Endothelial progenitor cells (EPCs) move towards injured endothelium or inflamed tissues and incorporate into foci of neovascularisation, thereby improving blood flow and tissue repair. Patients with cardiovascular diseases have been shown to exhibit reduced EPC number and function. It has become increasingly apparent that these changes may be effected in response to enhanced oxidative stress, possibly as a result of systemic and localised inflammatory responses. The interplay between inflammation and oxidative stress affects the initiation, progression, and complications of cardiovascular diseases. Recent studies suggest that inflammation and oxidative stress modulate EPC bioactivity. Clinical medications with anti-inflammatory and antioxidant properties, such as statins, thiazolidinediones, angiotensin II receptor 1 blockers, and angiotensin-converting enzyme inhibitors, are currently administered to patients with cardiovascular diseases. These medications appear to exert beneficial effects on EPC biology. This review focuses on EPC biology and explores the links between oxidative stress, inflammation, and development of cardiovascular diseases.

To investigate the effects of ellagic acid on the growth inhibition of TSGH8301 human bladder cancer cells in vitro, cells were incubated with various doses of ellagic acid for different time periods. The phase-contrast microscope was used for examining and photographing the morphological changes in TSGH8301 cells. Flow cytometric assay was used to measure the percentage of viable cells, cell cycle distribution, apoptotic cells, ROS, mitochondrial membrane potential (ΔΨm), Ca(2+) , caspase-9 and -3 activities in TSGH8301 cells after exposure to ellagic acid. Western blotting was used to examine the changes of cell cycle and apoptosis associated proteins levels. Results indicated that ellagic acid induced morphological changes, decreased the percentage of viable cells through the induction of G0/G1 phase arrest and apoptosis, and also showed that ellagic acid promoted ROS and Ca(2+) productions and decreased the level of ΔΨm and promoted activities of caspase-9 and -3. The induction of apoptosis also confirmed by annexin V staining, comet assay, DAPI staining and DNA gel electrophoresis showed that ellagic acid induced apoptosis and DNA damage in TSGH8301 cells. Western blotting assay showed that ellagic acid promoted p21, p53 and decreased CDC2 and WEE1 for leading to G0/G1 phase arrest and promoting BAD expression, AIF and Endo G, cytochrome c, caspase-9 and -3 for leading to apoptosis in TSGH8301 cells. On the basis of these observations, we suggest that ellagic acid induced cytotoxic effects for causing a decrease in the percentage of viable cells via G0/G1 phase arrest and induction of apoptosis in TSGH8301 cells.

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Dietary quercetin and resveratrol have been frequently used in treating various diseases, but the underlying mechanisms are not entirely clear. Here, we report combined transcriptomic and metabonomic profiling that showed that the combined supplementation with quercetin and resveratrol produced synergistic effects on a high-fat diet-induced metabolic phenotype in mice. Histological and phenotypic improvements in serum and hepatic total cholesterol, insulin, fasting blood glucose, and HbA1c were also observed in mice receiving combined quercetin and resveratrol supplementation. This combined quercetin and resveratrol supplementation resulted in significant restoration of gene sets in functional pathways of glucose/lipid metabolism, liver function, cardiovascular system, and inflammation/immunity, which were altered by high fat diet feeding. The integration of transcriptomic and metabonomic data indicated quercetin and resveratrol supplementation enhanced processes of glycolysis and fatty acid oxidation, as well as suppressed gluconeogenesis. These alterations discovered at both the transcriptional and metabolic levels highlight the significance of combined "omics" platforms for elucidating mechanistic pathways altered by dietary polyphenols, such as quercetin and resveratrol, in a synergistic manner.

Indole-3-carbinol (I3C), a potential anticancer substance, can be found in cruciferous (cabbage family) vegetables, mainly cauliflower and Chinese cabbage. However, the bioactivity of I3C on the apoptotic effects of murine leukemia WEHI-3 cells and promotion of immune responses in leukemia mice model are unclear. In this study, we investigated the effect of I3C on cell-cycle arrest and apoptosis in vitro and immunomodulation in vivo. I3C decreased the viable WEHI-3 cells and caused morphological changes in a concentration- and time-dependent manner. I3C also led to G0/G1 phase arrest, decreased the levels of cyclin A, cyclin D, and CDK2, and increased the level of p21(WAF1/CIP1). Flow cytometric analyses further proved that I3C promoted ROS and intracellular Ca(2+) production and decreased the levels of ΔΨ(m) in WEHI-3 cells. Cells after exposure to I3C for 24 h showed DNA fragmentation and chromatin condensation. Comet assay also indicated that I3C induced DNA damage in examined cells. I3C increased the levels of cytochrome c, FADD, GADD153, GRP78, and caspase-12 as well as induced activities of caspase-3, -8, and -9. Moreover, I3C attenuated NF-κB DNA binding activity in I3C-treated WEHI-3 cells as shown by EMSA and Western blotting analyses. In the in vivo study, we examined the effects of I3C on WEHI-3 leukemia mice. Results showed that I3C increased the level of T cells and decreased the level of macrophages. I3C also reduced the weights of liver and spleen, and it promoted phagocytosis by macrophages as compared to the nontreated leukemia mice group. On the basis of our results, I3C affects murine leukemia WEHI-3 cells both in vitro and in vivo.

