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1.
Biomater Sci ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31967113

RESUMO

Autografts are still regarded as the gold standard treatment for bone defects but they require additional surgery that causes pain for the patient. Thus, alternatives that can substitute for grafts are required. In the present study, a novel poly-GLP-1 molecule was developed using a polymeric pro-drug strategy which was found to accelerate bone healing in a mouse femoral defect model. Furthermore, the poly-GLP-1 molecule induced osteogenesis and inhibited adipogenesis in bone marrow-derived mesenchymal stem cells (BMSCs). The results demonstrate that poly-GLP-1 promoted M2 polarization of bone marrow-derived macrophages (BMDMs) and increased the levels of TGF-ß1 in the bone marrow, resulting in the migration of an increased number of CD29 + Sca-1 + BMSCs to the bone surface. Finally, we found that poly-GLP-1 facilitated the migration of BMSCs due to transduction of the Smad2 signaling pathway, causing increased numbers of CD31 + Endomucin + endothelial cells in bone marrow that promoted bone formation. These results support poly-GLP-1 as a potential bone-healing agent and suggest that it may play a promising role in the clinical treatment of fracture repair.

2.
Medicine (Baltimore) ; 99(1): e18447, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895773

RESUMO

Prenatal examination is a pivotal measure to prevent high-risk pregnancy and to ensure the safety of both mother and infant. However, pregnant women in Linzhi Prefecture in the Tibet Autonomous Region (TAR) often cannot obtain regular prenatal examinations due to limited accessibility of healthcare facilities, shortage of medical staff, and lack of medical equipment. Health education is an important approach to solve this ever-growing issue of pregnant women in rural Tibet.To evaluate the efficacy of flexible methods of health education programs on improving compliance among pregnant women from Tibet, China.In May to November of 2018, a total of 168 pregnant women receiving prenatal examination in a tertiary referral hospital in Linzhi Prefecture were recruited and randomly assigned to a control (n = 85) and intervention group (n = 83). All pregnant women were followed up until delivery. The pregnant women in the control group received regular prenatal examination and health education programs. Other than receiving routine prenatal care, participants of the interventional group also voluntarily joined the WeChat Social Messaging platform. Online resources posted by the maternity schools provided convenience and flexibility for the pregnant woman. The number of prenatal examinations was statistically significant between the 2 groups. The effect of flexible patterns of health education programs on improving the compliance of pregnant women in Tibet was assessed.The number of prenatal examinations in the intervention group was 2.646 times, which was higher than that in the control group (P < .01). Multivariate analysis demonstrated that interventional measures and ethnicity were the influencing factors of the number of prenatal examinations for pregnant women in Linzhi after the adjustment of age, history of adverse pregnancy, education level, ethnicity, multiparity, gestational complications, and medical history. The number of prenatal examinations for the pregnant Tibetan women was 0.535 times lower compared with that of the pregnant Han women (95% CI: -0.089, 1.157, P = .091).Flexible forms of health education during the antenatal period can effectively increase the compliance of pregnant women in Tibet.


Assuntos
Educação em Saúde/métodos , Cooperação do Paciente , Cuidado Pré-Natal/estatística & dados numéricos , Adulto , Feminino , Humanos , Gravidez , Rede Social , Tibet
3.
Sci Rep ; 8(1): 13664, 2018 09 12.
Artigo em Inglês | MEDLINE | ID: mdl-30209328

RESUMO

This paper presents a power-free, self-contained microfluidic device in which a number of nanoliter-sized droplets can be parallelly and accurately metered and mixed for high-throughput analysis and/or portable systems. In this system, the absorption of air by pre-degassed PDMS and the change of capillary force due to sudden narrowing of the channel cross-section provide the mechanism for actuating, metering and mixing the flow of fluid in the microfluidic channels and chambers. With an array of channels and capillary valves combined with an array of pre-degassed PDMS pump chambers, the device can perform multiple liquid dispensing and mixing in parallel, and its performance and reproducibility are also evaluated. As a practical application, the proposed device is used to screen crystallization conditions of lysozyme. This device needs neither external power nor complex instruments for fluid handling. Thus, it offers an easy-to-use, inexpensive and power-free way to perform multiple nanoliter-volume distinct reactions in parallel format and should be ideally suitable for individual laboratories for various applications such as enzyme assay, protein crystallization, drug discovery, and combinatorial chemistry.


