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1.
Madsen SH Andreassen KV Christensen ST Karsdal MA Sverdrup FM Bay-Jensen AC Henriksen K 《Steroids》2011,76(13):1474-1482
Introduction
Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthritis. This study aimed at characterizing the effect of glucocorticoids on chondrocytes, osteoclasts, and osteoblasts.Experimental
We used four model systems to investigate how glucocorticoids affect the cells of the joint; two intact tissues (femoral head- and cartilage-explants), and two separate cell cultures of osteoblasts (2T3-pre-osteoblasts) and osteoclasts (CD14+-monocytes). The model systems were cultured in the presence of two glucocorticoids; prednisolone or dexamethasone. To induce anabolic and catabolic conditions, cultures were activated by insulin-like growth factor I/bone morphogenetic protein 2 and oncostatin M/tumor necrosis factor-α, respectively. Histology and markers of bone- and cartilage-turnover were used to evaluate effects of glucocorticoid treatment.Results
Prednisolone treatment decreased collagen type-II degradation in immature cartilage, whereas glucocorticoids did not affect collagen type-II in mature cartilage. Glucocorticoids had an anti-catabolic effect on catabolic-activated cartilage from a bovine stifle joint and murine femoral heads. Glucocorticoids decreased viability of all bone cells, leading to a reduction in osteoclastogenesis and bone resorption; however, bone morphogenetic protein 2-stimulated osteoblasts increased bone formation, as opposed to non-stimulated osteoblasts.Conclusions
Using highly robust in vitro models of bone and cartilage turnover, we suggest that effects of glucocorticoids highly depend on the activation and differential stage of the cell targeted in the joint. Present data indicated that glucocorticoid treatment may be beneficial for articular cartilage, although detrimental effects on bone should be taken into account. 相似文献2.
Subhrojit SenShali Chen Biao FengYuexiu Wu Edmund LuiSubrata Chakrabarti 《Phytomedicine》2011,18(13):1110-1117
Purpose
Ginseng (Araliaceae), demonstrates widespread biological effects because of its purported antioxidant and other properties. The present study was undertaken to investigate the effects of American ginseng root extract on glucose-induced oxidative stress and associated oxidative damage to human umbilical vein endothelial cells (HUVECs).Methods
Following pretreatment with various concentrations of ginseng (alcoholic extract), HUVECs were incubated with various concentrations of d-glucose ranging from 5 to 25 mmol/l for 24 h. l-Glucose was used at a concentration of 25 mmol/l as a control.Results
Glucose-induced oxidative stress detected by intracellular reactive oxygen species accumulation, superoxide anion generation and DNA damage in HUVECs were significantly prevented by ginseng. Treatment of HUVECs with ginseng further led to significant prevention of glucose-induced NF-κB activation. Glucose-induced increase in fibronectin (FN), EDB+FN (a splice variant of FN), endothelin-1 (ET-1) and vascular endothelial growth factor (VEGF) mRNAs and protein levels were also prevented by ginseng treatment.Conclusion
These data indicate that American ginseng prevented glucose-induced damage in the HUVECs through its antioxidant properties. 相似文献3.
Background
Difference in the capacity of xenobiotic metabolising enzymes might be an important factor in genetic susceptibility to cancer.Methods
A case control study involving forty one gastric cancer patients and one hundred and thirty controls was carried out to determine the frequency of GSTM1 and GSTT1 null genotypes. The frequency of GSTM1 and GSTT1 null genotype was observed by carrying out multiplex PCR.Results
There was no difference in the frequencies of the GSTM1 and GSTT1 null and the combined GSTM1 and GSTT1 null genotype between patients and control.Conclusions
Our data suggest that GSTM1 and GSTT1 status may not influence the risk of developing gastric cancer. 相似文献4.
