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1.
J Exp Clin Cancer Res ; 38(1): 183, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053148

RESUMO

BACKGROUND: Acquired resistance to sorafenib greatly limits its therapeutic efficiency in the treatment of hepatocellular carcinoma (HCC). Increasing evidence indicates that long noncoding RNAs (lncRNAs) play important roles in the resistance to anti-cancer drugs. The present study aims to explore the involvement of lncRNA SNHG1 (small nucleolar RNA host gene 1) in sorafenib resistance and how SNHG1 is associated with overexpressed microRNA-21 (miR-21) and the activated Akt pathway, which have been demonstrated to mediate this resistance in HCC cells. METHODS: Sorafenib-resistant HCC (SR-HCC) cells were generated and their sorafenib-resistant properties were confirmed by cell viability and apoptosis assays. Potential lncRNAs were screened by using multiple bioinformatics analyses and databases. The expression of genes and proteins was detected by qRT-PCR, Western blot and in situ hybridization. Gene silencing was achieved by specific siRNA or lncRNA Smart Silencer. The effects of anti-SNHG1 were evaluated in vitro and in experimental animals by using quantitative measures of cell proliferation, apoptosis and autophagy. The binding sites of miR-21 and SNHG1 were predicted by using the RNAhybrid algorithm and their interaction was verified by luciferase assays. RESULTS: The Akt pathway was highly activated by overexpressed miR-21 in SR-HCC cells compared with parental HCC cells. Among ten screened candidates, SNHG1 showed the largest folds of alteration between SR-HCC and parental cells and between vehicle- and sorafenib-treated cells. Overexpressed SNHG1 contributes to sorafenib resistance by activating the Akt pathway via regulating SLC3A2. Depletion of SNHG1 enhanced the efficacy of sorafenib to induce apoptosis and autophagy of SR-HCC cells by inhibiting the activation of Akt pathway. Sorafenib induced translocation of miR-21 to the nucleus, where it promoted the expression of SNHG1, resulting in upregulation of SLC3A2, leading to the activation of Akt pathway. In contrast, SNHG1 was shown to have little effect on the expression of miR-21, which downregulated the expression of PTEN, leading to the activation of the Akt pathway independently of SNHG1. CONCLUSIONS: The present study has demonstrated that lncRNA SNHG1 contributes to sorafenib resistance by activating the Akt pathway and its nuclear expression is promoted by miR-21, whose nuclear translocation is induced by sorafenib. These results indicate that SNHG1 may represent a potentially valuable target for overcoming sorafenib resistance for HCC.


Assuntos
Carcinoma Hepatocelular/genética , Cadeia Pesada da Proteína-1 Reguladora de Fusão/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , RNA Longo não Codificante/genética , Animais , Apoptose/efeitos dos fármacos , Autofagia/genética , Carcinoma Hepatocelular/patologia , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Camundongos , PTEN Fosfo-Hidrolase/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Interferente Pequeno/genética , Sorafenibe/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto
2.
Sci Rep ; 8(1): 17828, 2018 12 13.
Artigo em Inglês | MEDLINE | ID: mdl-30546125

RESUMO

In this study, we explored the effects of particulate matter 2.5 (PM2.5) eye drops on the ocular surface structure and tear function in mice and established a novel animal model for dry eye research. We found that, following treatment with PM2.5, the tear volume and, the tear film break-up time showed statistical differences at each time point (P < 0.05). The FL score of the PM2.5-treated group was higher than that of others (P < 0.05). The average number of corneal epithelial layer cells in groups A and B was significantly lower than that in group C (P < 0.05). Scanning electron microscopy and transmission electron microscopy revealed that the number of corneal epithelial microvilli and corneal desmosomes was drastically reduced in group C. PM2.5 induced apoptosis in the corneal superficial and basal epithelium and led to abnormal differentiation and proliferation of the ocular surface with higher expression levels of Ki67 and a reduced number of goblet cells in the conjunctival fornix in group C. PM2.5 significantly increased the levels of TNF-α, NF-κB p65 (phospho S536), and NF-κB in the cornea. Thus, the topical administration of PM2.5 in mice induces ocular surface changes that are similar to those of dry eye in humans, representing a novel model of dry eye.


Assuntos
Poluentes Atmosféricos/toxicidade , Proliferação de Células/efeitos dos fármacos , Síndromes do Olho Seco , Epitélio Anterior , Proteínas do Olho/biossíntese , Regulação da Expressão Gênica/efeitos dos fármacos , Material Particulado/toxicidade , Animais , Linhagem Celular Transformada , Modelos Animais de Doenças , Síndromes do Olho Seco/induzido quimicamente , Síndromes do Olho Seco/metabolismo , Síndromes do Olho Seco/patologia , Epitélio Anterior/metabolismo , Epitélio Anterior/ultraestrutura , Humanos , Camundongos , Camundongos Endogâmicos BALB C
3.
Endocr Pract ; 24(7): 658-667, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30048168