Assuntos
Técnicas Analíticas Microfluídicas/instrumentação , Técnicas Analíticas Microfluídicas/métodos , Microfluídica/instrumentação , Microfluídica/métodos , Muramidase/química , Desenho de Equipamento , Ensaios de Triagem em Larga Escala/instrumentação , Ensaios de Triagem em Larga Escala/métodos
4.
Mol Med ; 24(1): 20, 2018 05 09.
Artigo em Inglês | MEDLINE | ID: mdl-30134793

RESUMO

BACKGROUND: Implant failure remains a major obstacle to successful treatment via TJA. Periprosthetic osteolysis and aseptic loosening are considered as proof of wear debris-induced disruption of local regulatory mechanisms related to excessive bone resorption associated with osteolysis and the damage at the bone-prosthesis interface. Therefore, there is an immediate need to explore strategies for limiting and curing periprosthetic osteolysis and aseptic loosening. METHODS: We analyzed the in vitro cytokine production by primary mouse bone marrow macrophages (BMMs) that were exposed to ultra-high molecular weight polyethylene (UHMWPE) particles and treated with metformin at different concentrations with or without 5-aminoimidazole-4-carboxamide ribonucleoside to activate or inhibit AMPK. A mouse calvarial model was used to examine the in vivo effects of metformin on UHMWPE particle-induced osteolysis. RESULTS: With particles, primary mouse BMMs secreted more pro-inflammatory cytokines tumor necrosis factor-α and interleukin (IL)-6. Treatment with metformin inhibited these variations and promoted the release of cytokine IL-10 with anti-inflammatory capability. In vivo, metformin reduced the production of pro-inflammatory cytokines, osteoclastogenesis, and osteolysis, increasing IL-10 production. Metformin also promoted the polarization of macrophages to an anti-inflammatory phenotype in vivo via AMPK activation. DISCUSSION: A crucial point in limiting and correcting the periprosthetic osteolysis and aseptic loosening is the inhibition of inflammatory factor production and osteoclast activation induced by activated macrophages. The ability of metformin to attenuate osteolysis induced in mouse calvaria by the particles was related to a reduction in osteoclast number and polarization of macrophages to an anti-inflammatory functional phenotype. CONCLUSIONS: Metformin could limit the osteolysis induced by implant debris. Therefore, we hypothesized that metformin could be a potential drug for osteolysis induced by implant debris.


Assuntos
Anti-Inflamatórios/uso terapêutico , Macrófagos/efeitos dos fármacos , Metformina/uso terapêutico , Osteólise/tratamento farmacológico , Crânio/efeitos dos fármacos , Animais , Células Cultivadas , Macrófagos/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Polietilenos , Próteses e Implantes
5.
Mol Med Rep ; 17(2): 2719-2723, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29207060

