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1.
Cancer Imaging ; 23(1): 82, 2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37667393

RESUMO

PURPOSE: This study aimed to develop and validate a model based on biparametric magnetic resonance imaging (bpMRI) for the detection of clinically significant prostate cancer (csPCa) in biopsy-naïve patients. METHOD: This retrospective study included 324 patients who underwent bpMRI and MRI targeted fusion biopsy (MRGB) and/or systematic biopsy, of them 217 were randomly assigned to the training group and 107 were assigned to the validation group. We assessed the diagnostic performance of three bpMRI-based scorings in terms of sensitivity and specificity. Subsequently, 3 models (Model 1, Model 2, and Model 3) combining bpMRI scorings with clinical variables were constructed and compared with each other using the area under the receiver operating characteristic (ROC) curves (AUC). The statistical significance of differences among these models was evaluated using DeLong's test. RESULTS: In the training group, 68 of 217 patients had pathologically proven csPCa. The sensitivity and specificity for Scoring 1 were 64.7% (95% CI 52.2%-75.9%) and 80.5% (95% CI 73.3%-86.6%); for Scoring 2 were 86.8% (95% CI 76.4%-93.8%) and 73.2% (95% CI 65.3%-80.1%); and for Scoring 3 were 61.8% (95% CI 49.2%-73.3%) and 80.5% (95% CI 73.3%-86.6%), respectively. Multivariable regression analysis revealed that scorings based on bpMRI, age, and prostate-specific antigen density (PSAD) were independent predictors of csPCa. The AUCs for the 3 models were 0.88 (95% CI 0.83-0.93), 0.90 (95% CI 0.85-0.94), and 0.88 (95% CI 0.83-0.93), respectively. Model 2 showed significantly higher performance than Model 1 (P = 0.03) and Model 3 (P < 0.01). CONCLUSION: All three scorings had favorite diagnostic accuracy. While in conjunction with age and PSAD the prediction power was significantly improved, and the Model 2 that based on Scoring 2 yielded the highest performance.


Assuntos
Nomogramas , Neoplasias da Próstata , Masculino , Humanos , Estudos Retrospectivos , Neoplasias da Próstata/diagnóstico por imagem , Biópsia Guiada por Imagem , Imageamento por Ressonância Magnética
2.
Global Spine J ; 13(4): 984-994, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-33906472

RESUMO

STUDY DESIGN: A prospective study. OBJECTIVES: Intervertebral disc degenerative disease is a common and frequently-occurring disease in adults and is the main cause of lower back pain. However, there is a lack of universal animal models to study disc degeneration. METHODS: Forty-two male New Zealand white rabbits aged 12 months were used in this study. We established an endplate ischemic disc degeneration model though surgical ligation of rabbit lumbar vertebral body segment arteries. Two weeks after surgery, 6 experimental animals were randomly selected for follow-up tests. First, ischemia and lumbar disc degeneration were confirmed using imaging techniques. Then, immunohistochemical staining was performed to observe the growth of the annulus fibrosus. Finally, quantitative polymerase chain reaction, enzyme-linked immunosorbent assay, and western blotting were used to detect mRNA expression and protein content of IL-1α, TNFα, collagen II, MMP-3, aggrecan, and PLA2 in the nucleus pulposus of the disc. RESULTS: Imaging examination confirmed the successful construction of a lumbar disc degeneration model. Histological analysis and biochemical analysis showed a damaged intervertebral disc structure, and collagen II and aggrecan, the key extracellular matrix components of intervertebral discs, were reduced in synthesis and content. The synthesis and expression of IL-1α, TNFα, PLA2, and MMP-3 related to disc catabolism and inflammatory response were enhanced. CONCLUSIONS: We successfully constructed a lumbar disc degeneration ischemia model, which provides a novel approach to study the pathological mechanisms involved in discogenic low back pain and to prevent and treat discogenic low back pain.

