排序方式: 共有78条查询结果,搜索用时 31 毫秒
31.
Camilli TC Xu M O'Connell MP Chien B Frank BP Subaran S Indig FE Morin PJ Hewitt SM Weeraratna AT 《Pigment cell & melanoma research》2011,24(1):175-186
We have previously shown that Wnt5A-mediated signaling can promote melanoma metastasis. It has been shown that Wnt signaling is antagonized by the protein Klotho, which has been implicated in aging. We show here that in melanoma cells, expressions of Wnt5A and Klotho are inversely correlated. In the presence of recombinant Klotho (rKlotho), we show that Wnt5A internalization and signaling is decreased in high Wnt5A-expressing cells. Moreover, in the presence of rKlotho, we observe an increase in Wnt5A remaining in the medium, coincident with an increase in sialidase activity, and decrease in syndecan expression. These effects can be inhibited using a sialidase inhibitor. In addition to its effects on Wnt5A internalization, we also demonstrate that Klotho decreases melanoma cell invasive potential by a second mechanism that involves the inhibition of calpain and a resultant decrease in filamin cleavage, which we demonstrate is critical for melanoma cell motility. 相似文献
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Lee SH Tura A Mari A Ko SH Kwon HS Song KH Yoon KH Lee KW Ahn YB 《American journal of physiology. Endocrinology and metabolism》2011,301(5):E984-E990
Improved glucose tolerance following a sequential meal is known as the second-meal phenomenon. We aimed to investigate its extent and underlying mechanisms in patients with type 2 diabetes. Metabolic responses after lunch in 12 diabetic patients were compared on two separate days: one with (Day BL) and another without (Day FL) breakfast. The responses of hormones were calculated by the incremental area under the curve (iAUC) values for 180 min after each meal. Indexes of early-phase insulin secretion were assessed, and β-cell function was estimated by mathematical modeling. [iAUC(glucose(180-360 min))] was significantly lower on Day BL than on Day FL (181 ± 43 vs. 472 ± 29 mmol·liter(-1)·min, P = 0.0005). The magnitude of the The second-meal phenomenon [iAUC(glucose(180-360 min)) on Day BL/Day FL] was 35 ± 9%. The peak levels of insulin and C-peptide were attained 45 min earlier after the second meal than after the first meal. iAUC(glucose(180-360 min)) correlated negatively with iAUC(insulin(180-210 min)) (r = -0.443, P = 0.0300), insulinogenic index (r = -0.769, P < 0.0001), acute C-peptide response (r = -0.596, P = 0.0021), and potentiation factor [i.e., potentiation effect on insulin secretion] ratio (180-360)/(0-20) (r = -0.559, P = 0.0045), while correlated positively with free fatty acid level before lunch (r = 0.679, P = 0.0003). The second-meal phenomenon was evident in patients with type 2 diabetes. Potentiation of the early-phase insulin response by a prior meal contributes to this phenomenon in type 2 diabetes. 相似文献
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Background
Ethiopia is among the countries with the highest neonatal mortality with the rate of 37 deaths per 1000 live births. In spite of many efforts by the government and other partners, non-significant decline has been achieved in the last 15 years. Thus, identifying the determinants and causes are very crucial for policy and program improvement. However, studies are scarce in the country in general and in Jimma zone in particular.Objective
To identify the determinants and causes of neonatal mortality in Jimma Zone, Southwest Ethiopia.Methods
A prospective follow-up study was conducted among 3463 neonates from September 2012 to December 2013. The data were collected by interviewer-administered structured questionnaire and analyzed by SPSS V.20.0 and STATA 13. Verbal autopsies were conducted to identify causes of neonatal death. Mixed-effects multilevel logistic regression model was used to identify determinants of neonatal mortality.Results
The status of neonatal mortality rate was 35.5 (95%CI: 28.3, 42.6) per 1000 live births. Though significant variation existed between clusters in relation to neonatal mortality, cluster-level variables were found to have non-significant effect on neonatal mortality. Individual-level variables such as birth order, frequency of antenatal care use, delivery place, gestation age at birth, premature rupture of membrane, complication during labor, twin births, size of neonate at birth and neonatal care practice were identified as determinants of neonatal mortality. Birth asphyxia (47.5%), neonatal infections (34.3%) and prematurity (11.1%) were the three leading causes of neonatal mortality accounting for 93%.Conclusions
This study revealed high status of neonatal mortality in the study area. Higher-level variables had less importance in determining neonatal mortality. Individual level variables related to care during pregnancy, intra-partum complications and care, neonatal conditions and the immediate neonatal care practices were identified as determinant factors. Improving antenatal care, intra-partum care and immediate neonatal care are recommended. 相似文献34.