RESUMO

Honokiol is the main active constituent of Magnolia officinalis. With effective and long­term pharmacological functions of being antibacterial, anti­oxidative, anti­inflammatory, antitumor, anti­spasmic, anti­anxiety and anti­viral, Honokiol is clinically used in the treatment of acute enteritis and chronic gastritis. The aim of the present study was to observe the possible anti­effects of honokiol on autophagy and apoptosis of osteosarcoma, and to investigate the role of the PI3K/Akt/mTOR signaling pathway in its anticancer effects. MTT assay was used to evaluate cell proliferation and Annexin V­fluorescein isothiocyanate/propidium iodide staining flow cytometry was used to analyze the apoptotic rate. The authors identified that honokiol could inhibit cell proliferation and induce the apoptotic rate of osteosarcoma cells. The expression level of Bcl­2­like protein 4, caspase­3 and p53 protein expression were induced and cyclin D1 protein expression was suppressed in osteosarcoma cells by honokiol. Autophagy­associated LC3II protein expression level was promoted, and PI3K, p­Akt and p­mTOR protein expression level was suppressed in osteosarcoma cells by honokiol. The present study demonstrated, to the best of the authors' knowledge, for the first time that honokiol induces autophagy and apoptosis of osteosarcoma cells through the PI3K/Akt/mTOR signaling pathway.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Apoptose/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Lignanas/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Neoplasias Ósseas/metabolismo , Caspase 3 , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Ciclina D1/genética , Ciclina D1/metabolismo , Humanos , Osteossarcoma/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Proteína X Associada a bcl-2/genética , Proteína X Associada a bcl-2/metabolismo
6.
Brain Res ; 1671: 85-92, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28716633

RESUMO

The essential role of GAPDH/Siah1 signaling pathway in the pathogenesis of various injurious conditions such as traumatic spinal cord injury (SCI) has been gradually recognized. However, the drugs targeting this signaling pathway are still lacking. The endocannabinoid system, including its receptors (CB1 and CB2), act as neuroprotective and immunomodulatory modulators in SCI. WIN55212-2, an agonist for CB1 and CB2 receptors, has been demonstrated with anti-inflammatory and anti-apoptotic effects in multiple neurological diseases. Therefore, the present study aimed to investigate whether WIN55212-2 could promote functional recovery after traumatic SCI via inhibition of the GAPDH/Siah1 signaling. The traumatic SCI was induced by dropping a 10-g impactor from 25mm on the dorsal surface of T9 and T10. Our results showed that WIN55212-2 alleviated the activation of GAPDH/Siah1 signaling pathway after SCI, as indicated by the reduction in GAPDH nuclear expression, GAPDH-Siah1 complex formation and iNOS protein expression. Furthermore, WIN55212-2 reduced apoptosis, production of IL-1ß and TNF-α and activation of NF-κB signaling in the spinal cord after SCI. The behavioral tests showed that WIN55212-2 improved the functional recovery after traumatic SCI as indicated by sustained increase in the locomotor scores. However, these neuroprotective effects of WIN55212-2 were blocked in the presence of the combined treatment of AM630 (an antagonist of CB2) rather than AM251 (an antagonist of CB1). In conclusion, our study indicates that, WIN55212-2 improves the functional recovery after SCI via inhibition of GAPDH/Siah1 cascades in a CB2 receptor dependent manner, indicative of its therapeutic potential for traumatic SCI or other traumatic conditions.


Assuntos
Benzoxazinas/farmacologia , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/antagonistas & inibidores , Morfolinas/farmacologia , Naftalenos/farmacologia , Proteínas Nucleares/antagonistas & inibidores , Receptor CB2 de Canabinoide/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Ubiquitina-Proteína Ligases/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Endocanabinoides/metabolismo , Gliceraldeído-3-Fosfato Desidrogenase (Fosforiladora)/metabolismo , Masculino , Fármacos Neuroprotetores/farmacologia , Proteínas Nucleares/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Recuperação de Função Fisiológica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Traumatismos da Medula Espinal/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
7.
Medicine (Baltimore) ; 96(23): e7106, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28591055