3.
BMC Musculoskelet Disord ; 23(1): 879, 2022 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-36138369

RESUMO

BACKGROUND: This study aimed to reveal the associations of osteoporotic vertebral compression refracture (OVCRF) incidence with sarcopenia and paravertebral muscles (PVM). METHODS: A total of 214 elderly patients who underwent percutaneous kyphoplasty in our hospital between January 2017 and December 2019 were analyzed. Data on possible risk factors, including sex, age, weight, height, diabetes, treated vertebral levels (thoracolumbar junction [(T10-L2]), vacuum clefts, and body mass index (BMI), were collected. Preoperative bone mineral density (BMD) and appendicular muscle mass were evaluated using dual-energy X-ray absorptiometry. Nutritional status was evaluated using the Mini Nutritional Assessment. Magnetic resonance imaging was performed to evaluate the physiological cross-sectional area of the PVM. RESULTS: Overall, 74 (15 men and 59 women) and 60 (55 women and 14 men) patients developed OVCRF and sarcopenia, respectively. Sarcopenia is related to advanced age, ower BMD and BMI values. Sarcopenia-related indicators (PVM fat rate, appendicular muscle mass index, grip strength) were significantly lower in the sarcopenia group. Univariate analysis showed a correlation between OVCRF and BMD, BMI, diabetes, sarcopenia, and age. Multivariate analysis suggested that fatty infiltration of the PVM, BMD, sarcopenia, diabetes, BMI, and treated vertebral level remained as the independent predictors of OVCRF (p < 0.05). CONCLUSIONS: The association between sarcopenia and PVM as independent risk factors for OVCRF was established in this study; therefore, sarcopenia should be greatly considered in OVCRF prevention.


Assuntos
Fraturas por Compressão , Cifoplastia , Fraturas por Osteoporose , Sarcopenia , Fraturas da Coluna Vertebral , Idoso , Feminino , Fraturas por Compressão/cirurgia , Humanos , Incidência , Cifoplastia/efeitos adversos , Cifoplastia/métodos , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/lesões , Vértebras Lombares/cirurgia , Masculino , Músculos/patologia , Fraturas por Osteoporose/diagnóstico por imagem , Fraturas por Osteoporose/epidemiologia , Fraturas por Osteoporose/etiologia , Estudos Retrospectivos , Sarcopenia/complicações , Sarcopenia/diagnóstico por imagem , Sarcopenia/epidemiologia , Fraturas da Coluna Vertebral/cirurgia
4.
J Biomater Appl ; 36(10): 1723-1736, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35235468

RESUMO

In this study, after optimizing the extraction process of CPP (Codonopsis pilosula polysaccharides), CPPM (CPP microcapsules) were prepared. Subsequently, the structural characteristics and physicochemical properties were studied. The results showed that CPPM is a hollow sac-like structure with rough folds and protuberances and comes in spherical or ellipsoidal shapes with uniform particle size. CPPM has certain swelling degree, low hardness, good adhesion, and stability. Then, the effect of CPPM on wounds repair was investigated by a rat model. The results showed that CPPM could improve the wound healing rate. Histological evaluation showed CPPM could promote neovascularization and fibroblast proliferation. By investigating the healing mechanism, it was found that CPPM increased the hydroxyproline content in granulation tissue and had an excellent antioxidant ability, and then inhibited lipid peroxidation, in addition, it significantly increased the transcript levels of VEGF and miRNA-21 genes, indicating that CPPM play an influential role in vascular remodeling during wound healing by up-regulating the expression of VEGF and miRNA-21 genes.


Assuntos
Codonopsis , Animais , Antioxidantes/química , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Cápsulas/química , Codonopsis/química , Polissacarídeos/química , Polissacarídeos/farmacologia , Polissacarídeos/uso terapêutico , Ratos , Cicatrização
5.
Biomass Convers Biorefin ; : 1-17, 2022 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-35342681

RESUMO

In this study, the second-order model, Fick's second law of diffusion, and the Peleg model were used to evaluate the extraction kinetic model of polysaccharide (CPP) from Codonopsis pilosula. The characteristic functional groups, surface structure, and physical and chemical properties of CPP were analyzed by multi-spectroscopic and microscopic techniques. The results showed that the extraction process agreed well with the second-order model, Fick's second diffusion law, and Peleg model. Rheological tests showed that CPP exhibited different viscosity changes under different conditions (Solution viscosity was inversely proportional to temperature, time, etc.; proportional to polysaccharide concentration, Na+ content, etc.). CPP was composed of molecular aggregates composed of small particles, with more pore structure and basically completely decomposed at 130 °C. The hypoglycemic study showed that CPP had a strong inhibitory effect on α-glycosidase than α-amylase. The morphology and subsequent structural features, anti-diabetic potential, and rheological properties of CPP were revealed to provide a theoretical basis for the development of pharmaceutical preparations or health food and functional food for the treatment of diabetes. Supplementary Information: The online version contains supplementary material available at 10.1007/s13399-022-02518-w.

