排序方式: 共有138条查询结果,搜索用时 15 毫秒
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Kennedy AR Pissios P Otu H Roberson R Xue B Asakura K Furukawa N Marino FE Liu FF Kahn BB Libermann TA Maratos-Flier E 《American journal of physiology. Endocrinology and metabolism》2007,292(6):E1724-E1739
Ketogenic diets have been used as an approach to weight loss on the basis of the theoretical advantage of a low-carbohydrate, high-fat diet. To evaluate the physiological and metabolic effects of such diets on weight we studied mice consuming a very-low-carbohydrate, ketogenic diet (KD). This diet had profound effects on energy balance and gene expression. C57BL/6 mice animals were fed one of four diets: KD; a commonly used obesogenic high-fat, high-sucrose diet (HF); 66% caloric restriction (CR); and control chow (C). Mice on KD ate the same calories as mice on C and HF, but weight dropped and stabilized at 85% initial weight, similar to CR. This was consistent with increased energy expenditure seen in animals fed KD vs. those on C and CR. Microarray analysis of liver showed a unique pattern of gene expression in KD, with increased expression of genes in fatty acid oxidation pathways and reduction in lipid synthesis pathways. Animals made obese on HF and transitioned to KD lost all excess body weight, improved glucose tolerance, and increased energy expenditure. Analysis of key genes showed similar changes as those seen in lean animals placed directly on KD. Additionally, AMP kinase activity was increased, with a corresponding decrease in ACC activity. These data indicate that KD induces a unique metabolic state congruous with weight loss. 相似文献
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Myrianthefs PM Lazaris N Venetsanou K Smigadis N Karabatsos E Anastasiou-Nana MI Baltopoulos GJ 《Cytokine》2007,37(2):150-154
Chronic heart failure (CHF) may be considered a state of immune activation and persistent inflammation expressed by increased circulating levels of pro- and anti-inflammatory cytokines. The purpose of the study was to investigate the immune status in patients with CHF compared to normal individuals. We measured serum cytokine levels as well as cytokine production after ex vivo LPS stimulation of whole blood taken from 14 patients with CHF and 14 healthy volunteers. We used 500 pg/ml of LPS for an incubation period of 4h to stimulate 100 microL of whole blood. Patients with CHF had significantly higher levels of TNF-RI, and TNF-RII in serum compared to normal individuals. TNF-alpha, IL-6, and IL-10 did not differ significantly. After LPS stimulation, patients with CHF had significantly higher levels of TNF-alpha and IL-10, and significantly lower IL-6 levels compared to normal individuals. TNF-alpha receptors did not differ significantly. Patients with CHF may be found in a pro- as well as an anti-inflammatory state. They also do not develop endotoxin tolerance in an ex vivo laboratory model using whole blood stimulated with LPS. They may have increased TNF-alpha and IL-10 production after LPS stimulation of whole blood, which may contribute to a worsening of heart function, more severe disease presentation and a worse outcome during infections. 相似文献
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Roxani Angelopoulou Konstantina Plastira Pavlos Msaouel 《Reproductive biology and endocrinology : RB&E》2007,5(1):36
Human sperm DNA damage may have adverse effects on reproductive outcome. Infertile men possess substantially more spermatozoa
with damaged DNA compared to fertile donors. Although the extent of this abnormality is closely related to sperm function,
the underlying etiology of ensuing male infertility is still largely controversial. Both intra-testicular and post-testicular
events have been postulated and different mechanisms have been proposed to explain the presence of damaged DNA in human spermatozoa.