RESUMO

This study aimed to introduce a new stereoelectroencephalography (SEEG) system based on Leksell stereotactic frame (L-SEEG) as well as Neurotech operation planning software, and to investigate its safety, applicability, and reliability.L-SEEG, without the help of navigation, includes SEEG operation planning software (Neurotech), Leksell stereotactic frame, and corresponding surgical instruments. Neurotech operation planning software can be used to display three-dimensional images of the cortex and cortical vessels and to plan the intracranial electrode implantation. In 44 refractory epilepsy patients, 364 intracranial electrodes were implanted through the L-SEEG system, and the postoperative complications such as bleeding, cerebral spinal fluid (CSF) leakage, infection, and electrode-related problems were also investigated.All electrodes were implanted accurately as preoperatively planned shown by postoperative lamina computed tomography and preoperative lamina magnetic resonance imaging. There was no severe complication after intracranial electrode implantation through the L-SEEG system. There were no electrode-related problems, no CSF leakage and no infection after surgery. All the patients recovered favorably after SEEG electrode implantation, and only 1 patient had asymptomatic frontal lateral ventricle hematoma (3 mL).The L-SEEG system with Neurotech operation planning software can be used for safe, accurate, and reliable intracranial electrode implantation for SEEG.


Assuntos
Eletrocorticografia , Software , Técnicas Estereotáxicas/instrumentação , Cirurgia Assistida por Computador , Adolescente , Adulto , Encéfalo/irrigação sanguínea , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Eletrocorticografia/instrumentação , Eletrocorticografia/métodos , Eletrodos Implantados , Feminino , Humanos , Imagem Tridimensional/métodos , Masculino , Cirurgia Assistida por Computador/instrumentação , Cirurgia Assistida por Computador/métodos , Adulto Jovem
8.
World Neurosurg ; 102: 434-441, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28249830

RESUMO

OBJECTIVE: Because of the balance between achieving complete seizure freedom and minimizing the postoperative neurologic deficits, surgery for refractory epilepsy originating from the primary motor cortex is difficult. Here, we report the outcomes of surgery for magnetic resonance imaging-negative refractory epilepsy originating from the primary motor cortex in a case series. METHODS: Nine patients with refractory epilepsy originating from the primary motor cortex underwent intracranial electrodes implantation after preoperative evaluation. Subdural grid electrodes and depth electrodes were implanted through craniotomy assisted by stereotactic technique. We delineated the epileptic zone and executed tailored resection according to results of intracranial electroencephalography and mapping. The patients were followed up for at least 1 year. Muscle strength was evaluated at different postoperative times (day 1, 2 weeks, and 1 year). RESULTS: Regarding seizure outcome at the last follow-up, Engel class I outcome was achieved in 5 patients, class II was achieved in 3 patients, and class III was achieved in 1 patient. All cases had postoperative hemiparesis of different degree on the first day after operation. Three patients experienced distal muscle strength of single limb with grade 3 or lower and had obvious dysfunction at 1 year after operation. Six patients experienced distal muscle strength of grade 4 or 5 (Medical Research Council 6-point scale) and had no obvious dysfunction at that time. CONCLUSIONS: Most patients of refractory epilepsy originating from the primary motor cortex were seizure free and had no obvious neurologic deficits at follow-up. Epileptogenic zone resection may not always be contraindicated for patients with nonlesional refractory epilepsy originating from the primary motor cortex.


Assuntos
Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Imagem por Ressonância Magnética , Córtex Motor/diagnóstico por imagem , Procedimentos Neurocirúrgicos/métodos , Adolescente , Adulto , Mapeamento Encefálico , Criança , Eletrodos Implantados , Eletroencefalografia , Feminino , Seguimentos , Humanos , Masculino , Adulto Jovem
9.
Artif Organs ; 41(2): 199-204, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27401022

