Complementary Roles in Cancer Prevention: Protease Inhibitor Makes the Cancer Preventive Peptide Lunasin Bioavailable

9 páginas, 6 figuras.-- et al.[Background]: The lower incidence of breast cancer among Asian women compared with Western countries has been partly attributed to soy in the Asian diet, leading to efforts to identify the bioactive components that are responsible. Soy Bowman Birk Inhibitor Concentrate (BBIC) is a known cancer preventive agent now in human clinical trials. [Methodology/Principal Findings]: The objectives of this work are to establish the presence and delineate the in vitro activity of lunasin and BBI found in BBIC, and study their bioavailability after oral administration to mice and rats. We report that lunasin and BBI are the two main bioactive ingredients of BBIC based on inhibition of foci formation, lunasin being more efficacious than BBI on an equimolar basis. BBI and soy Kunitz Trypsin Inhibitor protect lunasin from in vitro digestion with pancreatin. Oral administration of 3H-labeled lunasin with lunasin-enriched soy results in 30% of the peptide reaching target tissues in an intact and bioactive form. In a xenograft model of nude mice transplanted with human breast cancer MDA-MB- 231 cells, intraperitoneal injections of lunasin, at 20 mg/kg and 4 mg/kg body weight, decrease tumor incidence by 49% and 33%, respectively, compared with the vehicle-treated group. In contrast, injection with BBI at 20 mg/kg body weight shows no effect on tumor incidence. Tumor generation is significantly reduced with the two doses of lunasin, while BBI is ineffective. Lunasin inhibits cell proliferation and induces cell death in the breast tumor sections. [Conclusions/Significance]: We conclude that lunasin is actually the bioactive cancer preventive agent in BBIC, and BBI simply protects lunasin from digestion when soybean and other seed foods are eaten by humans.Project number 05B087 awarded by the American Institute for Cancer Research (http://www.aicr.org/site/PageServer). Project number W81XWH-04-1- 0128 awarded by the United States Department of Defense Congressionally Directed Medical Research Program (https://cdmrp.org). Project LUNAMICE 039241 awarded by the European Commission and the Spanish National Research Council for the Marie-Curie postdoctoral fellowship of BHL.Peer reviewe

Effect of moderate-intensity statin therapy on plaque inflammation in patients with acute coronary syndrome: A prospective interventional study evaluated by 18F-FDG PET/CT of the carotid artery

Background: Asian patients with acute coronary syndrome (ACS) are frequently prescribed moderate- -intensity statin in real practice, even during the early stage of ACS. Under assessment herein was the effect of moderate-intensity statin therapy on the resolution of plaque inflammation during the first month after ACS, a period with highest recurrent ischemic events, using dual time point 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT).Methods: This prospective study included statin-naïve patients with ACS and non-calcified carotid plaques (≥ 3 mm on ultrasound images). Baseline FDG PET/CT images of the carotid arteries of the patients were obtained. Then, all patients received atorvastatin (20 mg/day); follow-up FDG PET/CT images of the carotid arteries were then obtained after 1 month of therapy. The primary endpoint measurement was the change in the target-to-background ratio (TBR) of the carotid artery between the initial and follow-up FDG PET/CT scans.Results: Thirteen ACS patients completed the initial and follow-up FDG PET/CT scans. Moderate-intensity statin therapy failed to reduce plaque inflammation at 1 month after ACS (TBR 1.60 ± 0.20 at baseline vs. 1.50 ± 0.40 after therapy; p = 0.422) but significantly reduced serum low-density lipoprotein cholesterol (LDL-C) levels (mean LDL-C 101.2 ± 21.1 mg/dL at baseline vs. 70.7 ± 12.4 mg/dL after therapy; p < 0.001). Changes in the TBR and serum LDL-C levels were not correlated (r = –0.27, p = 0.243).Conclusions: Dual time point FDG PET/CT imaging demonstrates that moderate-intensity statin therapy was insufficient in suppressed plaque inflammation within the first month after ACS in Asian patients, even though achieving target LDL levels