Jesús Fortuño Godes Jordi Romea ViñetsMyriam Guerra Balic Gregorio Sainz PardoJosep Queralt Zueras 《Revista espa?ola de geriatría y gerontología》2011,46(3):147
Introduction
This pre-experimental study analyses the Functional Capacity (FC), Body Mass Index (BMI), Health Related Quality of Life (HRQoL) and Health Capital Stock (HCS) of elderly people participating in a Walking program in Granollers (Barcelona).Material and methods
One hundred and seventy-three participants were invited to participate. One hundred and one of them were users of the Municipal Program for Elderly People, and 72 received information by the communication media. One hundred and thirty-one (76.3%) of the participants completed the Program.The intervention consisted of a 6-month program, supervised by a specialist instructor once a week and controlled daily by a pedometer.The 6-minute walk test (6MWT) was analysed for the FC, and the EuroQoL for the HRQoL. The preferences derived from the EuroQoL scores and the Life Expectancy were used to calculate the FC. The monetary data were obtained using a fixed value.Results
An increase in the average number of steps was observed after the program, especially in men. The results also showed a decrease in the BMI. The participants showed a improvement in overall health perception at the end of the program. The HCS scores confirmed the improvement in the HRQoL in men.Conclusions
The Program was positive for increasing the number of steps and improving physical condition and health. The usefulness of the pedometer as a motivational tool of physical exercise is discussed. 相似文献5.
Background
Inflammation appears to be involved in processes leading to organ damage in preterm newborns, yet little is known about the relationships among elevated concentrations of inflammation-associated proteins in the blood of preterm newborns.Methods
In this exploratory study, we used an electrochemiluminescence method to measure 25 proteins in blood obtained on postnatal day 1 (range 1-3), day 7 (range 5-8), and day 14 (range 12-15) from 939 children born before the 28th week of gestation and evaluated to what extent those whose concentration of each protein was elevated (defined as in the highest quartile for gestational age and day the specimen was obtained) also had an elevated concentration of every other protein the same day or on a day 1 or 2 weeks later (p < .0001).Results
On each of the 3 days assessed, elevated concentrations of 17 proteins were associated with elevated concentrations of 15 or more of the other 24 proteins. VEGF, VEGF-R1, VEGF-R2 were among these proteins, while IGFBP-1 was associated with 13 other proteins on day 7. An elevated concentration of eight proteins on day 1 predicted an elevated concentration of 10 or more proteins on day 7, while an elevated concentration of only two proteins on day 7 were associated with elevated concentrations of 10 or more proteins on day-14. Few associations were seen between days 1 and 14.Conclusions/inferences
Inflammation is a diffuse process in ELGANs, with elevated concentrations of cytokines, chemokines, adhesion molecules, matrix metalloproteinases, a growth factor and its receptors, as well as a growth factor binding protein associated with each other the same day, as well as on subsequent days. 相似文献6.
Dionisio N Albarran L Berna-Erro A Hernandez-Cruz JM Salido GM Rosado JA 《Cellular signalling》2011,23(11):1850-1856
Background
All identified mammalian TRPC channels show a C-terminal calmodulin (CaM)- and inositol 1,4,5-trisphosphate receptors (IP3Rs)-binding (CIRB) site involved in the regulation of TRPC channel function.Objectives
To assess the basis of CaM/IP3Rs binding to the CIRB site of TRPC6 and its role in platelet physiology.Methods
Protein association was detected by co-immunoprecipitation and Western blotting, Ca2+ mobilization was measured by fluorimetric techniques and platelet function was analyzed by aggregometry.Results
Co-immunoprecipitation of TRPC6 with CaM or the IP3Rs at different cytosolic free Ca2+ concentrations ([Ca2+]c) indicates that the association between these proteins is finely regulated by cytosolic Ca2+ via association of CaM and displacement of the IP3Rs at high [Ca2+]c. Thrombin-stimulated association of TRPC6 with CaM or the IP3Rs was sensitive to 2-APB and partially inhibited by dimethyl BAPTA loading, thus suggesting that the association between these proteins occurs through both Ca2+-dependent and -independent mechanisms. Incorporation of an anti-TRPC6 C-terminal antibody, whose epitope overlaps the CIRB region, impaired the dynamics of the association of TRPC6 with CaM and the IP3Rs, which lead to both inhibition and enhancement of thrombin- and thapsigargin-evoked Ca2+ entry in the presence of low or high, respectively, extracellular Ca2+ concentrations, as well as altered thrombin-evoked platelet aggregation.Conclusions
Our results indicate that the CIRB site of TRPC6 plays an important functional role in platelets both modulating Ca2+ entry and aggregation through its interaction with CaM and IP3Rs. 相似文献7.