6.
Front Endocrinol (Lausanne) ; 12: 727272, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34912294

RESUMO

Mesenchymal stem cell-derived exosomes have been under investigation as potential treatments for a diverse range of diseases, and many animal and clinical trials have achieved encouraging results. However, it is well known that the biological activity of the exosomes is key to their therapeutic properties; however, till date, it has not been completely understood. Previous studies have provided different explanations of therapeutic mechanisms of the exosomes, including anti-inflammatory, immunomodulatory, and anti-aging mechanisms. The pathological effects of oxidative stress often include organ damage, inflammation, and disorders of material and energy metabolism. The evidence gathered from research involving animal models indicates that exosomes have antioxidant properties, which can also explain their anti-inflammatory and cytoprotective effects. In this study, we have summarized the antioxidant effects of exosomes in in vivo and in vitro models, and have evaluated the anti-oxidant mechanisms of exosomes by demonstrating a direct reduction in excessive reactive oxygen species (ROS), promotion of intracellular defence of anti-oxidative stress, immunomodulation by inhibiting excess ROS, and alteration of mitochondrial performance. Exosomes exert their cytoprotective and anti-inflammatory properties by regulating the redox environment and oxidative stress, which explains the therapeutic effects of exosomes in a variety of diseases, mechanisms that can be well preserved among different species.


Assuntos
Antioxidantes/metabolismo , Exossomos/transplante , Células-Tronco Mesenquimais/citologia , Terapias em Estudo , Animais , Exossomos/metabolismo , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Transplante de Células-Tronco Mesenquimais/tendências , Células-Tronco Mesenquimais/metabolismo , Estresse Oxidativo , Terapias em Estudo/métodos , Terapias em Estudo/tendências
7.
Front Mol Biosci ; 8: 703110, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34434966

RESUMO

ADAMTS5 is involved in the pathogenesis of OA. As the major aggrecanase-degrading articular cartilage matrix, ADAMTS5, has been regarded as a potential target for OA treatment. We here provide an updated insight on the regulation of ADAMTS5 and newly discovered therapeutic strategies for OA. Pathophysiological and molecular mechanisms underlying articular inflammation and mechanotransduction, as well as chondrocyte hypertrophy were discussed, and the role of ADAMTS5 in each biological process was reviewed, respectively. Senescence, inheritance, inflammation, and mechanical stress are involved in the overactivation of ADAMTS5, contributing to the pathogenesis of OA. Multiple molecular signaling pathways were observed to modulate ADAMTS5 expression, namely, Runx2, Fgf2, Notch, Wnt, NF-κB, YAP/TAZ, and the other inflammatory signaling pathways. Based on the fundamental understanding of ADAMTS5 in OA pathogenesis, monoclonal antibodies and small molecule inhibitors against ADAMTS5 were developed and proved to be beneficial pre-clinically both in vitro and in vivo. Recent novel RNA therapies demonstrated potentials in OA animal models. To sum up, ADAMTS5 inhibition and its signaling pathway-based modulations showed great potential in future therapeutic strategies for OA.

8.
Orthop Surg ; 13(5): 1628-1638, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34152699

RESUMO

OBJECTIVE: To assess the clinical efficacy and share the technique notes of Wiltse Approach TLIF for the treating single segment degenerative lumbar spinal disease. METHOD: In this retrospective controlled study, 780 patients with single segment degenerative lumbar disease who were operated in our hospital from January 2016 to December 2020 were analyzed retrospectively. The patients were randomly assigned to Wiltse approach group (group A, 410 cases) and conventional open approach group (group B, 370 cases). Patient's assessment of pain and disability were evaluated by the visual analogue scale (VAS) and the Oswestry disability index (ODI) before and after surgery. The incision length, operative time, exposure time, intraoperative blood loss, hidden blood loss, time to ambulation, total length of hospitalization, serum creatine kinase, X-rays, CT and MRI were also evaluated. RESULTS: There were no differences in sex, age, pre-operative ODI score, VAS score between the two groups (P > 0.05). The Wiltse approach group had a shorter incision length with 7.69 ± 0.44 cm compared to the conventional group with 11.13 ± 0.36 cm (P < 0.01). The average operative time was 119.20 ± 14.64 min with exposure time of 16.20 ± 3.42 min in the Wiltse approach group and 145.65 ± 16.98 min with 29.20 ± 3.42 min in the conventional group (P < 0.05, P < 0.01). Comparing the intraoperative blood loss, hidden blood loss, serum creatine kinase, time to ambulation, total length of hospitalization, the Wiltse approach group was less than the conventional open approach group (P < 0.05). The VAS score of the two groups decreased significantly with time, and the VAS score of the Wiltse group was significantly lower than that of the conventional open approach group (P < 0.05). At last investigation after operation, ODI scores of the two groups were significantly decreased compared with that before operation. Wiltse approach group was significantly lower than that of the conventional open approach group (P < 0.05). The multifidus of the two groups of patients had a certain degree of atrophy. But the Wiltse approach group multifidus muscle atrophy rate is significantly lower than the conventional open approach group. CONCLUSION: The Wiltse approach TLIF significantly reduces the damage to the paravertebral muscles and the postoperative incidence of chronic low back pain.


