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1.
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.

2.
Drug Des Devel Ther ; 13: 1163-1170, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31043769

RESUMO

Purpose: Umbelliferone (Umb), a member of coumarin family, is found in many plants and is a promising molecule with potential anti-inflammatory, anti-oxidative, and anti-tumor activities. However, the effect of Umb on arthritis remains unclear. Methods: A rat model with Freund's complete adjuvant (FCA)-induced arthritis was developed and used to test the efficacy of Umb on arthritis rats. Rats were given an intragastric injection of Umb (20 and 40 mg/kg) once daily from days 21 to 28 after the administration of FCA. Hind paw volume was assessed using a volume meter. The pro-inflammatory cytokine levels and prostaglandin E2 (PEG2) level in serum and synovial fluid were detected by ELISA. HE staining was used to determine representative histological changes in joint tissues, and Western blot analysis was employed to study the effects of Umb on MAPK/NF-κB signaling pathway. Results: Our results showed that Umb suppressed the release of IL-6, IL-1ß, tumor necrosis factor-alpha, and PEG2. In addition, Umb could also dramatically ameliorate the pathological changes observed in rat joints. Based on the results of Western blot, we also observed that Umb could strikingly suppress the expression of MAPK/NF-κB pathway molecules. Conclusion: These results proved that treatment with Umb is very effective for arthritis and inhibiting the MAPK/NF-κB signaling pathway may be a potential therapeutic target for treatment of arthritis.


Assuntos
Artrite Experimental/tratamento farmacológico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Umbeliferonas/farmacologia , Animais , Artrite Experimental/metabolismo , Citocinas/biossíntese , Citocinas/sangue , Injeções Intraventriculares , Proteínas Quinases Ativadas por Mitógeno/metabolismo , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Umbeliferonas/administração & dosagem , Umbeliferonas/química
3.
Stem Cells Int ; 2019: 2875189, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31065272

RESUMO

Vascular calcification (VC), characterized by hydroxyapatite crystal depositing in the vessel wall, is a common pathological condition shared by many chronic diseases and an independent risk factor for cardiovascular events. Recently, VC is regarded as an active, dynamic cell-mediated process, during which calcifying cell transition is critical. Mesenchymal stem cells (MSCs), with a multidirectional differentiation ability and great potential for clinical application, play a duplex role in the VC process. MSCs facilitate VC mainly through osteogenic transformation and apoptosis. Meanwhile, several studies have reported the protective role of MSCs. Anti-inflammation, blockade of the BMP2 signal, downregulation of the Wnt signal, and antiapoptosis through paracrine signaling are possible mechanisms. This review displays the evidence both on the facilitating role and on the protective role of MSCs, then discusses the key factors determining this divergence.

4.
Chin J Nat Med ; 16(3): 175-183, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29576053

RESUMO

Given the limited studies and conflicting findings, the transport character of ginsenosides crossing the blood-brain barrier (BBB) remains unclear. The present study was designed to qualitatively determine the distribution of ginsenosides in brain tissues after oral administration of ginseng total saponins, using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) combined with immunohistochemistry. In brain tissue homogenates, ginsenoside Rg1 was detectable and no other ginsenosides or their metabolites were found. No ginsenosides were detected in cerebrospinal fluid. Immunohistochemistry staining of brain tissue sections by using anti-ginsenoside polyclonal antibodies revealed the localization of ginsenosides in brain tissues. Furthermore, immunofluorescence double staining revealed that ginsenosides widely existed in vascular endotheliocytes and astrocytes, and in few neurons. These results indicated that Rg1 was the main component that entered the brain after oral administration of ginseng total saponins and that ginsenosides could cross the BBB, although the transport capability of ginsenosides through the BBB may be poor.


Assuntos
Química Encefálica , Encéfalo/metabolismo , Medicamentos de Ervas Chinesas/análise , Ginsenosídeos/análise , Panax/química , Administração Oral , Animais , Anticorpos/análise , Barreira Hematoencefálica/metabolismo , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Ginsenosídeos/administração & dosagem , Ginsenosídeos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem
5.
J Cell Physiol ; 233(4): 2804-2814, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-28467642

RESUMO

Vascular calcification (VC) is prevalent in aging, and patients with hypertension, chronic kidney disease (CKD), or diabetes. VC is regarded as an active and complex process that involves multiple mechanisms responsible for calcium deposition in vessel wall. In light of the complicated pathogenesis of VC, effective therapy for ameliorating VC is limited. Thus, it is urgent to explore the potential mechanisms and find new targets for the therapy of VC. Platelet-derived growth factor (PDGF), a potent mitogen, and chemoattractant have been found to disturb the vascular homeostasis by inducing inflammation, oxidative stress, and phenotype transition, all of which accelerate the process of VC. The aim of current review is to present a review about the roles of PDGF in affecting VC and to establish a potential target for treating VC.