Alexander Grundt Ute Liegibel 《Biochemical and biophysical research communications》2009,389(3):550-555
Purpose
Osteoprotegerin (OPG) affects bone metabolism by intercepting the RANK-RANKL interaction which prevents osteoclastic differentiation and consequently reduces bone resorption. Different bone phenotypes of mice overexpressing OPG and of mice with knockdown of receptor activator of NF-κB (RANK) or RANK-ligand (RANKL) suggest that the mechanism of action of the OPG-RANKL-RANK system in regulating bone remodeling is not completely understood. Furthermore, OPG increases bone mass and density independently from reduced osteoclastogenesis which is consistent with the possibility that OPG may directly affect bone metabolism beyond its known role as decoy receptor for RANKL.Methods
We treated primary human osteoblastic cells with OPG and inhibitory anti-RANKL antibodies and measured cellular ALP activity, in vitro mineralization, vitronectin receptor protein expression and ERK phosphorylation. We also analyzed the mRNA co-expression of ALP and OPG ex vivo in bone biopsies from acute and old stable vertebral fractures.Results
OPG directly increased ALP activity and in vitro mineralization of HOC, enhanced expression of the vitronectin receptor thereby increasing adherence of HOC to vitronectin and stimulated ERK phosphorylation. All OPG-mediated effects could be prevented by RANKL antibodies or RANKL-siRNA transfection and MAPK inhibitor PD98059 reduced the stimulatory effect of OPG on integrin αv expression. In acutely fractured vertebrae OPG and ALP mRNA expression was significantly increased compared to stable vertebral fractures. In conclusion, OPG exerts direct osteoanabolic effects on HOC metabolism via RANKL in addition to its well described role as decoy receptor for RANKL. 相似文献8.
9.
Background
Computational methods are needed to design multivalent vaccines against flaviviruses (FVs) such as the West Nile virus or the dengue virus (DENV).Objective
We aimed to use physicochemical property (PCP) consensus sequences of FV strains to delineate conserved motifs, areas of maximum variability, and specific loci that correlate with arthropod vector, serotype, and disease severity.Methods
PCP consensus sequences for 27 species were prepared from 928 annotated sequences catalogued in Flavitrack. Alignments of these correlated well with the known structures of the NS3 protease domain and envelope (E) proteins. The PCPMer suite was used to identify motifs common to all FVs. Areas of PCP variability that correlated with phenotype were plotted on the structures.Results
Despite considerable diversity at the amino acid level, PCPs for both proteins were well conserved throughout the FVs. A series of insertions in E separated tick- from mosquito-borne viruses and all arthropod-borne viruses from isolates with no known vector or directly from insects. Comparison of a PCP consensus sequence of E derived from 600 DENV strains (DENV600) with individual ones for DENV1-DENV4 showed that most major serotype-specific variation occurs near these insertions. The DENV600 differed from one prepared from eight hemorrhagic or fatal strains from four DENV serotypes at only three positions, two of which overlap known escape mutant sites.Conclusions
Comparing consensus sequences showed that substantial changes occur in only a few areas of the E protein. PCP consensus sequences can contribute to the design of multivalent vaccines. 相似文献10.