Assuntos
Degeneração do Disco Intervertebral/cirurgia , Fusão Vertebral/métodos , Idoso , Biomarcadores/sangue , Avaliação da Deficiência , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Medição da Dor , Estudos Retrospectivos
9.
Biomed Mater ; 16(4)2021 04 02.
Artigo em Inglês | MEDLINE | ID: mdl-33626520

RESUMO

In this study, the extraction conditions ofNostoc communeVauch polysaccharide (NCVP) were optimized by single factor and orthogonal experiments. Then, the NCVP microcapsules (NCVPM) were prepared. After analyzing the microcapsule structural and thermal characteristics, the skin wound healing ability was studied by establishing back trauma rat models. Results showed that the NCVP yield was 10.37% under the following optimum conditions: 210 min extraction time, solid-liquid ratio of 1:50 and extraction temperature of 90 °C. The overall performance of the microcapsule was the best when the concentration of sodium alginate, calcium chloride and chitosan was 2%, 3% and 0.3%, respectively. NCVPM had spherical morphology, typical microcapsule structural characteristics and good thermal stability, and NCVP was dispersed in the microcapsules. NCVPM showed good biocompatibility and biodegradability, which met the requirements for slow-release polymer materials. After 14 days of treatment, the wound healing rate was 92.4%, the cells were arranged neatly and regularly, the cell nucleus became large and elliptical, the cell had a tendency to divide, and the fibers and microvessel were significantly more. By evaluating the mechanism, NCVPM could increase the content of hydroxyproline and glutathione to protect cells from oxidative damage, leading in turn to accelerated wound healing and shorter wound healing times. It could also accelerate cell division, collagen and microvascular production by increasing transcription levels of vascular endothelial growth factor mRNA and miRNA-21.


Assuntos
Quitosana , Cicatrização , Animais , Cápsulas , Quitosana/química , Polissacarídeos/química , Ratos , Fator A de Crescimento do Endotélio Vascular/metabolismo
10.
Int J Biol Macromol ; 156: 906-917, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32234447

RESUMO

The extraction process of Glycyrrhiza soluble polysaccharide (GP) was optimized by RSM, a rat trauma model was established via longitudinal incision on the back skin. The effects of GP combined with microcapsule collagen on the repair of rat injury model were discussed at different levels, Based on the content of hydroxyproline at the whole animal level, the proliferation of granulation tissue stained by HE, the number of microvessels labeled by CD34, the production of collagen fibers stained by Masson, the level of phosphorylation of STAT3 protein and that of VEGF at protein level were investigated. The results showed that after the administration of GP combined with microcapsules, the content of hydroxyproline in granulation tissue increased, the proliferation of capillaries and fibroblasts in granulation tissue became active, and the number of microvessels in wound increased. The formation density of collagen fibers was uniform and orderly. GP combined with microcapsules could activate the expression of p-STAT3 and VEGF proteins and up-regulate the transcription level of VEGF mRNA and miRNA-21 genes. Furthermore, GP combined with microcapsules could accelerate wound healing and promote neovascularization.


Assuntos
Cápsulas/química , Glycyrrhiza uralensis/química , Substâncias Macromoleculares/química , Polissacarídeos/química , Cicatrização , Animais , Cápsulas/uso terapêutico , Fenômenos Químicos , Substâncias Macromoleculares/uso terapêutico , Modelos Animais , Neovascularização Fisiológica , Ratos , Solubilidade , Análise Espectral
11.
Free Radic Biol Med ; 143: 1-15, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31351174

RESUMO

Excessive oxidative stress and inflammation are the key early events in the development of intervertebral disc degeneration (IVDD). The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome has been identified as the major source of oxidative stress and the inflammatory responses and thus is an attractive therapeutic target for IVDD. However, currently, there are no reports on the use of mesenchymal stem cell (MSC)-derived exosomes to reduce NLRP3 inflammasome expression for IVDD treatment. The present study aimed to investigate the therapeutic effect of exosomes for use as IVDD therapeutics. We first manufactured and evaluated the characteristics of exosomes. Then, we investigated the effects of exosomes on H2O2-induced nucleus pulposus (NP) cell inflammation. Third, we tested the function of exosomes with respect to H2O2-induced ROS production and mitochondrial dysfunction. Finally, the therapeutic effect of exosomes on IVDD was investigated using a rabbit IVDD model. Results showed that exosomes play an anti-inflammatory role in pathological NP cells by suppressing inflammatory mediators and NLRP3 inflammasome activation. Moreover, it was suggested that exosomes might supply mitochondrial proteins to NP cells, and that the damaged mitochondria could be restored with this supplement. Further, in the rabbit IVDD model, exosomes significantly prevented the progression of degenerative changes. Our results confirmed that the NLRP3 inflammasome is an effective target for IVDD treatment and that the injection of exosomes could be a promising therapeutic strategy.


