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1.
Article in English | WPRIM | ID: wpr-903914

ABSTRACT

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

2.
Article in English | WPRIM | ID: wpr-896210

ABSTRACT

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

3.
Chinese Journal of Epidemiology ; (12): 914-919, 2018.
Article in Chinese | WPRIM | ID: wpr-736603

ABSTRACT

Objective To investigate the relationship between body mass index (BMI) and all-cause mortality in hypertensive population.Methods All participants were selected from a prospective cohort study based on a rural population from Henan province,China.Cox proportional hazards regression models were used to estimate the associations of different levels of BMI stratification with all-cause mortality.Restricted cubic spline models were used to detect the doseresponse relation.Results Among the 5 461 hypertensive patients,a total of 31 048.38 person-years follow-up was conducted.The median of follow-up time was 6 years,and 589 deaths occurred during the follow-up period.Compared to normal weight group (18.5 kg/m2<BMI<24.0 kg/m2) the multivariate-adjusted hazard ratios for all-cause mortality associated with BMI levels (< 18.5 kg/m2,24-28 kg/m2,and ≥28 kg/m2) were 0.83 (95%CI:0.37-1.87),0.81 (95%CI:0.67-0.97),and 0.72 (95%CI:0.56-0.91),respectively.The dose-response analysis showed a nonlinear,reverse "S" shaped relationship (non-linearity P<0.001).Conclusion Overweight or obese might have a protective effect on all-cause mortality in hypertensive population,which supports the "obesity paradox" phenomenon.

4.
Chinese Journal of Epidemiology ; (12): 765-769, 2018.
Article in Chinese | WPRIM | ID: wpr-736575

ABSTRACT

Objective To study the modification effect of age on the association between body mass index and the risk of hypertension.Methods People age ≥ 18 years old were selected by clusters,from a rural area of Henan province.In total,20 194 people were recruited at baseline during 2007 and 2008,and the follow-up study was completed from 2013 to 2014.Logistic regression model was used to assess the risk of incident hypertension by baseline BMI and age-specific BMI.Results During the 6-year follow-up period,1 950 hypertensive persons were detected,including 784 men and 1 166 women,with cumulative incidence rates as 19.96%,20.51%,and 19.61%,respectively.Compared with those whose BMI<22 kg/m2,the RRs of hypertension were 1.09 (0.93-1.27),1.17 (1.01-1.37),1.34 (1.14-1.58) and 1.31 (1.09-1.56) for participants with BMI as 22-,24-,26-and ≥28 kg/m2,respectively.In young and middle-aged populations,the risk of hypertension gradually increased with the rise of BMI (trend P<0.05).However,in the elderly,the increasing trend on the risk of hypertension risk was not as significantly obvious (trend P>0.05).Conclusion The effect of BMI on the incidence of hypertension seemed to depend on age.Our findings suggested that a weight reduction program would be more effective on young or middle-aged populations,to prevent the development of hypertension.

5.
Article in Chinese | WPRIM | ID: wpr-709809

ABSTRACT

Objective To evaluate the effect of dezocine on cognitive function after sevoflurane anesthesia in a rat model of physiological stress.Methods Physiological stress was induced by applying repeated foot shock stimulation and confirmed by open field test.Thirty Spragne-Dawley rats with physiological stress,weighing 180-220 g,were divided into 3 groups (n=10 each) using a random number table:control group (group C),sevoflurane group (group S) and dezocine plus sevoflurane group (group D+S).Normal saline 0.5 ml was intraperitoneally injected at 6 h of oxygen inhalation in group C.Normal saline 0.5 ml was intraperitoneally injected at 6 h of 3.0% sevoflurane inhalation in group S.Dezocine 3 mg/kg was intraperitoneally injected at 6 h of 3.0% sevoflurane inhalation in group D+S.At 1,12,24 and 48 h after the end of intraperitoneal injection (T1-4),Morris water maze test was performed,and the time of staying at the original platform quadrant and frequency of crossing the original platform were recorded.The rats were sacrificed after the end of Morris water maze test,brains were removed and hippocampi were isolated for determination of nitric oxide synthase-1 (nNOS) expression (by Western blot) and nNOS positive cells (by immunohistochemistry).Results Compared with group C,the time of staying at the original platform quadrant was significantly shortened at T1,2,the frequency of crossing the original platform was reduced at T1,the expression of nNOS in hippocampus was down-regulated,and the number of nNOS positive cells in hippocampal CA1 region was reduced in group S (P<0.05),and no significant change was found in the parameters mentioned above in group D+S (P>0.05).Compared with group S,the time of staying at the original platform quadrant was significantly prolonged at T1,the frequency of crossing the original platform was increased at T1,2,the expression of nNOS in hippocampus was up-regulated,and the number of nNOS positive cells in hippocampal CA1 region was increased in group D+S (P<0.05).Conclusion Dezocine can improve cognitive function after sevoflurane anesthesia in a rat model of physiological stress,and the mechanism may be related to up-regulating nNOS expression in hippocampi.