Assuntos
Fator de Crescimento Derivado de Plaquetas/metabolismo , Calcificação Vascular/metabolismo , Humanos , Modelos Biológicos , Transdução de Sinais
6.
Biomaterials ; 145: 23-32, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-28843064

RESUMO

Mechanics of the extracellular matrix (ECM) play a pivotal role in governing cell behavior, such as cell spreading and differentiation. ECM mechanics have been recapitulated primarily in elastic hydrogels, including with dynamic properties to mimic complex behaviors (e.g., fibrosis); however, these dynamic hydrogels fail to introduce the viscoelastic nature of many tissues. Here, we developed a two-step crosslinking strategy to first form (via platinum-catalyzed crosslinking) networks of polydimethylsiloxane (PDMS) and then to increase PDMS crosslinking (via thiol-ene click reaction) in a temporally-controlled manner. This photoinitiated reaction increased the compressive modulus of PDMS up to 10-fold within minutes and was conducted under cytocompatible conditions. With stiffening, cells displayed increased spreading, changing from ∼1300 to 1900 µm2 and from ∼2700 to 4600 µm2 for fibroblasts and mesenchymal stem cells, respectively. In addition, higher myofibroblast activation (from ∼2 to 20%) for cardiac fibroblasts was observed with increasing PDMS substrate stiffness. These results indicate a cellular response to changes in PDMS substrate mechanics, along with a demonstration of a mechanically dynamic and photoresponsive PDMS substrate platform to model the dynamic behavior of ECM.


Assuntos
Dimetilpolisiloxanos/farmacologia , Células 3T3 , Animais , Materiais Biocompatíveis/farmacologia , Bovinos , Reagentes para Ligações Cruzadas/química , Dimetilpolisiloxanos/química , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Camundongos , Microscopia de Força Atômica , Miofibroblastos/citologia , Miofibroblastos/efeitos dos fármacos , Ratos Sprague-Dawley , Compostos de Sulfidrila/química
7.
J Foot Ankle Surg ; 56(1): 15-18, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-27989338

RESUMO

Patellar subluxation is common in adolescents, and a variety of factors are related to this condition, with valgus of the knee joint an important factor. The results of many studies suggest that flatfoot can cause an abnormality of the lower limb power line. Structural abnormalities of the foot caused by the high stresses exerted by body weight can lead to structural deformity of the knee and can also cause knee valgus. Screening for foot problems can help determine the risk of patellar subluxation, and early intervention can lessen the incidence of this condition. The purpose of the present study was to investigate the effects of flatfoot on the structure and function of the knees and, especially, the risk of patellar subluxation. A total of 72 participants were recruited for this cross-sectional study. The mean age at examination was 15.4 ± 4.0 (range 9 to 22) years. The measured parameters were heel valgus angle, arch index, and quadriceps angle (Q-angle). Overall, the mean values of the heel valgus angle, arch index, and Q-angle were 5.9° ± 2.4° (range 1° to 11°), 0.33 ± 0.07 (range 0.23 to 0.46), and 19.1° ± 3.5° (range 9° to 26°), respectively. The Q-angle was directly associated with the heel valgus angle (r = 0.818, p < .001) and arch index (r = 0.655, p < .001). We found that flatfoot can affect the morphology of the knee joint and increase the risk of patellar subluxation.


Assuntos
Mau Alinhamento Ósseo/epidemiologia , Pé Chato/epidemiologia , Luxação Patelar/epidemiologia , Adolescente , Distribuição por Idade , Mau Alinhamento Ósseo/diagnóstico por imagem , Criança , Comorbidade , Estudos Transversais , Feminino , Pé Chato/diagnóstico por imagem , Humanos , Incidência , Masculino , Luxação Patelar/diagnóstico por imagem , Prognóstico , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Adulto Jovem
8.
Chin J Nat Med ; 12(11): 857-68, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25480518

RESUMO

AIM: Variation in structure-related components in plant products prompted the trend to establish methods, using multiple or total analog analysis, for their effective quality control. However, the general use of routine quality control is restricted by the limited availability of reference substances. Using an easily available single marker as a reference standard to determine multiple or total analogs should be a practical option. METHOD: In this study, the Ultra-HPLC method was used for the baseline separation of the main components in ginseng extracts. Using a plant chemical component database, ginsenosides in ginseng extracts were identified by Ultra-HPLC-MS analysis. The charged aerosol detection (CAD) system with post-column compensation of the gradient generates a similar response for identical amounts of different analytes, and thus, the content of each ginsenoside in ginseng extracts was determined by comparing the analyte peak area with the reference standard (determination of total analogs by single marker, DTSM). The total ginsenoside content was determined by the summation of reference standard and other ginsenoside components. RESULTS: The results showed that DTSM approaches were available for the determination of total ginsenosides in a high purity ginseng extract because of the removal of impurities. In contrast, DTSM approaches might be suitable for determination of multiple ginsenosides without interference from impurities in the crude ginseng extract. CONCLUSION: Future practical studies similar to the present study should be conducted to verify that DTSM approaches based on CAD with post-column inverse gradient for uniform response are ideal for the quality control of plant products.


