76 research outputs found

    The Chemopreventive Effects of Protandim: Modulation of p53 Mitochondrial Translocation and Apoptosis during Skin Carcinogenesis

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    Protandim, a well defined dietary combination of 5 well-established medicinal plants, is known to induce endogenous antioxidant enzymes, such as manganese superoxide dismutase (MnSOD). Our previous studies have shown through the induction of various antioxidant enzymes, products of oxidative damage can be decreased. In addition, we have shown that tumor multiplicity and incidence can be decreased through the dietary administration of Protandim in the two-stage skin carcinogenesis mouse model. It has been demonstrated that cell proliferation is accommodated by cell death during DMBA/TPA treatment in the two-stage skin carcinogenesis model. Therefore, we investigated the effects of the Protandim diet on apoptosis; and proposed a novel mechanism of chemoprevention utilized by the Protandim dietary combination. Interestingly, Protandim suppressed DMBA/TPA induced cutaneous apoptosis. Recently, more attention has been focused on transcription-independent mechanisms of the tumor suppressor, p53, that mediate apoptosis. It is known that cytoplasmic p53 rapidly translocates to the mitochondria in response to pro-apoptotic stress. Our results showed that Protandim suppressed the mitochondrial translocation of p53 and mitochondrial outer membrane proteins such as Bax. We examined the levels of p53 and MnSOD expression/activity in murine skin JB6 promotion sensitive (P+) and promotion-resistant (P-) epidermal cells. Interestingly, p53 was induced only in P+ cells, not P- cells; whereas MnSOD is highly expressed in P- cells when compared to P+ cells. In addition, wild-type p53 was transfected into JB6 P- cells. We found that the introduction of wild-type p53 promoted transformation in JB6 P- cells. Our results suggest that suppression of p53 and induction of MnSOD may play an important role in the tumor suppressive activity of Protandim

    Myocardial tissue and metabolism characterization in men with alcohol consumption by cardiovascular magnetic resonance and 11C-acetate PET/CT

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    Background: Chronic alcohol consumption initially leads to asymptomatic left ventricular dysfunction, but can result in myocardial impairment and heart failure if ongoing. This study sought to characterize myocardial tissues and oxidative metabolism in asymptomatic subjects with chronic alcohol consumption by quantitative cardiovascular magnetic resonance (CMR) and 11C-acetate positron emission tomography (PET)/computed tomography (CT). Methods: Thirty-four male subjects (48.8 +/- 9.1 years) with alcohol consumption > 28 g/day for > 10 years and 35 age-matched healthy male subjects (49.5 +/- 9.7 years) underwent CMR and 11C-acetate PET/CT. Native and post T1 values and extracellular volume (ECV) from CMR and Kmono and K1 from PET imaging were measured. Quantitative measurements by CMR and PET imaging were compared between subjects with moderate to heavy alcohol consumption and healthy controls, and their correlations were also analyzed. Results: Compared to healthy controls, subjects with alcohol consumption showed significantly shorter native T1 (1133 +/- 65 ms vs. 1186 +/- 31 ms, p 0.05). In contrast, subjects with heavy alcohol consumption showed significantly lower Kmono values compared to those with moderate alcohol consumption (52.9 +/- 12.1 min(- 1) x 10(- 3) vs. 63.7 +/- 9.2 min(- 1) x 10(- 3), p = 0.012). Strong and moderate correlations were found between K1 and ECV in healthy controls (r = 0.689, p = 0.013) and subjects with moderate alcohol consumption (r = 0.518, p = 0.048), respectively. Conclusion: Asymptomatic men with heavy alcohol consumption have detectable structural and metabolic changes in myocardium on CMR and 11C-acetate PET/CT. Compared with quantitative CMR, 11C-acetate PET/CT imaging may be more sensitive for detecting differences in myocardial damage among subjects with moderate to heavy alcohol consumption.</div

    Protandim, a Fundamentally New Antioxidant Approach in Chemoprevention Using Mouse Two-Stage Skin Carcinogenesis as a Model