Assuntos
Exossomos/metabolismo , Inflamação/metabolismo , Degeneração do Disco Intervertebral/terapia , Células-Tronco Mesenquimais/metabolismo , Núcleo Pulposo/metabolismo , Oxidantes/metabolismo , Oxigênio/metabolismo , Animais , Apoptose , Progressão da Doença , Peróxido de Hidrogênio/farmacologia , Degeneração do Disco Intervertebral/metabolismo , Bicamadas Lipídicas/metabolismo , Imageamento por Ressonância Magnética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Mitocôndrias/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Estresse Oxidativo , Proteômica , Coelhos , Ratos , Ratos Sprague-Dawley
12.
Mater Sci Eng C Mater Biol Appl ; 101: 588-595, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31029352

RESUMO

Articular cartilage lacks self-healing capacity, and there is no effective therapy facilitating cartilage repair. Osteoarthritis (OA) due to cartilage defects represents large and increasing healthcare burdens worldwide. Nowadays, the generation of scaffolds to preserve bioactive factors and the biophysical environment has received increasing attention. Furthermore, improved decellularization technology has provided novel insights into OA treatment. This review provides a comparative account of different cartilage defect therapies. Furthermore, some recent effective decellularization protocols have been discussed. In particular, this review focuses on the decellularization ratio of each protocol. Moreover, these protocols were compared particularly on the basis of immunogenicity and mechanical functionality. Further, various recellularization methods have been enlisted and the reparative capacity of decellularized cartilage scaffolds is evaluated herein. The advantages and limitations of different recellularization processes have been described herein. This provides a basis for the generation of decellularized cartilage scaffolds, thereby potentially promoting the possibility of decellularization as a clinical therapeutic target.


Assuntos
Cartilagem Articular/citologia , Engenharia Tecidual/métodos , Alicerces Teciduais/química , Animais , Matriz Extracelular/química , Humanos , Estudos Prospectivos
13.
Cell Transplant ; 27(4): 607-621, 2018 04.
Artigo em Inglês | MEDLINE | ID: mdl-29871513

RESUMO

OBJECTIVE: Although cerebral ischemia can activate endogenous reparative processes, such as proliferation of endogenous neural stem cells (NSCs) in the subventricular zone (SVZ) and subgranular zone (SGZ), the majority of these new cells die shortly after injury and do not appropriately differentiate into neurons, or migrate and functionally integrate into the brain. The purpose of this study was to examine a novel strategy for treatment of stroke after injury by optimizing the survival of ischemia-induced endogenous NSCs in the SVZ and SGZ. METHODS: Adult SVZ and SGZ NSCs were grown as neurospheres in culture and treated with a p53 inactivator, pifithrin-α (PFT-α), and an amyloid precursor protein (APP)-lowering drug, posiphen, and effects on neurosphere number, size and neuronal differentiation were evaluated. This combined sequential treatment approach was then evaluated in mice challenged with middle cerebral artery occlusion (MCAo). Locomotor behavior and cognition were evaluated at 4 weeks, and the number of new surviving neurons was quantified in nestin creERT2-YFP mice. RESULTS: PFT-α and posiphen enhanced the self-renewal, proliferation rate and neuronal differentiation of adult SVZ and SGZ NSCs in culture. Their sequential combination in mice challenged with MCAo-induced stroke mitigated locomotor and cognitive impairments and increased the survival of SVZ and SGZ NSCs cells. PFT-α and the combined posiphen+PFT-α treatment similarly improved locomotion behavior in stroke challenged mice. Notably, however, the combined treatment provided significantly more potent cognitive function enhancement in stroke mice, as compared with PFT-α single treatment. INTERPRETATION: Delayed combined sequential treatment with an inhibitor of p53 dependent apoptosis (PFT-α) and APP synthesis (posiphen) proved able to enhance stroke-induced endogenous neurogenesis and improve the functional recovery in stroke animals. Whereas the combined sequential treatment provided no further improvement in locomotor function, as compared with PFT-α alone treatment, suggesting a potential ceiling in the locomotion behavioral outcome in stroke animals, combined treatment more potently augmented cognitive function recovery after stroke.


Assuntos
Benzotiazóis/uso terapêutico , Neurogênese , Fisostigmina/análogos & derivados , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/fisiopatologia , Tolueno/análogos & derivados , Animais , Atrofia , Benzotiazóis/farmacologia , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Autorrenovação Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Cognição/efeitos dos fármacos , Quimioterapia Combinada , Ventrículos Laterais/patologia , Ventrículos Laterais/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Proteínas Associadas aos Microtúbulos/metabolismo , Atividade Motora/efeitos dos fármacos , Células-Tronco Neurais/efeitos dos fármacos , Células-Tronco Neurais/metabolismo , Neurogênese/efeitos dos fármacos , Fisostigmina/farmacologia , Fisostigmina/uso terapêutico , Recuperação de Função Fisiológica/efeitos dos fármacos , Esferoides Celulares/efeitos dos fármacos , Esferoides Celulares/metabolismo , Tolueno/farmacologia , Tolueno/uso terapêutico
14.
Adv Exp Med Biol ; 977: 205-213, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28685447