6.
Chinese Journal of Epidemiology ; (12): 914-919, 2018.
Article in Chinese | WPRIM | ID: wpr-738071

ABSTRACT

Objective To investigate the relationship between body mass index (BMI) and all-cause mortality in hypertensive population.Methods All participants were selected from a prospective cohort study based on a rural population from Henan province,China.Cox proportional hazards regression models were used to estimate the associations of different levels of BMI stratification with all-cause mortality.Restricted cubic spline models were used to detect the doseresponse relation.Results Among the 5 461 hypertensive patients,a total of 31 048.38 person-years follow-up was conducted.The median of follow-up time was 6 years,and 589 deaths occurred during the follow-up period.Compared to normal weight group (18.5 kg/m2<BMI<24.0 kg/m2) the multivariate-adjusted hazard ratios for all-cause mortality associated with BMI levels (< 18.5 kg/m2,24-28 kg/m2,and ≥28 kg/m2) were 0.83 (95%CI:0.37-1.87),0.81 (95%CI:0.67-0.97),and 0.72 (95%CI:0.56-0.91),respectively.The dose-response analysis showed a nonlinear,reverse "S" shaped relationship (non-linearity P<0.001).Conclusion Overweight or obese might have a protective effect on all-cause mortality in hypertensive population,which supports the "obesity paradox" phenomenon.

7.
Chinese Journal of Epidemiology ; (12): 765-769, 2018.
Article in Chinese | WPRIM | ID: wpr-738043

ABSTRACT

Objective To study the modification effect of age on the association between body mass index and the risk of hypertension.Methods People age ≥ 18 years old were selected by clusters,from a rural area of Henan province.In total,20 194 people were recruited at baseline during 2007 and 2008,and the follow-up study was completed from 2013 to 2014.Logistic regression model was used to assess the risk of incident hypertension by baseline BMI and age-specific BMI.Results During the 6-year follow-up period,1 950 hypertensive persons were detected,including 784 men and 1 166 women,with cumulative incidence rates as 19.96%,20.51%,and 19.61%,respectively.Compared with those whose BMI<22 kg/m2,the RRs of hypertension were 1.09 (0.93-1.27),1.17 (1.01-1.37),1.34 (1.14-1.58) and 1.31 (1.09-1.56) for participants with BMI as 22-,24-,26-and ≥28 kg/m2,respectively.In young and middle-aged populations,the risk of hypertension gradually increased with the rise of BMI (trend P<0.05).However,in the elderly,the increasing trend on the risk of hypertension risk was not as significantly obvious (trend P>0.05).Conclusion The effect of BMI on the incidence of hypertension seemed to depend on age.Our findings suggested that a weight reduction program would be more effective on young or middle-aged populations,to prevent the development of hypertension.

8.
Protein & Cell ; (12): 446-454, 2017.
Article in English | WPRIM | ID: wpr-757017

ABSTRACT

Obesity, which underlies various metabolic and cardiovascular diseases, is a growing public health challenge for which established therapies are inadequate. Given the current obesity epidemic, there is a pressing need for more novel therapeutic strategies that will help adult individuals to manage their weight. One promising therapeutic intervention for reducing obesity is to enhance energy expenditure. Investigations into human brown fat and the recently discovered beige/brite fat have galvanized intense research efforts during the past decade because of their pivotal roles in energy dissipation. In this review, we summarize the evolution of human brown adipose tissue (hBAT) research and discuss new in vivo methodologies for evaluating energy expenditure in patients. We highlight the differences between human and mouse BAT by integrating and comparing their cellular morphology, function, and gene expression profiles. Although great advances in hBAT biology have been achieved in the past decade, more cellular models are needed to acquire a better understanding of adipose-specific processes and molecular mechanisms. Thus, this review also describes the development of a human brown fat cell line, which could provide promising mechanistic insights into hBAT function, signal transduction, and development. Finally, we focus on the therapeutic potential and current limitations of hBAT as an anti-glycemic, anti-lipidemic, and weight loss-inducing 'metabolic panacea'.


