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1.
J Biomech ; 116: 110248, 2021 Feb 12.
Artigo em Inglês | MEDLINE | ID: mdl-33485146

RESUMO

The nano-biomechanical environment of the extracellular matrix is critical for cells to sense and respond to mechanical loading. However, to date, this important characteristic remains poorly understood in living tissue structures. This study reports the experimental measurement of the in vivo nano-elastic modulus of the tendon in a mouse tail model. The experiment was performed on the tail tendon of an 8-week-old C57BL/6 live mouse. Mechanical loading on tail tendons was regulated by changing both voltage and frequency of alternating current stimulation on the erector spinae. The nano-elastic modulus of the tail tendon was measured by atomic force microscope. The nano-elastic modulus showed significant variation (2.19-35.70 MPa) between different locations and up to 39% decrease under muscle contraction, suggesting a complicated biomechanical environment in which cells dwell. In addition, the nano-elastic modulus of the tail tendon measured in live mice was significantly lower than that measured in vitro, suggesting a disagreement of tissue mechanical properties in vivo and in vitro. This information is important for the designs of new extracellular biomaterial that can better mimic the biological environment, and improve clinical outcomes of musculoskeletal tissue degenerations and associated disorders.

2.
Biosci Rep ; 40(9)2020 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-32803252

RESUMO

OBJECTIVES: In the treatment of osteoarthritis (OA), tramadol, a common weak opioid, has become popular due to its effectiveness in inhibition of pain. In the present study, we aimed to explore the effect of tramadol on subchondral bone, especially changes in the microstructure and mechanical properties. METHODS: A mouse model of OA was established in the present study by destabilization of the medial meniscus (DMM). A vehicle or drug was administered for 4 weeks. Specimens were harvested and analyzed radiologically and histologically using micro-computed tomography (micro-CT), scanning electron microscopy (SEM), atomic force microscopy (AFM) and histological staining to evaluate the knee joints of mice undergoing different forms of intervention. RESULTS: In the early stages of OA induced by DMM, the subchondral bone volume fraction in the OA group was significantly higher than in the sham+vehicle (sham+veh) group, while the volume in the treatment groups was lower than in the DMM+vehicle (DMM+veh) and sham+veh groups. In addition, the elastic moduli in the treatment groups clearly decreased compared with the DMM+veh and sham+veh groups. Observations of the subchondral bone surface by SEM indicated serious destruction, principally manifesting as a decrease in lacunae and more numerous and scattered cracks. Histological staining demonstrated that there was no difference in the degeneration of either the articular cartilage or synovial cells whether tramadol was used or not. CONCLUSION: Although tramadol is effective in inhibiting pain in early OA, it negatively regulates the microstructure and mechanical properties of subchondral bone in joints.

3.
Int J Oncol ; 56(2): 606-617, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31894296

RESUMO

Abnormal metabolism serves a critical role in the development and progression of different types of malignancies including glioblastoma (GBM), and may therefore serve as a promising target for treatment of cancer. Preclinical studies have indicated that a ketogenic diet (KD) may exhibit beneficial effects in patients with GBM; however, the underlying mechanisms remain incompletely understood. The aim of the present study was to evaluate the effects of a KD on glioma stem­like cells (GSCs), by culturing patient­derived primary GSCs as well as a GSC cell line in glucose­restricted, ß­hydroxybutyrate­containing medium (BHB­Glow) which was used to mimic clinical KD treatment. GSCs cultured in BHB­Glow medium exhibited reduced proliferation and increased apoptosis compared with cells grown in the control medium. Furthermore, decreased expression of stem cell markers, diminished self­renewal in vitro, and reduced tumorigenic capacity in vivo, providing evidence that the stemness of GSCs was compromised. Mechanistically, culturing in BHB­Glow medium reduced glucose uptake and inhibited glycolysis in GSCs. Furthermore, culturing in the BHB­Glow medium resulted in morphological and functional disturbances to the mitochondria of GSCs. These metabolic changes may have reduced ATP production, promoted lactic acid accumulation, and thus, increased the production of reactive oxygen species (ROS) in GSCs. The expression levels and activation of mammalian target of rapamycin, hypoxia­inducible factor 1 and B­cell lymphoma 2 were decreased, consistent with the reduced proliferation of GSCs in BHB­Glow medium. ROS scavenging reversed the inhibitory effects of a KD on GSCs. Taken together, the results demonstrate that treatment with KD inhibited proliferation of GSCs, increased apoptosis and attenuated the stemness in GSCs by increasing ROS production.