Assuntos
Ginsenosídeos/análise , Panax/química , Cromatografia Líquida de Alta Pressão , Medicamentos de Ervas Chinesas/análise , Espectrometria de Massas , Padrões de Referência
9.
Cell Biochem Biophys ; 69(2): 341-6, 2014 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24604208

RESUMO

The aim of this study was to investigate the role of miR-208 in the invasion and metastasis of pancreatic cancer cells and the underlying molecular mechanism. miR-208 mimic, miR-208 inhibitor and NC were transfected into pancreatic cancer cell line Bxpc3 using liposome. Transwell invasion and scratch assays were used to test cell migratory and invasive abilities. Western blotting and quantitative PCR methods were used to detect E-cadherin, fibronectin and vimentin protein and mRNA expression in pancreatic cancer cell line BxPC3 after transfection by miR-208 mimic, miR-208 inhibitor and NC. Transwell invasion and scratch assays showed that after overexpressing miR-208, pancreatic cancer cell line BxPC3 exhibited enhanced in vitro migratory and invasive abilities, while after downregulating miR-208 expression, cell migratory and invasive abilities were decreased. Western blotting and quantitative PCR showed that after overexpressing miR-208, expression of E-cadherin, an epithelial cell marker, was decreased and expression of fibronectin and vimentin, interstitial cell markers, was increased in pancreatic cancer cell line BxPC3; however, after inhibiting miR-208, increased E-cadherin expression and decreased fibronectin and vimentin expression were observed in pancreatic cancer cell line BxPC3. After overexpressing miR-208, p-AKT and p-GSK-3ß expression was altered by activating AKT/GSK-3ß/snail signaling pathway. miR-208 induces epithelial to mesenchymal transition of pancreatic cancer cell line BxPC3 by activating AKT/GSK-3ß/snail signaling pathway and thereby promotes cell metastasis and invasion.


Assuntos
Transição Epitelial-Mesenquimal , MicroRNAs/metabolismo , Caderinas/genética , Caderinas/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Fibronectinas/genética , Fibronectinas/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Glicogênio Sintase Quinase 3 beta , Humanos , MicroRNAs/antagonistas & inibidores , Oligonucleotídeos Antissenso/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais , Fatores de Transcrição da Família Snail , Fatores de Transcrição/metabolismo , Vimentina/genética , Vimentina/metabolismo
10.
Med Oncol ; 30(1): 340, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23269581

RESUMO

Osteosarcoma is the most common human primary malignant bone tumor in children and young adults. Sensitive and non-invasive biomarkers that can facilitate disease detection at early stage are highly desirable to improve survival rate and help to determine optimized treatment for osteosarcoma. The small non-coding RNAs, microRNAs (miRNAs), have recently been identified as critical regulators for various diseases including cancer and may represent a novel class of cancer biomarkers. In this study, we aimed to detect the potential of circulating miRNAs as biomarkers for osteosarcoma. Levels of six candidate miRNAs (miR-21, miR-199a-3p, miR-143, miR-34, miR-140, and miR-132) that were previously demonstrated to be regulated in osteosarcoma were examined in plasma of 40 osteosarcoma patients and 40 matched healthy controls by quantitative reverse-transcription polymerase chain reaction assays. The results showed that circulating levels of miR-21 were significantly higher in osteosarcoma patients than controls, while miR-199a-3p and miR-143 were decreased in osteosarcoma patients. We replicated the findings in an independent study of 40 osteosarcoma patients and 40 matched controls and confirmed the results. Receiver operating characteristics curve analysis of the combined populations demonstrated that the three-miRNA signature could discriminate cases from controls with an area under the curve of 0.953 (95 % CI 0.924-0.984). In addition, circulating miR-21 and miR-143 were correlated with both metastasis status and histological subtype of the patients, while miR-199a-3p only correlated with histological subtype. Our data suggest that altered levels of circulating miRNAs might have great potential to serve as novel, non-invasive biomarkers for osteosarcoma.


Assuntos
Biomarcadores Tumorais/genética , MicroRNAs/análise , Osteossarcoma/genética , Transcriptoma/genética , Adolescente , Área Sob a Curva , Biomarcadores Tumorais/sangue , Feminino , Humanos , Masculino , Osteossarcoma/sangue , Curva ROC , Reação em Cadeia da Polimerase Via Transcriptase Reversa
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