RESUMO

Calcium phosphate cement (CPC) porous scaffold is widely used as a suitable bone substitute to repair bone defect, but the optimal pore size is unclear yet. The current study aimed to evaluate the effect of different pore sizes on the processing of bone formation in repairing segmental bone defect of rabbits using CPC porous scaffolds. Three kinds of CPC porous scaffolds with 5 mm diameters and 12 mm length were prepared with the same porosity but different pore sizes (Group A: 200-300 µm, Group B: 300-450 µm, Group C: 450-600 µm, respectively). Twelve millimeter segmental bone defects were created in the middle of the radius bone and filled with different kinds of CPC cylindrical scaffolds. After 4, 12, and 24 weeks, alkaline phosphatase (ALP), histological assessment, and mechanical properties evaluation were performed in all three groups. After 4 weeks, ALP activity increased in all groups but was highest in Group A with smallest pore size. The new bone formation within the scaffolds was not obvious in all groups. After 12 weeks, the new bone formation within the scaffolds was obvious in each group and highest in Group A. At 24 weeks, no significant difference in new bone formation was observed among different groups. Besides the osteoconductive effect, Group A with smallest pore size also had the best mechanical properties in vivo at 12 weeks. We demonstrate that pore size has a significant effect on the osteoconductivity and mechanical properties of calcium phosphate cement porous scaffold in vivo. Small pore size favors the bone formation in the early stage and may be more suitable for repairing segmental bone defect in vivo.


Assuntos
Cimentos para Ossos/uso terapêutico , Regeneração Óssea , Substitutos Ósseos/uso terapêutico , Fosfatos de Cálcio/uso terapêutico , Osteogênese , Fosfatase Alcalina/metabolismo , Animais , Fenômenos Biomecânicos , Cimentos para Ossos/química , Regeneração Óssea/efeitos dos fármacos , Substitutos Ósseos/química , Osso e Ossos/efeitos dos fármacos , Osso e Ossos/lesões , Fosfatos de Cálcio/química , Masculino , Osteogênese/efeitos dos fármacos , Porosidade , Coelhos , Tecidos Suporte/química
10.
Am J Transl Res ; 8(6): 2631-40, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27398146

RESUMO

Increasing evidence has demonstrated the role of endogenous cannabinoids system (ECS) on protecting brain injury caused by ischemia (IMI). Papers reported that microglia-mediated inflammation has become one of the most pivotal mechanisms for IMI. This study was aimed to investigate the potential roles of ECS on neuron protection under microglia-mediated inflammation. Inflammatory cytokines level both in vitro (BV-2 cells) and in vivo (brain tissue from constructed IMI model and brain-isolated microglia) was detected. ECS levels were detected, and its effects on inflammations was also analyzed. Influence of microglia-mediated inflammation on neuron injury was analyzed. Moreover, the effects of ECS on protecting neuron injury were also analyzed. Our results showed that the levels of inflammatory cytokines including TNFα and IL-1ß were higher while IKBα was lower in IMI model brain tissue, brain-isolated microglia and BV-2 cells compared to the control. Inflammation was activated in microglia, as well as the activation of ECS characterized by the increasing level of AEA and 2-AG. Furthermore, the activated microglia-mediated self-inflammation performed harmful influence on neurons via suppressing cell viability and inducing apoptosis. Moreover, ECS functioned as a protector on neuron injury though promoting cell proliferation and suppressing cell apoptosis which were caused by the activated BV-2 cells (LPS induced for 3 h). Our data suggested that ECS may play certain neuroprotective effects on microglia-mediated inflammations-induced IMI through anti-inflammatory function.

11.
Biochem Biophys Res Commun ; 460(2): 327-32, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25804637

RESUMO

Data from human and rodent studies have demonstrated that microgravity induces observed bone loss in real spaceflight or simulated experiments. The decrease of bone formation and block of maturation may play important roles in bone loss induced by microgravity. The aim of this study was to investigate the changes of proliferation and differentiation in bone marrow mesenchymal stem cells (BMSCs) induced by simulated microgravity and the mechanisms underlying it. We report here that clinorotation, a simulated model of microgravity, decreased proliferation and differentiation in BMSCs after exposure to 48 h simulated microgravity. The inhibited proliferation are related with blocking the cell cycle in G2/M and enhancing the apoptosis. While alterations of the osteoblast differentiation due to the decreased SATB2 expression induced by simulated microgravity in BMSCs.


