Fucoxanthin and lipid metabolism: A minireview.

AIMS: Accumulating data suggest that food supplementation with seaweeds which traditionally are an important part of food culture in South-East Asian countries might lead to essential health benefits. In this short review, we summarize findings from experimental studies on the effects of fucoxanthin (a carotenoid derived from brown seaweeds) on lipid metabolism, adiposity, and related conditions and discuss the possible underlying mechanisms. DATA SYNTHESIS: Supplementation of fucoxanthin or its derivatives consistently attenuated body and visceral fat weight gain, lipid accumulation in the liver, decreases insulin resistance, and improves the plasma lipid profile in rodents fed a high-fat diet. It should however be noted that in diabetic/obese KK-Ay mice with genetically compromised insulin signaling, fucoxanthin might increase the plasma levels of cholesterol and low-density lipoproteins. The anti-obesity effects of fucoxanthin are apparently mediated by the hormones leptin and adiponectin through their common target AMK-activated protein kinase, resulting in downregulation of lipogenic enzymes and upregulation of lipolytic enzymes. Fucoxanthin also suppresses adipocyte differentiation and induces the expression of uncoupling proteins in visceral adipose tissue. CONCLUSIONS: The results of experimental studies suggest that consumption of fucoxanthin and its derivatives as nutritional supplements is a promising option for prevention and treatment of obesity and a wide variety of related pathologies, including metabolic syndrome, type 2 diabetes, and heart disease. Yet, clinical trials are warranted to assess a therapeutic value of fucoxanthin.

Cafestol overcomes ABT-737 resistance in Mcl-1-overexpressed renal carcinoma Caki cells through downregulation of Mcl-1 expression and upregulation of Bim expression.

Although ABT-737, a small-molecule Bcl-2/Bcl-xL inhibitor, has recently emerged as a novel cancer therapeutic agent, ABT-737-induced apoptosis is often blocked in several types of cancer cells with elevated expression of Mcl-1. Cafestol, one of the major compounds in coffee beans, has been reported to have anti-carcinogenic activity and tumor cell growth-inhibitory activity, and we examined whether cafestol could overcome resistance against ABT-737 in Mcl-1-overexpressed human renal carcinoma Caki cells. ABT-737 alone had no effect on apoptosis, but cafestol markedly enhanced ABT-737-mediated apoptosis in Mcl-1-overexpressed Caki cells, human glioma U251MG cells, and human breast carcinoma MDA-MB231 cells. By contrast, co-treatment with ABT-737 and cafestol did not induce apoptosis in normal human skin fibroblast. Furthermore, combined treatment with cafestol and ABT-737 markedly reduced tumor growth compared with either drug alone in xenograft models. We found that cafestol inhibited Mcl-1 protein expression, which is important for ABT-737 resistance, through promotion of protein degradation. Moreover, cafestol increased Bim expression, and siRNA-mediated suppression of Bim expression reduced the apoptosis induced by cafestol plus ABT-737. Taken together, cafestol may be effectively used to enhance ABT-737 sensitivity in cancer therapy via downregulation of Mcl-1 expression and upregulation of Bim expression.

ß-Lapachone induces programmed necrosis through the RIP1-PARP-AIF-dependent pathway in human hepatocellular carcinoma SK-Hep1 cells.

ß-Lapachone activates multiple cell death mechanisms including apoptosis, autophagy and necrotic cell death in cancer cells. In this study, we investigated ß-lapachone-induced cell death and the underlying mechanisms in human hepatocellular carcinoma SK-Hep1 cells. ß-Lapachone markedly induced cell death without caspase activation. ß-Lapachone increased PI uptake and HMGB-1 release to extracellular space, which are markers of necrotic cell death. Necrostatin-1 (a RIP1 kinase inhibitor) markedly inhibited ß-lapachone-induced cell death and HMGB-1 release. In addition, ß-lapachone activated poly (ADP-ribosyl) polymerase-1(PARP-1) and promoted AIF release, and DPQ (a PARP-1 specific inhibitor) or AIF siRNA blocked ß-lapachone-induced cell death. Furthermore, necrostatin-1 blocked PARP-1 activation and cytosolic AIF translocation. We also found that ß-lapachone-induced reactive oxygen species (ROS) production has an important role in the activation of the RIP1-PARP1-AIF pathway. Finally, ß-lapachone-induced cell death was inhibited by dicoumarol (a NQO-1 inhibitor), and NQO1 expression was correlated with sensitivity to ß-lapachone. Taken together, our results demonstrate that ß-lapachone induces programmed necrosis through the NQO1-dependent ROS-mediated RIP1-PARP1-AIF pathway.

