The effect of "Nutramil^{TM} Complex," food for special medical purpose, on breast and prostate carcinoma cells

NutramilTM Complex is a multicomponent food product that meets the requirements of a food for special medical purpose. As a complete, high-energy diet it consists of properly balanced nutrients, vitamins and minerals. The aim of this study was to assess the effect of NutramilTM Complex on breast and prostate carcinoma cells. Our results showed that NutramilTM Complex reduced the viability and proliferation of breast and prostate cancer cells and that this process was associated with the induction of apoptosis via activation of caspase signalling. Data showed elevated levels of p53 tumour suppressor, up-regulation of p38 MAPK and SAPK / JNK proteins and downregulation of anti-apoptotic ERK1/2, AKT1 and HSP27. Treatment with NutramilTM Complex also affected the expression of the BCL2 family genes. Results also showed down-regulation of anti-apoptotic BCL-2 and up-regulation of pro-apoptotic members such as BAX, BAD, BID. In addition, we also observed regulation of many other genes, including Iκβα, Chk1 and Chk2, associated with apoptotic events. Taken together, our results suggest activation of the mitochondrial apoptotic pathway as most likely mechanism of anti-carcinogenic activity of NutramilTM Complex

Recent progress in discovering the role of carotenoids and metabolites in prostatic physiology and pathology - a review - part II : carotenoids in the human studies

Among the vast variety of plant-derived phytochemicals, the group of carotenoids has continuously been investigated in order to optimize their potential application in the area of dietary intervention related to chronic diseases. One organ that has been especially targeted in many of these studies and clinical trials is the human prostate. Without doubt, carotenoids (and their endogenous derivatives—retinoids and apo-carotenoids) are involved in a plethora of intra- and intercellular signaling, cell growth, and differentiation of prostate tissue. Due to the accumulation of new data on the role of different carotenoids, such as lycopene (LYC) and β-carotene (BC), in prostatic physiology and pathology, the present review aimed to cover the past ten years of research in this regard. Data from experimental studies are presented in the first part of the review, while epidemiological studies are disclosed in this second part. The objective of this compilation was to emphasize the present state of knowledge about the most potent molecular targets of carotenoids, as well as to propose promising carotenoid agents for the prevention and possible treatment of prostatic diseases

Single-centre, double-blinded, randomised placebo-controlled trial to determine the effect of a 12-week home-based programme of footplate neuromuscular electrical stimulation on walking capacity in people with peripheral artery disease: a protocol for the Foot-PAD trial

Introduction Patients with peripheral artery disease (PAD) can experience intermittent claudication, which limits walking capacity and the ability to undertake daily activities. While exercise therapy is an established way to improve walking capacity in people with PAD, it is not feasible in all patients. Neuromuscular electrical stimulation (NMES) provides a way to passively induce repeated muscle contractions and has been widely used as a therapy for chronic conditions that limit functional capacity. Preliminary trials in patients with PAD demonstrate that stimulation of the leg muscles using a footplate-NMES device can be performed without pain and may lead to significant gains in walking capacity. Studies, to date, have been small and have not been adequately controlled to account for any potential placebo effect. Therefore, the current trial will compare the effect of a 12-week programme of footplate-NMES with a placebo-control on walking capacity (6 min walking distance) and other secondary outcomes in patients with PAD. Methods and analysis The Foot-PAD trial is a double-blinded, randomised placebo-controlled trial to determine the effect of a 12-week home-based programme of footplate NMES on walking capacity in people with PAD. This is a single-centre trial with numerous recruitment locations. A total of 180 participants with stable PAD and intermittent claudication will be randomly assigned (1:1 ratio) to receive either footplate-NMES (intervention condition) or footplate-placebo (control condition) for two 30 min periods each day for 12 weeks. The footplate-NMES device will deliver stimulation sufficient to induce contraction of the leg muscles and repeated plantar and dorsiflexion at the ankles. The footplate-placebo device will deliver a momentary low-intensity transient stimulation that is insufficient to induce contraction of the leg muscles. Outcomes will be assessed at baseline (week 0), mid-intervention (week 6), postintervention (week 12) and 6 weeks after the completion of the intervention (week 18). The primary outcome is walking capacity at week 12, measured as maximum walking distance during the 6 min walk test. Secondary outcomes will include pain-free walking distance during the 6 min walk test; pain-free and maximum walking time during a graded treadmill walking test; disease-specific quality of life (Intermittent Claudication Questionnaire), self-reported walking impairment (Walking Impairment Questionnaire) and accelerometer-derived physical activity levels. Exploratory outcomes will include the Ankle-Brachial Index; leg vascular function; perception of device-use experience and symptom monitoring throughout the trial using the Claudication Symptom Instrument and a pain Visual Analogue Scale. Ethics and dissemination The Foot-PAD trial has received ethics approval from the Human Research Ethics Committees of Queensland Health Metro North Hospital and Health Service (78962) and the University of the Sunshine Coast (A21659). Regardless of the study outcomes, the study findings will be published in peer-reviewed scientific journals and presented at scientific meetings

Roles of GSK-3 and microRNAs on epithelial mesenchymal transition and cancer stem cells

Various signaling pathways exert critical roles in the epithelial to mesenchymal transition (EMT) and cancer stem cells (CSCs). The Wnt/beta-catenin, PI3K/PTEN/ Akt/mTORC, Ras/Raf/MEK/ERK, hedgehog (Hh), Notch and TP53 pathways elicit essential regulatory influences on cancer initiation, EMT and progression. A common kinase involved in all these pathways is moon-lighting kinase glycogen synthase kinase-3 (GSK-3). These pathways are also regulated by micro-RNAs (miRs). TP53 and components of these pathways can regulate the expression of miRs. Targeting members of these pathways may improve cancer therapy in those malignancies that display their abnormal regulation. This review will discuss the interactions of the multi-functional GSK-3 enzyme in the Wnt/beta-catenin, PI3K/PTEN/Akt/mTORC, Ras/Raf/MEK/ERK, Hh, Notch and TP53 pathways. The regulation of these pathways by miRs and their effects on CSC generation, EMT, invasion and metastasis will be discussed