Assuntos
Células da Medula Óssea/citologia , Diferenciação Celular , Proliferação de Células , Células-Tronco Mesenquimais/citologia , Animais , Sequência de Bases , Ciclo Celular , Linhagem Celular , Primers do DNA , Camundongos , Camundongos Endogâmicos C3H , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ausência de Peso
12.
Mol Cell Biochem ; 392(1-2): 85-93, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24752351

RESUMO

Estrogen deficiency is the main reason of bone loss, leading to postmenopausal osteoporosis, and estrogen replacement therapy (ERT) has been demonstrated to protect bone loss efficiently. Notch signaling controls proliferation and differentiation of bone marrow-derived mesenchymal stem cells (BMSCs). Moreover, imperfect estrogen-responsive elements (EREs) were found in the 5'-untranslated region of Notch1 and Jagged1. Thus, we examined the molecular and biological links between estrogen and the Notch signaling in postmenopausal osteoporosis in vitro. hBMSCs were obtained from healthy women and patients with postmenopausal osteoporosis. Notch signaling molecules were quantified using real-time polymerase chain reaction (real-time PCR) and Western Blot. Luciferase reporter constructs with putative EREs were transfected into hBMSCs and analyzed. hBMSCs were transduced with lentiviral vectors containing human Notch1 intracellular domain (NICD1). We also used N-[N-(3, 5-diflurophenylacetate)-l-alanyl]-(S)-phenylglycine t-butyl ester, a γ-secretase inhibitor, to suppress the Notch signaling. We found that estrogen enhanced the Notch signaling in hBMSCs by promoting the expression of Jagged1. hBMSCs cultured with estrogen resulted in the up-regulation of Notch signaling and increased proliferation and differentiation. Enhanced Notch signaling could enhance the proliferation and differentiation of hBMSCs from patients with postmenopausal osteoporosis (OP-hBMSCs). Our results demonstrated that estrogen preserved bone mass partly by activating the Notch signaling. Because long-term ERT has been associated with several side effects, the Notch signaling could be a potential target for treating postmenopausal osteoporosis.


Assuntos
Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Estrogênios/farmacologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Osteoporose Pós-Menopausa/patologia , Receptores Notch/metabolismo , Adulto , Estudos de Casos e Controles , Células Cultivadas , Feminino , Humanos , Células-Tronco Mesenquimais/citologia , Pessoa de Meia-Idade , Transdução de Sinais
13.
Zhonghua Nan Ke Xue ; 19(8): 689-93, 2013 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-24010201

RESUMO

OBJECTIVE: To evaluate contrast-enhanced ultrasonography (CEUS) in detecting testicular perfusion in acute testis contusion. METHODS: We established the model of testis contusion in 11 healthy male New Zealand rabbits by randomly hitting one side of the scrotum under general anesthesia. We examined the bilateral scrotums of all the animals before, immediately after and at 2, 4 and 6 hours after modeling by color Doppler flow imaging (CDFI) and CEUS, and analyzed the time-intensity curve (TIC), arriving time (AT), time to peak intensity (TTP), peak intensity (PI), half time of descending peak intensity (HT) and area under the curve (AUC) in the healthy and injured testis, respectively. RESULTS: CEUS exhibited a higher sensitivity in detecting tissue perfusion than CDFI. The mode of contrast agent perfusion in testicular contusion was fast in and slow out. There were no evident differences between the contused and the healthy testis in AT, TTP and PI before modeling. The contused testis showed significantly earlier AT and TTP, higher PI and larger AUC (P < 0.05) than the healthy one at different time points after modeling, but no statistically significant difference was found in HT (P > 0.05). CONCLUSION: Accurate parameters of testicular perfusion in acute testis contusion can be quantitatively obtained by CEUS, which are of important value for the diagnosis of testis contusion.