Antipsychotic agent thioridazine sensitizes renal carcinoma Caki cells to TRAIL-induced apoptosis through reactive oxygen species-mediated inhibition of Akt signaling and downregulation of Mcl-1 and c-FLIP(L).

Thioridazine has been known as an antipsychotic agent, but it also has anticancer activity. However, the effect of thioridazine on tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) sensitization has not yet been studied. Here, we investigated the ability of thioridazine to sensitize TRAIL-mediated apoptosis. Combined treatment with thioridazine and TRAIL markedly induced apoptosis in various human carcinoma cells, including renal carcinoma (Caki, ACHN, and A498), breast carcinoma (MDA-MB231), and glioma (U251MG) cells, but not in normal mouse kidney cells (TMCK-1) and human normal mesangial cells. We found that thioridazine downregulated c-FLIP(L) and Mcl-1 expression at the post-translational level via an increase in proteasome activity. The overexpression of c-FLIP(L) and Mcl-1 overcame thioridazine plus TRAIL-induced apoptosis. We further observed that thioridazine inhibited the Akt signaling pathway. In contrast, although other phosphatidylinositol-3-kinase/Akt inhibitors (LY294002 and wortmannin) sensitized TRAIL-mediated apoptosis, c-FLIP(L) and Mcl-1 expressions were not altered. Furthermore, thioridazine increased the production of reactive oxygen species (ROS) in Caki cells, and ROS scavengers (N-acetylcysteine, glutathione ethyl ester, and trolox) inhibited thioridazine plus TRAIL-induced apoptosis, as well as Akt inhibition and the downregulation of c-FLIP(L) and Mcl-1. Collectively, our study demonstrates that thioridazine enhances TRAIL-mediated apoptosis via the ROS-mediated inhibition of Akt signaling and the downregulation of c-FLIP(L) and Mcl-1 at the post-translational level.

Development and validation of a predictive model for foodborne pathogens in ready-to-eat pork as a function of temperature and a mixture of potassium lactate and sodium diacetate.

We developed and validated secondary models that can predict growth parameters of Salmonella Typhimurium and Staphylococcus aureus in cooked-pressed ready-to-eat (RTE) pork as a function of concentrations (0 to 3%) of a commercial potassium lactate and sodium diacetate mixture (PL+SDA) and temperature (10 to 30°C). The primary growth data were fitted to a Gompertz equation to determine the lag time (LT) and growth rate (GR). At 10°C, the growth of Salmonella Typhimurium and S. aureus in cooked-pressed RTE pork containing 2% and 3% PL+SDA was completely inhibited. The effects of temperature and concentration of PL+SDA on the growth kinetics of Salmonella Typhimurium and S. aureus in cooked-pressed RTE pork were modeled by response surface analysis using polynomial models of the natural logarithm transformation of both LT and GR. Model performance was also evaluated by use of the prediction bias (B(f)) and accuracy (A(f)) factors, median relative error, and mean absolute relative error, as well as the acceptable prediction zone method. The results showed that LT and GR models of Salmonella Typhimurium and S. aureus in cooked-pressed RTE pork are acceptable models. Thus, both the LT and GR growth models developed herein can be used for the development of tertiary models for Salmonella Typhimurium and S. aureus in cooked-pressed RTE pork in the matrix of conditions described in the present study.

Responses of acid-stressed Salmonella Typhimurium in broth and chicken patties to subsequent antimicrobial stress with epsilon-polylysine and combined potassium lactate and sodium diacetate.

We investigated the growth kinetics and morphological changes in acid-stressed Salmonella Typhimurium as well as the antimicrobial effects of epsilon-polylysine (SAVE-ORY GL610) and combined potassium lactate (PL) and sodium diacetate (SDA) (PURASAL Opti.Form PD Plus) on acid-stressed S. Typhimurium. Exposure to 0.5% acetic or lactic acid injured over 90% of the S. Typhimurium population. Although the lag time of the injured S. Typhimurium was extended, the injured cells were recovered at 10 degrees C and 24 degrees C, indicating a risk of using 10 degrees C as a storage temperature. Additionally, 4.5% PL/SDA mixture or 2% epsilon-polylysine completely inhibited the growth of acid-stressed S. Typhimurium in broth at 10, 24, or 35 degrees C. Although 3% PL/SDA mixture inhibited the growth of lactic acid-stressed S. Typhimurium at 10 degrees C, it did not inhibit the growth of unstressed S. Typhimurium at the same temperature. This finding indicates a different antimicrobial effect due to the physiological status of the pathogen. Furthermore, acid-stressed S. Typhimurium was not resistant to epsilon-polylysine or the PL/SDA mixture, although the antimicrobial effect of these compounds was enhanced at a lower storage temperature. TEM analysis revealed that most of the stressed cells lost their cellular integrity and membranes partially. Both dead and doubling cells were observed after recovery at 30 degrees C for 12 h. The addition of 2% epsilon-polylysine or 4.5% PL/SDA mixture resulted in the collapse of the structure of S. Typhimurium cells and cytoplasmic materials being released. These results provide valuable information regarding the morphological and physiological responses of acid-stressed S. Typhimurium cells in broth and chicken patties followed by antimicrobial stress with epsilon-polylysine or PL/SDA mixture.