Three among them, i.e. abnormal chromatin packaging, oxidative stress and apoptosis, are the most studied and discussed in
the present review. Furthermore, results from numerous investigations are presented, including our own findings on these pathological
conditions, as well as the techniques applied for their evaluation. The crucial points of each methodology on the successful
detection of DNA damage and their validity on the appraisal of infertile patients are also discussed. Along with the conventional
parameters examined in the standard semen analysis, evaluation of damaged sperm DNA seems to complement the investigation
of factors affecting male fertility and may prove an efficient diagnostic tool in the prediction of pregnancy outcome. 相似文献
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Jasreen Kular Jennifer C. Tickner Nathan J. Pavlos Helena M. Viola Tamara Abel Bay Sie Lim Xiaohong Yang Honghui Chen Robert Cook Livia C. Hool Ming Hao Zheng Jiake Xu 《The Journal of biological chemistry》2015,290(3):1729-1742
The maintenance of bone homeostasis requires tight coupling between bone-forming osteoblasts and bone-resorbing osteoclasts. However, the precise molecular mechanism(s) underlying the differentiation and activities of these specialized cells are still largely unknown. Here, we identify choline kinase β (CHKB), a kinase involved in the biosynthesis of phosphatidylcholine, as a novel regulator of bone homeostasis. Choline kinase β mutant mice (flp/flp) exhibit a systemic low bone mass phenotype. Consistently, osteoclast numbers and activity are elevated in flp/flp mice. Interestingly, osteoclasts derived from flp/flp mice exhibit reduced sensitivity to excessive levels of extracellular calcium, which could account for the increased bone resorption. Conversely, supplementation of cytidine 5′-diphosphocholine in vivo and in vitro, a regimen that bypasses CHKB deficiency, restores osteoclast numbers to physiological levels. Finally, we demonstrate that, in addition to modulating osteoclast formation and function, loss of CHKB corresponds with a reduction in bone formation by osteoblasts. Taken together, these data posit CHKB as a new modulator of bone homeostasis. 相似文献
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Evidence for evolutionary constraints in <Emphasis Type="Italic">Drosophila</Emphasis> metal biology
Mutations in single Drosophila melanogaster genes can alter total body metal accumulation. We therefore asked whether evolutionary constraints maintain biologically
abundant metal ions (iron, copper, manganese and zinc) to similar concentrations in different species of Drosophilidae, or
whether metal homeostasis is a highly adaptable trait as shown previously for triglyceride and glycogen storage. To avoid
dietary influences, only species able to grow and reproduce on a standard laboratory medium were selected for analysis. Flame
atomic absorption spectrometry was used to determine metal content in 5-days-old adult flies. Overall, the data suggest that
the metallome of the nine species tested is well conserved. Meaningful average values for the Drosophilidae family are presented.
Few statistically significant differences were noted for copper, manganese and zinc between species. In contrast, Drosophila erecta and Drosophila virilis showed a 50% increase above average and a 30% decrease below average in iron concentrations, respectively. The changes in
total body iron content correlated with altered iron storage in intestinal ferritin stores of these species. Hence, the variability
in iron content could be accounted for by a corresponding adaptation in iron storage regulation. We suggest that the relative
expression of the multitude of metalloenzymes and other metal-binding proteins remains overall similar between species and
likely determines relative metal abundances in the organism. The availability of a complete and annotated genome sequence
of different Drosophila species presents opportunities to study the evolution of metal homeostasis in closely related organisms that have evolved
separately for millions or dozens of million years. 相似文献
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Nikitovic D Chalkiadaki G Berdiaki A Aggelidakis J Katonis P Karamanos NK Tzanakakis GN 《The international journal of biochemistry & cell biology》2011,43(6):928-935
Human osteosarcoma cell lines were recently shown to express and secrete the small leucine rich proteoglycan (SLRP) lumican, with the ability to regulate the growth and motility of these cells. In this study, lumican-deficient Saos 2 cells were demonstrated to have increased adhesive capability onto fibronectin (FN) (p≤0.01). Upon neutralization of endogenous transforming growth factor β2 (TGF-β2) activity, no difference in the ability of lumican siRNA-transfected and scramble siRNA-transfected Saos 2 cells to adhere onto FN was detected (p=NS). Exogenous TGF-β2 was shown to stimulate Saos 2 cell adhesion to FN (p≤0.01). These results therefore, suggest that the inverse correlation existing between lumican expression and Saos 2 cell adhesion is dependent on active TGF-β2 signaling. Furthermore, the significant increase in Smad 2 activation present in lumican-deficient cells (p≤0.01) was annulled in the presence of the anti-TGF-β2 peptide, demonstrating that lumican is an upstream regulator of the TGF-β2/Smad 2 signaling cascade. Crucial to FN-dependent adhesion, β1 integrin expression and pFAK activation were likewise identified as downstream TGF-β2 effectors regulated by lumican expression. In conclusion, this study demonstrates a novel out-in signaling circuit in human osteosarcoma cells: secreted to extracellular matrix lumican is an endogenous inhibitor of TGF-β2 activity, resulting in downstream effector modulation including pSmad 2, integrin β1 and pFAK to regulate osteosarcoma adhesion. 相似文献
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Christopher Tzioupis Pavlos Panteliadis Zakareya Gamie Eleftherios Tsiridis 《Journal of medical case reports》2011,5(1):1-7