Assuntos
Contusões/diagnóstico por imagem , Testículo/diagnóstico por imagem , Animais , Meios de Contraste , Masculino , Coelhos , Testículo/irrigação sanguínea , Testículo/lesões , Ultrassonografia Doppler em Cores
14.
Int J Clin Exp Pathol ; 6(5): 841-52, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23638215

RESUMO

UNLABELLED: Osteoporosis is a major health problem affecting the aging population, especially in patients 65 years of age and older. The imbalance between bone formation and bone resorption is generally accepted as the essential mechanism leading to osteoporosis. In addition to the abnormal activation of osteoclast-mediated bone resorption, the dysfunction of bone marrow stromal cells (BMSCs) in mediating bone formation has been accepted as a major contributor to the progression of senile osteoporosis. RESULTS: In our study, senile osteoporotic hBMSCs displayed a decreasing capacity for proliferation and osteoblast differentiation, which was associated with the downregulation of integrin α2. Forced ectopic integrin α2 expression using a lentivirus vector reversed the dysfunction of senile osteoporotic hBMSCs. Additionally, the overexpression of integrin α2 upregulated the levels of Runx2 and Osterix. Mechanically, Western blot analyses revealed that integrin α2 phosphorylated ERK1/2 and the inactivation of ERK by PD98059 suppressed the osteoblastic differentiation of hBMSCs, suggesting that integrin α2 promotes osteoblast proliferation through the activation of ERK1/2 MAPK. CONCLUSION: Taken together, our results show that hBMSCs obtained from senile osteoporotic patients gradually lose their capability to differentiate along the osteogenic lineage and proliferate, which might be associated with the abnormal regulation of the integrin α2/ERK/Runx2 signaling pathway undergoing senile osteoporosis.


Assuntos
Diferenciação Celular/fisiologia , Integrina alfa2/biossíntese , Sistema de Sinalização das MAP Quinases/fisiologia , Células-Tronco Mesenquimais/metabolismo , Osteoporose/metabolismo , Idoso , Western Blotting , Proliferação de Células , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Osteoblastos/citologia , Osteoporose/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa
15.
Toxicology ; 304: 120-31, 2013 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-23313376

RESUMO

Osteosarcoma is a high-grade malignant bone tumor. Pterostilbene (PTE) is a natural, dimethylated analog of resveratrol with higher bioavailability. While PTE has been shown to have potent antitumor activity against various types of cancer, the molecular mechanisms underlying the effects of PTE remain largely unknown. The Janus kinase 2/Signal Transducer and Activator of Transcription 3 (JAK2/STAT3) signaling pathway plays a crucial role in tumorigenesis and immune development. In this study, we assessed the antitumor activity of PTE against human osteosarcoma cells and explored the role of JAK2/STAT3 and apoptosis-related signaling pathways on the activity of PTE. PTE treatment resulted in a dose- and time-dependent inhibition of osteosarcoma cell viability. Additionally, PTE exhibited strong antitumor activity, as evidenced not only by reductions in tumor cell adhesion, migration and mitochondrial membrane potential (MMP) but also by increases in the apoptotic index, reactive oxygen species (ROS) and several biochemical parameters. Furthermore, PTE treatment directly inhibited the phosphorylation of JAK2 at Tyr 1007 and the downstream activation of STAT3. PTE also down-regulated the expression of STAT3 target genes, including the anti-apoptotic proteins Bcl-xL and Mcl-1, leading to the up-regulation of mitochondrial apoptosis pathway-related proteins (Bax, Bak, cytosolic Cytochrome c, and cleaved Caspase3) and cyclin-dependent kinase inhibitors such as p21 and p27. PTE, used in combination with a known JAK2/STAT3 inhibitor, AG490, further decreased the viability of osteosarcoma cells. Taken together, PTE is a potent inhibitor of osteosarcoma cell growth that targets the JAK2/STAT3 signaling pathway. These data suggest that inhibition of JAK2/STAT3 signaling is a novel mechanism of action for PTE during therapeutic intervention in osteosarcoma cancers.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Janus Quinase 2/antagonistas & inibidores , Osteossarcoma/tratamento farmacológico , Fator de Transcrição STAT3/antagonistas & inibidores , Estilbenos/farmacologia , Antineoplásicos Fitogênicos/administração & dosagem , Apoptose/efeitos dos fármacos , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Osteossarcoma/patologia , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Estilbenos/administração & dosagem , Fatores de Tempo , Tirfostinas/farmacologia , Regulação para Cima/efeitos dos fármacos
16.
Sheng Wu Yi Xue Gong Cheng Xue Za Zhi ; 28(4): 708-14, 2011 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-21936367