Subject(s)
Adipose Tissue, Beige , Metabolism , Pathology , Adipose Tissue, Brown , Metabolism , Pathology , Animals , Cell Line , Energy Metabolism , Humans , Mice , Obesity , Metabolism , Pathology , Therapeutics
9.
Journal of Medical Postgraduates ; (12): 342-347, 2017.
Article in Chinese | WPRIM | ID: wpr-512212

ABSTRACT

Tacrolimus exhibits varied individual pharmacokinetic and a narrow therapeutic window, resulting in difficulties in personalized medication.In order to improve the safety of tacrolimus in clinical application and its efficiency and rationality in clinical practice, many countries and regions in the world have issued a number of guidelines for tacrolimus application.However, these guidelines generally aim at particular disease and race, and have certain limitation.In this article, the guidelines were explicated and analyzed in detail.Moreover, an individual tacrolimus medication recommendation for Chinese population was summarized based on the latest research of tacrolimus pharmacogenomics and therapeutic drug monitoring so as to provide assistance for the rational use of tacrolimus.

10.
Chinese Journal of Nursing ; (12): 707-711, 2017.
Article in Chinese | WPRIM | ID: wpr-620672

ABSTRACT

Objective To establish criteria for determination of sputum retention in elderly patients with non-ar-tificial airway. Methods Interview and Delphi methods were used to preliminarily determine clinical indication of sputum retentionand its classification through two-round expert consultation among 25 experts. Final criteria for de-termination of sputum retention were determined through experts group discussion. Results During the two rounds of consultation,all the questionnaires were collected,the experts' authority coefficients were 0.936 and 0.926 respec-tively,and the coordination coefficient of expert opinion was statistically significant.Criteria for determination of spu-tum retention included ineffective cough plus auscultation phlegm sound,with or without complaining of sputum,de-creased blood oxygen saturation,difficulty breathing and cyanosis. Conclusion Based on expert consultation and ar-gument,the criteria for determination of sputum retention can facilitate clinical nurses to detect sputum retention.

11.
Article in English | WPRIM | ID: wpr-728539

ABSTRACT

Abnormal localization of tumor suppressor proteins is a common feature of renal cancer. Nuclear export of these tumor suppressor proteins is mediated by chromosome region maintenance-1 (CRM1). Here, we investigated the antitumor eff ects of a novel reversible inhibitor of CRM1 on renal cancer cells. We found that S109 inhibits the CRM1-mediated nuclear export of RanBP1 and reduces protein levels of CRM1. Furthermore, the inhibitory eff ect of S109 on CRM1 is reversible. Our data demonstrated that S109 signifi cantly inhibits proliferation and colony formation of renal cancer cells. Cell cycle assay showed that S109 induced G1-phase arrest, followed by the reduction of Cyclin D1 and increased expression of p53 and p21. We also found that S109 induces nuclear accumulation of tumor suppressor proteins, Foxo1 and p27. Most importantly, mutation of CRM1 at Cys528 position abolished the eff ects of S109. Taken together, our results indicate that CRM1 is a therapeutic target in renal cancer and the novel reversible CRM1 inhibitor S109 can act as a promising candidate for renal cancer therapy.


Subject(s)
Active Transport, Cell Nucleus , Cell Cycle Checkpoints , Cell Cycle , Cell Proliferation , Cyclin D1 , Kidney Neoplasms , Tumor Suppressor Proteins
12.
Article in Chinese | WPRIM | ID: wpr-498152

ABSTRACT

Acute kidney injury(AKI)has become the public health problem that harms the human's health, is a common critically illness,characterized by complicated etiology,high prevalence,high risk of combine other organs'injury and high mortality,these become the huge challenge in clinic.Thus,it is valuable in clinic how to improve cog-nition about AKI,to early detection,to early treatment so that postpone pathogenetic condition,increae survival rate and improve prognosis.In recent years,the researchers have processed vast of reseaches about etiology,new biomark-er,risk fator,prognosis,etc.However,these parts are still controversial.This paper summarizes the research progress of AKI.

13.
Chinese Journal of Biotechnology ; (12): 1128-1133, 2014.
Article in Chinese | WPRIM | ID: wpr-279441

ABSTRACT

To compare two enrichment and preservation methods of urinary proteins, stored in polyvinylidene difluoride (PVDF) membrane (Urimem) or direct freezing, we examined the differences between the two methods in time, space, costs of supplies and electricity, degree of protein degradation and convenience of the sample handling. The urimem method is superior in the storage space, the cost of electricity and the clinical convenience compared to the direct freezing method. However, the direct freezing method is superior in the time and the cost of supplies to the urimem method. The enrichment and preservation of urinary proteins using urimem have more cost-effective benefits compared to those of the direct freezing method.