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus (DM). To discover early stage biomarkers of DN, untargeted liquid chromatography–mass spectrometry-based metabolomic analysis was performed in urine samples from healthy subjects and patients with micro- or macroalbuminuria due to nondiabetic disease (macro), type 2 DM without microalbuminuria (T2DM), and type 2 DM with microalbuminuria (T2DM+micro). Levels of four metabolites were significantly different among groups, and they were quantified in a larger group of 267 urine samples. Two metabolites were also discovered and validated in targeted metabolic study of amino acids. For diagnosis of nephropathy, N1-methylguanosine had the highest area-under-the-curve (AUC) value of 0.75 when compared to those of valine (0.68), xanthosine (0.67), and 7-methyluric acid (0.69). After combining fasting blood glucose and diastolic blood pressure (DBP) with N1-methylguanosine, the AUC increased to 0.987. To distinguish between T2DM and T2DM+micro conditions, xanthosine and N1-methylguanosine have AUC value of 0.612 and 0.624, respectively. After adjustment of HbA1c and DBP, AUC values of xanthosine and N1-methylguanosine increased to 0.716 and 0.723, respectively, and could be used to predict the development of nephropathy in T2DM patients.

A single-group crossover design was used to examine the effects of a warm footbath on body temperatures, distal-proximal skin temperature gradient (DPG), and sleep outcomes in 15 Taiwanese elders with self-reported sleep disturbance. Body temperatures and polysomnography were recorded for 3 consecutive nights. Participants were assigned randomly to receive a 41°C footbath for 40 minutes before sleep onset on night 2 or night 3. Mean DPG before lights off was significantly elevated on the bathing night. There were no significant differences in sleep outcomes between the two nights. However, when the first two non-rapid eye movement (NREM) sleep periods were examined, the amount of wakefulness was decreased in the second NREM period on the bathing night. Keywords sleep/rest; agingInsomnia is a common complaint in older adults. They have trouble falling asleep, as well as frequent or prolonged nocturnal or early morning awakenings with an inability to return to sleep (Ancoli-Israel, 1997;Ancoli-Israel & Roth, 1999;Floyd, Medler, Ager, & Janisse, 2000). The overall prevalence of insomnia in the elderly ranges from 14.0% -42.2% based on epidemiological surveys (Chiu et al., 1999;Kim, Uchiyama, Okawa, Liu, & Ogihara, 2000;Ohayon, 1996). As many as 25% of healthy elderly men and women may have chronic insomnia (Ohayon & Smirne, 2002). Global sleep dissatisfaction, defined as overall dissatisfaction with sleep, ranges from 7.7 -20.8% in the elderly, which is higher than in the general population (7.0-10.1%; Pallesen et al., 2001).Sleep is periodic resting behavior characterized by "few body movements, a recumbent posture, and complex brain electroencephalographic activity" (Carskadon & Dement, 2000, p.15). Human sleep architecture is defined by polysomnography (PSG) and divided into stages: four of non-rapid eye movement (NREM) sleep (stage 1 to 4), and one stage of rapid-eye movement (REM) sleep (Rechtschaffen & Kales 1968 Age has large effects on sleep architecture. Compared to young adults, PSG-derived sleep architecture in older adults shows increased amounts of nocturnal wakefulness, increased NREM stage 1 sleep with reduced amounts or complete absence of NREM stages 3 and 4 sleep (Floyd et al., 2000;Van Someren, 2000a). In some studies, the percentage of REM sleep was reduced slightly in older adults (Van Cauter, Leproult, & Plat, 2000), whereas findings from other studies showed that older adults experienced typical amounts of REM sleep (Campbell & Murphy, 1998). Long sleep latencies (e.g. > 30 minutes), reduced sleep efficiency (e.g. < 85%), and a sleep duration of ≤ 6 hours were common in older adults. These characteristics are consistent with the criteria of insomnia, although not all older adults complained of poor sleep (Vitiello, Larsen, & Moe, 2004).In addition to changes in sleep architecture, there are changes in the circadian rhythm of body temperature in older adults compared to young adults. A circadian rhythm is the variation in body functions and behaviors that occur in a regular pattern ar...

The data for IL1B polymorphisms and the association of GD and GO with plasma IL1β levels show that IL1B polymorphisms may be associated with the development of GD and GO.