RESUMO

The risk analysis of clinical claims of mechanical ventilator can provide the useful information to the application of the availability and safety of mechanical ventilators. This paper classifies the clinical claims of two types of mechanical ventilations, and tries to find the distribution characteristics of the failure rate of the clinical claims by using the hazard analysis method. All of the distribution characteristics are related to the factors as ventilator design, environment human factors, etc. The method of risk analysis, combining with the classification of clinical claims, is useful for the clinical application and engineering services of mechanical ventilation.


Assuntos
Análise de Falha de Equipamento/estatística & dados numéricos , Respiração Artificial/normas , Ventiladores Mecânicos/normas , Interpretação Estatística de Dados , Humanos , Respiração Artificial/efeitos adversos , Respiração Artificial/instrumentação , Medição de Risco , Ventiladores Mecânicos/efeitos adversos
17.
Biochem Biophys Res Commun ; 399(1): 49-54, 2010 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-20637731

RESUMO

Diabetic neuropathy is one of the most common complications in diabetes mellitus. Thus far, effective therapeutic agents for restoring the impaired motor and sensory nerve functions in diabetic neuropathy are still lacking. The antioxidant and neuroprotective properties of tanshinone IIA make it a promising candidate for the treatment of diabetic neuropathy. Therefore, the present study investigated the possible beneficial effect of tanshinone IIA on the impaired nerve functions displayed by a rat diabetic model. Insulin-dependent diabetes in rats was developed by a single dose of streptozotocin (STZ) at 50mg/kg. The diabetic rats were randomly divided into four groups (n=10 in each group), and were intraperitoneally administrated daily for 4 weeks with tanshinone IIA (20mg/kg, 50mg/kg and 100mg/kg), or normal saline from the fourth day after STZ injection, respectively. At the end of tanshinone IIA administration, thermal and mechanical nociceptive threshold were determined by a hot plate test and Von Frey hairs; motor nerve conducting velocity (MNCV) was determined by an electrophysiological method; nerve blood flow (NBF) was detected using a laser Doppler flow meter; Na(+),K(+)ATPase activity, the level of superoxide dismutase (SOD), catalase and malondialdehyde (MDA) in sciatic nerves, and the serum total antioxidant capability were also determined. We found that tanshinone IIA was capable of restoring diabetes-induced deficit in nerve functions (MNCV and NBF), and impairment in thermal and mechanical nociceptive capability. In addition, tanshinone IIA significantly increased the serum total antioxidant capability, improved the activities of Na(+),K(+)ATPase, increased the levels of SOD and catalase, and reduced the MDA level in sciatic nerves in diabetic rats. All the findings indicate the beneficial effect of tanshinone IIA on impaired nerve functions and raise the possibility of developing tanshinone IIA as a therapeutic agent for diabetic neuropathy.


Assuntos
Diabetes Mellitus Experimental/complicações , Neuropatias Diabéticas/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Hiperalgesia/tratamento farmacológico , Fenantrenos/uso terapêutico , Nervo Isquiático/efeitos dos fármacos , Animais , Glicemia/efeitos dos fármacos , Peso Corporal/efeitos dos fármacos , Catalase/metabolismo , Neuropatias Diabéticas/fisiopatologia , Medicamentos de Ervas Chinesas/farmacologia , Hiperalgesia/etiologia , Masculino , Malondialdeído/metabolismo , Fenantrenos/farmacologia , Ratos , Ratos Sprague-Dawley , Nervo Isquiático/enzimologia , Nervo Isquiático/fisiopatologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Superóxido Dismutase/metabolismo
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