María Ángeles Molina Rocío SchettiniMaría Dolores López-Bravo María Dolores ZamarrónRocío Fernández-Ballesteros 《Revista espa?ola de geriatría y gerontología》2011,46(6):297
Introduction
The aim of this study was to analyse whether the activity is a protective factor of intellectual decline, and specifically to examine whether intellectual activity versus other activities, is a better predictor for the maintenance of cognitive functioning in a group of people over 90 years, independent in basic daily living activities and having preserved cognitive capacity.Material and methods
This sample was selected from a bio-psycho-social longitudinal study of independent persons 90 and over. This is a longitudinal study involving 188 people, 67 males and 121 females. Measurements were taken of cognitive functioning and level of activity and repeated between 6 and 14 months; inferential analysis was performed at baseline and follow-up.Results
At base-line, there is a strong association between the level of activity and performance. Also, and most important, intellectual activities at baseline predict cognitive functioning at follow-up. According to our results, intellectual activities and the maintenance of cognitive functioning are associated with the absence of cognitive impairment in the very elderly.Conclusions
This has important implications for the scientific community in finding a predictive index and strategies, but also for the individual to identify factors of change on which to act to reduce problems associated with aging. 相似文献11.
12.
Claire Siemes Loes E. Visser Frank H. de Jong André G. Uitterlinden Albert Hofman Ron H.N. van Schaik 《Steroids》2010,75(12):1024-1032
Purpose
To study if polymorphisms in genes encoding for CYP3A enzymes, that play a role in steroid hormone metabolism, affect steroid hormone serum levels and prostate cancer incidence or mortality.Methods
3048 male participants of The Rotterdam Study were included. Prostate cancer cases and non-cases were studied for differences in baseline hormone levels with Student's t-test. General linear models were performed on different random subsets of hormone levels to study associations with genotype. Cox’ proportional hazard models were used to study prostate cancer incidence and mortality among genotypes.Results
Both DHEAS sulphate as free-testosterone were significantly increased at baseline in males who developed a prostate cancer within the study period. CYP3A4 G-allele carriage was associated with lower levels of estrone sulphate (p = 0.005) and higher levels of estradiol (p = 0.04) compared to non-carriers. CYP3A5 A-allele carriage was associated with increased levels of estrone sulphate (p = 0.02). CYP3A7 G-allele carriage was associated with the highest number of significant differences in steroid hormone levels. Carriers of the allele resulting in continued enzyme expression during adulthood had decreased levels of dehydroepiandrosterone (DHEA) sulphate (p = 0.05), androstenedione (p = 0.006), estrone (p = 0.0001) and estrone sulphate (p = 0.003) compared to mean levels of these hormones in homozygous wild type carriers. CYP3A43 genotype was not associated with any of the studied hormone levels. However, carriers of the CYP3A43 G-allele showed a significant 5-fold increase in mortality among early onset diagnosed prostate cancers.Conclusion
Increased levels of free testosterone and DHEA sulphate were associated with prostate cancer incidence along the study period. Primarily the amount of CYP3A7 expression seemed to affect steroid hormone levels. Nevertheless, testosterone, a precursor of the prostate growth and differentiation stimulating dehydrotestosterone, was not influenced by CYP3A genotype. In line with this, no significant associations were observed for CYP3A genotypes and prostate cancer incidence. 相似文献13.
Purpose
This study was designed to investigate the protective effect of tetramethylpyrazine isolated from Ligusticum chuanxiong, a traditional Chinese medicine, on diabetic nephropathy in a rat model, and to explore the possible mechanism involved in a protective function.Materials
Diabetes was induced in male Sprague-Dawley rats by a single intraperitoneal injection of 70 mg/kg of streptozotocin. One week later, 200 mg/kg/day of tetramethylpyrazine was administered intragastric gavage daily for 8 weeks. Renal functions and expression of vascular endothelial growth factor were examined at 4 and 8 weeks after tetramethylpyrazine administration.Results
Blood glucose and renal function were significantly improved in the tetramethylpyrazine-treated group compared to the untreated diabetic rats. Diabetic nephropathy resulted in an increase in the expression of vascular endothelial growth factor, while tetramethylpyrazine administration greatly decreased the expression.Conclusions
Our results suggest that administration of tetramethylpyrazine may reduce kidney damage caused by diabetes. This protective effect may be mediated, in part, by downregulated expression of vascular endothelial growth factor in the kidney. 相似文献14.
