The aim of this review, a summary of the putative biological actions of flavonoids, was to obtain a further understanding of the reported beneficial health effects of these substances. Flavonoids occur naturally in fruit, vegetables, and beverages such as tea and wine. Research in the field of flavonoids has increased since the discovery of the French paradox,ie, the low cardiovascular mortality rate observed in Mediterranean populations in association with red wine consumption and a high saturated fat intake. Several other potential beneficial properties of flavonoids have since been ascertained. We review the different groups of known flavonoids, the probable mechanisms by which they act, and the potential clinical applications of these fascinating natural substances.
Previous studies in lymphocytes have described two DNA‐binding HMG box proteins, TCF‐1 and LEF‐1, with affinity for the A/TA/TCAAAG motif found in several T cell‐specific enhancers. Evaluation of cotransfection experiments in non‐T cells and the observed inactivity of an AACAAAG concatamer in the TCF‐1/LEF‐1‐expressing T cell line BW5147, led us to conclude that these two proteins did not mediate the observed enhancer effect. We therefore searched for additional HMG box proteins. By a PCR‐aided strategy, we cloned Sox‐4, a gene with homology to the HMG box region of the sex determining gene SRY. Sox‐4 was expressed in T and pre‐B lymphocyte lines and in the murine thymus. Significantly, BW5147 T cells did not express Sox‐4. Recombinant Sox‐4 bound with high affinity (Kd 3 × 10(−11) M) to the minor groove of the AACAAAG motif, most likely contacting all seven base pairs. In contrast with observations on TCF‐1 and LEF‐1, cotransfection with Sox‐4 unveiled a transactivating capacity, which mapped to its serine‐rich C terminus. This region remained functional upon grafting onto a GAL4 DNA‐binding domain. Sox‐4 is thus the first ‘classical’ transcription factor in the Sox gene family with separable DNA‐binding and transactivation domains. Our observations indicate that a detailed understanding of T cell‐specific gene control must integrate the concerted activity of at least three tissue‐specific HMG box genes.
Cancer cachexia is characterised by metabolic alterations leading to loss of adipose tissue and lean body mass and directly compromises physical performance and the quality of life of cancer patients. In a murine cancer cachectic model, the effects of dietary supplementation with a specific combination of high protein, leucine and fish oil on weight loss, muscle function and physical activity were investigated. Male CD2F1 mice, 6 -7 weeks old, were divided into body weight-matched groups: (1) control, (2) tumourbearing, and (3) tumour-bearing receiving experimental diets. Tumours were induced by s.c. inoculation with murine colon adenocarcinoma (C26) cells. Food intake, body mass, tumour size and 24 h-activity were monitored. Then, 20 days after tumour/ vehicle inoculation, the animals were killed and muscle function was tested ex vivo. Tumour-bearing mice showed reduced carcass, muscle and fat mass compared with controls. EDL muscle performance and total daily activity were impaired in the tumour-bearing mice. Addition of single nutrients resulted in no or modest effects. However, supplementation of the diet with the all-in combination of high protein, leucine and fish oil significantly reduced loss of carcass, muscle and fat mass (loss in mass 45, 52 and 65% of TB-con, respectively (Po0.02)) and improved muscle performance (loss of max force reduced to 55 -64% of TB-con (Po0.05)). Moreover, total daily activity normalised after intervention with the specific nutritional combination (50% of the reduction in activity of TB-con (Po0.05)). In conclusion, a nutritional combination of high protein, leucine and fish oil reduced cachectic symptoms and improved functional performance in cancer cachectic mice. Comparison of the nutritional combination with its individual modules revealed additive effects of the single components provided.
Chemotherapy-induced fatigue is a multidimensional symptom. Oxidative stress has been proposed as a working mechanism for anthracycline-induced cardiotoxicity. In this study, doxorubicin (DOX) was tested on skeletal muscle function. Doxorubicin induced impaired ex vivo skeletal muscle relaxation followed in time by contraction impediment, which could be explained by DOXinduced changes in Ca 2 þ responses of myotubes in vitro. The Ca 2 þ responses in skeletal muscle, however, could not be explained by oxidative stress.
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