RESUMO

Over the past decade we have consistently shown that ketosis is neuroprotective against ischemic insults in rats. We reported that diet-induced ketotic rats had a significant reduction in infarct volume when subjected to middle cerebral artery occlusion (MCAO), and improved survival and recovery after cardiac arrest and resuscitation. The neuroprotective mechanisms of ketosis (via ketogenic diet; KG) include (i) ketones are alternate energy substrates that can restore energy balance when glucose metabolism is deficient and (ii) ketones modulate cell-signalling pathways that are cytoprotective. We investigated the effects of diet-induced ketosis following transient focal cerebral ischemia in mice. The correlation between levels of ketosis and hypoxic inducible factor-1alpha (HIF-1α), AKT (also known as protein kinase B or PKB) and 5' AMP-activated protein kinase (AMPK) were determined. Mice were fed with KG diet or standard lab-chow (STD) diet for 4 weeks. For the MCAO group, mice underwent 60 min of MCAO and total brain infarct volumes were evaluated 48 h after reperfusion. In a separate group of mice, brain tissue metabolites, levels of HIF-1α, phosphorylated AKT (pAKT), and AMPK were measured. After feeding a KG diet, levels of blood ketone bodies (beta-hydroxyburyrate, BHB) were increased. There was a proportional decrease in infarct volumes with increased blood BHB levels (KG vs STD; 4.2 ± 0.6 vs 7.8 ± 2.2 mm3, mean ± SEM). A positive correlation was also observed with HIF-1α and pAKT relative to blood BHB levels. Our results showed that chronic ketosis can be induced in mice by KG diet and was neuroprotective against focal cerebral ischemia in a concentration dependent manner. Potential mechanisms include upregulation of cytoprotective pathways such as those associated with HIF-1α, pAKT and AMPK.


Assuntos
Isquemia Encefálica/prevenção & controle , Dieta Cetogênica , Infarto da Artéria Cerebral Média/dietoterapia , Cetose/patologia , Animais , Isquemia Encefálica/etiologia , Modelos Animais de Doenças , Comportamento Alimentar/fisiologia , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Ataque Isquêmico Transitório/etiologia , Ataque Isquêmico Transitório/prevenção & controle , Cetose/etiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Fármacos Neuroprotetores
15.
Stroke ; 48(6): 1636-1645, 2017 06.
Artigo em Inglês | MEDLINE | ID: mdl-28487338

RESUMO

BACKGROUND AND PURPOSE: Because of the limitation in treatment window of the r-tPA (recombinant tissue-type plasminogen activator), the development of delayed treatment for stroke is needed. In this study, we examined the efficacy of delayed poststroke treatment (post 3-8 days) of the sonic hedgehog pathway agonist on functional recovery and the underlying mechanisms. METHODS: We evaluated functional recovery at 1 month after stroke using locomotion analysis and Barnes maze test for cognitive function. We used a genetically inducible neural stem cell-specific reporter mouse line (nestin-CreERT2-R26R-YFP) to label and track their proliferation, survival, and differentiation in ischemic brain. Brain tissue damage, angiogenesis, and cerebral blood flow recovery was evaluated using magnetic resonance imaging techniques and immunostaining. RESULTS: Our results show that delayed treatment of sonic hedgehog pathway agonist in stroke mice results in enhanced functional recovery both in locomotor function and in cognitive function at 1 month after stroke. Furthermore, using the Nestincre-ERT2-YFP mice, we showed that poststroke sonic hedgehog pathway agonist treatment increased surviving newly born cells derived from both subventricular zone and subgranular zone neural stem cells, total surviving DCX+ (Doublecortin) neuroblast cells, and neurons (NeuN+/YFP+) in the ischemic brain. Sonic hedgehog pathway agonist treatment also improved the brain tissue repair in ischemic region supported by our T2-weighted magnetic resonance imaging, cerebral blood flow map by arterial spin labeling, and immunohistochemistry (α-smooth muscle actin and CD31 immunostaining). CONCLUSIONS: These data confirm an important role for the hedgehog pathway in poststroke brain repair and functional recovery, suggesting a prolonged treatment window for potential treatment strategy to modulate sonic hedgehog pathway after stroke.