A model of the effect of temperature on the growth of pathogenic and nonpathogenic Vibrio parahaemolyticus isolated from oysters in Korea.

Vibrio parahaemolyticus is recognized as the leading cause of human gastroenteritis associated with the consumption of seafood. The objective of this study was to model the growth kinetics of pathogenic and nonpathogenic V. parahaemolyticus in broth and oyster slurry. Primary growth models of V. parahaemolyticus in broth and oyster slurry fit well to a modified Gomperz equation (broth R(2)=0.99; oyster slurry R(2)=0.96). The lag time (LT), specific growth rate (SGR), and maximum population density (MPD) of each primary model were compared. The growth of nonpathogenic V. parahaemolyticus was found to be more rapid than that of pathogenic V. parahaemolyticus, regardless of the model medium. In addition, significant (P<0.05) differences in the growth kinetics between pathogenic and nonpathogenic V. parahaemolyticus in broth were observed at 10 degrees C. When compared to growth in broth, the growth of V. parahaemolyticus was delayed in oyster slurry, and growth was not observed at 10 or 15 degrees C. The Davey and square root models were identified as appropriate secondary models for predicting the LT and SGR, respectively. For the broth model, the average B(f) and A(f) values for LT were found to be 0.97 and 1.3, respectively, whereas the average B(f) and A(f) values for SGR were 1.05 and 1.11, respectively. The model generated in this study predicted an LT that was shorter and an SGR that was similar to those that were actually observed, which indicates that these models provide a reliable and safe prediction of V. parahaemolyticus growth.

Apolipoprotein E genotype in Korean schizophrenic patients.

The apolipoprotein E (APOE) epsilon4 allele is a known risk factor for the development of Alzheimer's disease, however, an association of the APOE genotype with schizophrenia is controversial. We investigated the association in 60 Korean schizophrenic patients and 60 healthy controls. APOE genotypes were identified by reverse hybridization-based line probe assay. There were significant differences in the distribution of APOE genotypes between schizophrenic patients and controls. APOE epsilon2 and epsilon3 allele frequencies in schizophrenic patients were significantly different from those in controls. Our results suggest that APOE alleles seem to be operative in the pathogenesis of schizophrenic disorders.

Analysis of the immunologic mechanism of intravesical bacillus Calmette-Guerin therapy for superficial bladder tumors: distribution and function of immune cells.

Intravesical bacillus Calmette-Guerin (BCG) administration has been used as an adjuvant therapy after transurethral resection for superficial bladder cancer, but the exact mechanisms of its antitumor activity are not yet known. The aim of this study was to characterize the immunologic aspects of antitumor activity of BCG using an animal model. C3H/He inbred mice and murine bladder tumor cell line, MBT-2 were used. The changes in immune cells such as helper T cells, suppressor T cells, macrophages and natural killer cells in the bladder and spleen were analysed by immunohistochemical method in intravesical BCG instilled in normal bladder, MBT-2 implanted after electrocauterization of the bladder mucosa and MBT-2 implanted and intravesical BCG treated group. The changes in natural killer cell activity of the splenocytes and peritoneal lymphocytes were evaluated using 51chromium release assay at regular time intervals following intraperitoneal BCG instillation. The prophylactic anticancer effect was evaluated by observing the tumor growth in the intravesically BCG treated group after intravesical MBT-2 implantation. In immunohistochemical examination, a remarkable infiltration of macrophage and helper T cell was observed in the lamina propria of the bladder, and the helper and suppressor T cells ratio (Th/Ts ratio) was increased after intravesical BCG therapy. In 51chromium release assay, enhanced natural killer cell activity of the splenocytes and peritoneal lymphocytes was observed after intraperitoneal BCG inoculation. The growth of implanted tumor was suppressed following intravesical instillation of BCG. These results suggest that the antitumor activity of BCG is not related to the simple inflammatory reaction but to the local and systemic immune response in which helper T lymphocytes and mononuclear cells play an important role.