15.
Jia-feng Wang Man-li Yu Guang Yu Jin-jun Bian Xiao-jian Wan 《Biochemical and biophysical research communications》2010,394(1):184-188
Objective
Current biomarkers cannot completely distinguish sepsis from systemic inflammatory response syndrome (SIRS) caused by other non-infectious diseases. Circulating microRNAs (miRNAs) are promising biomarkers for several diseases, but their correlation with sepsis is not totally clarified.Methods
Seven miRNAs related to inflammation or infection were included in the present study. Serum miRNA expression was investigated in 50 patients diagnosed with sepsis, 30 patients with SIRS and 20 healthy controls to evaluate the diagnostic and prognostic value. Expression levels of serum miRNAs were determined by quantitative PCR using the Qiagen miScript system. Serum CRP and IL-6 levels were determined by enzyme linked immunosorbent assay.Results
Serum miR-146a and miR-223 were significantly reduced in septic patients compared with SIRS patients and healthy controls. The areas under the receiver operating characteristic curve of miR-146a, miR-223 and IL-6 were 0.858, 0.804 and 0.785, respectively.Conclusion
Serum miR-146a and miR-223 might serve as new biomarkers for sepsis with high specificity and sensitivity. (ClinicalTrials.gov number, NCT00862290.) 相似文献16.
Objective
VEGF and BMP play important roles in angiogenesis and osteogenesis. Combining these two factors may be a promising therapeutic strategy for avascular necrosis of the femoral head (ANFH).Methods
Rabbit bone marrow-derived mesenchymal stem cells (BMSCs) were isolated and purified by density gradient centrifugation combined with attachment culture methods. The purity and characteristics of the BMSCs were detected by cell surface antigen identification. The best MOI of BMSCs transfected with rAAV was detected by fluorescent cell counting, and cell viability was determined by MTT assay. Expression of the genes of interest was detected by GFP gene expression, RT-PCR assay, and ELISA assay. The biological activities of VEGF and BMP were detected by angiogenic and osteogenic assays.Results
The best MOI of BMSCs transfected with rAAV was 5 × 104 v.g./cell. Cell growth curves showed vigorous cell viability. Expressions of the GFP, VEGF165, and BMP7 genes were detected 1 day post-transfection and peaked 14 days post-transfection. Expression of the genes of interest was sustained over 1 month. VEGF and BMP proteins secreted from BMSCs transfected with rAAV-hVEGF165-IRES-hBMP7 enhanced angiogenesis and osteogenesis in vitro.Conclusion
Recombinant adeno-associated viral vectors co-expressing the hVEGF165 and hBMP7 genes showed efficient gene expression ability. The VEGF165 and BMP7 proteins expressed from the vector have efficient biological activity in vitro. 相似文献17.
