ligament rupture, 11 cases of posterolateral corner injury, and 2 cases of posteromedial corner injury. Preoperative Lysholm score was 53.8 +/- 7.1. According to the International Knee Documentation Committee (IKDC) rating criteria, 10 cases were classified as grade C and 22 cases as grade D. PCL was reconstructed with autogenous quadrupled hamstring tendons, the tendons were fixed with EndoButton at the femoral side and with interference screw at the tibial side; floats of stump were cleaned up, and the structural stability and continuity ligament remnants were preserved. RESULTS: Primary healing was obtained in all incisions; no early complication occurred after operation. Thirty-two patients were followed up 23.4 months on average (range, 12-36 months). All patients had no symptom of knee instability; the results of tibia sags sign, posterior drawer test, and Lachman test were negative. At last follow-up, the knee range of motion (ROM) returned to normal in all cases. The Lysholm score was 92.3 +/- 2.0, showing significant difference when compared with preoperative score (t = -34.32, P = 0.00). According to the IKDC rating criteria, 26 cases were classified as grade A and 6 cases as grade B at last follow-up, showing significant difference when compared with preoperative grade (Z = -5.57, P = 0.00). CONCLUSION: Arthroscopic single-bundle reconstruction of PCL with remnant preservation and quadrupled hamstring tendons has advantages of minimal trauma, simple operation, and good knee function recovery.


Assuntos
Artroscopia , Traumatismos do Joelho/cirurgia , Ligamento Cruzado Posterior/cirurgia , Procedimentos Cirúrgicos Reconstrutivos/métodos , Tendões/transplante , Adulto , Placas Ósseas , Parafusos Ósseos , Feminino , Humanos , Instabilidade Articular/cirurgia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Ligamento Cruzado Posterior/lesões , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
20.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 26(11): 1306-9, 2012 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-23230662

RESUMO

OBJECTIVE: To analyze the impact of ivaroxaban on hidden blood loss and blood transfusion rate after primary total knee arthroplasty (TKA) by comparing with the use of low molecular weight heparin. METHODS: Between December 2009 and January 2011, the clinical data from 90 patients undergoing primary TKA were retrospectively analyzed. At 12 hours after operation, 45 patients were given ivaroxaban (10 mg/d) in the trial group and low molecular weight heparin injection (0.4 mL/d) in the control group for 14 days, respectively. There was no significant difference in gender, age, disease duration, or range of motion between 2 groups (P > 0.05). RESULTS: The operation time was (92.32 +/- 23.13) minutes in the trial group and (89.81 +/- 18.65) minutes in the control group, showing no significant difference (t=0.26, P=0.79). The hidden blood loss was (40.18 +/- 14.85) g/L in the trial group and (34.04 +/- 12.96) g/L in the control group, showing significant difference (t=2.09, P=0.00); the dominant blood loss was (30.60 +/- 2.89) g/L and (28.85 +/- 8.10) g/L respectively, showing no significant difference (t=1.37, P=0.17). The blood transfusion rate was 73.33% (33/45) in the trial group and 55.56% (25/45) in the control group, showing no sigificant difference (chi2=3.10, P=0.08); the transfusion volume was (1.44 +/- 1.09) U and (1.06 +/- 1.17) U respectively, showing no significant difference (t=1.58, P=0.11). Stress ulcer occurred in 1 case of the trial group; symptomatic deep vein thrombosis of lower extremity and asymptomatic muscular venous thrombosis developed in 1 case and 4 cases of the control group respectively. CONCLUSION: Ivaroxaban has effect on the hidden blood loss after primary TKA, which may increase postoperative blood loss and blood transfusion rate. The changes in hemoglobin should be monitored during the anticoagulant therapy, and the blood volume should be added promptly.


Assuntos
Artroplastia do Joelho , Transfusão de Sangue , Heparina de Baixo Peso Molecular/uso terapêutico , Morfolinas/uso terapêutico , Hemorragia Pós-Operatória/prevenção & controle , Tiofenos/uso terapêutico , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/prevenção & controle , Amplitude de Movimento Articular , Estudos Retrospectivos , Rivaroxabana , Resultado do Tratamento , Trombose Venosa/epidemiologia , Trombose Venosa/prevenção & controle
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