Subspecific Status of the Korean Tiger Inferred by Ancient DNA Analysis

The tiger population that once inhabited the Korean peninsula was initially considered a unique subspecies (Panthera tigris coreensis), distinct from the Amur tiger of the Russian Far East (P. t. altaica). However, in the following decades, the population of P. t. coreensis was classified as P. t. altaica and hence forth the two populations have been considered the same subspecies. From an ecological point of view, the classification of the Korean tiger population as P. t. altaica is a plausible conclusion. Historically, there were no major dispersal barriers between the Korean peninsula and the habitat of Amur tigers in Far Eastern Russia and northeastern China that might prevent gene flow, especially for a large carnivore with long-distance dispersal abilities. However, there has yet to be a genetic study to confirm the subspecific status of the Korean tiger. Bone samples from four tigers originally caught in the Korean peninsula were collected from two museums in Japan and the United States. Eight mitochondrial gene fragments were sequenced and compared to previously published tiger subspecies\u27 mtDNA sequences to assess the phylogenetic relationship of the Korean tiger. Three individuals shared an identical haplotype with the Amur tigers. One specimen grouped with Malayan tigers, perhaps due to misidentification or mislabeling of the sample. Our results support the conclusion that the Korean tiger should be classified as P. t. altaica, which has important implications for the conservation and reintroduction of Korean tigers

Immune reconstitution after allogeneic hematopoietic stem cell transplantation in children: a single institution study of 59 patients

PurposeLymphocyte subset recovery is an important factor that determines the success of hematopoietic stem cell transplantation (HSCT). Temporal differences in the recovery of lymphocyte subsets and the factors influencing this recovery are important variables that affect a patient's post-transplant immune reconstitution, and therefore require investigation.MethodsThe time taken to achieve lymphocyte subset recovery and the factors influencing this recovery were investigated in 59 children who had undergone HSCT at the Department of Pediatrics, The Catholic University of Korea Seoul St. Mary's Hospital, and who had an uneventful follow-up period of at least 1 year. Analyses were carried out at 3 and 12 months post-transplant. An additional study was performed 1 month post-transplant to evaluate natural killer (NK) cell recovery. The impact of pre- and post-transplant variables, including diagnosis of Epstein-Barr virus (EBV) DNAemia posttransplant, on lymphocyte recovery was evaluated.ResultsThe lymphocyte subsets recovered in the following order: NK cells, cytotoxic T cells, B cells, and helper T cells. At 1 month post-transplant, acute graft-versus-host disease was found to contribute significantly to the delay of CD16+/56+ cell recovery. Younger patients showed delayed recovery of both CD3+/CD8+ and CD19+ cells. EBV DNAemia had a deleterious impact on the recovery of both CD3+ and CD3+/CD4+ lymphocytes at 1 year post-transplant.ConclusionIn our pediatric allogeneic HSCT cohort, helper T cells were the last subset to recover. Younger age and EBV DNAemia had a negative impact on the post-transplant recovery of T cells and B cells

Testosterone deficiency caused by castration increases adiposity in male rats in a tissue-specific and diet-dependent manner

Abstract Background Testosterone deficiency in men is clinically associated with the development of metabolic syndrome, which manifests as obesity, hepatic steatosis, and type-2 diabetes. We investigated the effects of castration-induced testosterone deficiency on body adiposity and the expression of genes related to lipid metabolism and glucose uptake and androgen signaling in male rats fed a normal diet (ND) or a high-fat diet (HFD). Methods Changes in lipid and glucose metabolism and androgen signaling were investigated at physiological and molecular levels in the muscle, liver, and adipose tissues of non-castrated and castrated rats under ND or HFD feeding. Results Castration-induced testosterone deficiency predisposed animals on ND to early development of fatty liver by activating fatty acid (FA) synthesis, whereas HFD activated hepatic FA uptake CD36 expression, leading to the development of hepatic steatosis. In rats fed ND, castration induced muscle fat accumulation by activating CD36 expression. In the subcutaneous fat of ND-fed rats, castration increased adiposity and the expression of FA synthesis-related genes, but it decreased glucose transporter gene expression. In the abdominal fat of rats fed ND, castration increased adiposity by upregulating FA synthesis-related genes, and HFD promoted adiposity by inducing FA uptake, glucose transporter, and FA synthesis-related gene expression. In rats fed ND, castration decreased body growth and muscle weight and downregulated the expression of genes androgen signaling in the longissimus dorsi muscle. Conclusions Testosterone deficiency increases adiposity in a tissue-specific and diet-dependent manner. Testosterone deficiency decreases body and muscle weights and downregulates androgen signaling