Curcumin as Treatment for Bladder Cancer : A Preclinical Study of Cyclodextrin-Curcumin Complex and BCG as Intravesical Treatment in an Orthotopic Bladder Cancer Rat Model

Objective. To evaluate the antitumor effect of cyclodextrin-curcumin complex (CDC) on human and rat urothelial carcinoma cells in vitro and to evaluate the effect of intravesical instillations of CDC, BCG, and the combination in vivo in the AY-F344 orthotopic bladder cancer rat model. Curcumin has anticarcinogenic activity on urothelial carcinoma and is therefore under investigation for the treatment of non-muscle invasive bladder cancer. Curcumin and BCG share immunomodulating pathways against urothelial carcinoma. Methods. Curcumin was complexed with cyclodextrin to improve solubility. Four human urothelial carcinoma cell lines and the AY-27 rat cell line were exposed to various concentrations of CDC in vitro. For the in vivo experiment, the AY-27 orthotopic bladder cancer F344 rat model was used. Rats were treated with consecutive intravesical instillations of CDC, BCG, the combination of CDC+BCG, or NaCl as control. Results. CDC showed a dose-dependent antiproliferative effect on all human urothelial carcinoma cell lines tested and the rat AY-27 urothelial carcinoma cell line. Moreover, intravesical treatment with CDC and CDC+BCG results in a lower percentage of tumors (60% and 68%, respectively) compared to BCG (75%) or control (85%). This difference with placebo was not statistically significant (p=0.078 and 0.199, respectively). However, tumors present in the placebo and BCG-treated rats were generally of higher stage. Conclusions. Cyclodextrin-curcumin complex showed an antiproliferative effect on human and rat urothelial carcinoma cell lines in vitro. In the aggressive orthotopic bladder cancer rat model, we observed a promising effect of CDC treatment and CDC in combination with BCG.Peer reviewe

Natural Variation in Arabidopsis Cvi-0 Accession Reveals an Important Role of MPK12 in Guard Cell CO2 Signaling

Plant gas exchange is regulated by guard cells that form stomatal pores. Stomatal adjustments are crucial for plant survival; they regulate uptake of CO2 for photosynthesis, loss of water, and entrance of air pollutants such as ozone. We mapped ozone hypersensitivity, more open stomata, and stomatal CO2-insensitivity phenotypes of the Arabidopsis thaliana accession Cvi-0 to a single amino acid substitution in MITOGEN-ACTIVATED PROTEIN (MAP) KINASE 12 (MPK12). In parallel, we showed that stomatal CO2-insensitivity phenotypes of a mutant cis (CO2-insensitive) were caused by a deletion of MPK12. Lack of MPK12 impaired bicarbonate-induced activation of S-type anion channels. We demonstrated that MPK12 interacted with the protein kinase HIGH LEAF TEMPERATURE 1 (HT1)-a central node in guard cell CO2 signaling-and that MPK12 functions as an inhibitor of HT1. These data provide a new function for plant MPKs as protein kinase inhibitors and suggest a mechanism through which guard cell CO2 signaling controls plant water management.</p

Cyclodextrin Curcumin Formulation Improves Outcome in a Preclinical Pig Model of Marginal Kidney Transplantation

International audienceDecreasing organ quality is prompting research toward new methods to alleviate ischemia reperfusion injury (IRI). Oxidative stress and nuclear factor kappa beta (NF‐κB) activation are well‐described elements of IRI. We added cyclodextrin‐complexed curcumin (CDC), a potent antioxidant and NF‐κB inhibitor, to University of Wisconsin (UW) solution (Belzer's Solution, Viaspan), one of the most effective clinically approved preservative solutions. The effects of CDC were evaluated on pig endothelial cells and in an autologous donation after circulatory death (DCD) kidney transplantation model in large white pigs. CDC allowed rapid and lasting uptake of curcumin into cells. In vitro, CDC decreased mitochondrial loss of function, improved viability and lowered endothelial activation. In vivo, CDC improved function recovery, lowered histological injury and doubled animal survival (83.3% vs. 41.7%). At 3 months, immunohistochemical staining for epithelial‐to‐mesenchymal transition (EMT) and fibrosis markers was intense in UW grafts while it remained limited in the UW + CDC group. Transcriptional analysis showed that CDC treatment protected against up‐regulation of several pathophysiological pathways leading to inflammation, EMT and fibrosis. Thus, use of CDC in a preclinical transplantation model with stringent IRI rescued kidney grafts from an unfavorable prognosis. As curcumin has proved well tolerated and nontoxic, this strategy shows promise for translation to the clini

Child undernutrition in Kenya: trend analyses from 1993 to 2008-09

Background: Research on trends in child undernutrition in Kenya has been hindered by the challenges of changing criteria for classifying undernutrition, and an emphasis in the literature on international comparisons of countries’ situations. There has been little attention to within-country trend analyses. This paper presents child undernutrition trend analyses from 1993 to 2008–09, using the 2006 WHO criteria for undernutrition. The analyses are decomposed by child’s sex and age, and by maternal education level, household Wealth Index, and province, to reveal any departures from the overall national trends. Methods: The study uses the Kenya Demographic and Health Survey data collected from women aged 15–49 years and children aged 0–35 months in 1993, 1998, 2003 and 2008–09. Logistic regression was used to test trends. Results: The prevalence of wasting for boys and girls combined remained stable at the national level but declined significantly among girls aged 0–35 months (p &lt; 0.05). While stunting prevalence remained stagnant generally, the trend for boys aged 0–35 months significantly decreased and that for girls aged 12–23 months significantly increased (p &lt; 0.05). The pattern for underweight in most socio-demographic groups showed a decline. Conclusion: The national trends in childhood undernutrition in Kenya showed significant declines in underweight while trends in wasting and stunting were stagnant. Analyses disaggregated by demographic and socio-economic segments revealed some significant departures from these overall trends, some improving and some worsening. These findings support the importance of conducting trend analyses at detailed levels within countries, to inform the development of better-targeted childcare and feeding interventions