RESUMO

OBJECTIVE: It is uncertain whether there is an increased retinal vessel density in patients with thyroid-associated ophthalmology (TAO), or if ocular hemodynamic changes are associated with their vision. Many techniques have been applied to analyze ocular hemodynamic changes in TAO patients; however, they suffer from limitations. Optical coherence tomography angiography (OCTA) is more sensitive to hemodynamic changes. We performed OCTA to determine whether there is an increased retinal vessel density in TAO patients, and investigate associations with their vision. METHODS: Twenty TAO patients (right eye) and 20 normal controls (right eye) were recruited for the study. Three-dimensional OCTA images were generated with 6 × 6-mm angiographic OCT scans of the superficial retinal layer (SRL) and deeper retinal layer (DRL) of the macular retina for each eye. We calculated the microvascular (MIR) and macrovascular (MAR) densities and compared MIR, MAR, and total MIR (TMI) density in the healthy control and TAO groups separately. We used the annular partition (C1-C6) and quadrant partition method to analyze retinal vessel density alterations. Correlation analyses were used to examine the association of MIR density and visual acuity. RESULTS: In the SRL, STMI (superficial TMI) and SMIR (superficial MIR) density increased in the macular area of TAO patients ( P<.05). For the DRL, the density of DMIR (deeper MIR) increased in macular area only ( P<.05). However, with the annular partition method, TAO patients showed significantly increased SMIR density in the C1 and C2 regions ( P<.05), and increased DMIR density only in the C1 region ( P<.05). In the SRL, the correlation coefficient of the STMI/SMIR density in the TAO group was -0.538 ( r = -0.538, P = .032), and visual acuity was -0.624 ( r = -0.624, P = .010). CONCLUSION: OCTA findings suggest that active TAO patients present with an increased retinal MIR density. Moreover, increased macular STMI and SMIR density might affect visual acuity. ABBREVIATIONS: CDI = color Doppler imaging; DMIR = deeper MIR; DRL = deeper retinal layer; EDV = end diastolic velocity; FAZ = foveal avascular zone; GO = Graves ophthalmopathy; MAR = macrovascular; MIR = microvascular; OCT = optical coherence tomography; OCTA = optical coherence tomography angiography; RI = resistance index; ROC = receiver operating characteristic; SMIR = superficial MIR; SOV = superior ophthalmic vein; SRL = superficial retinal layer; SSADA = split-spectrum amplitude-decor-relation angiography; STMI = superficial TMI; TAO = thyroid-associated ophthalmology; TMI = total MIR.

4.
Am J Med Sci ; 355(6): 597-606, 2018 06.
Artigo em Inglês | MEDLINE | ID: mdl-29891043

RESUMO

BACKGROUND: This study aimed to determine whether erythropoietin could repair glucocorticoid-induced osteonecrosis of the femoral head after the systemic or local administration of recombinant human erythropoietin. MATERIALS AND METHODS: Gelatin microspheres were used to load recombinant human erythropoietin for local delivery. Forty-eight Wistar rats were included in the glucocorticoid-induced osteonecrosis of the femoral head model and randomly divided into the placebo, systemic erythropoietin and local erythropoietin groups. Eight weeks later, all rats were killed and their tissues were subjected to radiographic, histological, histometric, quantitative polymerase chain reaction and western blot analyses. RESULTS: Our results show that the use of recombinant human erythropoietin increased bone volume, trabecular number, trabecular thickness and trabecular separation compared with the placebo. Erythropoietin administration significantly improved the expression of runt-related transcription factor 2, alkaline phosphates, hypoxia-inducible factor-1α and vascular endothelial growth factor in the femoral head. We also found that the local injection of erythropoietin could better mediate hypoxia-inducible factor-1α-controlled osteogenic and angiogenic factor expression and better repair the glucocorticoid-induced osteonecrosis of the femoral head. CONCLUSIONS: The use of recombinant human erythropoietin exerted effects on improving the bone structures in glucocorticoid-induced osteonecrosis of the femoral head and up-regulated the expression of runt-related transcription factor 2, alkaline phosphates, hypoxia-inducible factor-1α and vascular endothelial growth factor. It provided a novel idea that erythropoietin administration could repair glucocorticoid-induced osteonecrosis of the femoral head by improving bone formation and angiogenesis and may be associated with the hypoxia-inducible factor-1α pathway. The sequential delivery of erythropoietin from gelatin microspheres seems worth recommending.

5.
Int J Mol Med ; 42(1): 71-80, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29568941

RESUMO

Bradykinin (BK) has been demonstrated to induce proliferation in several types of cell in ex vivo corneas. However, the mechanisms underlying the action of BK on corneal endothelial cells (CECs) remain largely unknown. The present study aimed to investigate the effect of BK on rabbit corneal endothelial cell (RCEC) proliferation, and assess the involvement of the zonula occludens­1(ZO­1)/ZO­1associated nucleic acid binding protein (ZONAB) pathway. Cell proliferation and cell cycle distribution was analyzed following treatment with BK (0.01, 0.1,1.0 or 10.0 µM) for the indicated time intervals (24, 48, 72 and 96 h), or following BK treatment combined with transfection of ZONAB­small interfering (si)RNA for 72 h. In addition, the expression of tight junction ZO­1, nuclear ZONAB, proliferating cell nuclear antigen(PCNA) and cyclin D1 were evaluated using western blotting or immunofluorescence. BK treatment was demonstrated to induce time­ and concentration­dependent cell proliferation and cell cycle progression, along with the upregulation of tight junction ZO­1 and nuclear ZONAB, as well as PCNA and cyclin D1 protein expression. Furthermore, knockdown with ZONAB­siRNA inhibited cell proliferation, induced cell cycle arrest and downregulated PCNA and cyclin D1 protein expression. ZONAB knockdown therefore successfully reversed the increase in proliferation induced by BK treatment. Taken together, these results suggested that BK stimulated RCEC proliferation, potentially via the ZO­1/ZONAB pathway. The signaling paradigm disclosed in the present study potentially serves as an important therapeutic target for cornea regeneration and transplantation.