Ozensoy O Arslan O Kockar F 《Journal of enzyme inhibition and medicinal chemistry》2008,23(4):579-585
Hypoxia is a common characteristic of locally advanced solid tumors that has been associated with diminished therapeutic response and malignant progression. Human carbonic anhydrase (hCA) hCA IX and XII isozymes are tumor associated isoforms which contribute to acidification of the tumor environment by catalyzing the hydration of carbon dioxide to bicarbonate and protons.In the present study our goal was to investigate the inhibition effects of 15 different antibiotics belonging to the following classes: Lactams, cephalosporins, macrolides etc., on the tumor associated carbonic anhydrase isozymes hCA-IX, hCA-XII and cytosolic carbonic anhydrase hCA-I and hCA-II. 相似文献
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Expression of P21(WAF1/CIP1/SID1) cyclin-dependent kinase inhibitor in hematopoietic progenitor cells 总被引:5,自引:0,他引:5
Campanini F Santucci MA Brusa G Pattacini L Arpinati M Rondelli D Gamberi B Barbieri E Babini L Tura S 《Gene》2001,273(2):173-180
P21(Waf1/Cip1/Sid1) is a critical component of biomolecular pathways leading to the G(1) arrest evoked in response to DNA damage, growth arrest signals and differentiation commitment. It belongs to the Cip/Kip class of cyclin-dependent kinase inhibitors and is at least partly regulated by p53. P21(Waf1/Cip1/Sid1) functional inactivation possibly resulting from mutations of the gene itself or, more likely, from p53 mutations may be critical for either the cell fate following DNA-damaging insults or clonal evolution toward malignancy. In the study presented here we describe a competitive polymerase chain reaction (PCR) strategy whose sensitivity and reproducibility enable us to attain a precise quantitation of p21(Waf1/Cip1/Sid1) expression levels in hematopoietic progenitors, the cell compartment which mostly suffers from the side effects of genotoxic drugs in use for cancer cure. The strategy was set in the M07 factor-dependent hematopoietic progenitor cell line. We confirmed that its p21(waf1/cip1/sid1) constitutive expression level is very low and up-modulated by DNA-damaging agents: ionizing radiations and ultraviolet light. Gene up-modulation resulted in checkpoint activation and, in particular, in a significant G(1) arrest, required for either the repair of damaged DNA sequences or apoptotic cell death. Our competitive PCR strategy was further validated in CD34(+) purified hematopoietic progenitors from healthy donors mobilized into the peripheral blood by granulocyte colony-stimulating factor and intended for allogeneic bone marrow transplantation. The constitutive p21(WAF1/CIP1/SID1) expression levels, measured in three separate harvests, were very low and no significant differences were apparent. Our results support the use of a competitive PCR strategy as a useful tool for clinical purposes, to assess the individual biomolecular response of early hematopoietic progenitors to antiblastic drugs. 相似文献
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François Guerrero Sanéo Thioub Christelle Goanvec Sigrid Theunissen Annie Feray Costantino Balestra Jacques Mansourati 《Journal of physiology and biochemistry》2013,69(2):277-287
We examined whether the improvement of impaired NO-dependent vasorelaxation by exercise training could be mediated through a BH4-dependent mechanism. Male spontaneously hypertensive rats (SHR, n?=?20) and Wistar-Kyoto rats (WKY, n?=?20) were trained (Tr) for 9 weeks on a treadmill and compared to age-matched sedentary animals (Sed). Endothelium-dependent vasorelaxation (EDV) was assessed with acetylcholine by measuring isometric tension in rings of femoral artery precontracted with 10?5?M phenylephrine. EDV was impaired in SHR-Sed as compared to WKY-Sed (p?=?0.02). Training alone improved EDV in both WKY (p?=?0.01) and SHR (p?=?0.0001). Moreover, EDV was not different in trained SHR than in trained WKY (p?=?0.934). Pretreatment of rings with L-NAME (50 μM) cancelled the difference in ACh-induced relaxation between all groups, suggesting that NO pathway is involved in these differences. The presence of 10?5?M BH4 in the organ bath significantly improved EDV for sedentary SHR (p?=?0.030) but not WKY group (p?=?0.815). Exercise training turned the beneficial effect of BH4 on SHR to impairment of ACh-induced vasorelaxation in both SHR-Tr (p?=?0.01) and WKY-Tr groups (p?=?0.04). These results suggest that beneficial effect of exercise training on endothelial function is due partly to a BH4-dependent mechanism in established hypertension. 相似文献
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Márcia Gisele Santos da Costa Marisa da Silva Santos Flávia Mori Sarti Kátia Marie Sim?es e. Senna Bernardo Rangel Tura Marcelo Correia Goulart 《PloS one》2014,9(10)
ObjectivesThe study performs a cost-effectiveness analysis of procedures for atrial septal defects occlusion, comparing conventional surgery to septal percutaneous implant.MethodsA model of analytical decision was structured with symmetric branches to estimate cost-effectiveness ratio between the procedures. The decision tree model was based on evidences gathered through meta-analysis of literature, and validated by a panel of specialists. The lower number of surgical procedures performed for atrial septal defects occlusion at each branch was considered as the effectiveness outcome. Direct medical costs and probabilities for each event were inserted in the model using data available from Brazilian public sector database system and information extracted from the literature review, using micro-costing technique. Sensitivity analysis included price variations of percutaneous implant.ResultsThe results obtained from the decision model demonstrated that the percutaneous implant was more cost effective in cost-effectiveness analysis at a cost of US$8,936.34 with a reduction in the probability of surgery occurrence in 93% of the cases. Probability of atrial septal communication occlusion and cost of the implant are the determinant factors of cost-effectiveness ratio.ConclusionsThe proposal of a decision model seeks to fill a void in the academic literature. The decision model proposed includes the outcomes that present major impact in relation to the overall costs of the procedure. The atrial septal defects occlusion using percutaneous implant reduces the physical and psychological distress to the patients in relation to the conventional surgery, which represent intangible costs in the context of economic evaluation. 相似文献
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Christian-Heinz Anderwald Andrea Tura Alois Gessl Sabina Smajis Christian Bieglmayer Rodrig Marculescu Anton Luger Giovanni Pacini Michael Krebs 《PloS one》2014,9(12)