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    Oxidative stress is an important contributor to cancer development. Consistent with that, antioxidant enzymes have been demonstrated to suppress tumorigenesis when being elevated both in vitro and in vivo, making induction of these enzymes a more potent approach for cancer prevention. Protandim, a well-defined combination of widely studied medicinal plants, has been shown to induce superoxide dismutase (SOD) and catalase activities and reduce superoxide generation and lipid peroxidation in healthy human subjects. To investigate whether Protandim can suppress tumor formation by a dietary approach, a two-stage mouse skin carcinogenesis study was performed. At the end of the study, the mice on a Protandim-containing basal diet had similar body weight compared with those on the basal diet, which indicated no overt toxicity by Protandim. After three weeks on the diets, there was a significant increase in the expression levels of SOD and catalase, in addition to the increases in SOD activities. Importantly, at the end of the carcinogenesis study, both skin tumor incidence and multiplicity were reduced in the mice on the Protandim diet by 33% and 57% respectively, compared with those on basal diet. Biochemical and histological studies revealed that the Protandim diet suppressed tumor promoter-induced oxidative stress (evidenced by reduction of protein carbonyl levels), cell proliferation (evidenced by reduction of skin hyperplasia and suppression of PKC/JNK/Jun pathway), and inflammation (evidenced by reduction of ICAM-1/VCAM-1 expression, NF-ÎşB binding activity, and nuclear p65/p50 levels). Overall, induction of antioxidant enzymes by Protandim may serve as a practical and potent approach for cancer prevention

    Evolutionary Game of Group Cooperation Institutions for Chaoshan Businessmen in Ming and Qing Dynasties

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    Chaoshan businessmen were widely involved in internal group cooperation. Based on historical and comparative institutional analysis, it is found that the cooperative behavior of Chaoshan businessmen in the Ming and Qing Dynasties is not simply an economic behavior. It reflects the historical evolution of the interaction between the regional cultures concerning the sea, clan and Confucianism, the governance of merchant groups with blood and geographical characteristics, and the beliefs of merchants in Mazu and Guan Yu. The evolutionary game theory is used to investigate the evolutionary process and the evolutionary stable strategy of the internal cooperative behavior of Chaoshan businessmen. It shows that due to the joint influence of regional culture, governance of merchant groups and beliefs of merchants, a multilateral collective punishment mechanism for untrustworthy merchants and a loss compensation mechanism for trustworthy merchants are established through channels such as chambers of commerce and ancestral temples. Thus, it reinforces the group cooperation institutions of integrity within Chaoshan merchant groups in the Ming and Qing Dynasties

    Studies of combustion characteristics of heavy hydrocarbons in simple and complex flows

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    The main focus of this dissertation was the experimental and numerical investigations of laminar flames of heavy liquid and solid hydrocarbons under simple (one-dimensional, steady state flow field using canonical configuration) and complex (two/three-dimensional, transient flow at high Karlovitz number) flow conditions. A number of theories that have developed based on simplified assumptions and asymptotic analysis and more important for light fuels such as methane, were examined both experimentally and numerically in two steady state and canonical configuration, namely counter-flow configuration and Bunsen flame configuration. The counter-flow configuration was used to determine laminar flame speeds and extinction strain rates over a wide range of heavy hydrocarbons including normal alkanes (up to carbon number 16), practical gasolines and jet fuels and aromatics (cyclopentadiene). The analytical solution derived from asymptotic analysis provides good agreement for laminar flame speeds for fuel lean conditions. However notable discrepancies have been identified for fuel rich conditions due to lack of consideration of fuel-oxygen differential diffusion especially for heavy fuels for which the molecular weight disparity between oxygen and fuel is large. For the Bunsen flame configuration, the area and angle methods were examined to measure laminar flame speeds of methane/air flames (representative of light fuel) and propane/air flames given that propane is the lightest hydrocarbon with distinctly higher molecular weight than oxygen. The results indicated that apart from issues raised from inlet boundary condition, flame extinction induced complex flow distribution at burner edge and flame tip effect, such configuration can’t produce quantitative results for fuels heavier than methane due to lack of consideration of flame speed variation to stretch for fuel/air mixtures with non-unity Lewis number. Based on the understanding of the propagation of flames of heavy fuels, accurate measurements of laminar flame speeds were carried out using the counter-flow configuration at atmospheric pressure for a variety of complex fuel molecules for which data are non-existing and which are of direct relevance to practical fuels. The interaction between a flame and turbulence is a fundamental aspect of combustion. To further illustrate the difference of flame behaviors between light and heavy fuels, the vortex laminar flame interaction was studied numerically in a canonical two-dimensional configuration for methane and n-dodecane flames. The n-dodecane exhibits early decomposition prior entering the flame due to the local temperature rise caused by the vortex, and such phenomenon is not observed in methane/air flames. In summary, the main conclusion of this dissertation is that the fuel complexity that has been frequently ignored in flame research needs to be accounted for in simple and complex flows. It was shown that the fuel effects are both of physical and chemical nature