Assuntos
Bradicinina/farmacologia , Proteínas de Ligação a DNA/metabolismo , Células Epiteliais/citologia , Epitélio Anterior/citologia , Proteína da Zônula de Oclusão-1/metabolismo , Animais , Ciclo Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Proliferação de Células/efeitos dos fármacos , Proteínas de Ligação a DNA/genética , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/genética , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/metabolismo , Técnicas de Silenciamento de Genes , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/metabolismo , Coelhos , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/metabolismo , Fatores de Tempo , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Proteína da Zônula de Oclusão-1/genética
6.
Int J Mol Med ; 41(3): 1427-1436, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29286080

RESUMO

In the present study, the effects of erlotinib on mouse tear function and corneal epithelial tissue structure were investigated. Throughout the 3 weeks of treatment, no notable differences were observed in the body, eye or lacrimal gland weights of the control and experimental mice. However, in the experimental group, the tear volume and break­up times of tear film were significantly lower following treatment with erlotinib compared with the control group. Corneal fluorescein staining in the experimental group revealed patchy staining, and the Lissamine green staining and inflammatory index were significantly higher in the experimental group at 3 weeks than in the control group. In the experimental group, the number of corneal epithelium layers increased significantly following treatment with erlotinib for 3 weeks and a significant increase in the number of vacuoles was observed compared with the control group. Treatment with erlotinib significantly increased the corneal epithelial cell apoptosis, and led to a significantly increased number of epithelial cell layers and increased keratin 10 expression. It also significantly reduced the number of conjunctival goblet cells. Transmission electron microscopy and scanning electron microscopy revealed that the corneal epithelial surface was irregular and there was a substantial reduction and partial loss of the microvilli in the experimental group. Mice treated with erlotinib also exhibited an increased protein expression of tumor necrosis factor­α and decreased protein expression of phosphorylated­epidermal growth factor receptor in the corneal epithelial cells. The topical application of erlotinib eye drops was revealed to induce dry eyes in mice. This is a novel method of developing a model of dry eyes in mice.


Assuntos
Síndromes do Olho Seco/induzido quimicamente , Cloridrato de Erlotinib/administração & dosagem , Cloridrato de Erlotinib/efeitos adversos , Soluções Oftálmicas/administração & dosagem , Administração Tópica , Animais , Contagem de Células , Córnea/efeitos dos fármacos , Córnea/patologia , Córnea/ultraestrutura , Modelos Animais de Doenças , Síndromes do Olho Seco/patologia , Fator de Crescimento Epidérmico/metabolismo , Epitélio/efeitos dos fármacos , Epitélio/patologia , Epitélio/ultraestrutura , Células Caliciformes/efeitos dos fármacos , Células Caliciformes/patologia , Inflamação/tratamento farmacológico , Masculino , Camundongos Endogâmicos BALB C , Fosforilação/efeitos dos fármacos , Lágrimas/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismo
7.
Mol Med Rep ; 17(2): 2187-2194, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29207076

RESUMO

To investigate the effects of catalpol on corneal neovascularization (CNV) and associated inflammation, eye drops (5 mM catalpol or PBS) were administered four times daily to alkali­burn rat models of CNV and inflammation. Clinical evaluations of CNV and the degree of inflammation were performed on days 0, 4, 7, 10 and 14 under slit lamp microscopy. Eyes were collected on day 14 and prepared for hematoxylin and eosin, and immunofluorescence staining; corneal cell apoptosis was investigated via terminal deoxynucleotidyl transferase­mediated nick end labeling (TUNEL) staining. Protein expression levels of angiogenic and proinflammatory factors, including vascular endothelial growth factor (VEGF), pigment epithelium­derived factor (PEDF), tumor necrosis factor­α (TNF­α) and necrosis factor­κB (NF­κB) were determined by western blotting. The effects of catalpol on cell proliferation were investigated in vitro using human umbilical vein endothelial cells (HUVECs) and a Cell Counting kit­8 (CCK­8); alterations in migration and tube formation were investigated via HUVEC wound closure and tube formation assays. HUVEC viability and proliferative ability were inhibited in a dose­dependent manner; catalpol also decreased HUVEC cell migration and tube forming ability. Within alkali­burn rat models, decreased inflammation and CNV was associated with catalpol administration; as demonstrated with TUNEL, corneal cell apoptosis was decreased in response to catalpol. Western blot analysis revealed reduced protein expression levels of VEGF and TNF­α; however, PEDF and phosphorylated­NF­κB p65 were increased due to catalpol administration. The present study demonstrated the inhibitory effects exerted by catalpol on CNV and inflammation within alkali­burned rat models. Topical application of catalpol in vivo was associated with reduced CNV and inflammation; therefore, catalpol may be considered an anti­inflammatory agent for the clinical treatment of CNV.