Héctor Molina Meenakshisundaram Ananthanarayanan Juan Francisco Miquel 《生物化学与生物物理学报:生物膜》2008,1778(5):1283-1291
Background
The relevance of discrete localization of hepatobiliary transporters in specific membrane microdomains is not well known.Aim
To determine whether the Na+/taurocholate cotransporting polypeptide (Ntcp), the main hepatic sinusoidal bile salt transporter, is localized in specific membrane microdomains.Methods
Presence of Ntcp in membrane rafts obtained from mouse liver was studied by immunoblotting and immunofluorescence. HEK-293 cells stably transfected with rat Ntcp were used for in vitro studies. Expression, localization and function of Ntcp in these cells were assessed by immunoblotting, immunofluorescence and biotinylation studies and Na+-dependent taurocholate uptake assays, respectively. The effect of cholesterol depletion/repletion assays on Ntcp function was also investigated.Results
Ntcp localized primarily to membrane rafts in in vivo studies and localized partially in membrane rafts in transfected HEK-293 cells. In these cells, membrane cholesterol depletion resulted in a shift of Ntcp localization into non-membrane rafts, which correlated with a 2.5-fold increase in taurocholate transport. Cholesterol repletion shifted back part of Ntcp into membrane rafts, and normalized taurocholate transport to values similar to control cells.Conclusion
Ntcp localizes in membrane rafts and its localization and function are regulated by membrane cholesterol content. This may serve as a novel regulatory mechanism of bile salt transport in liver. 相似文献18.
María Dolores López María Dolores ZamarrónRocío Fernández-Ballesteros 《Revista espa?ola de geriatría y gerontología》2011,46(1):15
Background
Gerontology research shows the importance of physical exercise for active aging. This study demonstrates the relationship between the practice of aerobic exercise, and physical fitness (muscle strength, respiratory capacity and motor speed) and cognitive performance (memory and visual-perceptual speed) and analyzes whether age is a modulating factor of this relationship.Material and methods
The sample included 690 subjects with an age range of 30-85 years. The level of physical exercise was assessed using self-report form. Two sub-scales were used for the evaluation of cognitive performance: Digit Span Backwards and Digit Symbol (both are sub-scales of the Wechsler Adult Intelligence Scale - WAIS). The physical fitness was assessed using bio-behavioral measurements (strength, lung capacity, speed). To test the combined effect of exercise and age on the two variables (physical fitness and cognitive performance) two separate factorial analysis of variance were performed (procedure - general linear model: Univariate).Result
The most significant result showed that scores on cognitive performance is a function of the intensity of the physical activity (F=4.8; P<0.002). With regard to physical fitness, its relationship with physical exercise is also significant (F=4.10; P<0.007) as well as the interaction between exercise and age (F=2.2; P<0.001).Conclusions
The intensity in achieving aerobic exercise is associated with physical fitness and cognitive performance. Age has a specific weight in the association between exercise and physical fitness, this effect is higher in the older age groups (65-74 and 75-85 years for 30-49 and 50-64 years). These data suggest the compensatory effect of exercise on decline in old age. 相似文献19.
Background
Case reports provide essential information on adverse effects. Yet there is little consistency in the quality and format of reporting them.Aim
In this study, we aimed to assess the quality of case reports of adverse effect of herbal medicinal products (HMPs) published during three time periods, 1986-1988, 1996-1998, and 2006-2008.Methods
We conducted literature searches in four major databases: Medline, EMBASE, AMED, and CINALH. Each case report was subject to specific inclusion criteria related to the intervention (i.e. herbal medicine) and outcome measurement (i.e. adverse effect). A 21-item scale was used to assess the quality of all included reports. Each report was categorised into low quality (score between 0 and 14), lower medium quality (score between 15 and 21), upper medium quality (score between 22 and 28), and high quality (score between 29 and 42).Results
In total, 137 case reports were included. The percentage of high quality case reports rose from 0% in 1986-1988 to 27.9% in 1996-1998 and 34.2% in 2006-2008; conversely, the percentages of low quality case reports dropped from 13.3% in 1986-1988 to 0% in 1996-1998 and 2.5% in 2006-2008.Conclusion
These findings are consistent with the notion that the quality of case reports is improving. However, due to several caveats, our data should be interpreted with caution. 相似文献20.
N. Yeni M. Vermandel D. Huglo A. BéronS. Adib G. LionA.-S. Dewalle-Vignion 《Médecine Nucléaire》2011,35(3):146-155