Assuntos
Isquemia Encefálica/tratamento farmacológico , Proteínas Hedgehog/agonistas , Proteínas Hedgehog/farmacologia , Neovascularização Fisiológica/efeitos dos fármacos , Neurogênese/efeitos dos fármacos , Recuperação de Função Fisiológica/efeitos dos fármacos , Acidente Vascular Cerebral/tratamento farmacológico , Animais , Comportamento Animal , Modelos Animais de Doenças , Proteína Duplacortina , Proteínas Hedgehog/administração & dosagem , Masculino , Aprendizagem em Labirinto , Camundongos , Camundongos Endogâmicos C57BL , Atividade Motora , Nestina , Células-Tronco Neurais
16.
Oncol Lett ; 11(3): 2075-2083, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26998125

RESUMO

Anterior gradient protein 2 (AGR2) has been reported as a novel biomarker with a potential oncogenic role. However, its association with the prognosis and survival rate of gastric cancer (GC) has not yet been determined. Therefore, the present study aimed to examine the expression and prognostic significance of AGR2 in patients with GC. Immunohistochemistry was used to analyze AGR2 and cathepsin D (CTSD) protein expression in 436 clinicopathologically characterized GC cases and 92 noncancerous tissue samples. AGR2 and CTSD expression were both elevated in GC lesions compared with noncancerous tissues. In 204/436 (46.8%) GC patients, high expression of AGR2 was positively correlated with the expression of CTSD (r=0.577, P<0.01). Furthermore, several clinicopathological parameters were significantly associated with AGR2 expression level, including tumor size, depth of invasion and TNM stage (P<0.05). Using Kaplan-Meier survival analysis, it was determined that the mean survival time of patients with low levels of AGR2 expression was significantly longer than those with high ARG2 expression (in stages I, II and III; P<0.05). For stage IV disease, no significant difference in survival time was identified. Multivariate survival analysis demonstrated that AGR2 was an independent prognostic factor and was associated in the progression of GC. The findings of the present study indicate that AGR2 expression is significantly associated with location and size of GC, depth of invasion, TNM stage, lymphatic metastasis, vessel invasion, distant metastasis, Lauren's classification, high CTSD expression and poor prognosis. Thus, AGR2 may be a novel GC marker and may present a potential therapeutic target for GC.

17.
J Clin Densitom ; 18(2): 198-202, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25937308

RESUMO

The aim of the study was to investigate the association between duration of playing video games and bone mineral density (BMD) in Chinese adolescents. Three hundred eighty-four Chinese adolescents aged 14-18 yr (148 males and 236 females) were analyzed. Anthropometric measurements were obtained using standard procedures. Total body and regional BMD were measured using dual-energy X-ray absorptiometry. Duration of playing video games, defined as hours per day, was measured by a self-report questionnaire. We examined the association between duration of playing video games and BMD using multiple linear regression analysis. After adjustment for age, sex, pubertal stage, parental education, body mass index, adolescents with longer video game duration were more likely to have lower legs, trunk, pelvic, spine, and total BMD (p < 0.05). We concluded that duration of video game was negatively associated with BMD in Chinese adolescents. These findings provide support for reducing duration of playing video games as a possible means to increase BMD in adolescents. Future research is needed to elucidate the underlined mechanisms linking playing video games and osteoporosis.


Assuntos
Densidade Óssea , Osso e Ossos/diagnóstico por imagem , Atividade Motora , Jogos de Vídeo/estatística & dados numéricos , Absorciometria de Fóton , Adolescente , China , Feminino , Humanos , Masculino , Ossos Pélvicos/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Inquéritos e Questionários , Tíbia/diagnóstico por imagem , Fatores de Tempo
18.
J Clin Densitom ; 18(1): 44-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-24815308

RESUMO

The purpose of the study was to investigate the associations of fat mass (FM) and fat distribution with bone mineral density (BMD) in Chinese obese population. Three hundred and forty-seven Chinese obese females and 339 males aged 20-39 years were analyzed. Lean mass (LM), FM, percent body fat (%BF), android FM, gynoid FM, and total and regional BMD were measured using dual-energy X-ray absorptiometry. Fat distribution was assessed by android-to-gynoid FM ratio (AOI). As a result, increased central body fat had an inverse association with total and leg BMD in females but not in males. Increased FM and %BF were positively associated with arm, trunk, and pelvic BMD in Chinese obese females. Increased FM was positively associated with total, rib, and trunk BMD in Chinese obese males. The results remained almost unchanged after adjusting for LM, and LM was significantly positively associated with spine BMD in female group. FM was positively associated with trunk BMD in male group after adjusting for LM. AOI was inversely associated with total and leg BMD, and %BF was positively associated with arm, trunk, and pelvic BMD when replacing FM with %BF in female group. The results remained almost unchanged after adjusting for LM. There is no significant association in male group when replacing FM with %BF. In conclusion, our findings demonstrate that there are different associations of FM and fat distribution with BMD, and AOI has a negative association with BMD.