Assuntos
Inibidores da Angiogênese/farmacologia , Neovascularização da Córnea/patologia , Glucosídeos Iridoides/farmacologia , Animais , Apoptose/efeitos dos fármacos , Queimaduras Químicas , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular , Neovascularização da Córnea/tratamento farmacológico , Neovascularização da Córnea/metabolismo , Modelos Animais de Doenças , Proteínas do Olho/genética , Proteínas do Olho/metabolismo , Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , NF-kappa B/metabolismo , Fatores de Crescimento Neural/genética , Fatores de Crescimento Neural/metabolismo , Ratos , Serpinas/genética , Serpinas/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
8.
Expert Rev Gastroenterol Hepatol ; 12(1): 1-8, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28847184

RESUMO

BACKGROUND: Sorafenib remains the only standard first-line drug for advanced hepatocellular carcinoma (HCC). Hand-foot skin reaction (HFSR) is a very common side-effect in patients treated with sorafenib, and also affects the treatment schedule and quality of life. However, the association of HFSR and response of HCC to sorafenib remain unclear. METHODS: Databases including PubMed, EMBASE, Web of Science and Cochrane Central Register of Controlled Trials were searched up to May 7th, 2017. Review Manager 5.3 software was adopted for performing meta-analyses, Newcastle-Ottawa Scale for assessing the bias of cohort studies, and GRADEprofler software for further assessing outcomes obtained from meta-analyses. RESULTS: 1478 articles were reviewed, and 12 cohort studies with 1017 participants were included in the analyses. The pooled hazard ratio (HR) of overall survival is 0.45 (95% confidence interval (CI) 0.36, 0.55; P < 0.00001; I2 = 35%). The pooled HR of time to progression is 0.41 (95% CI 0.28, 0.60; P < 0.00001; I2 = 0%). Patients suffering HFSR had significantly better outcomes from sorafenib therapy than those without HFSR. CONCLUSIONS: The results indicate that HFSR is a beneficial indicator for HCC patients receiving sorafenib therapy. However, molecular mechanisms accounting for sorafenib-induced HFSR in HCC patients remain.


Assuntos
Antineoplásicos/efeitos adversos , Carcinoma Hepatocelular/tratamento farmacológico , Síndrome Mão-Pé/etiologia , Neoplasias Hepáticas/tratamento farmacológico , Niacinamida/análogos & derivados , Compostos de Fenilureia/efeitos adversos , Distribuição de Qui-Quadrado , Progressão da Doença , Síndrome Mão-Pé/diagnóstico , Humanos , Niacinamida/efeitos adversos , Razão de Chances , Qualidade de Vida , Fatores de Risco , Sorafenibe , Resultado do Tratamento
9.
J Int Med Res ; 46(1): 392-402, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28679330

RESUMO

Objective To investigate the underlying functional network brain-activity changes in patients with adult comitant exotropia strabismus (CES) and the relationship with clinical features using the voxel-wise degree centrality (DC) method. Methods A total of 30 patients with CES (17 men, 13 women), and 30 healthy controls (HCs; 17 men, 13 women) matched in age, sex, and education level participated in the study. DC was used to evaluate spontaneous brain activity. Receiver operating characteristic (ROC) curve analysis was conducted to distinguish CESs from HCs. The relationship between mean DC values in various brain regions and behavioral performance was examined with correlation analysis. Results Compared with HCs, CES patients exhibited decreased DC values in the right cerebellum posterior lobe, right inferior frontal gyrus, right middle frontal gyrus and right superior parietal lobule/primary somatosensory cortex (S1), and increased DC values in the right superior temporal gyrus, bilateral anterior cingulate, right superior temporal gyrus, and left inferior parietal lobule. However, there was no correlation between mean DC values and behavioral performance in any brain regions. Conclusions Adult comitant exotropia strabismus is associated with abnormal brain network activity in various brain regions, possibly reflecting the pathological mechanisms of ocular motility disorders in CES.


Assuntos
Exotropia/diagnóstico por imagem , Rede Nervosa/diagnóstico por imagem , Lobo Parietal/diagnóstico por imagem , Estrabismo/diagnóstico por imagem , Lobo Temporal/diagnóstico por imagem , Adulto , Mapeamento Encefálico , Estudos de Casos e Controles , Cerebelo/diagnóstico por imagem , Cerebelo/fisiopatologia , Exotropia/fisiopatologia , Feminino , Giro do Cíngulo/diagnóstico por imagem , Giro do Cíngulo/fisiopatologia , Humanos , Imagem por Ressonância Magnética , Masculino , Rede Nervosa/fisiopatologia , Lobo Parietal/fisiopatologia , Curva ROC , Estrabismo/fisiopatologia , Lobo Temporal/fisiopatologia
10.
Biomed Pharmacother ; 96: 524-534, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-29032336