Assuntos
Ácido 3-Hidroxibutírico/farmacologia , Neoplasias Encefálicas/dietoterapia , Dieta Cetogênica , Glioblastoma/dietoterapia , Células-Tronco Neoplásicas/patologia , Adolescente , Adulto , Idoso , Animais , Apoptose/efeitos dos fármacos , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Proliferação de Células/efeitos dos fármacos , Meios de Cultura/farmacologia , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Glioblastoma/patologia , Glioblastoma/cirurgia , Glucose/metabolismo , Glicólise/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Células-Tronco Neoplásicas/metabolismo , Cultura Primária de Células , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas , Adulto Jovem
4.
Mol Med Rep ; 14(1): 380-6, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27175997

RESUMO

Glioblastoma multiforme (GBM) is the most common and aggressive type of brain tumor, and is associated with a poor prognosis. Saponin 6, derived from Anemone taipaiensis, exerts potent cytotoxic effects against the human hepatocellular carcinoma HepG2 cell line and the human promyelocytic leukemia HL­60 cell line; however, the effects of saponin 6 on glioblastoma remain unknown. The present study aimed to evaluate the effects of saponin 6 on human U87 malignant glioblastoma (U87 MG) cells. The current study revealed that saponin 6 induced U87 MG cell death in a dose­ and time­dependent manner, with a half maximal inhibitory concentration (IC50) value of 2.83 µM after treatment for 48 h. However, saponin 6 was needed to be used at a lesser potency in HT­22 cells, with an IC50 value of 6.24 µM. Cell apoptosis was assessed by flow cytometry using Annexin V­fluorescein isothiocyanate/propidium iodide double staining. DNA fragmentation and alterations in nuclear morphology were examined by terminal deoxynucleotidyl transferase­mediated dUTP nick end labeling and transmission electron microscopy, respectively. The present study demonstrated that treatment with saponin 6 induced cell apoptosis in U87 MG cells, and resulted in DNA fragmentation and nuclear morphological alterations typical of apoptosis. In addition, flow cytometric analysis revealed that saponin 6 was able to induce cell cycle arrest. The present study also demonstrated that saponin 6­induced apoptosis of U87 MG cells was attributed to increases in the protein expression levels of Fas, Fas ligand, and cleaved caspase­3, ­8 and ­9, and decreases in the levels of B­cell lymphoma 2. The current study indicated that saponin 6 may exhibit selective cytotoxicity toward U87 MG cells by activating apoptosis via the extrinsic and intrinsic pathways. Therefore, saponin 6 derived from A. taipaiensis may possess therapeutic potential for the treatment of GBM.


Assuntos
Anemone/química , Apoptose/efeitos dos fármacos , Glioblastoma/metabolismo , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Saponinas/farmacologia , Receptor fas/metabolismo , Animais , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Humanos , Camundongos , Extratos Vegetais/toxicidade , Células Piramidais/efeitos dos fármacos , Células Piramidais/metabolismo , Saponinas/toxicidade , Transdução de Sinais/efeitos dos fármacos
5.
Cancer Lett ; 349(1): 67-76, 2014 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-24705306

RESUMO

Hypoxia contributes to GSC expansion principally through Hif-1α and Hif-2α, but how these two factors work together has not been completely understood. We show that hypoxia promoted proliferation, self-renewal and inhibited the conversion of GSCs into INP-like cells through activating Notch signaling. Further data suggested that Hif-2α interacted with NICD and repressed the activity of Notch signaling, in contrast to the role of Hif-1α in Notch signaling. Together, our findings suggest that Hif-1α and Hif-2α competitively bind to NICD and dynamically regulate the activation of Notch signaling in GSCs likely depending on different oxygen tensions, providing improved therapeutic opportunities for malignant gliomas.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Glioma/metabolismo , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Receptores Notch/metabolismo , Células-Tronco/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Células COS , Processos de Crescimento Celular/fisiologia , Hipóxia Celular/fisiologia , Linhagem Celular Tumoral , Chlorocebus aethiops , Glioma/genética , Células HeLa , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Estrutura Terciária de Proteína , Receptores Notch/genética , Transdução de Sinais , Ativação Transcricional
6.
J Colloid Interface Sci ; 407: 416-24, 2013 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-23880520

RESUMO

Homogeneously distributed self-assembling hybrid graphene-based aerogels with 3D interconnected pores, employing three types of carbohydrates (glucose, ß-cyclodextrin, and chitosan), have been fabricated by a simple hydrothermal route. Using three types of carbohydrates as morphology oriented agents and reductants can effectively tailor the microstructures, physical properties, and electrochemical performances of the products. The effects of different carbohydrates on graphene oxide reduction to form graphene-based aerogels with different microcosmic morphologies and physical properties were also systemically discussed. The electrochemical behaviors of all graphene-based aerogel samples showed remarkably strong and stable performances, which indicated that all the 3D interpenetrating microstructure graphene-based aerogel samples with well-developed porous nanostructures and interconnected conductive networks could provide fast ionic channels for electrochemical energy storage. These results demonstrate that this strategy would offer an easy and effective way to fabricate graphene-based materials.

7.
Nanotechnology ; 24(27): 275602, 2013 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-23743520

RESUMO

We have demonstrated an environmentally friendly in situ assembly method for the preparation of novel three-dimensional TiO2/graphene oxide (TiO2/GO) nanostructures with favorable flower-shaped architectures. Very little information on such a morphology of TiO2/GO nanostructures is available in the literature. The as-synthesized sample was characterized by x-ray diffraction, scanning electron microscopy, transmission electron microscopy, N2 adsorption-desorption measurements and Raman spectroscopy. Also the TiO2/GO composites exhibited enhanced photocatalytic properties.


Assuntos
Grafite/química , Nanopartículas/química , Óxidos/química , Titânio/química , Catálise , Química Verde , Nanopartículas/ultraestrutura
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