Assuntos
Densidade Óssea , Obesidade , Osteoporose , Absorciometria de Fóton/métodos , Tecido Adiposo/metabolismo , Adulto , Distribuição da Gordura Corporal/métodos , Osso e Ossos/diagnóstico por imagem , China/epidemiologia , Feminino , Humanos , Masculino , Obesidade/complicações , Obesidade/epidemiologia , Obesidade/metabolismo , Osteoporose/diagnóstico , Osteoporose/epidemiologia , Osteoporose/etiologia , Osteoporose/metabolismo , Fatores de Risco , Estatística como Assunto
19.
Zhongguo Gu Shang ; 27(5): 379-84, 2014 May.
Artigo em Chinês | MEDLINE | ID: mdl-25167666

RESUMO

OBJECTIVE: To explore the efficacy and safety of zero-profile implant for anterior cervical discectomy and fusion (ACDF) in treating single cervical disc herniation. METHODS: From August 2011 to June 2012,30 patients with single cervical disc herniation were treated with ACDF using zero-profile implant in one motion segment. There were 18 males and 12 females with a mean age of 55.3 years old (ranged, 36 to 68). Incidence of dysphagia, height of intervertebral space and condition of bone fusion were observed after operation. Spinal nerves function and clinical results were assessed according to Japanese Orthopaedic Association (JOA) score, Odom criteria. RESULTS: All patients were followed up from 12 to 24 months with an average of 15.9 months. The mean intraoperative blood loss was (85.3 +/- 14.2) ml (70 to 120 ml) and operative time was (90.0 +/- 12.8) min (70 to 120 ml). Preoperative, postoperative at 3 months and 1 year, JOA score was 8.72 +/- 2.36 (5.0 to 13.0), 14.72 +/- 1.66 (11.5 to 17.0) and 15.65 +/- 1.03 (13.5 to 17.0), respectively. One year after operation, according Odom criteria to assess, 22 cases got excellent results, 7 good, 1 fair. All dysphagiaes vanished completely at 3 months after operation. The lost height of intervertebral space was (0.34 +/- 0.13) mm (0.1 to 0.6 mm) and (0.39 +/- 0.15) mm (0.2 to 0.7 mm) at 3, 12 months after operation, respectively. All patients obtained bone fusion at 1 year after operation. CONCLUSION: The zero-profile implant is a valid alternative to anterior cervical plate in treating single cervical disc herniation with ACDF, it has advantages of convenient procedure, satisfactory effect, lower incidence of postoperative dysphagia, reliable stability and less implant-related complications.


Assuntos
Vértebras Cervicais/cirurgia , Discotomia/métodos , Deslocamento do Disco Intervertebral/cirurgia , Próteses e Implantes , Adulto , Idoso , Discotomia/efeitos adversos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Segurança , Fusão Vertebral/efeitos adversos , Resultado do Tratamento
20.
Hear Res ; 309: 44-54, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24291808

RESUMO

Amino acids have important roles in the chemistry of the auditory system, including communication among neurons. There is much evidence for glutamate as a neurotransmitter from auditory nerve fibers to cochlear nucleus neurons. Previous studies in rodents have examined effects of removal of auditory nerve input by cochlear ablation on levels, uptake and release of glutamate in cochlear nucleus subdivisions, as well as on glutamate receptors. Effects have also been reported on uptake and release of γ-aminobutyrate (GABA) and glycine, two other amino acids strongly implicated in cochlear nucleus synaptic transmission. We mapped the effects of cochlear ablation on the levels of amino acids, including glutamate, GABA, glycine, aspartate, glutamine, taurine, serine, threonine, and arginine, in microscopic subregions of the rat cochlear nucleus. Submicrogram-size samples microdissected from freeze-dried brainstem sections were assayed for amino acid levels by high performance liquid chromatography. After cochlear ablation, glutamate and aspartate levels decreased by 2 days in regions receiving relatively dense innervation from the auditory nerve, whereas the levels of most other amino acids increased. The results are consistent with a close association of glutamate and aspartate with auditory nerve fibers and of other amino acids with other neurons and glia in the cochlear nucleus. A consistent decrease of GABA level in the lateral superior olive could be consistent with a role in some lateral olivocochlear neurons. The results are compared with those obtained with the same methods for the rat vestibular nerve root and nuclei after vestibular ganglionectomy.


Assuntos
Técnicas de Ablação , Aminoácidos/metabolismo , Cóclea/cirurgia , Núcleo Coclear/metabolismo , Núcleo Olivar/metabolismo , Animais , Ácido Aspártico/metabolismo , Vias Auditivas/metabolismo , Cromatografia Líquida de Alta Pressão , Ácido Glutâmico/metabolismo , Microdissecção , Ratos , Taurina/metabolismo , Fatores de Tempo
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