RESUMO

AIM: To introduce a novel dry eye mouse model induced by topical administration of the air pollutant particulate matter 10 (PM10). METHOD: A total of 60 male BALB/c mice were used in this study and divided into two groups: group A (PBS eye drops, n=30) and group B (PM10 eye drop group, n=30). Each treatment was dosed four times a day, every time 50ul with the concentration of 5mg/ml PM10, for 14 consecutive days in the right eye. The clinical manifestations of dry eye were measured before therapy and 4, 7 and 14days post-treatment respectively, which included the tear volume, tear break-up (BUT) time, corneal fluorescein staining, rose bengal staining, Lissamine Green staining and inflammatory index. Eye samples were collected on D14 and examined by histologic light microscopy, transmission electron microscopy (TEM) and scanning electron microscopy (SEM), corneal cytokeration 10 (K10) immunnostaining, and tumor necrosis factor-α (TNF-α), NF-κB-p65 and NF-κB Western Blot analysis. RESULTS: At 0d, 7d and 14d, there were no statistical changes in tear volume, BUT after treatment (P>0.05) with PBS in group A. In group B, all items showed statistical differences at each time point (P<0.05). At 14d after therapy, the fluorescein staining score of group B was higher than group A (P<0.05). The score of rose bengal staining and Lissamine Green staining in group B was also higher than that in group A (P<0.05). The number of mean layers of corneal epithelial cells in the group A was significantly lower than that in the group B (P<0.05). TEM and SEM revealed that the number of corneal epithelial microvilli were drastically reduced in group B. The number of corneal chondriosome/desmosomes was also reduced in group B by TEM. PM10 induced apoptosis in the superficial and basal corneal epithelium, and leaded to abnormal differentiation and proliferation of the ocular surface with higher expression levels of K10 and reduced number of goblet cells in the conjunctival fornix in group B. PM10 significantly increased the levels of TNF-α, NF-κB-p65 and NF-κB in the cornea. CONCLUSION: PM10 can damage the tear film function and cause the destruction of the structural organization of ocular surface in mice. Topical administration of PM10 in mice induces ocular surface changes that are similar to those of dry eye in humans, representing a novel model of DES.


Assuntos
Poluentes Atmosféricos/toxicidade , Modelos Animais de Doenças , Síndromes do Olho Seco/induzido quimicamente , Síndromes do Olho Seco/patologia , Material Particulado/toxicidade , Administração Tópica , Animais , Linhagem Celular Transformada , Córnea/efeitos dos fármacos , Córnea/patologia , Córnea/ultraestrutura , Relação Dose-Resposta a Droga , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Material Particulado/administração & dosagem , Lágrimas/efeitos dos fármacos
11.
Endocrine ; 57(2): 326-334, 2017 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-28620866

RESUMO

PURPOSE: To investigate the characteristics of difficult intubation and identify novel efficient predictors in patients with acromegaly. METHODS: Patients with either untreated acromegaly or non-functional pituitary adenomas were enrolled. Patients with acromegaly underwent hormone assays, upper airway computed tomography and magnetic resonance imaging examinations and preoperative overnight polysomnography. The modified Mallampati classification, mouth opening, neck circumference, and neck extension were assessed, and the Cormack-Lehane grades and the time of tracheal intubation were recorded. RESULTS: Patients with acromegaly had a higher incidence of difficult intubation (62.5%). The time of tracheal intubation was prolonged, the neck circumference was enlarged, and the neck extension was confined. In patients with acromegaly and difficult intubation, the insulin-like growth factor 1 levels and apnea/hypoxia index were significantly higher compared to patients without difficult intubation (1115.40 ± 253.73 vs. 791.67 ± 206.62 ng/ml, P = 0.020; 22.17 ± 23.25 vs. 2.47 ± 2.84, P = 0.026, respectively). The bilateral regression analysis revealed that high levels of insulin-like growth factor 1 were an independent risk factor for developing difficult intubation (p = 0.042, Exp B = 1.006). The modified Mallampati classification was positively correlated with apnea/hypoxia index and could be calculated using the following logarithmic equation: MMC = 0.2982 * ln (AHI) + 2.1836. CONCLUSIONS: In patients with acromegaly, neck movement is confined, the time of tracheal intubation is prolonged, and the neck circumference is enlarged, and these patients suffer from an increased incidence of difficult intubation (62.5%) during anesthesia induction. The apnea/hypoxia index and insulin-like growth factor 1 levels are both increased in acromegalic patients with difficult intubation, and elevated insulin-like growth factor 1 levels are an independent risk factor of difficult intubation in acromegalic patients.


Assuntos
Acromegalia/sangue , Acromegalia/complicações , Manuseio das Vias Aéreas/métodos , Fator de Crescimento Insulin-Like I/análise , Intubação Intratraqueal , Adolescente , Adulto , Idoso , Anestesia/métodos , Apneia/fisiopatologia , Feminino , Adenoma Hipofisário Secretor de Hormônio do Crescimento/metabolismo , Humanos , Hipóxia/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Pescoço/anatomia & histologia , Pescoço/diagnóstico por imagem , Polissonografia , Valor Preditivo dos Testes , Estudos Prospectivos , Fatores de Risco , Tomografia Computadorizada por Raios X , Traqueia/diagnóstico por imagem , Adulto Jovem
12.
Sensors (Basel) ; 17(3)2017 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-28304336