Subject(s)
Cost-Benefit Analysis , Freezing , Humans , Polyvinyls , Preservation, Biological , Methods , Proteins , Chemistry , Urine , Chemistry
14.
Article in Chinese | WPRIM | ID: wpr-427110

ABSTRACT

ObjectiveTo establish the urinary proteome profile of the metabolic syndrome ( MetS ) patients,compare the different urinary proteins between the MetS patients and the normal individuals,and analyze the function of the different proteins,so as to explore the pathogenesis of MetS.MethodsOvernight urine were collected from normal controls (n =6) and MetS patients ( n =6).Acetone precipitation method was used to precipitate proteins of urine.Intra-group proteins were mixed together,identified by reversed phase liquid chromatography-mass spectrometry/mass spectrometry and quantified relatively using spectral counting method.The functions of differential proteins were analyzed using Panther.ResultsA total of 807 and 630 proteins were identified respectively in normal controls and MetS patients.Comparing MetS patients with normal controls,sixty different proteins were found,of which 23 proteins were up-regulated and 37 proteins were down-regulated in MetS patients.In the up-regulated proteins,plasminogen was involved in the plasminogen activation cascade and isoform of alphaenolase,phosphoglycerate kinase 1 and fructose-bisphosphate aldolase B down-regulated in MetS patients were involved in the process of glycolysis and fructose metabolism.ConclusionsThe urinary proteome profile of patients with MetS was established by reversed phase liquid chromatography-mass spectrometry/mass spectrometry.Different proteins between MetS patients and normal people were identified.The plasminogen activation cascade,glycolysis and fructose metabolism play key roles in the pathogenesis of MetS.

15.
Article in Chinese | WPRIM | ID: wpr-416945

ABSTRACT

Objective To investigate the relationship between the urinary albumin excretion (UAE) and serum uric acid in general population. Methods The study participants were derived from the epidemiological study on the association of metabolic syndrome and chronic kidney disease (CKD) in Pinggu district, Beijing. A total of 992 participants (463 men and 529 women) aged from 30 to 75 years were enrolled in this study. For each participant, UAE, serum uric acid, serum creatinine, and serum lipids were detected and other potential risk factors for CKD were surveyed. Results ( 1 ) The frequencies of microalbuminuria, macroalbuminuria and hyperuricemia were 12.9% , 1.8% and 4.3% respectively. The persons with hyperuricemia had significantly higher frequency of albuminuria than those without hyperuricemia (37. 2% vs 13. 7% , P <0. 01). (2) The participants were divided according to the quartiles (25% , 50% , 75% ) of serum uric acid level, and the frequencies of albuminuria in males were 13. 2% , 13. 9% , 17. 2% and 25.4% , while those in females were 8. 4% , 6. 2% , 9. 6% and 24. 8%. ( 3 ) Multivariate logistic regression analysis showed, hyperuricemia was significantly associated with albuminuria in females (OR =2. 31, 95% CI 1. 15-4. 68; P=0.02), but not in males. If the persons with reduced renal function were excluded, similar result still could be gained. Conclusions The prevalence of albuminuria increases gradually with uric acid elevation. Serum uric acid is an independent risk factor of elevated UAE, especially in females.

16.
Chinese Journal of Nephrology ; (12): 807-811, 2010.
Article in Chinese | WPRIM | ID: wpr-382897

ABSTRACT

Objective To investigate the discriminator value of Han Chinese first morning urine albumin creatinine ratio (ACR) for determining the microalbuminuria. Methods A total of 1056 participants (494 males and 562 females) were selected from epidemiologic study of the metabolic syndrome and chronic kidney disease in Pinggu district, Beijing. Eight-hour overnight urinary albumin excretion (UAE) was regarded as the gold standard for defining the albuminuria,and the ROC curve analysis was used to determine the ACR discriminator value for microalbuminuria. Results (1)Microalbuminuria was found in 12.5% of participants,macroalbuminuria in 1.7%. (2)The ACR discriminator value for microalbuminuria by ROC curve analysis was 1.95 g/mol (sensitivity 97.6% and specitivity 88.6%) for men, 3.62 g/mol(sensitivity 83.8% and specitivity 89.1%) for women, 2.78 g/mol (sensitivity 88.7% and specitivity 85.9%)for overall. The upper boundary of microalbuminuria by ROC curve analysis was 22.59 g/mol (sensitivity 100.0% and specitivity 98.8%) . (3)The inter-rater agreement of the result in this study showed that sensitivity was 91.3% and specitivity was 88.2%, positive likelihood ratio was 7.56 and negative likelihood ratio was 0.10, positive predictive value was 56.9% and negative predictive value was 98.4%. Conclusions The ACR discriminator value for determining microalbuminuria is obviously higher in women than that in men, and is higher than recommendation of international guidelines. The result by ROC curve analysis has better sensitivity and specitivity.

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