Abstract:Bladder cancer is one of the most frequent cancers among males, and its poor survival rate reflects problems with aggressiveness and chemo-resistance. Recent interest has focused on the use of chemopreventatives (nontoxic natural agents that may suppress cancer progression) to induce targeted apoptosis for cancer therapy. Capsaicin, which has anti-cancer properties, is one such agent. It is known to preferentially inhibit a tumor-associated NADH oxidase (tNOX) that is preferentially expressed in cancer/transformed cells. Here, we set out to elucidate the correlation between tNOX expression and the inhibitory effects of capsaicin in human bladder cancer cells. We showed that capsaicin downregulates tNOX expression and decreases bladder cancer cell growth by enhancing apoptosis. Moreover, capsaicin was found to reduce the expression levels of several proteins involved in cell cycle progression, in association with increases in the cell doubling time and enhanced cell cycle arrest. Capsaicin was also shown to inhibit the activation of ERK, thereby reducing the phosphorylation of paxillin and FAK, which leads to decreased cell migration. Finally, our results indicate that RNA interference-mediated tNOX depletion enhances spontaneous apoptosis, prolongs cell cycle progression, and reduces cell migration and the epithelial-mesenchymal transition. We also observed a downregulation of sirtuin 1 (SIRT1) in these tNOX-knockdown cells, a deacetylase that is important in multiple cellular functions. Taken together, our results indicate that capsaicin inhibits the growth of bladder cancer cells by inhibiting tNOX and SIRT1 and thereby reducing proliferation, attenuating migration, and prolonging cell cycle progression.

No abstract

Numerous PID tuning rules exist, and new rules continue to be proposed in the literature. The primary objective of this article is to evaluate comprehensively and compare several recent or popular PID tuning methods based on the integral of absolute error in the controlled variable, total variation of the manipulated variable and maximum sensitivity. Several tuning rules such as internal model control, direct synthesis, and optimizationbased methods were considered and evaluated for a range of first-order plus dead time process dynamics subjected to set-point changes and/or load disturbances via simulation. On the basis of the results, recommendations were then provided for selecting the optimal tuning rule for industrial processes according to the desired control objective (servo versus regulatory) and the process dead time to time constant ratio.

No abstract

ObjectiveSpousal clustering of diabetes merits attention. Whether old-age vulnerability or a shared family environment determines the concordance of diabetes is also uncertain. This study investigated the spousal concordance of diabetes and compared the risk of diabetes concordance between couples and noncouples by using nationally representative data.MethodsA total of 22,572 individuals identified from the 2002–2013 National Health Insurance Research Database of Taiwan constituted 5,643 couples and 5,643 noncouples through 1:1 dual propensity score matching (PSM). Factors associated with concordance in both spouses with diabetes were analyzed at the individual level. The risk of diabetes concordance between couples and noncouples was compared at the couple level. Logistic regression was the main statistical method. Statistical data were analyzed using SAS 9.4. C&RT and Apriori of data mining conducted in IBM SPSS Modeler 13 served as a supplement to statistics.ResultsHigh odds of the spousal concordance of diabetes were associated with old age, middle levels of urbanization, and high comorbidities (all P < 0.05). The dual PSM analysis revealed that the risk of diabetes concordance was significantly higher in couples (5.19%) than in noncouples (0.09%; OR = 61.743, P < 0.0001).ConclusionsA high concordance rate of diabetes in couples may indicate the influences of assortative mating and shared environment. Diabetes in a spouse implicates its risk in the partner. Family-based diabetes care that emphasizes the screening of couples at risk of diabetes by using the identified risk factors is suggested in prospective clinical practice interventions.

Capsaicin (8-methyl-N-vanillyl-6-noneamide), which is an active component in red chili peppers, is used as a chemopreventive agent that shows favorable cytotoxicity against cancer cells. Accumulating evidence indicates that capsaicin preferentially inhibits a tumor-associated NADH oxidase (tNOX, ENOX2) that is ubiquitously expressed in cancer but not in non-transformed cells. This attenuates cancer cell growth by inducing apoptosis. The capsaicin-mediated inhibition of tNOX was recently shown to prolong the cell cycle. However, the molecular events underlying this regulation have not yet been investigated. In the present study, we used a cellular thermal shift assay (CETSA) to detect “target engagement” of capsaicin and its consequent impact on cell cycle progression. Our results indicated that capsaicin engaged with tNOX and triggered the proteasomal degradation of tNOX, which leads to the inhibition of NAD+-dependent SIRT1 deacetylase. Ultimately, the acetylation levels of c-Myc and p53 were enhanced, which suppressed the activation of G1 cyclin/Cyclin-dependent kinase complexes and triggered cell cycle arrest in cancer cells. The results obtained when tNOX was overexpressed in non-cancer cells validated its importance in cell cycle progression. These findings provide the first molecular insights into the regulatory role of tNOX and the anti-proliferative property of capsaicin in regulating the cell cycle of bladder cancer cells.

No abstract

No abstract