RESUMO

Grassland fire is one of the most important disturbance factors of the natural ecosystem. Climate factors influence the occurrence and development of grassland fire. An analysis of the climate conditions of fire occurrence can form the basis for a study of the temporal and spatial variability of grassland fire. The purpose of this paper is to study the effects of monthly time scale climate factors on the occurrence of grassland fire in HulunBuir, located in the northeast of the Inner Mongolia Autonomous Region in China. Based on the logistic regression method, we used the moderate-resolution imaging spectroradiometer (MODIS) active fire data products named thermal anomalies/fire daily L3 Global 1km (MOD14A1 (Terra) and MYD14A1 (Aqua)) and associated climate data for HulunBuir from 2000 to 2010, and established the model of grassland fire climate index. The results showed that monthly maximum temperature, monthly sunshine hours and monthly average wind speed were all positively correlated with the fire climate index; monthly precipitation, monthly average temperature, monthly average relative humidity, monthly minimum relative humidity and the number of days with monthly precipitation greater than or equal to 5 mm were all negatively correlated with the fire climate index. We used the active fire data from 2011 to 2014 to validate the fire climate index during this time period, and the validation result was good (Pearson's correlation coefficient was 0.578), which showed that the fire climate index model was suitable for analyzing the occurrence of grassland fire in HulunBuir. Analyses were conducted on the temporal and spatial distribution of the fire climate index from January to December in the years 2011-2014; it could be seen that from March to May and from September to October, the fire climate index was higher, and that the fire climate index of the other months is relatively low. The zones with higher fire climate index are mainly distributed in Xin Barag Youqi, Xin Barag Zuoqi, Zalantun Shi, Oroqen Zizhiqi, and Molidawa Zizhiqi; the zones with medium fire climate index are mainly distributed in Chen Barag Qi, Ewenkizu Zizhiqi, Manzhouli Shi, and Arun Qi; and the zones with lower fire climate index are mainly distributed in Genhe Shi, Ergun city, Yakeshi Shi, and Hailar Shi. The results of this study will contribute to the quantitative assessment and management of early warning and forecasting for mid-to long-term grassland fire risk in HulunBuir.

13.
Sensors (Basel) ; 17(3)2017 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-28241476

RESUMO

Grassland, as one of the most important ecosystems on Earth, experiences fires that affect the local ecology, economy and society. Notably, grassland fires occur frequently each year in northeastern China. Fire occurrence is a complex problem with multiple causes, such as natural factors, human activities and land use. This paper investigates the disruptive effects of grassland fire in the northeastern Inner Mongolia Autonomous Region of China. In this study, we relied on thermal anomaly detection from the Moderate Resolution Imaging Spectroradiometer (MODIS) sensor to identify fire occurrences, and land use data were acquired by Landsat Thematic Mapper/Enhanced Thematic Mapper (TM/ETM). We discussed the relationship between land use and the spatial distribution of grassland fires. The results showed that the impact of land use on grassland fires was significant. Spatially, approximately 80% of grassland fires were clustered within 10 km of cultivated land, and grassland fires generally occurred in areas of intense human activity. The correlation between the spatial distribution of grassland fires and the land use degree in 2000, 2005 and 2010 was high, with R² values of 0.686, 0.716, 0.633, respectively (p < 0.01). These results highlight the importance of the relationship between land use and grassland fire occurrence in the northeastern Inner Mongolia Autonomous Region. This study provides significance for local fire management and prevention.

14.
Mol Oncol ; 11(3): 320-334, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28164434

RESUMO

Sorafenib displays a limited efficacy for advanced hepatocellular carcinoma (HCC). Some patients with HCC initially respond to sorafenib, but eventually succumb to the disease, indicating that the acquired resistance to sorafenib reduces its beneficial effects. No alternative drugs are available after the failure of sorafenib therapy. Therefore, investigation of the mechanisms underlying the acquired resistance and development of second-line treatments for sorafenib-resistant HCC are urgently required. In this study, sorafenib-resistant HCC cells generated from sorafenib-sensitive human HCC cells were shown to overproduce hepatocyte growth factor (HGF) and overexpress c-Met kinase and its phosphorylated form, leading to the activation of Akt and ERK (extracellular signaling-regulated kinase) pathways. Use of specific c-Met inhibitors enhanced the effects of sorafenib by inhibiting the growth of sorafenib-resistant HCC cells. Akt inhibitors, a class of second-line therapeutic drugs under investigation for treating HCC in clinical trials, enhanced the effects of sorafenib, but also activated the c-Met pathway in sorafenib-resistant cells. Dual inhibition of Akt and c-Met by their respective inhibitors, MK2206 and capmatinib, additively or synergistically suppressed sorafenib-resistant HCC cells in vitro and sorafenib-resistant HCC xenografts in mice. The anticancer activities of MK2206 mainly rely on its ability to induce cell apoptosis and autophagic death, while capmatinib treatment leads to cell cycle arrest at phase G1. These results provide strong evidence for further investigation on the clinical utility of dual inhibition of Akt and c-Met, particularly MK2206 and capmatinib, as a second-line therapy for advanced HCC that has acquired resistance to sorafenib.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Fígado/efeitos dos fármacos , Niacinamida/análogos & derivados , Compostos de Fenilureia/uso terapêutico , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-met/antagonistas & inibidores , Animais , Antineoplásicos/farmacologia , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Células Hep G2 , Humanos , Fígado/metabolismo , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Niacinamida/farmacologia , Niacinamida/uso terapêutico , PTEN Fosfo-Hidrolase/metabolismo , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-met/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sorafenibe
15.
Science ; 355(6329): 1062-1066, 2017 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-28183998

RESUMO

Passive radiative cooling draws heat from surfaces and radiates it into space as infrared radiation to which the atmosphere is transparent. However, the energy density mismatch between solar irradiance and the low infrared radiation flux from a near-ambient-temperature surface requires materials that strongly emit thermal energy and barely absorb sunlight. We embedded resonant polar dielectric microspheres randomly in a polymeric matrix, resulting in a metamaterial that is fully transparent to the solar spectrum while having an infrared emissivity greater than 0.93 across the atmospheric window. When backed with a silver coating, the metamaterial shows a noontime radiative cooling power of 93 watts per square meter under direct sunshine. More critically, we demonstrated high-throughput, economical roll-to-roll manufacturing of the metamaterial, which is vital for promoting radiative cooling as a viable energy technology.