    Evolutionary Game Analysis on Group Cooperation of Heterogeneous Chaoshan Firms

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    In developing global trade and commerce, firms founded by Chaoshan merchants have gradually formed informal institutions of group cooperation. This study constructs an asymmetric evolutionary game model for Chaoshan firms from the HCIA (historical and comparative institutional analysis) perspective of group cooperation institutions. Furthermore, it analyses the evolutionary path and the constraint mechanism of group cooperation institutions of heterogeneous Chaoshan firms. The results suggest that if the net payoffs to one party from cooperation are less than those from a breach, it is detrimental for both parties to continue group cooperation. When the net payoffs from cooperation are more than those from a breach, both parties choose group cooperation if reputational compensation covers the losses. Otherwise, the ultimate cooperation between both parties depends on the distribution of benefits, the profitability of cooperation, the penalty cost of a breach, the cost of cooperation and the loss from a breach suffered by adhering to cooperation

    The mitochondrial genome of Anthalia sp. (Diptera: Empididae)

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    The dance fly Anthalia sp. belongs to the subfamily Ocydromiinae of Empididae. The mitogenome (GenBank accession number: MT483943) of Anthalia sp. was sequenced, the new representative of the mitogenome of the subfamily. The nearly complete mitogenome is 15,142 bp totally, consisting of 13 protein-coding genes, 2 rRNAs, and 22 transfer RNAs. All genes have the similar locations and strands with that of other published species of Empididae. The nucleotide composition biases toward A and T, which together made up 78.6% of the entirety. Bayesian inference analysis strongly supported the monophyly of Empidoidea, Empididae, and Dolichopodidae. It is clear that the phylogenetic relationship within Empidoidea: (Dolichopodinae + Neurigoninae) + ((Empidinae + (Trichopezinae + Oreogetoninae)) + Ocydromiinae) in this study

    Design Scheme of Public Transport Comprehensive Dispatching MIS based on MAS

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    A MAS (Multi-agent system) is made from independent and interactional multi-agents with some attributes: independence, adaptability, consecution, better cognition ability with actively openness, etc. Public Transport Comprehensive Dispatching MIS is an intelligent service platform that manages urban public transport systems. It has some functions, such as collecting and promulgating information about passengers and means of transportation; forecasting and assigning public transportation flow; optimizing and scheduling the bus route network; evaluating traffic infrastructure and service level, etc. This paper utilizes MAS to separate complicated dynamic urban public transport systems, which includes a variety of factors such as man, vehicle, road, environment and so on, into small concerted system that are easy to manage. The Public Transport Comprehensive Dispatching Management Information System design frame was discussed in conformity to China\u27s city character. In this paper, main contents are stated as follows: the function and demand of this platform are analyzed; control model of this platform is designed based on MAS; variety and action of the agents which belong to the service platform system are separately described. This research is beneficial to improve the efficiency of transportation systems and apply MAS to other traffic aspects
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