Mindfulness induction and executive function after high-intensity interval training with and without mindful recovery intervals.

OBJECTIVES: Determine the effect of incorporating mindfulness-based activities into the recovery intervals of high-intensity interval training (HIIT) on mindfulness induction and subsequent executive function performance. DESIGNS: A within-subject crossover trial. METHODS: Forty adults participated in two experimental conditions, including a 30-min bout of HIIT involving mindfulness recovery intervals (Mindful) and a 30-min bout of HIIT without mindfulness recovery intervals (Non-mindful), on two separate days in counterbalanced order. Before and after each condition, participants completed the flanker task, switch-flanker task, and n-back task to measure inhibitory control, cognitive flexibility, and working memory, respectively. RESULTS: A higher level of mindfulness state was observed following the Mindful condition than the Non-mindful condition. Dispositional mindfulness was positively correlated with the level of the mindful state only during the Mindful condition but not the Non-mindful condition. The switch-flanker response accuracy was improved from the pretest to posttest during the Non-mindful condition but remained unchanged over time during the Mindful condition. Time-related improvements in the flanker and n-back task outcomes were observed for both the Mindful and Non-mindful conditions and did not differ between conditions. CONCLUSION: Although incorporating mindfulness-based activities during the recovery intervals of HIIT successfully led to greater state-related mindfulness, such a heightened mindful state did not correspond with additional modulation in inhibitory control and working memory performance while attenuating HIIT-related positive changes in task performance requiring cognitive flexibility.

Acute effects of mindful interval exercise on cognitive performance in a higher education setting.

Interval exercise (IE) has been shown to have acute facilitating effects on cognition; however, the existing literature has been limited to laboratory settings and has focused on manipulating the parameters of exercise bouts during IE. This study included two classroom-based experiments to (1) investigate the effect of an acute bout of IE delivering mindfulness activity during its recovery intervals (mindful IE) on cognitive performance, and (2) compare cognitive performance following acute bouts of mindful IE with non-mindful IE. Experiment 1: Using a class-based within-subject crossover design, 59 participants completed the Stroop, d2, and trail-making tests to measure inhibitory control, attention, and cognitive flexibility, after a 30-min non-exercise or mindful IE session on separate counterbalanced days. Experiment 2: Using a similar design, 70 participants were assigned to two groups to receive a non-exercise and an IE session with (mindful) or without (non-mindful) mindfulness-based recovery intervals on separate counterbalanced days. Results from Experiment 1 showed superior d2 performance following the mindful IE than the non-exercise session. Although Experiment 2 found exercise-related decreases in commission error rate during the d2 test in both groups, the non-mindful group showed additional decreases in omission and total error rates. Further, higher scores on the nonreactivity facet of dispositional mindfulness were correlated with larger decreases in omission and total error rates during the d2 test for the mindful IE group. No exercise-related effect was found for outcomes of the Stroop and trail-making tests in both experiments. These findings in the selective improvements in d2 test performance are the first to suggest the feasibility of integrating mindfulness activity into the recovery intervals of IE for enhanced cognitive performance that may depend on individual differences in dispositional mindfulness.

Gold(III)-dithiocarbamato peptidomimetics in the forefront of the targeted anticancer therapy: preclinical studies against human breast neoplasia.

Since the serendipitous discovery of cisplatin, platinum-based drugs have become well-established antitumor agents, despite the fact that their clinical use is limited by many severe side-effects. In order to both improve the chemotherapeutic index and broaden the therapeutic spectrum of current drugs, our most recent anti-neoplastic agents, Au(III) complexes, were designed as carrier-mediated delivery systems exploiting peptide transporters, which are up-regulated in some cancers. Among all, we focused on two compounds and tested them on human MDA-MB-231 (resistant to cisplatin) breast cancer cell cultures and xenografts, discovering the proteasome as a major target both in vitro and in vivo. 53% inhibition of breast tumor growth in mice was observed after 27 days of treatment at 1.0 mg kg(-1) d(-1), compared to control. Remarkably, if only the most responsive mice are taken into account, 85% growth inhibition, with some animals showing tumor shrinkage, was observed after 13 days. These results led us to file an international patent, recognizing this class of gold(III) peptidomimetics as suitable candidates for entering phase I clinical trials.

Targeting the ubiquitin-proteasome pathway: an emerging concept in cancer therapy.

Selective degradation of proteins by the ubiquitin-proteasome pathway is a critical determinant for maintaining cellular homeostasis. Most intracellular proteins are degraded by the proteasome, a multicatalytic enzyme complex containing a 20S catalytic core and two 19S regulatory complexes. Many proteasome target proteins are involved in the regulation of important processes of carcinogenesis and cancer cell survival, such as cell cycle progression, cell proliferation, differentiation and apoptosis. Indeed, the ubiquitin-proteasome-dependent degradation pathway plays an essential role in both the up-regulation of cell proliferation and down-regulation of cell death in human cancer cells. Both in vitro and in vivo experimental and clinical results have demonstrated the potential use of proteasome inhibitors as novel anticancer drugs. Proteasome inhibition in cancer cells leads to accumulation of pro-apoptotic target proteins followed by induction of cell death. The clinical efficacy of the proteasome inhibitor bortezomib toward multiple myeloma and other hematologic malignancies provides the "proof of concept" that targeting the proteasome is a promising strategy for cancer treatment. Several other proteasome inhibitors have also been identified from natural resources, such as marine microbial metabolites, green tea polyphenols, flavonoids, and medicinal compounds. Additionally, the use of metal complexes as proteasome inhibitors has also been investigated as a potential anticancer strategy. The clinical significance of targeting the tumor survival-associated proteasome pathway for cancer treatment, intervention and prevention will be discussed.

Inhibition of tumor cellular proteasome activity by triptolide extracted from the Chinese medicinal plant 'thunder god vine'.

AIMS: The molecular mechanisms of triptolide responsible for its antitumor properties are not yet fully understood. The ubiquitin/proteasome system is an important pathway of protein degradation in cells. This study investigated whether triptolide may inhibit proteasomal activity and induce apoptosis in human cancer cells. MATERIALS AND METHODS: In vitro proteasome inhibition was measured by incubation of a purified 20S proteasome with triptolide. Human breast and prostate cancer cell lines were also treated with different doses of triptolide for different times, followed by measurement of proteasome inhibition (levels of the chymotrypsin-like activity, ubiquitinated proteins and three well-known proteasome target proteins, p27, IκB-α and Bax) and apoptosis induction (caspase-3 activity and PARP cleavage). RESULTS: Triptolide did not inhibit the chymotrypsin-like activity of purified 20S proteasome. However, treatment of triptolide was able to cause decreased levels of cellular proteasomal chymotrypsin-like activity and accumulation of ubiquitinated proteins and three well-known proteasome target proteins in human breast and prostate cancer cells, associated with apoptosis induction. CONCLUSION: It is possible that at least one of metabolites of triptolide has proteasome-inhibitory activity.