16.
J Vasc Surg ; 65(2): 501-508.e1, 2017 02.
Artigo em Inglês | MEDLINE | ID: mdl-26781077

RESUMO

OBJECTIVE: Infrarenal aortic cross-clamping (IAC) is a common procedure during infrarenal vascular operations. It often causes ischemia-reperfusion injury to lower limbs, resulting in systemic inflammation response and damage to remote organs (particularly lungs). Hydrogen sulfide (H2S) is a gaseous mediator that has been shown to have a protective effect against lung injury. METHODS: Wistar rats underwent IAC for 2 hours, followed by 4 hours of reperfusion. GYY4137 (a slow-releasing H2S donor) and dl-propargylglycine (PAG, an inhibitor of cystathionine γ-lyase) were preadministered to rats 1 hour before IAC, and their effects on severity of lung injury and related mechanisms were investigated. RESULTS: IAC induced a significant increase in plasma levels of H2S, H2S-synthesizing activity, and cystathionine γ-lyase expression in lung tissues compared with sham operation. Administration of GYY4137 significantly increased the levels of H2S but had little effect on H2S-synthesizing activity, whereas PAG reduced H2S levels and H2S-synthesizing activity. Preadministration of GYY4137 significantly attenuated acute lung injury induced by IAC, evidenced by reduced histologic scores and wet lung contents; improved blood gas parameters; reduced cell counts and protein amounts in bronchoalveolar lavage fluids; and reduced myeloperoxidase activity in lung tissues and plasma levels of tumor necrosis factor α, interleukin 6, and interleukin 1ß. However, PAG further aggravated the severity of lung injury and displayed opposite effects to GYY4137. In exploration of the mechanisms, we found that IAC increased the release of angiopoietin 2 (Ang2) and its expression in lung tissues. GYY4137 attenuated the increase of Ang2 release and expression and increased the phosphorylation of Akt and the activation of its downstream factors, glycogen synthase kinase 3ß and ribosomal protein S6 kinase; PAG showed opposite effects. CONCLUSIONS: The study indicates that H2S may play a protective role in IAC-induced acute lung injury in rats by inhibiting inflammation and Ang2 release.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Angiopoietina-2/metabolismo , Anti-Inflamatórios/farmacologia , Aorta Abdominal/cirurgia , Sulfeto de Hidrogênio/farmacologia , Pulmão/efeitos dos fármacos , Morfolinas/farmacologia , Compostos Organotiofosforados/farmacologia , Pneumonia/prevenção & controle , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Alquinos/farmacologia , Animais , Anti-Inflamatórios/metabolismo , Constrição , Cistationina gama-Liase/antagonistas & inibidores , Cistationina gama-Liase/metabolismo , Citoproteção , Modelos Animais de Doenças , Regulação para Baixo , Inibidores Enzimáticos/farmacologia , Glicina/análogos & derivados , Glicina/farmacologia , Sulfeto de Hidrogênio/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Liases/metabolismo , Masculino , Morfolinas/metabolismo , Compostos Organotiofosforados/metabolismo , Pneumonia/etiologia , Pneumonia/metabolismo , Pneumonia/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos Wistar
17.
Chemosphere ; 169: 162-170, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27875717

RESUMO

The co-combustion of sludge (sewage and dredged sludge) with rice husk is expected to become a trend because of its economic and environmental benefits. However, the massive residues from the co-combustion process and the mobility of heavy metals (HMs) warrant special attention. The basic performance and environmental properties of the trace elements (Cr, Cu, Fe, Mn, Ba and Zn) from the co-combustion ashes were studied to promote the further utilization of these materials. These ashes have a shell particle shape, high specific area, high amorphous content and low crystalline phase content. The investigation mainly focused on the environmental properties of these ashes to evaluate the risk of these by-products to the environment. Results show Cu, Mn, and Zn have cumulative leaching concentrations of 1.033, 23.32, and 3.363 mg/L for W, by contrast, Cr, Cu, Fe, Mn, Ba, and Zn have cumulative leaching concentrations of 0.488, 0.296, 8.069, 10.44, 2.568, and 2.691 mg/L for H, which are much greater than the Chinese ground water standard (GB/T14848-93). Meanwhile Mn, Zn, Ba, Cr, and Fe all pose a very high risk for H, while Cu only poses a medium risk, and all HMs in W exhibit much lower contamination levels than those in H by the method of risk assessment code (RAC). It indicates that these ashes have undesirably high levels of HMs that demonstrate high mobility and pose environmental risks according to their leachability and chemical speciation. And the HMs in W show lower mobility and environmental hazards than those in H.


Assuntos
Monitoramento Ambiental , Poluentes Ambientais/análise , Incineração , Metais Pesados/análise , Oryza/química , Esgotos/química , Metais Pesados/química , Medição de Risco
18.
Chin Med Sci J ; 31(2): 107-115, 2016 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-28031099

RESUMO

Objective To determine whether the myotoxic side effects of statin simvastatin affect skeletal muscle's sensitivity to caffeine and halothane.Methods Primary cultured neonate rat skeletal myotubes were treated with 0.01-5.0 µmol/L simvastatin for 48 hours. MTT was used to evaluate cellular viability. The gross morphology and microstructure of the myotubes were observed with a light and electron microscope, respectively. The intracellular calcium concentrations ([Ca2+]i) at rest and in response to caffeine and halothane were investigated by fluorescence calcium imaging. Data were analyzed by analysis of variance (ANOVA) test.Results Simvastatin (0.01-5.0 µmol/L) decreased myotube viability, changed their morphological features and microstructure, and increased the resting [Ca2+]i in a dose-dependent manner. Simvastatin did not change myotube's sensitivity to low doses of caffeine (0.625-2.5 mmol/L) or halothane (1.0-5.0 mmol/L). In response to high-dose caffeine (10.0 mmol/L, 20.0 mmol/L) and halothane (20.0 mmol/L, 40.0 mmol/L), myotubes treated with 0.01 µmol/L simvastatin showed a significant increase in sensitivity, but those treated with 1.0 µmol/L and 5.0 µmol/L simvastatin showed a significant decrease. The sarcoplasmic reticulum Ca2+ storage peaked in the myotubes treated with 0.01 µmol/L simvastatin, but it decreased when cells were treated with higher doses of simvastatin (0.1-5.0 µmol/L).Conclusions The myotoxic side effect of simvastatin was found to change the sensitivity of myotubes in response to high-dose caffeine and halothane. When dose was low, sensitivity increased mainly because of increased Ca2+ content in the sarcoplasmic reticulum, which might explain why some individuals with statin-induced myotoxic symptoms may show positive caffeine-halothane contracture test results. However, when the dose was high and the damage to the myotubes was severer, sensitivity was lower. It is here supposed that the damage itself might put individuals with statin-induced myotoxic symptoms at greater risks of presenting with rhabdomyolysis during surgery or while under anesthesia.


Assuntos
Músculo Esquelético , Animais , Cafeína , Cálcio , Relação Dose-Resposta a Droga , Halotano , Ratos , Sinvastatina
19.
Oncotarget ; 7(45): 73257-73269, 2016 11 08.
Artigo em Inglês | MEDLINE | ID: mdl-27689326

RESUMO

Sorafenib resistance remains a major obstacle for the effective treatment of hepatocellular carcinoma (HCC), and a number of miRNAs contribute to this resistance. However, the regulatory networks of miRNAs are very complex, thus inhibiting a single miRNA may sequentially activate other compensatory pathways. In the present study, we generated an artificial long non-coding RNA (AlncRNA), which simultaneously targets multiple miRNAs including miR-21, miR-153, miR-216a, miR-217, miR-494 and miR-10a-5p. These miRNAs have been shown to be upregulated in sorafenib-resistant cells and participate in the mechanisms underlying sorafenib resistance. The AlncRNA contains tandem sequences of 6 copies of the complementary binding sequences to the target miRNAs and is expressed by an adenoviral vector (Ad5-AlncRNA). Infection of Ad5-AlncRNA into sorafenib-resistant HCC cells blocked the function of miRNAs, and sequentially inhibited the downregulation of PTEN and activation of AKT. Ad5-AlncRNA significantly inhibited proliferation and induced apoptosis of sorafenib-resistant cells and enhanced the effects of sorafenib in vitro and in animal models. Inhibition of autophagy decreased the sensitivity of sorafenib-resistant cells to Ad5-AlncRNA, while its induction had the opposite effect. These results indicate that targeting multiple miRNAs by the artificial lncRNA could be a potential promising strategy for overcoming sorafenib resistance in the treatment of HCC.


Assuntos
Antineoplásicos/farmacologia , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/genética , Niacinamida/análogos & derivados , Compostos de Fenilureia/farmacologia , Inibidores de Proteínas Quinases/farmacologia , Interferência de RNA , RNA Longo não Codificante/genética , Adenoviridae/genética , Animais , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Modelos Animais de Doenças , Vetores Genéticos/genética , Humanos , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Niacinamida/farmacologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sorafenibe , Ensaios Antitumorais Modelo de Xenoenxerto
20.
Neuropsychiatr Dis Treat ; 12: 2015-20, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27570455

RESUMO

OBJECTIVE: The aim of this study was to evaluate altered spontaneous brain activities in patients with unilateral acute open globe injury (OGI) using amplitude of low-frequency fluctuation (ALFF) method and its relationship with their clinical manifestations. PATIENTS AND METHODS: A total of 18 patients with acute OGI (16 males and two females) and 18 healthy controls (HCs, 16 males and two females) closely matched in age, sex, and education were recruited in this study. The ALFF method was used to evaluate the altered spontaneous brain activities. The relationships between the mean ALFF signal values of different brain regions and the clinical features were evaluated by correlation analysis. Acute OGI patients were distinguished from HCs by receiver operating characteristic curve. RESULTS: Compared with HCs, acute OGI patients had significantly higher ALFF values in the left cuneus, left middle cingulum cortex, and bilateral precuneus. Furthermore, the age of OGI patients showed a negative correlation with the ALFF signal value of the left middle cingulum cortex (r=-0.557, P=0.016) and a negative correlation with the mean ALFF signal value of the bilateral precuneus (r=-0.746, P<0.001). The ALFF signal value of the bilateral precuneus was negatively correlated with the duration of OGI (r=-0.493, P=0.038) and positively correlated with the vision acuity of the injured eye (r=0.583, P=0.011). CONCLUSION: Acute OGI mainly induces dysfunction in the left cuneus, left middle cingulum cortex, and bilateral precuneus, which may reflect the underlying pathologic mechanisms of abnormal brain activities in OGI patients.

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